2,8-disubstituted naphthyridine derivatives
View Patent ↗Disclosed are compounds of formula A: and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 2 ′, R 3 , R 21 , A 1 , A 2 , X, and Z are as defined herein. Compounds of formula A are useful in the treatment of diseases and/or conditions related to cell differentiation, such as cancer, inflammation, arthritis, angiogenesis, or the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.
1. A compound of the formula:
or a pharmaceutically acceptable salt thereof, wherein each ----- independently represents a single bond or a double bond;
A 1 is N, or an N-oxide;
A 2 is N, an N-oxide, NH, or N(C 1 -C 6 ) alkyl; provided that when ----- is a single bond, then A 2 is NH, or N(C 1 -C 6 ) alkyl;
X is NR x R y , or —C(O)R 20 ; wherein
R x and R y are independently H, C 1 -C 6 alkyl, alkoxycarbonyl, arylalkoxycarbonyl, aryl, arylalkyl, —C(O)—aryl, heteroaryl, heteroarylalkyl, or —C(O) heteroaryl;
Z is a bond, —CH 2 , —NH—, —O—, —N(C 1 -C 6 alkyl)—, —S—, —S(O)—, —SO 2 —, —SO 2 NH—, or —SO 2 N(C 1 -C 6 alkyl)—;
R 1 is C 1 -C 6 alkanoyl, C 2 -C 6 alkynyl, aryl, heteroaryl, heterocycloalkyl, or C 3 -C 8 cycloalkyl, each of which is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CN, CO 2 H, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, —OC(O) —C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, —C(O)R 10 , NR 6 R 7 , —(C 1 -C 4 alkyl)—NR 6 R 7 , —C(O)NR 6 R 7 , phenyl, or naphthyl, wherein the phenyl and naphthyl groups are optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , wherein
each R 6 and R 7 is independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, 2, or 3, groups that are independently halogen, OH, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 alkyl) or N (C 1 -C 6 alkyl) (C 1 -C 6 alkyl); or
R 6 and R 7 and the nitrogen to which they are attached form a ring having from 5 to 8 members, wherein the ring optionally contains 1-3 additional heteroatoms selected from N, O, and S, where the ring is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, amino, NH (C 1 -C 6 alkyl), or N (C 1 -C 6 alkyl) (C 1 -C 6 alkyl);
R 10 is C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, aryl, heteroaryl, or cycloalkyl, wherein the cyclic portions are optionally substituted with 1, 2, or 3 groups that are independently halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, OH, CO 2 H, CN, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy;
wherein the heterocycloalkyl and the cycloalkyl portions of R 1 and R 10 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 ;
R 2 , R 2 ′, and R 3 are independently H, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 alkyl) —C(O)N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl), or aryl;
R 20 is H, OH, C 1 -C 6 alkoxy, or NR 4 R 5 ; wherein
R 4 and R 5 are independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxy C 1 -C 6 alkyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkylalkynyl, heterocycloalkyl, heterocycloalkylalkyl, heterocycloalkylalkenyl, heterocycloalkylalkynyl, aryl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkynyl, arylalkyl, arylalkenyl, or arylalkynyl, wherein the cyclic portion of each of the above is unsubstituted or substituted with one or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —SO 2 — (C 1 -C 6 ) alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , CN, OH, aryl C 1 -C 6 alkyl, C 1 -C 6 alkoxy C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 7 R 8 , or —C(O)NR 7 R 8 ,
wherein R 7 and R 8 are independently H or C 1 -C 6 alkyl, wherein the alkyl is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkoxycarbonyl, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkanoyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl) or CO 2 H; or
R 7 and R 8 and the nitrogen to which they are attached form a ring having from 5 to 8 members, wherein the ring optionally contains 1-3 additional heteroatoms selected from N, O, and S, where the ring is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, amino, NH(C 1 -C 6 alkyl), or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl);
wherein the heterocycloalkyl and the cycloalkyl portions of R 4 and R 5 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 ; or
