US2011237608A1PendingUtilityA1
Pyridopyrimidinone Inhibitors of PI3Kalpha
Est. expiryOct 7, 2025(expired)· nominal 20-yr term from priority
Inventors:Tae-Gon BaikChris A. BuhrKatherine LaraSunghoon MaMorrison B. MacJohn M. NussLongcheng WangYong WangBryan K. S. Yeung
A61P 35/00A61P 35/02A61P 43/00C07D 471/04A61K 9/4858A61K 9/2018A61K 9/10A61K 9/08A61K 31/519A61K 9/0095A61K 9/02A61K 31/505
44
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Claims
Abstract
The invention is directed to Compounds of Formula I: and pharmaceutically acceptable salts or solvates thereof, as well as methods of making and using the compounds.
Claims
exact text as granted — not AI-modified1 . A Compound of Formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;
R 2 is hydrogen or alkyl where the alkyl is optionally substituted with 1, 2, 3, 4, or 5 R 8 groups;
X is —NR 3 —;
R 3 hydrogen;
R 4 is optionally substituted alkyl;
R 5 is hydrogen; and
R 6 is phenyl, acyl, or heteroaryl wherein the phenyl and heteroaryl are optionally substituted with 1, 2, 3, 4, or 5 R 9 groups;
each R 8 , when present, is independently hydroxy, halo, alkoxy, haloalkoxy, amino, alkylamino, dialkylaminoalkyl, or alkoxyalkylamino; and
each R 9 , when present, is independently halo, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, amino, alkylamino, dialkylamino, alkoxyalkyl, carboxyalkyl, alkoxycarbonyl, aminoalkyl, cycloalkyl, aryl, arylalkyl, aryloxy, heterocycloalkyl, or heteroaryl and where the cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each either alone or as part of another group within R 9 , are independently optionally substituted with 1, 2, 3, or 4 groups selected from halo, alkyl, haloalkyl, hydroxy, alkoxy, haloalkxy, amino, alkylamino, and dialkylamino.
2 . The Compound of claim 1 where R 1 is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkylalkyl, or optionally substituted arylalkyl; X is —NH—; R 2 is hydrogen or alkyl where the alkyl is optionally substituted with one or two R 8 groups; R 4 is alkyl; R 5 is hydrogen; R 6 is phenyl or heteroaryl wherein the phenyl and heteroaryl are optionally substituted with one, two, or three R 9 groups; each R 8 , when present, is independently amino, alkylamino, dialkylamino, or halo; and each R 9 , when present, is independently alkyl, arylalkyl, cyano, aryl, alkoxycarbonyl, or halo.
3 . The Compound of claim 1 where R 2 is hydrogen.
4 . The Compound of claim 3 where R 4 is methyl.
5 . The Compound of claim 3 where R 1 is optionally substituted alkyl or cycloalkyl.
6 . The Compound of claim 4 where R 1 is optionally substituted alkyl.
7 . The Compound of claim 3 where R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
8 . The Compound of claim 7 where each R 9 , when present, is independently aryl, halo, alkoxy, aryloxy, or haloalkyl.
9 . The Compound of claim 7 where R 4 is methyl.
10 . The Compound of claim 3 where R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups.
11 . The Compound of claim 10 where each R 9 , when present, is independently alkyl, arylalkyl, cyano, aryl, alkoxycarbonyl, or halo.
12 . The Compound of claim 3 where R 6 is pyrazolyl, imidazolyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, furanyl, pyrrolyl, triazolyl, or tetrazolyl; each of which is optionally substituted with 1, 2, or 3 R 9 groups.
13 . The Compound of claim 3 where R 6 is pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, thien-2-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-4-yl, isoxazol-5-yl, 1,2,4-oxadiazol-5-yl, furan-2-yl, furan-3-yl, pyrrol-2-yl, pyrrol-3-yl, triazol-4-yl; triazol-5-yl, or tetrazol-5-yl; each of which is optionally substituted with 1, 2, or 3 R 9 groups.
14 . The Compound of claim 12 where R 4 is methyl.
15 . The Compound of claim 3 where R 6 is pyrazinyl, pyrimidinyl, or pyridazinyl each of which is optionally substituted with 1, 2, or 3 R 9 groups.
16 . The Compound of claim 15 where R 4 is methyl.
