USRE39197EExpiredUtility
Cell adhesion-inhibiting antiinflammatory and immune-suppressive compounds
Est. expiryDec 29, 2018(expired)· nominal 20-yr term from priority
A61P 37/06A61P 37/02A61P 37/00A61P 29/00A61P 19/00C07D 207/27C07D 213/75C07D 241/24C07D 211/54C07D 207/20C07D 413/14C07D 241/04C07D 211/26C07D 317/58C07D 207/14C07D 491/10C07D 487/08C07D 295/13C07D 213/74C07D 403/12C07D 401/06C07C 2601/08C07D 243/08C07C 323/62C07D 209/08C07D 239/42C07D 405/12C07D 317/62C07D 413/04C07D 207/22C07D 211/74C07D 471/10C07D 211/60C07D 265/30C07D 207/26C07D 319/18C07D 295/32C07D 217/06C07D 235/26C07D 319/20C07D 211/62C07D 295/185C07D 295/205C07D 211/46C07D 213/81C07D 295/215C07D 405/14C07D 307/52C07C 2601/02C07D 401/04C07D 207/09C07D 211/22C07D 215/36C07C 2601/04C07D 211/42C07D 295/26C07D 401/12C07D 209/18C07D 307/68
49
PatentIndex Score
0
Cited by
157
References
35
Claims
Abstract
The present invention relates to novel cinnamide compounds that are useful for treating inflammatory and immune diseases, to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a mammal.
Claims
exact text as granted — not AI-modified1. A compound of the formula I:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug thereof of a compound of formula I,
wherein R 1 , R 2 , R 3 , R 4 , and R 5 are independently
selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde, and
with the proviso that at least one of R 1 or and R 3 is a “cis-cinnamide” or a “trans-cinnamide”, defined as
wherein R 8 and R 9 are each independently selected from
a. hydrogen, and
b. alkyl,
c. carboxy alkyl,
d. alkylaminocarbonyl alkyl, and
e. dialkylaminocarbonyl alkyl,
and R 10 and R 11 are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or where NR 10 R 11 is R 10 and R 11 are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1) alkyl,
2) alkoxy,
3) alkoxyalkyl,
4) cycloalkyl,
5) aryl,
6) heterocyclyl,
7) heterocyclylcarbonyl,
8) heterocyclylalkylaminocarbonyl,
9) hydroxy,
10) hydroxyalkyl,
11) hydroxyalkoxyalkyl,
12) carboxy,
13) carboxycarbonyl,
14) carboxaldehyde,
15) alkoxycarbonyl,
16) arylalkoxycarbonyl,
17) aminoalkanoyl,
18) carboxamido,
19) alkoxycarbonylalkyl,
20) carboxamidoalkyl,
21) alkanoyl,
22) hydroxyalkanoyl,
23) alkanoyloxy,
24) alkanoylamino,
25) alkanoyloxyalkyl, and
26) alkylsulfonyl,
and wherein Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where substitutions the substituents are each independently selected from
a. hydrogen,
ba. halogen,
cb. alkyl,
dc. aryl,
ed. haloalkyl,
fe. hydroxy,
gf. alkoxy,
hg. alkoxycarbonyl,
ih. alkoxyalkoxy,
ji. hydroxyalkyl,
kj. aminoalkyl,
lk. alkyl(alkoxycarbonylalkyl)aminoalkyl,
ml. unsubstituted heterocyclylalkyl,
nm. substituted heterocyclylalkyl,
on. carboxaldehyde,
po. carboxaldehyde hydrazone,
qp. carboxamide,
rq. alkoxycarbonyl alkyl,
sr. hydroxycarbonylalkyl (carboxyalkyl),
ts. cyano,
ut. amino,
vu. heterocyclylalkylamino, and
wv. “trans-cinnamide”,
or a pharmaceutically-acceptable salt or prodrug thereof.
subject to the proviso that when R 3 is a “cis-cinnamide” or a “trans-cinnamide,” as defined above, one or more than one of the following conditions is fulfilled: (A) Ar is an unsubstituted heteroaryl group, a substituted heteroaryl group, or a substituted aryl group wherein when Ar is a pyridyl group, Ar is substituted and Ar is not substituted by only one alkyl group; (B) one or more than one of R 1 , R 2 , R 4 , and R 5 , as defined above, are other than hydrogen; and (C) R 10 and R 11 are taken together with N to form a substituted or unsubstituted heterocyclyl group, as defined above.
2. A compound according to claim 1 wherein R 1 is a “cis-cinnamide” or a “trans-cinnamide”, and R 3 is hydrogen.
3. A compound according to claim 1 wherein R 3 is a “cis-cinnamide” or a “trans-cinnamide”, and R 1 is hydrogen .
4. A compound according to claim 1 wherein R 3 is a “cis-cinnamide” or a “trans-cinnamide”, and one or more than one of R 1 , R 8 , and R 9 are each hydrogen.
