US2016152577A1PendingUtilityA1
2,4-Diaminoquinazolines for Spinal Muscular Atrophy
Assignee: FAMILIES OF SPINAL MUSCULAR ATROPHYPriority: Jun 8, 2004Filed: Jun 29, 2015Published: Jun 2, 2016
Est. expiryJun 8, 2024(expired)· nominal 20-yr term from priority
A61P 25/00C07D 405/12C07D 413/12C07D 409/12C07D 239/95C07D 401/12C07D 417/12A61P 21/00
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Claims
Abstract
2,4-Diaminoquinazolines of formulae I-IV and VI are useful for treating spinal muscular atrophy (SMA).
Claims
exact text as granted — not AI-modified1 . A 2,4-diaminoquinazoline compound selected from:
(A) 2,4-diaminoquinazoline compounds selected from the group consisting of formulae I, II and III:
wherein
L 1 is selected from the group consisting of a bond and a linker of empirical formula C p H q N r O s S t in which
p is 2-20;
q is 0-40;
r is 0-3;
s is 0-6;
t is 0-2;
R 1 is selected from the group consisting of cycloalkyl, aryl, fused cycloalkylaryl, heterocyclyl, heteroaryl, substituted cycloalkyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, and substituted heteroaryl;
G is selected from the group consisting of —NR 6 —, —CH 2 —, SO 2 — and —CH 2 O—;
G 1 is selected from the group consisting of —O—, NR 6 —, —S— and —OCH(CH 3 )—;
R 2 is selected from the group consisting of cycloalkyl, aryl, fused cycloalkylaryl, heterocyclyl, heteroaryl; substituted cycloalkyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, and substituted heteroaryl with the proviso that when G is —CH 2 — then R 2 is other than phenyl or substituted phenyl;
R 6 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl; and
Q is selected from the group consisting of —CH 2 OCH 3 , —CH 2 OCH 2 CH═CH 2 , C 6 -C 20 hydrocarbon, heterocyclyl, and heteroaryl; substituted C 6 -C 20 hydrocarbon, substituted heterocyclyl, and substituted heteroaryl; and —C(OH)Ar 2 , wherein Ar is phenyl or substituted phenyl, with the proviso that when G 1 is —O— or —S—, then Q is other than 4-chlorophenyl;
(B) 2,4-diaminoquinazoline compounds of formula IV:
wherein G 2 is selected from the group consisting of —O—, —S—, and —NH—; and
R 12 is selected from the group consisting of C 7 -C 10 polycyclic hydrocarbon, substituted C 7 -C 10 polycyclic hydrocarbon, and
wherein the wavy line indicates the point of attachment; and
wherein one or more carbon atoms in the cyclopentyl ring is optionally replaced by a heteroatom independently selected from the group consisting of N, O, and S; and
R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloalkyl, hydroxy, carboxy, C 1 -C 6 alkoxycarbonyl, carboxamido, cyano, formyl, nitro, amino, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino, mercapto, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfoxide, C 1 -C 6 alkylsulfone, C 1 -C 6 acylamino, amidino, phenyl, benzyl, phenoxy and benzyloxy, with the proviso that at least one of R 3 , R 4 , and R 5 must be other than hydrogen; and
(C) 2,4-diaminoquinazoline compounds of formula VI:
wherein
L is a linker of empirical formula C p H q N r O s S t in which
p is 0-20;
q is 0-40;
r is 0-3;
s is 0-6;
t is 0-2; and
R is selected from the group consisting of cycloalkyl, aryl, fused cycloalkylaryl, heterocyclyl, heteroaryl, C 3 -C 10 alkyl and C 3 -C 10 oxaalkyl; substituted cycloalkyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, substituted heteroaryl, substituted C 3 -C 10 alkyl, and substituted C 3 -C 10 oxaalkyl; and
R 10 and R 11 are independently selected from the group consisting of H, —NH 2 , —NH(alkyl), —NHOH, —NHO(alkyl), and acyl, with the proviso that at least one of R 10 and R 11 is other than H;
or a pharmaceutically acceptable salt of such a compound, in any stereoisomeric or tautomeric form, or a mixture of any such compounds in any ratio.
