US2008070864A1PendingUtilityA1
Quinazolinone Modulators Of Nuclear Receptors
Est. expiryMar 7, 2022(expired)· nominal 20-yr term from priority
A61P 3/10A61P 37/00A61P 9/10A61P 3/06A61P 9/00A61P 7/00A61P 29/00A61P 3/04A61P 3/00A61P 35/00A61P 27/00A61P 25/16A61P 25/28C07D 239/91A61P 1/16C07D 413/12A61P 17/10C07D 409/12C07D 239/90A61P 17/00
48
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Claims
Abstract
Compounds, pharmaceutical compositions and methods for modulating the activity of nuclear receptors are provided. In particular, quinazolinones are provided for modulating the activity of farnesoid X receptor (FXR) and/or orphan nuclear receptors.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
wherein:
m is an integer from 0 to 4;
R 1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 or —N(R 8 )R 9 , with the proviso that R 1 is not 3- or 4-(1,1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)phenyl;
R 2 , R 4 , R 5 and R 6 are selected from (a) and (b) as follows:
(a) R 2 and R 6 are selected from (i) and (ii) as follows: (i) R 2 and R 6 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocyclylalkyl; or (ii) R 2 and R 6 together form optionally substituted alkylene or optionally substituted alkenylene; and
R 4 and R 5 are selected from (i) and (ii) as follows: (i) R 4 and R 5 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 8 )R 9 ), —OR 7 , —S(O) j R 11 where j is 1 or 2, —B(R 22 ) 2 , —P(R 22 ) 2 , —P(O)(R 22 ) 2 and —C(E)R 23 , where E is selected from O, S and NR 7 ; or (ii) R 4 and R 5 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene; or
(b) R 2 and R 5 , or R 2 and R 4 , or R 6 and R 5 , or R 6 and R 4 , together form a 4, 5, 6 or 7 membered optionally substituted heterocyclyl group, or a 5 or 6 membered optionally substituted heteroaryl group; and the remainder of R 2 , R 4 , R 5 and R 6 are each independently selected as in (i) above;
each R 3 is independently selected from the group consisting of halo, pseudohalo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 12 )R 13 , —OR 14 , —C(E)R 15 where E is O, S or NR 7 , and —S(O) y R 16 where y is 0, 1 or 2;
or any two R 3 groups, which substitute adjacent carbons on the ring, together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkylenedioxy, optionally substituted thioalkylenoxy, or optionally substituted alkylenedithioxy;
each R 7 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
R 8 and R 9 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —S(O) j R 10 where j is 1 or 2, and —C(M)R 11 , where M is selected from O and S;
or R 8 and R 9 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 10 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
each R 11 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 and —N(R 7 ) 2 ;
R 12 and R 13 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —C(M)R 17 where M is O or S, and —S(O) j R 18 where j is 1 or 2;
or R 12 and R 13 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene;
R 14 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl or —C(M)R 17 where M is O or S;
R 15 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 14 or —N(R 12 )R 13 ;
R 16 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 19 or —N(R 20 )R 21 ;
R 17 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 18 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 19 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl;
R 20 and R 21 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl,
or R 20 and R 21 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 22 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 and —N(R 7 ) 2 ;
R 23 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 , —N(R 7 ) 2 , or —N(R 7 )N(R 7 ) 2 ;
wherein each of the above R 1 -R 23 groups, when substituted, are substituted with one or more substituents each independently selected from Q 1 , where Q 1 is halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 1 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 1 groups, which substitute the same atom, together form alkylene;
each R 24 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl;
each R 25 is independently selected from the group consisting of hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl and —N(R 27 )R 28
R 26 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or —N(R 27 )R 28 R 27 and R 28 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl,
or R 27 and R 28 together form alkylene, azaalkylene, oxaalkylene or thiaalkylene;
and each Q 1 is optionally substituted by one or more substituents selected from Q 2 ; where each Q 2 is independently halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 2 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 2 groups, which substitute the same atom, together form alkylene,
where R 24 , R 25 , R 26 , R 27 and R 28 are as defined above;
as a stereoisomer, racemate or mixture thereof; or as a pharmaceutically acceptable derivative thereof;
with the proviso that the compound of formula (I) can not be N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide.
2 . The compound of claim 1 wherein the compound of formula (I) is a compound of formula (II):
wherein:
n is an integer from 0 to 5;
m is an integer from 0 to 4;
each R 1a and R 3 are independently selected from the group consisting of halo, pseudohalo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 12 )R 13 , —OR 14 , —C(E)R 15 where E is O, S or NR 7 , and —S(O) y R 16 where y is 0, 1 or 2, with the proviso that R 1a is not 3- or 4-C(OH)(CF 3 ) 2 ;
or any two R 1a groups or R 3 groups, which substitute adjacent carbons on the ring, together with atoms to which they are attached, form optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, or optionally substituted aryl;
R 2 , R 4 , R 5 and R 6 are selected from (a) and (b) as follows:
(a) R 2 and R 6 are selected from (i) and (ii) as follows: (i) R 2 and R 6 are each independently hydrogen or optionally substituted alkyl; or (ii) R 2 and R 6 together form alkylene or alkenylene;
R 4 and R 5 are selected from (i) and (ii) as follows: (i) R 4 and R 5 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 8 )R 9 , —OR 7 , S(O) j R 11 where j is 1 or 2, —B(R 22 ) 2 , —P(R 22 ) 2 , —P(O)(R 22 ) 2 , and —C(E)R 23 where E is selected from O, S and NR 7 ; or (ii) R 4 and R 5 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene;
(b) R 2 and R 5 , or R 2 and R 4 , or R 6 and R 5 , or R 6 and R 4 , together form a 5, 6 or 7 membered optionally substituted heterocyclyl group, or a 5 or 6 membered optionally substituted heteroaryl group; and the remainder of R 2 , R 4 , R 5 and R 6 are each independently selected as in (i) above;
each R 7 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
R 8 and R 9 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —S(O) j R 10 where j is 1 or 2, and —C(M)R 11 , where M is selected from O and S;
or R 8 and R 9 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 10 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
each R 11 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 and —N(R 7 ) 2 ;
R 12 and R 13 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —C(M)R 17 where M is O or S, and —S(O) j R 14 where j is 1 or 2;
or R 12 and R 13 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
R 14 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl or —C(M)R 17 where m is O or S;
R 15 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 19 or —N(R 20 )R 21 ;
R 16 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 19 or —N(R 20 )R 21 ;
R 17 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 18 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 19 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl;
R 20 and R 21 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl,
or R 20 and R 2 together form alkylene, alkenylene or alkyleneoxyalkylene;
each R 22 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 and —N(R 7 ) 2 ;
R 23 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 , —N(R 7 ) 2 , —N(R 7 )N(R 7 ) 2 ;
wherein each of the above R 1 -R 23 groups, when substituted, are substituted with one or more substituents each independently selected from Q 1 , where Q 1 is halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 1 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 1 groups, which substitute the same atom, together form alkylene;
each R 24 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl;
each R 25 is independently selected from the group consisting of hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl and —N(R 27 )R 28 ,
R 26 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or —N(R 27 )R 28 ;
R 27 and R 28 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl,
or R 27 and R 28 together form alkylene, azaalkylene, oxaalkylene or thiaalkylene;
and each Q 1 is optionally substituted by one or more substituents selected from Q 2 ; where each Q 2 is independently halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 2 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 2 groups, which substitute the same atom, together form alkylene,
where R 24 , R 25 R 26 , R 27 and R 28 are as defined above;
as a stereoisomer, racemate or mixture thereof; or as a pharmaceutically acceptable derivative thereof.