5. A compound according to claim 4 wherein R 3 is a “cis-cinnamide”.
6. A compound according to claim 4 wherein R 3 is a “trans-cinnamide”.
7. A compound according to claim 1 wherein R 3 is a “cis-cinnamide” or a “trans-cinnamide”, and R 1 , R 2 , and R 4 are each independently hydrogen or alkyl; and R 5 is selected from halogen, haloalkyl, and nitro.
8. A compound according to claim 4 wherein Ar is aryl, a substituted aryl group, an unsubstituted heteroaryl group, or a substituted heteroaryl group.
9. A compound according to claim 4 wherein one or both of R 10 and R 11 are each independently selected from hydrogen, alkyl, cycloalkyl, alkoxycarbonylalkyl, hydroxyalkyl, and heterocyclylalkyl.
10. A compound according to claim 4 wherein NR 10 R 11 is R 10 and R 11 are taken together with N to form an unsubstituted heterocyclyl group or a substituted heterocyclyl group.
11. A compound according to claim 8 4 wherein Ar is selected from substituted phenyl, 1,3-benzimidazol-2-one, 1,4-benzodioxane, 1,3-benzodioxole, 1-benzopyr-2-en-4-one, indole, isatin, 1,3-quinazolin-4-one, and quinoline.
12. A compound according to claim 11 wherein R 3 is a “trans-cinnamide”; and Ar is selected from 1 , 3 -benzimidazol- 2 -one, 1 , 4 -benzodioxane, 1 , 3 -benzodioxole, 1 -benzopyr- 2 -en- 4 -one, indole, isatin, phenyl, 1 , 3 -quinazolin- 4 -one, and quinoline .
13. A compound according to claim 12 wherein one or both of R 10 and R 11 are each independently selected from hydrogen, alkyl, cycloalkyl, alkoxycarbonylalkyl, hydroxyalkyl, and heterocyclylalkyl.
14. A compound according to claim 12 wherein NR 10 R 11 is R 10 and R 11 are taken together with N to form an unsubstituted heterocyclyl group or a substituted heterocyclyl as described above group.
15. A composition comprising a compound of according to claim 1 in and a pharmaceutically-acceptable carrier.
16. A method of inhibiting inflammation comprising the administration of a compound of claim 1 formula I to a patient:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R 1 , R 2 , R 3 , R 4 , and R 5 are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
with the proviso that at least one of R 1 and R 3 is a “cis-cinnamide” or a “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R 10 and R 11 are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R 10 and R 11 are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents, are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl(alkoxycarbonylalkyl)aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl(carboxyalkyl),
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”.
17. A method of inhibiting inflammation comprising the administration of a composition comprising a compound of claim 15 formula I to a patient:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R 1 , R 2 , R 3 , R 4 , and R 5 are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
with the proviso that at least one of R 1 and R 3 is a “cis-cinnamide” or a “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R 10 and R 11 are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R 10 and R 11 are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents, are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl( carboxyalkyl ) ,
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”
and a pharmaceutically-acceptable carrier.
18. A method of suppressing immune response comprising the administration of a compound of claim 1 formula I to a patient:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R
1
, R
2
, R
3
, R
4
, and R
5
are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
with the proviso that at least one of R
1
and R
3
is a “cis-cinnamide” or a “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents, are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ) ,
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide” .
19. A method of suppressing immune response comprising the administration of a composition comprising a compound of claim 15 formula I to a patient:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R 1 , R 2 , R 3 , R 4 , and R 5 are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
with the proviso that at least one of R 1 and R 3 is a “cis-cinnamide” or a “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents, are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ) ,
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”
and a pharmaceutically-acceptable carrier .