2 . A compound according to claim 1 of formula III;
wherein
G 1 is selected from the group consisting of —O— and —S—; and
Q is selected from the group consisting of —CH 2 OCH 3 , —CH 2 OCH 2 CH═CH 2 , cycloalkyl, cycloalkenyl, aryl, fused cycloalkylaryl, heterocyclyl, and heteroaryl;
substituted cycloalkyl, substituted cycloalkenyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, and substituted heteroaryl with the proviso that Q is other than 4-chlorophenyl.
3 . A compound according to claim 1 of formula II:
wherein
G is —CH 2 O—; and
R 2 is selected from the group consisting of cycloalkyl, aryl, fused cycloalkylaryl, heterocyclyl, heteroaryl, substituted cycloalkyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, and substituted heteroaryl.
4 . A compound according to claim 1 of formula I:
wherein
L 1 is selected from the group consisting of a bond and a linker of empirical formula —C 2-7 H 4-15 O 1-3 —; and
R 1 is selected from the group consisting of cycloalkyl, aryl, fused cycloalkylaryl, heterocyclyl, heteroaryl, substituted cycloalkyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, and substituted heteroaryl.
5 . A compound according to claim 4 , wherein L 1 is selected from the group consisting of a bond, —O(CH 2 ) 2 —; —(CH 2 ) 2 O—; —O(CH 2 ) 3 —; —CH(CH 3 )O—; —OCH(CH 3 )—; —CH 2 CH 2 —; —O(CH 2 ) 6 CH 3 —, —OCH(CH 2 CH 3 )—; —CH(CH 2 OH)O—; —CH(CH 2 OCH 3 )O—; —OCH(tBu)-; —OCH(C 6 H 5 )—; —OCH 2 CH(OH)—; —O(CH 3 ) 2 —; —OCH(CH 2 OH)—; —OCH(CH 2 OCH 3 )—; —OCH 2 CH(OCH 3 )—; —OCH(COOH)—; —OCH 2 CH(CH 2 OCH 2 OCH 3 )—; —OCH 2 CH(CH 2 OH)—; —OCH(CH 2 OCH 2 OCH 3 )—; —OCH(CH 2 CH 2 CH 3 )—; —OCH 2 CH(OCH 2 OCH 3 )—; —C═C—,
wherein the wavy lines indicate the points of attachment.
6 . A compound according to claim 1 selected from the group consisting of
5-(2-p-Tolylethoxy)quinazoline-2,4-diamine;
5-[2-(4-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-(1-Phenylethoxy)quinazoline-2,4-diamine;
5-[3-(4-Chlorophenyl)propoxy]quinazoline-2,4-diamine;
5-[1-(3-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-p-Tolylethynylquinazoline-2,4-diamine;
5-Phenethyloxyquinazoline-2,4-diamine;
5-((S)-1-Phenylethoxy)quinazoline-2,4-diamine;
5-(1-Pyridin-4-ylethoxy)quinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)propoxy]quinazoline-2,4-diamine;
5-Benzhydryloxyquinazoline-2,4-diamine;
5-((R)-1-Phenylethoxy)quinazoline-2,4-diamine;
5-(1-Pyridin-2-ylethoxy)quinazoline-2,4-diamine;
5-(1-Thiazol-2-ylethoxy)quinazoline-2,4-diamine;
5-(1-Benzo[1,3]dioxol-5-ylethoxy)quinazoline-2,4-diamine;
5-[1-(3-Methoxyphenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(3,5-Dimethoxyphenyl)ethoxy]quinazoline-2,4-diamine;
5-[2-(4-Chlorophenyl)-3-methoxymethoxypropoxy]quinazoline-2,4-diamine;
2-(4-Chlorophenyl)-3-(2,4-diaminoquinazolin-5-yloxy)propan-1-ol;
5-[1-(3,4-Dichlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(2,6-Difluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-(3-Chlorophenyl)quinazoline-2,4-diamine;