3 . The compound of claim 2 wherein the compound of formula (II) is a compound of formula (III):
wherein:
n is an integer from 0 to 5;
m is an integer from 0 to 4;
t is an integer from 0 to 5;
each R 1a is independently selected from the group consisting of alkyl, hydroxy, alkoxy, alkoxyalkoxy, aralkoxy, amino, alkylamino, dialkylamino, halo, haloalkyl, haloalkoxy, cyano, carboxy, alkoxycarbonyl, alkoxycarbonylalkoxy, heteroaryl, heterocyclyl, heterocyclylalkoxy, and aryl (optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halo, cyano, carboxy, cyano, and alkoxycarbonyl);
R 2 is hydrogen or alkyl′
each R 3 is independently selected from the group consisting of alkyl, alkoxy, halo, hydroxy, aralkoxy, alkoxycarbonylalkoxy, aryl (optionally substituted by one or more substituents independently selected from the group consisting of alkyl, halo, alkoxy, carboxy, alkoxycarbonyl, cyano), heteroaryl and heterocyclyl;
R 4 is hydrogen or alkyl;
each R 5a is independently selected from the group consisting of alkyl, alkoxy, halo, alkylcarbonyl, haloalkyl, haloalkoxy, aryl, cyano, carboxy, alkoxycarbonyl, nitro, and —N(R 24 )C(O)R 26 ;
or two adjacent R 5a groups form an aryl, heterocyclyl or heteroaryl; and
R 6 is hydrogen or alkyl.
4 . The compound of claim 3 wherein m is 0 or 1, n is 1 and R 1a is independently selected from alkoxy, halo, haloalkyl, haloalkoxy, cyano, optionally substituted aryl, heterocyclyl and heteroaryl.
5 . The compound of claim 4 selected from the group consisting of the following:
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzenesulfonamide;
N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-methylbenzenesulfonamide;
4-tert-butyl-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzenesulfonamide;
4-methoxy-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzenesulfonamide;
4-chloro-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
4-({1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-methyl-sulfamoyl)-benzoic acid;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
4-methoxy-N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-butyl-N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
2,4,6-trichloro-N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
4-methoxy-N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-butyl-N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
2,4,6-trichloro-N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
4-methoxy-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-butyl-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
2,4,6-trichloro-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzenesulfonamide;
N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
4-tert-butyl-N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzenesulfonamide;
N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
2,4,6-trichloro-N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
4-methoxy-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
4-butyl-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
2,4,6-trichloro-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[8-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[8-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[8-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[5-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[5-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[5-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[6-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[6-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[6-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(2-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-isopropyl-N-{1-[3-(2-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(2-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[8-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[8-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[8-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-isopropoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-isobutoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-n-butoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-methoxy-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-methoxy-N-{1-[3-(4-cyanophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide.
4-tert-butyl-N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide:
N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzenesulfonamide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-tert-butyl-N-methylbenzenesulfonamide:
4-tert-butyl-N-{1-[3-(4-cyanophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]-ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide:
biphenyl-4-sulfonic acid-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]-ethyl}-4,N-dimethylbenzenesulfonamide,
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-chloro-N-methylbenzenesulfonamide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-trifluoromethoxyphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide,
4-isopropyl-N-methyl-N-{1-[4-oxo-3-(4-trifluoromethoxyphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide,
biphenyl-4-sulfonic acid methyl-{1-[4-oxo-3-(4-trifluoromethoxyphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-amide;
4-tert-butyl-N-{1-[3-(4-fluorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide,
N-{1-[3-(4-fluorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-fluorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-trifluoromethylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide;
4-isopropyl-N-methyl-N-{1-[4-oxo-3-(4-trifluoromethylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide;
biphenyl-4-sulfonic acid methyl-{1-[4-oxo-3-(4-trifluoromethylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-amide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzenesulfonamide;
N-[1-(3-biphenyl-4-yl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]-4-tert-butyl-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(3′-methoxy-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(3′-chloro-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide:
4-tert-butyl-N-methyl-N-{1-[3-(4′-methyl-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide;
4-tert-butyl-N-{1-[3-(2′-chloro-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4′-chloro-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]-ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(2′-methoxy-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4′-methoxy-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4′-(2-{1-[(4-tert-butylbenzenesulfonyl)methylamino]ethyl}-4-oxo-4H-quinazolin-3-yl)-biphenyl-4-carboxylic acid;
4-tert-butyl-N-{1-[3-(4′-cyano-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-thiophen-3-ylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}benzenesulfonamide;
4′-(2-{1-[(4-tert-butylbenzenesulfonyl)methylamino]ethyl}-4-oxo-4H-quinazolin-3-yl)-biphenyl-3-carboxylic acid methyl ester;
4′-(2-{1-[(4-tert-butylbenzenesulfonyl)methylamino]ethyl}-4-oxo-4H-quinazolin-3-yl)-biphenyl-4-carboxylic acid methyl ester,
4′-(2-{1-[(4-tert-butylbenzenesulfonyl)-methylamino]ethyl}-4-oxo-4H-quinazolin-3-yl)-biphenyl-3-carboxylic acid;
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-pyrrolidin-1-ylphenyl)-3,4-dihydroquinazolin-2-yl]-ethyl}benzenesulfonamide;
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-piperidin-1-yl-phenyl)-3,4-dihydroquinazolin-2-yl]ethyl}benzenesulfonamide; and
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-thiophen-2-ylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}benzenesulfonamide.
6 . The compound of claim 3 wherein m is 0 or 1, n is 1, 2 or 3 and each R 1a is selected from alkyl.