R 4 and R 5 and the nitrogen to which they are attached form a heterocycloalkyl ring, which is unsubstituted or substituted with 1 or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, aryl C 1 -C 6 alkyl, C 1 -C 6 alkanoyl, OH, ═O, heteroaryl, heteroarylalkyl, phenyl, naphthyl, —OCH 2 -CH 2 O—, —OCH 2 O—,
wherein the heteroaryl, phenyl and naphthyl groups are unsubstituted or substituted with 1 or more groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, CF 3 or OCF 3 ;
R 21 is H, CN, amino, monoalkylamino, dialkylamino, OH, halogen, aryl, heteroaryl, C 1 -C 6 alkyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl, —C(O)NH 2 , —C(O)NH(C 1 -C 6 alkyl), or —C(O)N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl);
provided that when
R 20 is NR 4 R 5 and R 4 is C 1-6 alkyl, C 2-6 alkenyl or C 3-7 cyoloalkyl optionally substituted with OH, halogen, amino, carboxyl or saturated or unsaturated C 3-10 (carbocycle or heterocycle) optionally substituted with OH, halogen, amino, mercapto, carboxy, C 1-4 (alkyl, alkoxy, alkylthio, acyl, acyloxy or alkoxycarbonyl) optionally substituted with OH, halogen, amino or C 1-4 alkoxy; and C 3-7 cycloalkyl fused to C 6-10 aryl optionally substituted with OH, halogen, amino, mercapto, carboxy, C 1-4 (alkyl, alkoxy, alkylthio, acyl, acyloxy or alkoxycarbonyl) optionally substituted with OH, halogen, amino or C 1-4 alkoxy;
R 5 is H, or C 1-4 alkyl; and
(1) Z is a bond; and
R 2 or R 3 is H, OH, halogen, amino, cyano, C 1-6 (alkyl, alkoxy, acyl, acyloxy or alkoxycarbonyl) optionally substituted with OH, halogen, amino or C 1-4 alkoxy, and saturated or unsaturated C 3-10 (carbocycle or heterocycle) optionally substituted with OH, halogen, amino, mercapto, C 1-4 alkylthio, C 1-4 alkoxycarbonyl, halo substituted C 1-4 alkyl or halo-substituted C 1-4 alkoxy, C 1-4 alkyl, C 1-4 alkoxy or carboxy; or
(2) Z is a bond;
R 2 or R 3 is H, OH, halogen, amino, cyano, C 1-6 (alkyl, alkoxy, acyl, acyloxy or alkoxycarbonyl) optionally substituted with OH, halogen, amino or C 1-4 alkoxy, and saturated or unsaturated C 3-10 (carbocycle or heterocycle) optionally substituted with OH, halogen, amino, mercapto, C 1-4 alkylthio, C 1-4 alkoxycarbonyl, halo substituted C 1-4 alkyl or halo-substituted C 1-4 alkoxy, C 1-4 alkyl, C 1-4 alkoxy or carboxy; and
R 4 and R 5 together form a saturated or unsaturated 5 or 6 member heterocycle optionally fused to C 6-10 aryl or heteroaryl; then
R 1 is not OH, amino, cyano, C 1-6 (alkoxy, acyl, acyloxy or alkoxycarbonyl) optionally substituted with OH, halogen, amino or C 1-4 alkoxy, and saturated or unsaturated C 3-10 (carbocycle or heterocycle) optionally substituted with OH, halogen, amino, mercapto, C 1-4 alkylthio, C 1-4 alkoxycarbonyl, halo substituted C 1-4 alkyl or halo-substituted C 1-4 alkoxy, C 1-4 alkyl, C 1-4 alkoxy or carboxy.
2. A compound according to claim 1 , wherein
R 1 is C 1 -C 6 alkanoyl, C 2 -C 6 alkynyl, phenyl, naphthyl, thienyl, furanyl, indolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazolyl, imidazolyl, oxazolyl, isoxazolyl, benzofuranyl, 3,4 dihydropyrimidin-2 (1H)—onyl, piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, S,S -dioxothiomorpholinyl, or C 3 -C 8 cycloalkyl, each of which is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, ON, CO 2 H, phenyl, naphthyl, wherein the phenyl and naphthyl groups are optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, —OC(O)—C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, —C(O)R 10 , NR 6 R 7 , —(C 1 -C 4 alkyl)-NR 6 R 7 , or —C(O)NR 6 R 7 , wherein
Each R 6 and R 7 is independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, 2, or 3, groups that are independently halogen, OH, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 alkyl) or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl);
R 10 is C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, phenyl, naphthyl, pyridyl, quinolinyl, pyrimidyl, furanyl, indolyl, benzofuranyl, thienyl, cycloalkyl, wherein the cyclic portions are optionally substituted with halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, OH, CO 2 H, CN, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy;
wherein the heterocycloalkyl and the cycloalkyl portions of R 1 and R 10 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 .