20. A compound according to claim 1 selected from:
( 2 , 4 -Dichlorophenyl ) [ 2 -( E -(( 6 -hydroxyhexylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -( E -(( 3 -( 1 -imidazolyl) propylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 2 -hydroxyethylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 6 -hydroxyhexylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( bis -( 2 -hydroxyethyl ) ainino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 3 -( 2 -oxopyrrolidin- 1 -yl ) propylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -methylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -( 2 -pyridyl ) piperazin- 1 -yl) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -( Hydroxymethyl ) phenyl ) ( 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -( 2 -hydroxyethyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -( 2 -hydroxyethoxyethyl ) piperazin- 1 -yl) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( 3 -( hydroxymethyl ) piperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( 2 -( hydroxymethyl ) piperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( 3 -acetamidopyrrolidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( 4 -( hydroxypiperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( piperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 3 -carboxypiperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -carboxypiperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl ) [ 2 -chloro- 4 -( E -(( 4 -acetylhomopiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl) [ 2 -chloro- 4 -( E -(( thiomorpholin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl ) [ 2 -chloro- 4 -( E -(( 4 -( 2 -oxo,- 2 , 3 -dihydro- 1 H-benzimidazol- 1 -yl ) piperidin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Bromophenyl ) [ 2 -chloro- 4 -( E -(( 2 -tetrahydroisoquinolinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -trifluoromethyl- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -trifluoromethyl- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -trifluoromethyl- 4 -( E -(( 2 -( 1 -morpholinyl ) ethylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -trifluoromethyl- 4 -( E -(( 4 -phenylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -trifluoromethyl- 4 -( E -(( 3 -( 2 -oxopyrrolidin- 1 -yl ) propylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -trifluoromethyl- 4 -( E -(( cyclopropylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) 2 -nitro- 4 -( E -(( 3 -( 2 -oxopyrrolidin- 1 -yl ) propylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 3 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 4 -Bromophenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 4 -Methylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -( tert-butoxycarbonyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -( 2 -furoylcarbonyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -( methanesulfonyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -( diethylaminocarbonylmethyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -( diethylaminocarbonyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) ( 2 -nitro- 4 -( E -(( 4 -( carboxycarbonyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -( carboxymethyl ) piperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Methylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Chlorophenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Aminophenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Hydroxymethylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Ethylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -iso-Propylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -tert-Butylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Chlorophenyl ) [ 2 -chloro- 4 -( E -(( 4 -acetylpiperain- 1 -yl ) carbonyl )) 2 -propenyl ) phenyl]sulfide;
( 2 -( 1 -Morpholinylmethyl ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -( 4 -( 1 , 3 -Benzodioxolyl- 5 -methyl ) piperazin- 1 -ylmethyl ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -( 4 -( iso-Propylaminocarbonylmethyl ) piperazin- 1 -ylmethyl ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -(( N-Ethoxycarbonylmethyl-N-methyl ) aminomethyl ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Formylphenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -( 4 -Formylpiperazin- 1 -ylmethyl ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -( E -(( 1 -Morpholinyl ) carbonyl ) ethenyl ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Formylphenyl ) [ 2 -nitro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 -Formylphenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide, N,N-dimethyl hydrazone;
( 2 -(( 3 -( 1 -Morpholinyl ) propyl )- 1 -amino ) phenyl ) [ 2 -chloro- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -bromo- 4 -( E -(( 3 -( 2 -oxopyrrolidin- 1 -yl ) propylamino ) carbonyl ) ethenyl ) phenyl]sulfide;
( 2 , 4 -Dichlorophenyl ) [ 2 -formyl- 4 -( E -(( 1 -morpholinyl ) carbonyl ) ethenyl ) phenyl]sulfide; and
( 2 -Chloro- 6 -formylphenyl ) [ 2 -chloro- 4 -( E -(( 4 -acetylpiperazin- 1 -yl ) carbonyl ) ethenyl ) phenyl]sulfide.
21. A compound of formula I:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R
1
, R
2
, R
3
, R
4
, and R
5
are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
with the proviso that at least one of R
1
and R
3
is a “cis-cinnamide” or a “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ) ,
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”,
subject to the proviso that when R
3
is a “cis-cinnamide” or a “trans-cinnamide,” as defined above, one or more than one of the following conditions is fulfilled:
( A ) R 1 , as defined above, is other than hydrogen;
( B ) R 8 and R 9 are both hydrogen and Ar is not pyridyl; and
( C ) R 10 and R 11 are taken together with N to form a substituted or unsubstituted heterocyclyl group, as defined above.
22. A compound of formula I:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R
1
, R
2
, R
3
, R
4
, and R
5
are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
with the proviso that at least one of R
1
and R
3
is a “cis-cinnamide” or a “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ) ,
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”,
subject to the proviso that one or more than one of the following conditions is fulfilled:
( A ) Ar is an unsubstituted heteroaryl group, a substituted heteroaryl group, or a substituted aryl group;
( B ) two or more than two of R 1 , R 2 , R 3 , R 4 , and R 5 , as defined above, are other than hydrogen; and
( C ) R 10 and R 11 are taken together with N to form a substituted or unsubstituted heterocyclyl group, as defined above.
23. A compound of formula I:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R
1
, R
2
, R
4
, and R
5
are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
where R
3
is a “cis-cinnamide” or “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ),
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”,
wherein when Ar is pyridyl, Ar is substituted by two or more than two substituents.