7 . The compound of claim 6 selected from the group consisting of the following:
quinoline-8-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
naphthalene-1-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
naphthalene-2-sulfonic acid {1-[3-(2,4-dim ethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
2-naphthalen-1-yl-ethanesulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,N-dimethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-3,N-dimethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-C-phenyl-methanesulfonamide;
4-acetyl-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-3-trifluoromethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethoxy-benzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,5,N-trimethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-3,4-dimethoxy-N-methylbenzenesulfonamide;
N-[4-({1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-methyl-sulfamoyl)-phenyl]-acetamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,4,6,N-tetramethylbenzenesulfonamide;
2-phenyl-ethenesulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
2,2,5,6,8-pentamethyl-chroman-7-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-3,4-difluoro-N-methylbenzenesulfonamide;
3-chloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,N-dimethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-5-fluoro-2,N-dimethylbenzenesulfonamide;
3,5-dimethyl-isoxazole-4-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-3-fluoro-N-methylbenzenesulfonamide;
2,4,6-trichloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
3-chloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-fluoro-N-methylbenzenesulfonamide;
2-chloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
5-chloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2-methoxy-N-methylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,5-dimethoxy-N-methylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,3,4-trifluoro-N-methylbenzenesulfonamide;
3-chloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-cyano-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-butyl-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-(1,1-dimethyl-propyl)-N-methylbenzenesulfonamide;
4-butoxy-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-3-methoxy-N-methylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2-methoxy-4,N-dimethylbenzenesulfonamide;
4-chloro-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2,5,N-trimethylbenzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-methanesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-methylbenzenesulfonamide;
4-tert-butyl-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-methoxy-benzenesulfonamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzenesulfonamide;
4-tert-butyl-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-methoxy-N-methylbenzenesulfonamide;
4-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
octane-1-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
quinoline-8-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
naphthalene-1-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,N-dimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-3,N-dimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4,N-dimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methyl-3-trifluoromethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methyl-4-trifluoromethoxy-benzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,5,N-trimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-3,4-dimethoxy-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,4,6,N-tetramethylbenzenesulfonamide;
2,2,5,6,8-pentamethyl-chroman-7-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-3,4-difluoro-N-methylbenzenesulfonamide;
3-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,N-dimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-5-fluoro-2,N-dimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methyl-4-trifluoromethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-3-fluoro-N-methylbenzenesulfonamide;
2,4,6-trichloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
3-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-fluoro-N-methylbenzenesulfonamide;
2-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
5-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2-methoxy-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,5-dimethoxy-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,3,4-trifluoro-N-methylbenzenesulfonamide;
3-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
4-cyano-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
4-butyl-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-(1,1-dimethyl-propyl)-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-4-isopropyl-N-methylbenzenesulfonamide;
4-butoxy-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-3-methoxy-N-methylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2-methoxy-4,N-dimethylbenzenesulfonamide;
4-chloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-2,5,N-trimethylbenzenesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methyl-3,5-bis-trifluoromethylbenzenesulfonamide; and
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methyl-4-nitro-benzenesulfonamide;
4-tert-butyl-N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4,N-dimethylbenzenesulfonamide;
N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzenesulfonamide;
N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-chloro-N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-4-trifluoromethylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-tert-butyl-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-tert-butyl-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-tert-butyl-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-isopropyl-N-methyl-N-[1-(4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
biphenyl-4-sulfonic acid methyl-[1-(4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]amide;
4-tert-butyl-N-[1-(6-methoxy-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-N-methylbenzenesulfonamide;
4-tert-butyl-N-[1-(6-hydroxy-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-N-methylbenzenesulfonamide;
N-[1-(6-bromo-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-4-tert-butyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid [1-(6-bromo-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]methylamide;
N-[1-(6-bromo-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-4-isopropyl-N-methylbenzenesulfonamide;
N-[1-(6-benzyloxy-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-4-tert-butyl-N-methylbenzenesulfonamide;
4-tert-butyl-N-[1-(6-isobutoxy-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-N-methylbenzenesulfonamide;
N-[1-(6-butoxy-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-4-tert-butyl-N-methylbenzenesulfonamide;
(2-{1-[(4-tert-butylbenzenesulfonyl)methylamino]ethyl}-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-6-yloxy)acetic acid ethyl ester;
4-tert-butyl-N-[1-(6-ethoxy-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-6-thiophen-3-yl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-6-phenyl-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-6-thiophen-2-yl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-{1-[3-(2′-methyl-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide;
4-tert-butyl-N-methyl-N-{1-[3-(3′-methyl-biphenyl-4-yl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-benzenesulfonamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-6-o-tolyl-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-3,6-di-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-tert-butyl-N-{1-[6-(2-chlorophenyl)-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[6-(4-chlorophenyl)-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[6-(2-methoxyphenyl)-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[6-(3-methoxyphenyl)-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[6-(4-methoxyphenyl)-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
3-(2-{1-[(4-tert-butyl-benzenesulfonyl)methylamino]ethyl}-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-6-yl)benzoic acid methyl ester;
4-(2-{1-[(4-tert-butyl-benzenesulfonyl)methylamino]ethyl}-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-6-yl)-benzoic acid methyl ester;
3-(2-{1-[(4-tert-butylbenzenesulfonyl)methylamino]ethyl}-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-6-yl)benzoic acid;
4-tert-butyl-N-{1-[6-(4-cyanophenyl)-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-[1-(6-morpholin-4-yl-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide; and
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-6-m-tolyl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-6-pyrrolidin-1-yl-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-[2-{1-[(4-tert-butyl-benzenesulfonyl)methylamino]ethyl}-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl]benzoic acid;
4-tert-butyl-N-methyl-N-[1-(4-oxo-6-piperidin-1-yl-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide; and
4-tert-butyl-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide.
8 . (canceled)
9 . (canceled)
10 . The compound of claim 3 wherein m is 0 or 1, n is 0 or 1 and each R 1a is selected from carboxy, dialkylamino, hydroxy, alkoxyalkoxy, alkoxycarbonylalkoxy, aralkoxy, and heterocyclylalkoxy.