5-[(R)-1-(3-Chlorophenyl)ethoxy]quinazolin-2,4-diamine;
5-[1-(3-Fluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(3-Trifluoromethylphenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(4-fluorophenyl)-1-methylethoxy]quinazoline-2,4-diamine;
5-[1-(2-Fluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(2-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(4-Trifluoromethylphenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(3,5-Difluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-((S)-1-Naphthalen-2-ylethoxy)quinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)-2-methoxyethoxy]quinazoline-2,4-diamine;
(4-Chlorophenyl)(2,4-diaminoquinazolin-5-yloxy)acetic acid;
5-(1-Cyclopentylethoxy)quinazoline-2,4-diamine;
5-(1-Cyclohexylbutoxy)quinazoline-2,4-diamine;
5-(1-Cyclohexylethoxy)quinazoline-2,4-diamine;
5-(1-Cyclohexylpropoxy)quinazoline-2,4-diamine;
5-[1-(3-Chlorophenyl)cyclopropoxy]quinazoline-2,4-diamine;
5-[1-(4-Fluorophenyl)-2-methoxymethoxyethoxy]quinazoline-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-2-(4-fluorophenyl)ethanol;
5-(2-Benzo[1,3]dioxol-5-yl-2-methoxymethoxyethoxy)quinazoline-2,4-diamine;
5-(1-Benzo[1,3]dioxol-5-yl-2-methoxymethoxyethoxy)quinazoline-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-1-phenyl-ethanol;
1-(4-Chlorophenyl)-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
1-(3-Chlorophenyl)-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
5-[(S)-1-(3-Chlorophenyl)ethoxy]quinazolin-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-1-(4-trifluoromethylphenyl)ethanol;
2-(4-Chlorophenyl)-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
5-[2-(4-Chlorophenyl)-2-methoxyethoxy]quinazoline-2,4-diamine;
5-(2-Methoxy-1-phenylethoxy)quinazoline-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-1-(4-fluorophenyl)ethanol;
5-(2-Benzo[1,3]dioxol-5-yl-2-methoxyethoxy)quinazoline-2,4-diamine;
2-Benzo[1,3]dioxol-5-yl-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
5-((S)-1-Naphthalen-1-ylethoxy)quinazoline-2,4-diamine;
5-((R)-1-Naphthalen-1-ylethoxy)quinazoline-2,4-diamine;
5-(1-Naphthalen-1-ylethoxy)quinazoline-2,4-diamine;
5-[1-(3-Chlorophenyl)-1-methylethoxy]quinazoline-2,4-diamine;
5-[1-(3-Chlorophenyl)cyclohexyloxylquinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)-2,2-dimethylpropoxy]quinazoline-2,4-diamine;
5-[1-(2-Trifluoromethylphenyl)ethoxy]quinazoline-2,4-diamine;
5-Thiophen-3-ylquinazoline-2,4-diamine;
5-(4-Chlorophenoxymethyl)quinazoline-2,4-diamine;
5-p-Tolyloxymethylquinazoline-2,4-diamine;
5-(4-Fluorophenoxymethyl)quinazoline-2,4-diamine;
5-Thiophen-3-ylmethylquinazoline-2,4-diamine;
5-[1-(3-Iodophenyl)ethoxy]quinazoline-2,4-diamine;
5-((1R,2R,4S)-Bicyclo[2.2.1]hept-2-yloxy)quinazoline-2,4-diamine;
5-(Adamantan-2-yloxy)quinazoline-2,4-diamine;
5-(Bicyclo[2.2.1]hept-2-yloxy)quinazoline-2,4-diamine;