17 . The Compound of claim 1 where R 2 is hydrogen, R 4 is methyl, R 1 is optionally substituted alkyl or cycloalkyl, and R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
18 . The Compound of claim 1 where R 2 is hydrogen, R 4 is methyl, R 1 is optionally substituted alkyl or cycloalkyl, and R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups.
19 . The Compound of claim 3 where R 1 is heterocycloalkyl and R 4 is methyl.
20 . The Compound of claim 19 where R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
21 . The Compound of claim 19 where R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups.
22 . The Compound of claim 3 where R 1 is heterocycloalkylalkyl and R 4 is methyl.
23 . The Compound of claim 22 where R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
24 . The Compound of claim 22 where R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups.
25 . The Compound of claim 1 where R 2 is alkyl optionally substituted with 1, 2, or 3 R 9 groups.
26 . The Compound of claim 25 where R 4 is methyl.
27 . The Compound of claim 25 where R 1 is optionally substituted alkyl or cycloalkyl.
28 . The Compound of claim 25 where R 1 is optionally substituted alkyl.
29 . The Compound of claim 25 where R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
30 . The Compound of claim 29 where each R 9 , when present, is independently aryl, halo, alkoxy, aryloxy, and haloalkyl.
31 . The Compound of claim 29 where R 4 is methyl.
32 . The Compound of claim 25 where R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups.
33 . The Compound of claim 32 where each R 9 , when present, is independently alkyl, arylalkyl, cyano, aryl, alkoxycarbonyl, or halo.
34 . The Compound of claim 25 where R 6 is pyrazolyl, imidazolyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, furanyl, pyrrolyl, triazolyl, or tetrazolyl; each of which is optionally substituted with 1, 2, or 3 R 9 groups.
35 . The Compound of claim 25 where R 6 is pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl, thien-2-yl, thien-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, furan-2-yl, furan-3-yl, pyrrol-2-yl, pyrrol-3-yl, triazol-4-yl, triazol-5-yl, or tetrazol-5-yl; each of which is optionally substituted with 1, 2, or 3 R 9 groups.
36 . The Compound of claim 34 where R 4 is methyl.
37 . The Compound of claim 25 where R 6 is pyrazinyl, pyrimidinyl, or pyridazinyl each of which is optionally substituted with 1, 2, or 3 R 9 groups.
38 . The Compound of claim 37 where R 4 is methyl.
39 . The Compound of claim 1 where R 2 is hydrogen, R 4 is methyl, R 1 is optionally substituted alkyl or cycloalkyl, and R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
40 . The Compound of claim 1 where R 2 is hydrogen, R 4 is methyl, R 1 is optionally substituted alkyl or cycloalkyl, and R 6 is heteroaryl optionally substituted with 1, 2, 3, 4, or 5 R 9 groups.
41 . The Compound of claim 25 where R 1 is heterocycloalkyl or heterocycloalkylalkyl and R 4 is methyl.
42 . The Compound of claim 41 where R 6 is phenyl optionally substituted with 1, 2, or 3 R 9 groups.
43 . The Compound of claim 41 where R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups.