11 . The compound of claim 10 selected from the group consisting of the following:
4-(2-{1-[(4-tert-butyl-benzenesulfonyl)methylamino]ethyl}-4-oxo-4H-quinazolin-3-yl)-benzoic acid;
4-tert-butyl-N-{1-[3-(4-dimethylamino-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
N-{1-[3-(4-dimethylamino-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-dimethylamino-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-isopropyl-N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
biphenyl-4-sulfonic acid methyl-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]amide;
N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-methoxy-N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4,N-dimethyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-chloro-N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]-4-trifluoromethylbenzenesulfonamide;
N-{1-[3-(4-benzyloxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-tert-butyl-N-methylbenzenesulfonamide;
N-{1-[3-(4-benzyloxy-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide;
biphenyl-4-sulfonic acid {1-[3-(4-benzyloxy-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-hydroxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[5-hydroxy-3-(4-hydroxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-(1-{4-oxo-3-[4-(2-piperidin-1-yl-ethoxy)phenyl]-3,4-dihydroquinazolin-2-yl}ethyl)benzenesulfonamide;
4-tert-butyl-N-methyl-N-(1-{3-[4-(2-morpholin-4-yl-ethoxy)phenyl]-4-oxo-3,4-dihydroquinazolin-2-yl}ethyl)benzenesulfonamide;
[4-(2-{1-[(4-tert-butylbenzenesulfonyl)methylamino]ethyl}-4-oxo-4H-quinazolin-3-yl)phenoxy]acetic acid ethyl ester; and
4-tert-butyl-N-(1-{3-[4-(2-methoxyethoxy)phenyl]-4-oxo-3,4-dihydroquinazolin-2-yl}ethyl)-N-methylbenzenesulfonamide.
12 . (canceled)
13 . (canceled)
14 . (canceled)
15 . The compound of claim 2 wherein the compound of formula (II) is a compound of formula (V):
wherein:
m is an integer from 0 to 4;
n is an integer from 0 to 5;
t is an integer from 0 to 5;
each R 1a is selected from the group consisting of alkyl, alkoxy, aralkoxy, halo, haloalkyl, haloalkoxy, amino, alkylamino, and dialkylamino;
R 2 , R 4 and R 6 are each independently hydrogen or alkyl;
each R 3 is independently selected from the group consisting of alkyl, alkoxy, and halo; and
each R 5a is independently selected from the group consisting of alkyl, alkoxy, alkoxycarbonyl, halo, and aryl
or two adjacent R 5a groups form an aryl, heterocyclyl or heteroaryl.
16 . The compound of claim 15 wherein m is 0 or 1, n is 1 and each R 1a is alkoxy.
17 . The compound of claim 16 selected from the group consisting of the following:
4-chloro-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
3-methoxy-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
4-methoxy-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
4-tert-butyl-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-terephthalamic acid methyl ester;
2,4-dichloro-N-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
benzo[1,3]dioxole-5-carboxylic acid [3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]amide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-terephthalamic acid methyl ester;
2-methoxy-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl)-N-methylbenzamide;
3-methoxy-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
4-methoxy-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-8-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-5-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[7-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[8-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[8-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[5-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[5-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[6-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[6-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
4-tert-butyl-N-{1-[3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(3-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(2-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(2-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[8-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[8-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide; and
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide.
18 . The compound of claim 15 wherein m is 0 or 1, n is 1, or 3 and each R 1a is selected from alkyl.
19 . The compound of claim 18 selected from the group consisting of the following:
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
4-tert-butyl-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
benzo[1,3]dioxole-5-carboxylic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]amide;
2,4-dichloro-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]benzamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-terephthalamic acid methyl ester;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-terephthalamic acid methyl ester;
benzo[1,3]dioxole-5-carboxylic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
4-tert-butyl-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylbenzamide;
4-tert-butyl-N-{1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-tert-butyl-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-tert-butyl-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-benzamide;
benzo[1,3]dioxole-5-carboxylic acid methyl-[1-(4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]amide;
benzo[1,3]dioxole-5-carboxylic acid [1-(6-bromo-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]methylamide; and
N-[1-(6-bromo-4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]-4-tert-butyl-N-methylbenzamide.
20 . The compound of claim 15 wherein m is 0 or 1, n is 0 or 1 and each R 1a is independently selected from dialkylamino, aralkoxy, halo, haloalkyl and haloalkoxy.
21 . The compound of claim 20 selected from the group consisting of the following:
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-dimethylamino-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-{1-[3-(4-dimethylamino-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-benzyloxy-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-benzyloxy-phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-tert-butyl-N-methylbenzamide;
N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-2-methoxy-N-methylbenzamide;
N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-3-methoxy-N-methylbenzamide;
N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-methoxy-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-terephthalamic acid methyl ester;
4-tert-butyl-N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]benzamide;
benzo[1,3]dioxole-5-carboxylic acid methyl-[1-(4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl]amide;
benzo[1,3]dioxole-5-carboxylic acid {1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-tert-butyl-N-methylbenzamide;
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-trifluoromethoxyphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}benzamide; and
benzo[1,3]dioxole-5-carboxylic acid methyl-{1-[4-oxo-3-(4-trifluoromethoxyphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-amide;
4-tert-butyl-N-{1-[3-(4-fluorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzamide;
benzo[1,3]dioxole-5-carboxylic acid methyl-{1-[4-oxo-3-(4-trifluoromethylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-amide; and
4-tert-butyl-N-methyl-N-{1-[4-oxo-3-(4-trifluoromethylphenyl)-3,4-dihydroquinazolin-2-yl]ethyl}-benzamide.
22 . The compound of claim 1 wherein R 1 is hydrogen, optionally substituted alkyl, optionally substituted aryl, or optionally substituted aralkyl.
23 . (canceled)
24 . (canceled)
25 . The compound of claim 22 wherein R 1 is optionally substituted phenyl, and is selected with the proviso that it is not substituted at the 3- or 4-position with —C(OH)(CF 3 ) 2 .
26 . The compound of claim 2 wherein any two R 1a or R 3 groups, which substitute adjacent carbons on the ring, together form alkylene, alkenylene, alkylenedioxy, thioalkylenoxy, or alkylenedithioxy.
27 . The compound of claim 2 wherein R 1a is not —C(OH)(CF 3 ) 2 .
28 . The compound of claim 1 wherein R 6 is hydrogen.
29 . The compound of claim 1 wherein n is 0, 1 or 2.
30 . The compound of claim 1 wherein m is 1.
31 . The compound of claim 2 wherein each R 1a is independently halo, pseudohalo, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted dialkylamino, optionally substituted aralkoxy, hydroxy, optionally substituted heteroaryl, optionally substituted heterocyclyl or optionally substituted cycloalkyl.
32 . (canceled)
33 . The compound of claim 31 wherein each R 1a is independently chloro, fluoro, ethyl, methyl, methoxy, bromo, cyano, phenyl, tert-butyl, trifluoromethoxy, dimethylamino, trifluoromethyl, benzyloxy, hydroxy, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, ethoxy, isopropoxy, butoxy, isobutoxy, 2-(N-morpholino)ethoxy, 2-methoxyethoxy, 4-cyanophenyl, 2-thienyl, 3-thienyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 3-carboxyphenyl, N-pyrrolidinyl, or N-morpholinyl.