5-(2-Chlorophenoxymethyl)quinazoline-2,4-diamine;
5-(4-Chloro-2-methylphenoxymethyl)quinazoline-2,4-diamine;
5-(4-Chloro-3-methylphenoxymethyl)quinazoline-2,4-diamine;
5-(2,4-Difluorophenoxymethyl)quinazoline-2,4-diamine;
5-(3-Chlorophenoxymethyl)quinazoline-2,4-diamine;
5-(2-Iodophenoxymethyl)quinazoline-2,4-diamine;
5-(4-Chlorobenzenesulfonyl)quinazoline-2,4-diamine;
N-5-Cyclooctylquinazoline-2,4,5-triamine;
5-(Toluene-3-sulfonyl)quinazoline-2,4-diamine;
5-(4-Methoxyphenoxymethyl)quinazoline-2,4-diamine;
5-(4-Methylbenzyloxy)quinazoline-2,4-diamine;
5-(4-Chlorobenzyloxy)quinazoline-2,4-diamine;
5-(4-Iodobenzyloxy)quinazoline-2,4-diamine;
5-(3-Chlorobenzyloxy)quinazoline-2,4-diamine;
5-(2-Chlorobenzyloxy)quinazoline-2,4-diamine;
5-(2-Methylbenzyloxy)quinazoline-2,4-diamine;
5-(3-Methylbenzyloxy)quinazoline-2,4-diamine;
5-(Pyridin-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Cyclohex-3-enylmethoxy)quinazoline-2,4-diamine;
5-(Cyclobutylmethoxy)quinazoline-2,4-diamine;
5-(2-Methoxyethoxy)quinazoline-2,4-diamine;
5-(Cyclopropylmethoxy)quinazoline-2,4-diamine;
5-(Cyclopentylmethoxy)quinazoline-2,4-diamine;
5-(2-Allyloxyethoxy)quinazoline-2,4-diamine;
5-(1-Methylpiperidin-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Furan-2-ylmethoxy)quinazoline-2,4-diamine;
5-(Thiophen-2-ylmethoxy)quinazoline-2,4-diamine;
5-(Furan-3-ylmethoxy)quinazoline-2,4-diamine;
5-Benzyloxyquinazoline-2,4-diamine;
5-(Pyridin-2-ylmethoxy)quinazoline-2,4-diamine;
5-Octyloxyquinazoline-2,4-diamine;
5-(Thiophen-3-ylmethoxy)quinazoline-2,4-diamine;
5-(5-Methylisoxazol-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Benzo[1,3]dioxol-5-ylmethoxy)quinazoline-2,4-diamine;
5-(Tetrahydropyran-2-ylmethoxy)quinazoline-2,4-diamine;
5-(4-Bromobenzyloxy)quinazoline-2,4-diamine;
5-(3,4-Dimethoxybenzyloxy)quinazoline-2,4-diamine;
[4,5-Dichloro-2-(2,4-diaminoquinazolin-5-yloxymethyl)phenyl]methanol;
5-(Adamantan-1-ylmethoxy)quinazoline-2,4-diamine;
5-(2-Bromo-benzyloxy)quinazoline-2,4-diamine;
5-(2-Iodo-benzyloxy)quinazoline-2,4-diamine;
5-(3-Bromobenzyloxy)quinazoline-2,4-diamine;
5-(3-Iodo-benzyloxy)quinazoline-2,4-diamine;
5-(3,5-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,3,5-Trifluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,5-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,4-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,6-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(3,4-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(5-Chloro-2-methoxybenzyloxy)quinazoline-2,4-diamine;
[4-Chloro-2-(2,4-diaminoquinazolin-5-yloxymethyl)phenyl]methanol;
5-(2-Fluorobenzyloxy)quinazoline-2,4-diamine;
5-(4-Fluorobenzyloxy)quinazoline-2,4-diamine;
5-(3-Trifluoromethylbenzyloxy)quinazoline-2,4-diamine;
5-(2-Trifluoromethylbenzyl oxy)quinazoline-2,4-diamine;
5-(4-Trifluoromethylbenzyl oxy)quinazoline-2,4-diamine;
5-(3-Fluorobenzyloxy)quinazoline-2,4-diamine;