44 . A Compound selected from
8-ethyl-2-(ethylamino)-4-methyl-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-8-ethyl-4-methyl-2-[(1-methylethyl)amino]pyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-2-[(1,1-dimethylethyl)amino]-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-
one;
6-biphenyl-4-yl-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(2,4-difluorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(3-chloro-4-fluorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[4-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-(2,4-dichlorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(3,4-difluorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[2-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-bromo-2-{[3-(dimethylamino)propyl]amino}-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[4-(phenyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-[2,4-bis(methyloxy)phenyl]-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-6-(3-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-6-(2-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[3-(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-6-(4-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[3-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-(3-chlorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(4-chlorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(4-methyl-2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
1,1-dimethylethyl 2-[8-ethyl-2-(ethylamino)-4-methyl-7-oxo-7,8-dihydropyrido[2,3-
d]pyrimidin-6-yl]-1H-pyrrole-1-carboxylate
8-ethyl-2-(ethylamino)-4-methyl-6-(1H-pyrrol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
6-(5-chloro-2-thienyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-pyrimidin-5-ylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-6-(3-fluoropyridiN-4-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-2-(ethylamino)-6-furan-3-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[1-(phenylmethyl)-1H-pyrazol-4-yl]pyrido[2,3-
d]pyrimidin-7(8H)-one;
6-bromo-2-(ethylamino)-4-methyl-8-(1-methylethyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-4-methyl-8-(1-methylethyl)-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-2-(ethylamino)-6-(1H-indol-6-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(5-phenyl-2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-6-furan-3-yl-4-methyl-8-(1-methylethyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-cyclohexyl-2-(ethylamino)-4-methyl-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-2-(ethylamino)-4-methyl-8-[3-(methyloxy)propyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-bromo-2-(ethylamino)-8-[2-(ethyloxy)ethyl]-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-2-(ethylamino)-4-methyl-8-(2-piperidin-1-ylethyl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-bromo-2-(ethylamino)-8-[3-(ethyloxy)propyl]-4-methylpyrido[2,3-d]pyrimidin-7(8H)-
one;
6-bromo-2-(ethylamino)-4-methyl-8-{3-[(1-methylethyl)oxy]propyl}pyrido[2,3-
d]pyrimidin-7(8H)-one;
6-bromo-2-(ethylamino)-8-(3-hydroxypropyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-2-(ethylamino)-8-(2-hydroxyethyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-8-cyclopropyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
6-bromo-8-cyclopentyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-cyclopentyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
2-(ethylamino)-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-1-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-1-yl)pyrido[2,3-d]pyrimidin-
7(8H)-one;
8-cyclopentyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-1-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)-2-[(2,2,2-trifluoroethyl)amino]pyrido[2,3-
d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-4-methyl-2-(methylamino)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-cyclopentyl-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-[(2-fluoroethyl)amino]-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-
7(8H)-one;
2-amino-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
2-amino-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-4-methyl-8-(phenylmethyl)-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
2-amino-8-ethyl-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(4-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(3-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(2-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-furan-3-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-[4-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-(4-chlorophenyl)-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-(3-chlorophenyl)-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-isoxazol-4-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-furan-2-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-(2,4-dichlorophenyl)-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
5-(2-amino-8-ethyl-4-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)thiophene-2-
carbonitrile
2-amino-8-ethyl-4-methyl-6-pyrimidin-5-ylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(1H-imidazol-5-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-1,2,3-triazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-tetrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1-methyl-1H-pyrrol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-bromo-8-cyclopentyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-4,8-diethyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one; and
2-amino-8-cyclopentyl-4-methyl-6-(1,3-thiazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one
45 . The Compound of claim 1 selected from
8-ethyl-2-(ethylamino)-4-methyl-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-biphenyl-4-yl-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(2,4-difluorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(3-chloro-4-fluorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[4-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-(2,4-dichlorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-
one;
6-(3,4-difluorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[2-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-2-(ethylamino)-4-methyl-6-[4-(phenyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-[2,4-bis(methyloxy)phenyl]-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-6-(3-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-6-(2-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[3-(trifluoromethyl)phenyl]pyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-6-(4-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[3-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-
one;
6-(3-chlorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
6-(4-chlorophenyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(4-methyl-2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
1,1-dimethylethyl 2-[8-ethyl-2-(ethylamino)-4-methyl-7-oxo-7,8-dihydropyrido[2,3-
d]pyrimidin-6-yl]-1H-pyrrole-1-carboxylate