34 . The compound of claim 1 wherein R 2 is hydrogen or optionally substituted alkyl, and R 6 is hydrogen.
35 . (canceled)
36 . The compound of claim 34 wherein R 2 is hydrogen, methyl or ethyl.
37 . The compound of claim 1 wherein each R 3 is independently optionally substituted alkyl, halo, pseudohalo, optionally substituted alkoxy, hydroxy, optionally substituted aralkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or optionally substituted cycloalkyl.
38 . (canceled)
39 . The compound of claim 37 wherein each R 3 is independently methyl, chloro, methoxy, hydroxy, bromo, ethoxy, isopropoxy, isobutoxy, butoxy, benzyloxy, ethoxycarbonylmethoxy, phenyl, 2-thienyl, 3-thienyl, 2-methylphenyl, 3-methylphenyl, 4-methylpheny, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-carboxyphenyl, N-pyrrolidinyl, N-morpholinyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 3-carboxyphenyl, 4-cyanophenyl, or piperidinyl.
40 . The compound of claim 1 wherein one of R 4 and R 1 is —SO 2 — (optionally substituted aryl).
41 . The compound of claim 1 wherein one of R 4 and R 5 is —SO 2 — (optionally substituted phenyl).
42 . The compound of claim 2 wherein the compound has formula (III):
or a pharmaceutically acceptable derivative thereof, wherein:
t is an integer from 0 to 5;
R 1a , R 2 , R 3 , R 4 , R 6 , n and m are as defined above;
each R 5a is independently optionally substituted alkyl, optionally substituted alkoxy, optionally substituted heteroaryl, optionally substituted aryl, optionally substituted heterocyclyl, halo, pseudohalo;
or any two R 5a substituents, which substitute adjacent atoms on the ring, together form a optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl ring having 5 or 6 members in the ring and where the heteroatoms, if present, are selected from O, S and optionally substituted N;
where R 5a , when substituted, is substituted with one or more, in one embodiment one to five, in another embodiment one, two or three, substituents each independently selected from Q 1 , as defined above.
43 . The compound of claim 42 wherein any two R 5a groups, which substitute adjacent carbons on the ring, together form —N═C(R 29 )—C(R 29 )═C(R 29 )— or —C(R 29 )═C(R 29 )—C(R 29 )═C(R 29 )—,
where each R 29 is independently hydrogen, halo, pseudohalo, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, or optionally substituted heteroaralkyl; where R 5a and R 29 , when substituted, are substituted with one or more, in one embodiment one to five, in another embodiment one, two or three, substituents each independently selected from Q 1 , as defined above.
44 . (canceled)
45 . The compound of claim 42 wherein each R 5a is independently tert-butyl, methoxy, methyl, trifluoromethoxy, 2-thienyl, fluoro, chloro, trifluoromethyl, phenyl, cyano, n-propyl, 1,1-dimethylpropyl, isopropyl, butoxy or n-butyl; or any two R 5a groups, which substitute adjacent carbons on the ring, together form —N═C(H)—C(H)═CH— or —C(H)═C(H)—C(H)═C(H)—.
46 . The compound of claim 42 wherein R 4 is hydrogen, optionally substituted alkyl, optionally substituted aralkyl, or optionally substituted heteroaralkyl.
47 . (canceled)
48 . The compound of claim 46 wherein R 4 is hydrogen, methyl, 2-methoxy-1-ethyl, propyl, isobutyl, butyl, pentyl, isopentyl, hexyl, benzyl, phenethyl or 2-thienylmethyl.
49 . The compound of claim 42 wherein one R 5a group is 4-tert-butyl or 4-isopropyl.
50 . The compound of claim 2 wherein the compound has formula (IV):
or a pharmaceutically acceptable derivative thereof, wherein R 1a , R 2 , R 3 , R 4 , R 6 , R 5a , m and n are selected as above; u is an integer from 0 to 4; and R 5b is tert-butyl or isopropyl.
51 . The compound of claim 50 wherein R 5b is tert-butyl or isopropyl.
52 . (canceled)
53 . The compound of claim 1 wherein one of R 4 and R 5 is —C(O)— (optionally substituted aryl).
54 . The compound of claim 53 wherein one of R 4 and R 5 is —C(O)— (optionally substituted phenyl).
55 . The compound of claim 2 wherein the compound has formula (V):
or a pharmaceutically acceptable derivative thereof, wherein R 1a , R 2 , R 3 , R 4 , R 6 , R 5a , t, n and m are as defined above.
56 . The compound of claim 55 wherein each R 1a is independently halo, optionally substituted alkyl, or optionally substituted alkoxy, where the substituents, when present, are each independently selected from Q 1 , as defined above.
57 . (canceled)
58 . The compound of claim 56 wherein each R 1a is independently methoxy, methyl, chloro or fluoro.
59 . The compound of claim 55 wherein R 2 is hydrogen or optionally substituted alkyl, where the substituents, when present, are each independently selected from Q 1 , as defined above.
60 . (canceled)
61 . The compound of claim 59 wherein R 2 is hydrogen or methyl.
62 . The compound of claim 55 wherein each R 3 is independently hydrogen or optionally substituted alkoxy, where the substituents, when present, are each independently selected from Q 1 , as defined above.
63 . (canceled)
64 . The compound of claim 62 wherein each R 3 is independently hydrogen or methoxy.
65 . The compound of claim 55 wherein R 4 is optionally substituted alkyl, where the substituents, when present, are each independently selected from Q 1 , as defined above.
66 . (canceled)
67 . The compound of claim 65 wherein R 4 is methyl or butyl.
68 . The compound of claim 55 wherein R 6 is hydrogen.
69 . The compound of claim 55 wherein each R 5a is independently optionally substituted alkyl, where the substituents, when present, are each independently selected from Q 1 , as defined above.
70 . (canceled)
71 . The compound of claim 69 wherein R 5a is tert-butyl.
72 . The compound of claim 1 wherein one of R 4 and R 1 is —C(O)— (optionally substituted alkyl), where the substituents, when present, are each independently selected from Q 1 , as defined above.
73 . (canceled)
74 . The compound of claim 72 wherein one of R 4 and R 5 is —C(O)-octyl.
75 . The compound of claim 1 wherein one of R 4 and R 5 is —C(O)—N(R 8 )R 9 , where R 8 and R 9 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
or R 8 and R 9 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene; where R 8 and R 9 are each independently unsubstituted or substituted with one or more, in one embodiment one to five, in another embodiment one, two or three, substituents each independently selected from Q 1 , as defined above.
76 . The compound of claim 75 wherein R 8 and R 9 are each independently selected from hydrogen, optionally substituted cycloalkyl, and optionally substituted aryl.