5-(3,5-Dichlorobenzyloxy)quinazoline-2,4-diamine;
5-(Quinolin-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Quinolin-8-ylmethoxy)quinazoline-2,4-diamine;
5-(Piperidin-4-ylmethoxy)quinazoline-2,4-diamine;
5-(1-Methyl-piperidin-2-ylmethoxy)quinazoline-2,4-diamine;
4-(2,4-Diaminoquinazolin-5-yloxymethyl)piperidin-1-carboxylic acid tert-butyl ester
5-(Bicyclo[2.2.1]hept-5-en-2-ylmethoxy)quinazoline-2,4-diamine;
(4-Chlorophenyl)[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone;
5-(3-Methyl-oxetan-3-ylmethoxy)quinazoline-2,4-diamine;
5-((1 S,2R,5 S)-6,6-Dimethylbicyclo[3.1.1]hept-2-ylmethoxy)quinazoline-2,4-diamine;
5-(2,4-Diaminoquinazolin-5-yloxymethyl)bicyclo[2.2.1]heptane-2,3-diol;
5-[1-(3,4-Dichlorobenzyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine;
(2-Chlorophenyl)[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone;
(3-Chlorophenyl)[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone;
[4-(2,4-Diaminoquinzolin-5-yloxymethyl)piperidin-1-yl](3-iodophenyl)methanone;
[4-(2,4-Diaminoquinzolin-5-yloxymethyl)piperidin-1-yl](4-iodophenyl)methanone;
[4-(2,4-Diaminoquinzolin-5-yloxymethyl)piperidin-1-yl](2-iodophenyl)methanone;
5-(2-Methoxybenzyloxy)quinazoline-2,4-diamine;
5-(3-Methoxybenzyloxy)quinazoline-2,4-diamine;
5-(4-Methoxybenzyloxy)quinazoline-2,4-diamine;
5-(Bicyclo[2.2.1]hept-2-ylmethoxy)quinazoline-2,4-diamine;
5-((1S,2S,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-ylmethoxy)quinazoline-2,4-diamine;
5-(Cyclohexylmethoxy)quinazoline-2,4-diamine;
5-(3-Methyl-4,5-dihydroisoxazol-5-ylmethoxy)quinazoline-2,4-diamine; and
1,1-Bis-4-chlorophenyl)-3-(2,4-diaminoquinazolin-5-yloxy)butan-1-ol.
7 . A compound according to claim 6 selected from the group consisting of
5-(2-p-Tolylethoxy)quinazoline-2,4-diamine;
5-[2-(4-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-(1-Phenylethoxy)quinazoline-2,4-diamine;
5-[3-(4-Chlorophenyl)propoxy]quinazoline-2,4-diamine;
5-[1-(3-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-p-Tolylethynylquinazoline-2,4-diamine;
5-Phenethyloxyquinazoline-2,4-diamine;
5-((S)-1-Phenylethoxy)quinazoline-2,4-diamine;
5-(1-Pyridin-4-ylethoxy)quinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)propoxy]quinazoline-2,4-diamine;
5-Benzhydryloxyquinazoline-2,4-diamine;
5-((R)-1-Phenylethoxy)quinazoline-2,4-diamine;
5-(1-Pyridin-2-ylethoxy)quinazoline-2,4-diamine;
5-(1-Thiazol-2-ylethoxy)quinazoline-2,4-diamine;
5-(1-Benzo[1,3]dioxol-5-ylethoxy)quinazoline-2,4-diamine;
5-[1-(3-Methoxyphenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(3,5-Dimethoxyphenyl)ethoxy]quinazoline-2,4-diamine;
5-[2-(4-Chlorophenyl)-3-methoxymethoxypropoxy]quinazoline-2,4-diamine;
2-(4-Chlorophenyl)-3-(2,4-diaminoquinazolin-5-yloxy)propan-1-ol;
5-[1-(3,4-Dichlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(2,6-Difluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-(3-Chlorophenyl)quinazoline-2,4-diamine;
5-[(R)-1-(3-Chlorophenyl)ethoxy]quinazolin-2,4-diamine;