24. A compound according to claim 23 where one or more than one of R 1 , R 2 , R 4 , and R 5 are other than hydrogen.
25. A compound according to claim 23 where R 10 and R 11 are taken together with N to form a substituted or unsubstituted heterocyclyl group.
26. A compound of formula I:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R
1
, R
2
, R
4
, and R
5
are independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
subject to the proviso that one or more than one of R
1
, R
2
, R
4
, and R
5
are other than hydrogen,
where R
3
is a “cis-cinnamide” or “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are each independently selected from
a. hydrogen,
b. alkyl,
c. cycloalkyl,
d. alkoxycarbonylalkyl,
e. hydroxyalkyl, and
f. heterocyclylalkyl,
or R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ),
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”.
27. A compound according to claim 26 where R 10 and R 11 are taken together with N to form a substituted heterocyclyl group or an unsubstituted heterocyclyl group.
28. A compound of formula I:
or a pharmaceutically-acceptable salt or pharmaceutically-acceptable prodrug of a compound of formula I,
wherein R
1
, R
2
, R
4
, and R
5
are each independently selected from
a. hydrogen,
b. halogen,
c. alkyl,
d. haloalkyl,
e. alkoxy,
f. cyano,
g. nitro, and
h. carboxaldehyde,
where R
3
is a “cis-cinnamide” or “trans-cinnamide”, defined as
where R 8 and R 9 are each independently selected from a. hydrogen, b. alkyl, c. carboxyalkyl, d. alkylaminocarbonylalkyl, and e. dialkylaminocarbonylalkyl,
R
10
and R
11
are taken together with the N to form an unsubstituted heterocyclyl group, or a substituted heterocyclyl group, where the substituted heterocyclyl group is substituted by one or more than one substituent, where the substituents are each independently selected from
1 ) alkyl,
2 ) alkoxy,
3 ) alkoxyalkyl,
4 ) cycloalkyl,
5 ) aryl,
6 ) heterocyclyl,
7 ) heterocyclylcarbonyl,
8 ) heterocyclylalkylaminocarbonyl,
9 ) hydroxy,
10 ) hydroxyalkyl,
11 ) hydroxyalkoxyalkyl,
12 ) carboxy,
13 ) carboxycarbonyl,
14 ) carboxaldehyde,
15 ) alkoxycarbonyl,
16 ) arylalkoxycarbonyl,
17 ) aminoalkanoyl,
18 ) carboxamido,
19 ) alkoxycarbonylalkyl,
20 ) carboxamidoalkyl,
21 ) alkanoyl,
22 ) hydroxyalkanoyl,
23 ) alkanoyloxy,
24 ) alkanoylamino,
25 ) alkanoyloxyalkyl, and
26 ) alkylsulfonyl,
and Ar is an unsubstituted aryl group, an unsubstituted heteroaryl group, a substituted aryl group, or a substituted heteroaryl group, where the substituted aryl group and the substituted heteroaryl group are substituted by one or more than one substituent, where the substituents are each independently selected from
a. halogen,
b. alkyl,
c. aryl,
d. haloalkyl,
e. hydroxy,
f. alkoxy,
g. alkoxycarbonyl,
h. alkoxyalkoxy,
i. hydroxyalkyl,
j. aminoalkyl,
k. alkyl ( alkoxycarbonylalkyl ) aminoalkyl,
l. unsubstituted heterocyclylalkyl,
m. substituted heterocyclylalkyl,
n. carboxaldehyde,
o. carboxaldehyde hydrazone,
p. carboxamide,
q. alkoxycarbonylalkyl,
r. hydroxycarbonylalkyl ( carboxyalkyl ) ,
s. cyano,
t. amino,
u. heterocyclylalkylamino, and
v. “trans-cinnamide”.
29. A compound according to claim 1 wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .
30. A compound according to claim 21 , wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .
31. A compound according to claim 22 wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .
32. A compound according to claim 23 wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .
33. A compound according to claim 26 wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .
34. A compound according to claim 27 wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .
35. A compound according to claim 28 wherein Ar is an unsubstituted heteroaryl group or a substituted heteroaryl group and wherein the heteroaryl group is selected from benzimidazolyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, cinnolinyl, dihydroindolyl, furyl, imidazolyl, indolyl, isoquinolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrimidyl, pyrrolyl, quinolinyl, tetrahydroisoquinolyl, tetrahydroquinolyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, and compounds of the formula:
wherein X* and Z* are independently selected from —CH 2 —, —CH 2 NH—, —CH 2 O—, —NH—, and —O— with the proviso that at least one of X* and Z* is not —CH 2 —, and Y* is selected from —C ( O )— and — ( C ( R″ ) 2 ) v — where R′ is hydrogen or C 1-4 alkyl and v is 1 - 3 .Cited by (0)
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