77 . (canceled)
78 . The compound of claim 76 wherein R 8 is hydrogen and R 9 is cyclohexyl, 4-nitrophenyl, 2-methoxyphenyl, 3-cyanophenyl, 3,4-dichlorophenyl, 2,6-diisopropylphenyl, 2-methylphenyl, 2-trifluoromethylphenyl, 2-fluorophenyl, 3-fluorophenyl, 3-methylphenyl, 3-chlorophenyl, 2,6-dimethylphenyl or 3-trifluoromethylphenyl.
79 . (canceled)
80 . The compound of claim 1 wherein R 4 and R 5 together form —CH 2 —C(H)(Me)—N(R 30 )—CH 2 —CH 2 —, where R 30 is optionally substituted heteroarylcarbonyl, optionally substituted alkylcarbonyl, optionally substituted arylcarbonyl, optionally substituted arylsulfonyl, optionally substituted alkylaminocarbonyl, or optionally substituted arylaminocarbonyl.
81 . The compound of claim 80 wherein R 30 is 2-thienylcarbonyl, butyryl, 4-fluorobenzoyl, benzyloxyacetyl, diphenylacetyl, 4-nitrobenzoyl, 2,5-dichlorobenzenesulfonyl, tert-butylaminocarbonyl, phenylaminocarbonyl, 2,3-dichlorophenylaminocarbonyl, 4-tert-butylphenylsulfonyl or 3,4-methylenedioxybenzoyl.
82 . (canceled)
83 . The compound of claim 1 wherein Q 2 is nitro, fluoro, benzyloxy or chloro; or any two Q 2 groups, which substitute adjacent carbons, together form methylenedioxy.
84 . A method of treating, preventing, or ameliorating the symptoms of a disease or disorder that is modulated or otherwise affected by nuclear receptor activity or in which nuclear receptor activity is implicated, comprising administering to a subject in need thereof an effective amount of a compound of 3 claim 1 .
85 . The method of claim 84 , wherein the disease or disorder is selected from hypercholesterolemia, hyperlipoproteinemia, hypertriglyceridemia, lipodystrophy, hyperglycemia, diabetes mellitus, dyslipidemia, atherosclerosis, gallstone disease, acne vulgaris, acneiform skin conditions, diabetes, Parkinson's disease, cancer, Alzheimer's disease, inflammation, immunological disorders, lipid disorders, obesity, conditions characterized by a perturbed epidermal barrier function, hyperlipidemia, cholestasis, peripheral occlusive disease, ischemic stroke, conditions of disturbed differentiation or excess proliferation of the epidermis or mucous membrane, and cardiovascular disorders.
86 . A method of reducing cholesterol levels in a subject in need thereof, comprising administering an effective amount of a compound of claim 1 .
87 . A method of treating, preventing, or ameliorating one or more symptoms of a disease or disorder which is affected by cholesterol, triglyceride, or bile acid levels, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 .
88 . A method of modulating nuclear receptor activity, comprising contacting the nuclear receptor with a compound claim 1 .
89 . The method of claim 88 , wherein the nuclear receptor is an orphan nuclear receptor.
90 . The method of claim 88 , wherein the nuclear receptor is farnesoid X receptor (FXR).
91 . The method of claim 88 , wherein the compound is a nuclear receptor agonist.
92 . The method of claim 88 , wherein the compound is a nuclear receptor antagonist.
93 . A method of modulating cholesterol metabolism, comprising administering an effective amount of a compound of claim 1 .
94 . A method of treating, preventing or ameliorating one or more symptoms of hypocholesterolemia in a subject in need thereof, comprising administering an effective amount of a compound of claim 1 .
95 . A method of increasing cholesterol efflux from cells of a subject, comprising administering an effective amount of a compound of claim 1 .
96 . A method of increasing the expression of ATP-Binding Cassette (ABC1) in the cells of a subject, comprising administering an effective amount of a compound of claim 1 .
97 . An in vitro method for altering nuclear receptor activity, comprising contacting the nuclear receptor with a compound of claim 1 .
98 . The method of claim 84 , wherein a second active agent selected from antihyperlipidemic agents, plasma HDL-raising agents, antihypercholesterolemic agents, cholesterol biosynthesis inhibitors (such as HMG CoA reductase inhibitors, such as lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and rivastatin), acyl-coenzyme A:cholesterol acytransferase (ACAT) inhibitors, probucol, raloxifene, nicotinic acid, niacinamide, cholesterol absorption inhibitors, bile acid sequestrants (such as anion exchange resins, or quaternary amines (e.g., cholestyramine or colestipol)), low density lipoprotein receptor inducers, clofibrate, fenofibrate, benzofibrate, cipofibrate, gemfibrizol, vitamin B 6 , vitamin B 12 , anti-oxidant vitamins, 8-blockers, anti-diabetes agents, angiotensin II antagonists, angiotensin converting enzyme inhibitors, platelet aggregation inhibitors, fibrinogen receptor antagonists, aspirin and fibric acid derivatives; is administered simultaneously with, prior to, or after administration of the compound.