5-[1-(3-Fluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(3-Trifluoromethylphenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(4-fluorophenyl)-1-methylethoxy]quinazoline-2,4-diamine;
5-[1-(2-Fluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(2-Chlorophenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(4-Trifluoromethylphenyl)ethoxy]quinazoline-2,4-diamine;
5-[1-(3,5-Difluorophenyl)ethoxy]quinazoline-2,4-diamine;
5-((S)-1-Naphthalen-2-ylethoxy)quinazoline-2,4-diamine;
5-[1-(4-Chlorophenyl)-2-methoxyethoxy]quinazoline-2,4-diamine;
(4-Chlorophenyl)(2,4-diaminoquinazolin-5-yloxy)acetic acid;
5-(1-Cyclopentylethoxy)quinazoline-2,4-diamine;
5-(1-Cyclohexyl-butoxy)quinazoline-2,4-diamine;
5-(1-Cyclohexylethoxy)quinazoline-2,4-diamine;
5-(1-Cyclohexylpropoxy)quinazoline-2,4-diamine;
5-[1-(3-Chlorophenyl)cyclopropoxy]quinazoline-2,4-diamine;
5-[1-(4-Fluorophenyl)-2-methoxymethoxyethoxy]quinazoline-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-2-(4-fluorophenyl)ethanol;
5-(2-Benzo[1,3]dioxol-5-yl-2-methoxymethoxyethoxy)quinazoline-2,4-diamine;
5-(1-Benzo[1,3]dioxol-5-yl-2-methoxymethoxyethoxy)quinazoline-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-1-phenyl-ethanol;
1-(4-Chlorophenyl)-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
1-(3-Chlorophenyl)-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
5-[(S)-1-(3-Chlorophenyl)ethoxy]quinazolin-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-1-(4-trifluoromethylphenyl)ethanol;
2-(4-Chlorophenyl)-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
5-[2-(4-Chlorophenyl)-2-methoxyethoxy]quinazoline-2,4-diamine;
5-(2-Methoxy-1-phenylethoxy)quinazoline-2,4-diamine;
2-(2,4-Diaminoquinazolin-5-yloxy)-1-(4-fluorophenyl)ethanol;
5-(2-Benzo[1,3]dioxol-5-yl-2-methoxyethoxy)quinazoline-2,4-diamine;
2-Benzo[1,3]dioxol-5-yl-2-(2,4-diaminoquinazolin-5-yloxy)ethanol;
5-(4-Chlorophenoxymethyl)quinazoline-2,4-diamine;
5-p-Tolyloxymethylquinazoline-2,4-diamine;
5-(4-Fluorophenoxymethyl)quinazoline-2,4-diamine;
5-Thiophen-3-ylmethylquinazoline-2,4-diamine;
5-[1-(3-Iodophenyl)ethoxy]quinazoline-2,4-diamine;
5-((1R,2R,4S)-Bicyclo[2.2.1]hept-2-yloxy)quinazoline-2,4-diamine;
5-(Adamantan-2-yloxy)quinazoline-2,4-diamine;
5-(Bicyclo[2.2.1]hept-2-yloxy)quinazoline-2,4-diamine;
5-(2-Chlorophenoxymethyl)quinazoline-2,4-diamine;
5-(4-Chloro-2-methylphenoxymethyl)quinazoline-2,4-diamine;
5-(4-Chloro-3-methylphenoxymethyl)quinazoline-2,4-diamine;
5-(2,4-Difluorophenoxymethyl)quinazoline-2,4-diamine;
5-(3-Chlorophenoxymethyl)quinazoline-2,4-diamine;
5-(2-Iodophenoxymethyl)quinazoline-2,4-diamine;
5-(4-Methylbenzyloxy)quinazoline-2,4-diamine;
5-(4-Chlorobenzyloxy)quinazoline-2,4-diamine;
5-(4-Iodobenzyloxy)quinazoline-2,4-diamine;
5-(3-Chlorobenzyloxy)quinazoline-2,4-diamine;
5-(2-Chlorobenzyloxy)quinazoline-2,4-diamine;
5-(2-Methylbenzyloxy)quinazoline-2,4-diamine;