3. A compound according to claim 1 , wherein
R 20 is NR 4 R 5 ; wherein
R 4 and R 5 are independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxy C 1 -C 6 alkyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl C 2 -C 6 alkenyl, cycloalkyl C 2 -C 6 alkynyl, piperidinyl, pyrrolidinyl, imidazolidinyl, morpholinyl, thiomorpholinyl, S,S-dioxothiomorpholinyl, tetrahydrofuranyl, tetrahydrothienyl, morpholinyl C 1 -C 6 alkyl, thiomorpholinyl C 1 -C 6 alkyl, S,S-dioxothiomorpholinyl C 1 -C 6 alkyl, piperidinyl C 1 -C 6 alkyl, pyrrolidinyl C 1 -C 6 alkyl, imidazolidinyl C 1 -C 6 alkyl, piperidinyl C 2 -C 6 alkenyl, pyrrolidinyl C 2 -C 6 alkenyl, imidazolidinyl C 2 -C 6 alkenyl, morpholinyl C 2 -C 6 alkenyl, thiomorpholinyl C 2 -C 6 alkenyl, S,S-dioxothiomorpholinyl C 2 -C 6 alkenyl, tetrahydrofuranyl C 2 -C 6 alkenyl, tetrahydrothienyl C 2 -C 6 alkenyl, piperidinyl C 2 -C 6 alkynyl, pyrrolidinyl C 2 -C 6 alkynyl, imidazolidinyl C 2 -C 6 alkynyl, morpholinyl C 2 -C 6 alkynyl, thiomorpholinyl C 2 -C 6 alkynyl, S,S-dioxothiomorpholinyl C 2 -C 6 alkynyl, tetrahydrofuranyl C 2 -C 6 alkynyl, tetrahydrothienyl C 2 -C 6 alkynyl, phenyl, naphthyl, furanyl, pyridyl, pyrimidyl, pyrazinyl, thienyl, imidazolyl, pyrazinyl C 1 -C 6 alkyl, pyridyl C 1 -C 6 alkyl, pyrimidyl C 1 -C 6 alkyl, pyrazinyl C 1 -C 6 alkyl, imidazolyl C 1 -C 6 alkyl, furanyl C 1 -C 6 alkyl, thienyl C 1 -C 6 alkyl, heteroarylalkenyl, heteroarylalkynyl, phenyl C 1 -C 6 alkyl, naphthyl C 1 -C 6 alkyl, phenyl C 2 -C 6 alkenyl, naphthyl C 2 -C 6 alkenyl, phenyl C 2 -C 6 alkynyl, naphthyl C 2 -C 6 alkynyl, wherein the cyclic portion of each of the above is unsubstituted or substituted with one or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —SO 2 —(C 1 -C 6 ) alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , CN, OH, phenyl C 1 -C 6 alkyl wherein the phenyl is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, CN, halogen, OH, and alkanoyl, C 1 -C 6 alkoxy C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 7 R 8, or —C(O)NR 7 R 8 ,
wherein R 7 and R 8 are independently H or C 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkoxycarbonyl, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkanoyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl) or CO 2 H;
wherein the heterocycloalkyl and the cycloalkyl portions of R 4 and R 5 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 ; or
R 4 and R 5 and the nitrogen to which they are attached form a piperazinyl, morpholinyl, piperidinyl, pyrrolidinyl, thiomorpholinyl, imidazolidinyl, S,S,-dioxothiomorpholinyl, piperidinyl, pyrrolidinyl, ring, which is unsubstituted or substituted with 1 or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, phenyl C 1 -C 6 alkyl, naphthyl C 1 -C 6 alkyl, C 1 -C 6 alkanoyl, OH, ═O, pyridyl, pyrimidyl, pyrazinyl, pyrimidyl C 1 -C 6 alkyl, pyrazinyl C 1 -C 6 alkyl, phenyl, naphthyl, —OCH 2 CH 2 O—, —OCH 2 O—,
wherein the pyridyl, pyrimidyl, pyrazinyl, pyrimidyl C 1 -C 6 alkyl, phenyl and naphthyl groups are unsubstituted or substituted with 1 or more groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, CF 3 or OCF 3 .