99 . A pharmaceutical composition, comprising, in a pharmaceutically acceptable carrier, a compound of formula (I):
wherein:
m is an integer from 0 to 4;
R 1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 or —N(R 8 )R 9 , with the proviso that R 1 is not 3- or 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)phenyl;
R 2 , R 4 , R 5 and R 6 are selected from (a) and (b) as follows:
(a) R 2 and R 6 are selected from (i) and (ii) as follows: (i) R 2 and R 6 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocyclylalkyl; or (ii) R 2 and R 6 together form optionally substituted alkylene or optionally substituted alkenylene; and
R 4 and R 5 are selected from (i) and (ii) as follows: (i) R 4 and R 5 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 8 )R 9 ), —OR 7 , —S(O) j R 11 where j is 1 or 2, —B(R 22 ) 2 , —P(R 22 ) 2 , —P(O)(R 22 ) 2 and —C(E)R 23 , where E is selected from O, S and NR 7 ; or (ii) R 4 and R 5 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene; or
(b) R 2 and R 5 , or R 2 and R 4 , or R 6 and R 5 , or R 6 and R 4 , together form a 4, 5, 6 or 7 membered optionally substituted heterocyclyl group, or a 5 or 6 membered optionally substituted heteroaryl group; and the remainder of R 2 , R 2 , R 5 and R 6 are each independently selected as in (i) above;
each R 3 is independently selected from the group consisting of halo, pseudohalo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 12 )R 13 , —OR 14 , —C(E)R 15 where E is O, S or NR 7 , and —S(O) y R 16 where y is 0, 1 or 2;
or any two R 3 groups, which substitute adjacent carbons on the ring, together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkylenedioxy, optionally substituted thioalkylenoxy, or optionally substituted alkylenedithioxy;
each R 7 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
R 8 and R 9 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —S(O) j R 10 where j is 1 or 2, and —C(M)R 11 , where M is selected from O and S;
or R 8 and R 9 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 10 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
each R 11 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 and —N(R 7 ) 2 ;
R 12 and R 13 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —C(M)R 17 where M is O or S, and —S(O) j R 18 where j is 1 or 2;
or R 12 and R 13 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene;
R 14 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl or —C(M)R 17 where M is O or S;
R 15 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 14 or —N(R 12 )R 13 ;
R 16 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 19 or —N(R 20 )R 21 ;
R 17 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 18 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 19 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl;
R 20 and R 21 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl,
or R 20 and R 21 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 22 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 and —N(R 7 ) 2 ;
R 23 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 , —N(R 7 ) 2 , or —N(R 7 )N(R 7 ) 2 ;
wherein each of the above R 1 -R 23 groups, when substituted, are substituted with one or more substituents each independently selected from Q 1 , where Q 1 is halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 1 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 1 groups, which substitute the same atom, together form alkylene;
each R 24 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl;
each R 25 is independently selected from the group consisting of hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl and —N(R 27 )R 28 ,
R 26 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or —N(R 27 )R 28 ;
R 27 and R 28 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl,
or R 27 and R 28 together form alkylene, azaalkylene, oxaalkylene or thiaalkylene;
and each Q 1 is optionally substituted by one or more substituents selected from Q 2 ; where each Q 2 is independently halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 21 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 2 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 2 groups, which substitute the same atom, together form alkylene,
where R 24 , R 25 , R 26 , R 27 and R 28 are as defined above;
as a stereoisomer, racemate or mixture thereof; or as a pharmaceutically acceptable derivative thereof
100 . A pharmaceutical composition, comprising, in a pharmaceutically acceptable carrier:
(i) a compound of formula (I):
wherein:
m is an integer from 0 to 4;
R 1 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 or —N(R 8 )R 9 , with the proviso that R 1 is not 3- or 4-(1,1,1,3,3,3-hexafluoro-2-hydroxy-2-propyl)phenyl;
R 2 , R 4 , R 5 and R 6 are selected from (a) and (b) as follows:
(a) R 2 and R 6 are selected from (i) and (ii) as follows: (i) R 2 and R 6 are each independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, or optionally substituted heterocyclylalkyl; or (ii) R 2 and R 6 together form optionally substituted alkylene or optionally substituted alkenylene; and
R 4 and R 5 are selected from (i) and (ii) as follows: (i) R 4 and R 5 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 8 )R 9 ), —OR 7 , —S(O) j R 11 where j is 1 or 2, —B(R 22 ) 2 , —P(R 22 ) 2 , —P(O)(R 22 ) 2 and —C(E)R 23 , where E is selected from O, S and NR 7 ; or (ii) R 4 and R 5 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene; or
(b) R 2 and R 5 , or R 2 and R 4 , or R 6 and R 5 , or R 6 and R 4 , together form a 4, 5, 6 or 7 membered optionally substituted heterocyclyl group, or a 5 or 6 membered optionally substituted heteroaryl group; and the remainder of R 2 , R 4 , R 5 and R 6 are each independently selected as in (i) above;
each R 3 is independently selected from the group consisting of halo, pseudohalo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —N(R 12 )R 13 , —OR 14 , —C(E)R 15 where E is O, S or NR 7 , and —S(O) y R 16 where y is 0, 1 or 2;
or any two R 3 groups, which substitute adjacent carbons on the ring, together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkylenedioxy, optionally substituted thioalkylenoxy, or optionally substituted alkylenedithioxy;
each R 7 is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
R 8 and R 9 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —S(O) j R 10 where j is 1 or 2, and —C(M)R 11 , where M is selected from O and S;
or R 8 and R 9 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 10 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, and optionally substituted heterocyclylalkyl;
each R 11 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 and —N(R 7 ) 2 ;
R 12 and R 13 are each independently selected from hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —C(M)R 17 where M is O or S, and —S(O) j R 18 where j is 1 or 2;
or R 12 and R 13 together form optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkyleneoxyalkylene or optionally substituted alkyleneazaalkylene;
R 14 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl or —C(M)R 17 where M is O or S;
R 15 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 14 or —N(R 12 )R 13 .
R 16 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OH, —OR 19 or —N(R 20 )R 21 ;
R 17 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 18 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 19 or —N(R 20 )R 21 ;
R 19 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl or heteroaralkyl;
R 20 and R 21 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl,
or R 20 and R 21 together form alkylene, alkenylene, alkyleneoxyalkylene or alkyleneazaalkylene;
each R 22 is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 7 and —N(R 7 ) 2 ;
R 23 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclylalkyl, —OR 10 , —N(R 7 ) 2 , or —N(R 7 )N(R 7 ) 2 ;
wherein each of the above R 1 -R 23 groups, when substituted, are substituted with one or more substituents each independently selected from Q 1 , where Q 1 is halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, cycloalkylcarbonyl, heterocyclylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 1 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 1 groups, which substitute the same atom, together form alkylene;
each R 24 is independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl and heterocyclylalkyl;
each R 25 is independently selected from the group consisting of hydroxy, alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl and —N(R 27 )R 28 ,