5-(3-Methylbenzyloxy)quinazoline-2,4-diamine;
5-(Pyridin-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Cyclohex-3-enylmethoxy)quinazoline-2,4-diamine;
5-(Cyclobutylmethoxy)quinazoline-2,4-diamine;
5-(2-Methoxyethoxy)quinazoline-2,4-diamine;
5-(Cyclopropylmethoxy)quinazoline-2,4-diamine;
5-(Cyclopentylmethoxy)quinazoline-2,4-diamine;
5-(2-Allyloxyethoxy)quinazoline-2,4-diamine;
5-(1-Methylpiperidin-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Furan-2-ylmethoxy)quinazoline-2,4-diamine;
5-(Thiophen-2-ylmethoxy)quinazoline-2,4-diamine;
5-(Furan-3-ylmethoxy)quinazoline-2,4-diamine;
5-Benzyloxyquinazoline-2,4-diamine;
5-(Pyridin-2-ylmethoxy)quinazoline-2,4-diamine;
5-Octyloxyquinazoline-2,4-diamine;
5-(Thiophen-3-ylmethoxy)quinazoline-2,4-diamine;
5-(5-Methylisoxazol-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Benzo[1,3]dioxol-5-ylmethoxy)quinazoline-2,4-diamine;
5-(Tetrahydropyran-2-ylmethoxy)quinazoline-2,4-diamine;
5-(4-Bromobenzyloxy)quinazoline-2,4-diamine;
5-(3,4-Dimethoxybenzyloxy)quinazoline-2,4-diamine;
[4,5-Dichloro-2-(2,4-diaminoquinazolin-5-yloxymethyl)phenyl]methanol;
5-(Adamantan-1-ylmethoxy)quinazoline-2,4-diamine;
5-(2-Bromo-benzyloxy)quinazoline-2,4-diamine;
5-(2-Iodo-benzyloxy)quinazoline-2,4-diamine;
5-(3-Bromobenzyloxy)quinazoline-2,4-diamine;
5-(3-Iodo-benzyloxy)quinazoline-2,4-diamine;
5-(3,5-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,3,5-Trifluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,5-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,4-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(2,6-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(3,4-Difluorobenzyloxy)quinazoline-2,4-diamine;
5-(5-Chloro-2-methoxybenzyloxy)quinazoline-2,4-diamine;
[4-Chloro-2-(2,4-diaminoquinazolin-5-yloxymethyl)phenyl]methanol;
5-(2-Fluorobenzyloxy)quinazoline-2,4-diamine;
5-(4-Fluorobenzyloxy)quinazoline-2,4-diamine;
5-(3-Trifluoromethylbenzyloxy)quinazoline-2,4-diamine;
5-(2-Trifluoromethylbenzyloxy)quinazoline-2,4-diamine;
5-(4-Trifluoromethylbenzyloxy)quinazoline-2,4-diamine;
5-(3-Fluorobenzyloxy)quinazoline-2,4-diamine;
5-(3,5-Dichlorobenzyloxy)quinazoline-2,4-diamine;
5-(Quinolin-3-ylmethoxy)quinazoline-2,4-diamine;
5-(Quinolin-8-ylmethoxy)quinazoline-2,4-diamine;
5-(Piperidin-4-ylmethoxy)quinazoline-2,4-diamine;
5-(1-Methyl-piperidin-2-ylmethoxy)quinazoline-2,4-diamine;
4-(2,4-Diamino-quinzaolin-5-yloxymethyl)piperidin-1-carboxylic acid tert-butyl ester;
5-(Bicyclo[2.2.1]hept-5-en-2-ylmethoxy)quinazoline-2,4-diamine;
(4-Chlorophenyl)[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone;
5-(3-Methyl-oxetan-3-ylmethoxy)quinazoline-2,4-diamine;
5-((1S,2R,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-ylmethoxy)quinazoline-2,4-diamine;
5-(2,4-Diaminoquinazolin-5-yloxymethyl)bicyclo[2.2.1]heptane-2,3-diol;
5-[1-(3,4-Dichlorobenzyl)piperidin-4-ylmethoxy]quinazoline-2,4-diamine;
(2-Chlorophenyl)[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone;