8-ethyl-2-(ethylamino)-4-methyl-6-(1H-pyrrol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
6-(5-chloro-2-thienyl)-8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-pyrimidin-5-ylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-6-(3-fluoropyridiN-4-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-2-(ethylamino)-6-furan-3-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-[1-(phenylmethyl)-1H-pyrazol-4-yl]pyrido[2,3-
d]pyrimidin-7(8H)-one;
2-(ethylamino)-4-methyl-8-(1-methylethyl)-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-2-(ethylamino)-6-(1H-indol-6-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(5-phenyl-2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-6-furan-3-yl-4-methyl-8-(1-methylethyl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-cyclohexyl-2-(ethylamino)-4-methyl-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-cyclopentyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
2-(ethylamino)-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-
7(8H)-one;
8-ethyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-1-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-1-yl)pyrido[2,3-d]pyrimidin-
7(8H)-one;
8-cyclopentyl-2-(ethylamino)-4-methyl-6-(1H-pyrazol-1-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)-2-[(2,2,2-trifluoroethyl)amino]pyrido[2,3-
d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-(ethylamino)-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-4-methyl-2-(methylamino)-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-cyclopentyl-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
8-ethyl-2-[(2-fluoroethyl)amino]-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-
7(8H)-one;
2-amino-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
2-amino-4-methyl-8-(phenylmethyl)-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-
one;
2-amino-8-ethyl-4-methyl-6-(4-methyl-3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(2-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(4-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(3-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(2-fluorophenyl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(3-thienyl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-furan-3-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-phenylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-[4-(methyloxy)phenyl]pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-(4-chlorophenyl)-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-(3-chlorophenyl)-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-isoxazol-4-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-furan-2-yl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-6-(2,4-dichlorophenyl)-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
5-(2-amino-8-ethyl-4-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)thiophene-2-
carbonitrile
2-amino-8-ethyl-4-methyl-6-pyrimidin-5-ylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-6-(1H-imidazol-5-yl)-4-methylpyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-1,2,3-triazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-4-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1H-tetrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-8-ethyl-4-methyl-6-(1-methyl-1H-pyrrol-2-yl)pyrido[2,3-d]pyrimidin-7(8H)-one;
2-amino-4,8-diethyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one; and
2-amino-8-cyclopentyl-4-methyl-6-(1,3-thiazol-5-yl)pyrido[2,3-d]pyrimidin-7(8H)-one
46 . A pharmaceutical composition which comprises a compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier, excipient, or diluent.
47 . A method for treating a disease, disorder, or syndrome which method comprises administering to a patient a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, excipient, or diluent.
48 . The method of claim 47 where the disease is cancer.
49 . The method of claim 47 where the cancer is breast cancer, colon cancer, rectal cancer, endometrial cancer, gastric carcinoma, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, cervical cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), or thyroid carcinoma.
50 . The method of claim 47 where the cancer is ovarian cancer, cervical cancer, breast cancer, colon cancer, rectal cancer, or glioblastoma.
51 . A method of treating a disease, disorder, or syndrome which method comprises administering to a patient a therapeutically effective amount of a compound of Formula II or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a compound of Formula II and a pharmaceutically acceptable carrier, excipient, or diluent; where the Compound of Formula II is that wherein:
or a pharmaceutically acceptable salt or solvate thereof, wherein
R 1 is hydrogen, optionally substituted alkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;
X is S, SO 2 , or —NR 3 —;
R 2 is hydrogen, haloalkyl, optionally substituted alkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heterocycloalkyl-aryl- or optionally substituted heteroaryl; R 2 is optionally further substituted with one or more R 8 groups;
R 3 , R 3a , and R 3b are independently hydrogen, optionally substituted alkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted heterocycloalkyl or optionally substituted heteroaryl;
R 4 is hydrogen, halo, haloalkyl, haloalkoxy, —NR 3a —, optionally substituted alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
R 5 is hydrogen, halo, haloalkyl, haloalkoxy, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 alkoxyalkyl, optionally substituted aminoalkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted aryl C 1 -C 6 alkyl or optionally substituted heteroaryl; and
R 6 is hydrogen, halo, haloalkyl, haloalkoxy, —NR 3b —, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 alkoxyalkyl, optionally substituted acyl, optionally substituted aminoalkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl; substitutable R 6 groups are optionally further substituted with 1, 2, 3, 4, or 5 R 9 groups;
each R 8 , when present, is independently hydroxy, halo, haloalkyl, haloalkoxy, optionally substituted alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 alkoxyalkyl, optionally substituted C 1 -C 6 alkoxyalkylaminoalkyl, C 1 -C 6 alkylcarboxyheterocycloalkyl, oxy C 1 -C 6 alkylheterocycloalkyl, optionally substituted aminoalkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted aryl C 1 -C 6 alkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl;
each R 9 , when present, is independently halo, haloalkyl, haloalkoxy, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 alkoxyalkyl, optionally substituted C 1 -C 6 carboxyalkyl, optionally substituted alkoxycarbonyl, optionally substituted aminoalkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted aryl, optionally substituted aryl C 1 -C 6 alkyl, optionally substituted aryloxy, optionally substituted heterocycloalkyl, or optionally substituted heteroaryl.
52 . The method of claim 51 where the disease is cancer.Cited by (0)
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