R 26 is alkoxy, aralkoxy, alkyl, heteroaryl, heterocyclyl, aryl or —N(R 27 )R 28 ;
R 27 and R 28 are each independently hydrogen, alkyl, aralkyl, aryl, heteroaryl, heteroaralkyl or heterocyclyl,
or R 27 and R 28 together form alkylene, azaalkylene, oxaalkylene or thiaalkylene;
and each Q 1 is optionally substituted by one or more substituents selected from Q 2 ; where each Q 2 is independently halo, pseudohalo, hydroxy, oxo, thia, nitrile, nitro, formyl, mercapto, carboxy, carboxyalkyl, alkyl, haloalkyl, polyhaloalkyl, aminoalkyl, diaminoalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, heteroaryl, aralkyl, aralkenyl, aralkynyl, heteroarylalkyl, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkylidene, arylalkylidene, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryloxycarbonyl, aryloxycarbonylalkyl, aralkoxycarbonyl, aralkoxycarbonylalkyl, arylcarbonylalkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, arylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkoxy, aryloxy, heteroaryloxy, heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, cycloalkoxy, perfluoroalkoxy, alkenyloxy, alkynyloxy, aralkoxy, alkylcarbonyloxy, arylcarbonyloxy, aralkylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, aralkoxycarbonyloxy, aminocarbonyloxy, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylarylaminocarbonyloxy, diarylaminocarbonyloxy, guanidino, isothioureido, amidino, alkylamidino, arylamidino, aminothiocarbonyl, alkylaminothiocarbonyl, arylaminothiocarbonyl, amino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, arylaminoalkyl, diarylaminoalkyl, alkylarylaminoalkyl, alkylamino, dialkylamino, haloalkylamino, arylamino, diarylamino, alkylarylamino, alkylcarbonylamino, alkoxycarbonylamino, aralkoxycarbonylamino, arylcarbonylamino, arylcarbonylaminoalkyl, aryloxycarbonylaminoalkyl, aryloxyarylcarbonylamino, aryloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, heterocyclylsulfonylamino, heteroarylthio, azido, —N + (R 24 ) 3 , —P(R 25 ) 2 , —P(O)(R 25 ) 2 , —OP(O)(R 25 ) 2 , —N(R 24 )C(O)R 26 , dialkylphosphonyl, alkylarylphosphonyl, diarylphosphonyl, hydroxyphosphonyl, alkylthio, arylthio, perfluoroalkylthio, carboxyalkylthio, thiocyano, isothiocyano, alkylsulfinyloxy, alkylsulfonyloxy, arylsulfinyloxy, arylsulfonyloxy, hydroxysulfonyloxy, alkoxysulfonyloxy, aminosulfonyloxy, alkylaminosulfonyloxy, dialkylaminosulfonyloxy, arylaminosulfonyloxy, diarylaminosulfonyloxy, alkylarylaminosulfonyloxy, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, hydroxysulfonyl, alkoxysulfonyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, arylaminosulfonyl, diarylaminosulfonyl or alkylarylaminosulfonyl; or two Q 2 groups, which substitute atoms in a 1,2 or 1,3 arrangement, together form alkylenedioxy (i.e., —O—(CH 2 ) y —O—), thioalkylenoxy (i.e., —S—(CH 2 ) y —O—) or alkylenedithioxy (i.e., —S—(CH 2 ) y —S—) where y is 1 or 2; or two Q 2 groups, which substitute the same atom, together form alkylene,
where R 24 , R 25 , R 26 , R 27 and R 28 are as defined above;
as a stereoisomer, racemate or mixture thereof; or as a pharmaceutically acceptable derivative thereof; and
(ii) one or more of a second active agent selected from antihyperlipidemic agents, plasma HDL-raising agents, antihypercholesterolemic agents, cholesterol biosynthesis inhibitors (such as HMG CoA reductase inhibitors, such as lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin and rivastatin), acyl-coenzyme A:cholesterol acytransferase (ACAT) inhibitors, probucol, raloxifene, nicotinic acid, niacinamide, cholesterol absorption inhibitors, bile acid sequestrants (such as anion exchange resins, or quaternary amines (e.g., cholestyramine or colestipol)), low density lipoprotein receptor inducers, clofibrate, fenofibrate, benzofibrate, cipofibrate, gemfibrizol, vitamin B 6 , vitamin B 12 , anti-oxidant vitamins, β-blockers, LXR □ or agonists or antagonists, anti-diabetes agents, angiotensin II antagonists, angiotensin converting enzyme inhibitors, platelet aggregation inhibitors, fibrinogen receptor antagonists, aspirin and fibric acid derivatives.
101 . A compound of claim 1 selected from the group consisting of the following:
2-naphthalen-1-yl-ethanesulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-C-phenyl-methanesulfonamide;
2-phenyl-ethenesulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
thiophene-2-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-methanesulfonamide;
3,5-dimethyl-isoxazole-4-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methyl-methanesulfonamide;
octane-1-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
2-naphthalen-1-yl-ethanesulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
2-phenyl-ethenesulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
thiophene-2-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
C-(7,7-dimethyl-2-oxo-bicyclo[2.2.1]hept-1-yl)-N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methyl-methanesulfonamide;
N-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-N-methylmethanesulfonamide;
butane-1-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
3-chloropropane-1-sulfonic acid [3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]methylamide;
[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]-carbamic acid benzyl ester;
nonanoic acid {1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
nonanoic acid [3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-ylmethyl]amide;
nonanoic acid {1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
nonanoic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide;
4-tert-butyl-N-methyl-N-[1-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-isopropyl-N-methyl-N-[1-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
biphenyl-4-sulfonic acid methyl-[1-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]amide;
4-methoxy-N-methyl-N-[1-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-chloro-N-methyl-N-[1-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-tert-butyl-N-methyl-N-[1-(3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl]benzamide;
3-(4-methoxyphenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
3-(3,5-dimethylphenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
2-(1-methylaminoethyl)-3-phenyl-3H-quinazolin-4-one;
3-(4-bromophenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
3-(4-methoxyphenyl)-7-methyl-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
8-methoxy-3-(4-methoxyphenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
5-methoxy-3-(4-methoxyphenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
6-methoxy-3-(4-methoxyphenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
3-(4-dimethylamino-phenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
3-(4-fluorophenyl)-2-(1-methylaminoethyl)-3H-quinazolin-4-one;
4-tert-butyl-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-dimethylbenzenesulfonamide,
4-tert-butyl-N-{1-[6-methoxy-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide:
4-tert-butyl-N-{1-[3-(4-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-ter-t-butyl-N-{1-[3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-methyl-N-[1-(4-oxo-3-p-tolyl-3,4-dihydroquinazolin-2-yl)ethyl]benzenesulfonamide;
4-tert-butyl-N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[3-(4-methoxyphenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide;
4-tert-butyl-N-{1-[6-chloro-3-(4-methoxyphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-N-methylbenzenesulfonamide:
N-{1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-isopropyl-N-methylbenzenesulfonamide; and
biphenyl-4-sulfonic acid {1-[3-(2,4-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}methylamide.
102 . (canceled)
103 . The compound of claim 50 having one or more features selected from the group consisting of the following:
a) R 1a is selected from the group consisting of alkyl, hydroxy, alkoxy alkoxyalkoxy and aralkoxy; b) R 4 is hydrogen or alkyl; c) R 3 is independently selected from the group consisting of hydrogen, alkyl, alkoxy and halo; and d) R 5a is independently selected from the group consisting of alkyl, alkoxy, halo and alkylcarbonyl.
104 . The compound of claim 103 having one or more features selected from the group consisting of the following:
a) R 1a is alkoxy; b) R 4 is alkyl; c) R 3 is selected from the group consisting of hydrogen, halo, alkoxy and alkyl; and d) R 5a is selected from the group consisting of tert-butyl and isopropyl.Cited by (0)
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