(3-Chlorophenyl)[4-(2,4-diaminoquinazolin-5-yloxymethyl)piperidin-1-yl]methanone;
[4-(2,4-Diaminoquinzolin-5-yloxymethyl)piperidin-1-yl](3-iodophenyl)methanone;
[4-(2,4-Diaminoquinzolin-5-yloxymethyl)piperidin-1-yl](4-iodopheny)methanone;
[4-(2,4-Diaminoquinzolin-5-yloxymethyl)piperidin-1-yl](2-iodophenyl)methanone;
5-(2-Methoxybenzyloxy)quinazoline-2,4-diamine;
5-(3-Methoxybenzyloxy)quinazoline-2,4-diamine;
5-(4-Methoxybenzyloxy)quinazoline-2,4-diamine;
5-(Bicyclo[2.2.1]hept-2-ylmethoxy)quinazoline-2,4-diamine; and
5-((1S,2S,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-ylmethoxy)quinazoline-2,4-diamine.
8 . A 2,4-diaminoquinazoline compound according to claim 1 of formula VI:
wherein
L is a linker of empirical formula C p H q N r O s S t in which
p is 0-20;
q is 0-40;
r is 0-3;
s is 0-6;
t is 0-2; and
R is selected from the group consisting of cycloalkyl, aryl, fused cycloalkylaryl, heterocyclyl, heteroaryl, C 3 -C 10 alkyl and C 3 -C 10 oxaalkyl; substituted cycloalkyl, substituted aryl, substituted fused cycloalkylaryl, substituted heterocyclyl, substituted heteroaryl, substituted C 3 -C 10 alkyl, and substituted C 3 -C 10 oxaalkyl; and
R 10 and R 11 are independently selected from the group consisting of H, —NH 2 ,
—NH(alkyl), —NHOH, —NHO(alkyl), and acyl, with the proviso that at least one of R 10 and R 11 is other than H;
or a pharmaceutically acceptable salt thereof, in any stereoisomeric or tautomeric form, or a mixture of any such compounds in any ratio.
9 . A 2,4-diaminoquinazoline compound according to claim 1 of formula IV
wherein G 2 is selected from the group consisting of —O—, —S—, and —NH—; and
R 12 is selected from the group consisting of C 7 -C 10 polycyclic hydrocarbon, substituted C 7 -C 10 polycyclic hydrocarbon, and
wherein the wavy line indicates the point of attachment; and
wherein one or more carbon atoms in the cyclopentyl ring is optionally replaced by a heteroatom independently selected from the group consisting of N, O, and S; and
R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen,
halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, haloalkyl, hydroxy, carboxy, C 1 -C 6 alkoxycarbonyl, carboxamido, cyano, formyl, nitro, amino, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino, mercapto, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfoxide, C 1 -C 6 alkylsulfone, C 1 -C 6 acylamino, amidino, phenyl, benzyl, phenoxy and benzyloxy, with the proviso that at least one of R 3 , R 4 , and R 5 must be other than hydrogen;
or a pharmaceutically acceptable salt thereof, in any stereoisomeric or tautomeric form, or a mixture of any such compounds in any ratio.
10 . A compound according to claim 9 wherein R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkoxy, and haloalkyl.
11 .- 20 . (canceled)Join the waitlist — get patent alerts
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