4. A compound according to claim 1 , wherein
R 1 is C 1 -C 6 alkanoyl, C 2 -C 6 alkynyl, phenyl, naphthyl, thienyl, furanyl, indolyl, pyridyl, pyridazinyl, pyrimidyl, pyrazinyl, triazolyl, imidazolyl, oxazolyl, isoxazolyl, benzofuranyl, 3,4-dihydropyrimidin-2(1H)-onyl, piperidinyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, S,S-dioxothiomorpholinyl, or C 3 -C 8 cycloalkyl, each of which is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CN, CO 2 H, phenyl, naphthyl, wherein the phenyl and naphthyl groups are optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, —OC(O)—C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, —C(O)R 10 , NR 6 R 7 , —(C 1 -C 4 alkyl)-NR 6 R 7 , or —C(O)NR 6 R 7 , wherein
each R 6 and R 7 is independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, 2, or 3, groups that are independently halogen, OH, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 alkyl) or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl);
R 10 is C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, phenyl, naphthyl, pyridyl, quinolinyl, pyrimidyl, furanyl, indolyl, C 3 -C 8 cycloalkyl, wherein the cyclic portions are optionally substituted with halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, OH, CO 2 H, CN, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy;
wherein the heterocycloalkyl and the cycloalkyl portions of R 1 and R 10 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 ; and
R 4 and R 5 are independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxy C 1 -C 6 alkyl, C 2 -C 6 alkynyl, C 2 -C 6 alkenyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkyl C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl C 2 -C 6 alkenyl, cycloalkyl C 2 -C 6 alkynyl, piperidinyl, pyrrolidinyl, imidazolidinyl, morpholinyl, thiomorpholinyl, S,S-dioxothiomorpholinyl, tetrahydrofuranyl, tetrahydrothienyl, morpholinyl C 1 -C 6 alkyl, thiomorpholinyl C 1 -C 6 alkyl, S,S-dioxothiomorpholinyl C 1 -C 6 alkyl, piperidinyl C 1 -C 6 alkyl, pyrrolidinyl C 1 -C 6 alkyl, imidazolidinyl C 1 -C 6 alkyl, piperidinyl C 2 -C 6 alkenyl, pyrrolidinyl C 2 -C 6 alkenyl, imidazolidinyl C 2 -C 6 alkenyl, morpholinyl C 2 -C 6 alkenyl, thiomorpholinyl C 2 -C 6 alkenyl, S,S-dioxothiomorpholinyl C 2 -C 6 alkenyl, tetrahydrofuranyl C 2 -C 6 alkenyl, tetrahydrothienyl C 2 -C 6 alkenyl, piperidinyl C 2 -C 6 alkynyl, pyrrolidinyl C 2 -C 6 alkynyl, imidazolidinyl C 2 -C 6 alkynyl, morpholinyl C 2 -C 6 alkynyl, thiomorpholinyl C 2 -C 6 alkynyl, S,S-dioxothiomorpholinyl C 2 -C 6 alkynyl, tetrahydrofuranyl C 2 -C 6 alkynyl, tetrahydrothienyl C 2 -C 6 alkynyl, phenyl, naphthyl, furanyl, pyridyl, pyrimidyl, pyrazinyl, thienyl, imidazolyl, pyrazinyl C 1 -C 6 alkyl, pyridyl C 1 -C 6 alkyl, pyrimidyl C 1 -C 6 alkyl, pyrazinyl C 1 -C 6 alkyl, imidazolyl C 1 -C 6 alkyl, furanyl C 1 -C 6 alkyl, thienyl C 1 -C 6 alkyl, heteroarylalkenyl, heteroarylalkynyl, phenyl C 1 -C 6 alkyl, naphthyl C 1 -C 6 alkyl, phenyl C 2 -C 6 alkenyl, naphthyl C 2 -C 6 alkenyl, phenyl C 2 -C 6 alkynyl, naphthyl C 2 -C 6 alkynyl, wherein the cyclic portion of each of the above is unsubstituted or substituted with one or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —SO 2 -(C 1 -C 6 ) alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , CN, OH, phenyl C 1 -C 6 alkyl wherein the phenyl is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, CN, halogen, OH, and alkanoyl, C 1 -C 6 alkoxy C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 7 R 8 , or —C(O)NR 7 R 8 ,
wherein R 7 and R 8 are independently H or C 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkoxycarbonyl, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkanoyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl) or CO 2 H;
wherein the heterocycloalkyl and the cycloalkyl portions of the above are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 ; or
R 4 and R 5 and the nitrogen to which they are attached form a piperazinyl, morpholinyl, piperidinyl, thiomorpholinyl, imidazolidinyl, S,S,-dioxothiomorpholinyl, piperidinyl, pyrrolidinyl, ring, which is unsubstituted or substituted with 1 or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, phenyl C 1 -C 6 alkyl, naphthyl C 1 -C 6 alkyl, C 1 -C 6 alkanoyl, OH, ═O, pyridyl, pyrimidyl, pyrazinyl, pyrimidyl C 1 -C 6 alkyl, pyrazinyl C 1 -C 6 alkyl, phenyl, naphthyl, —OCH 2 CH 2 O—, —OCH 2 O—,
wherein the pyridyl, pyrimidyl, pyrazinyl, pyrimidyl C 1 -C 6 alkyl, phenyl and naphthyl groups are unsubstituted or substituted with 1 or more groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, CF 3 or OCF 3 .
5. A compound according to claim 4 , wherein
R 2 and R 3 are independently H, halogen, or C 1 -C 6 alkyl.
6. A compound according to claim 5 , wherein
Z is a bond, —CH 2 —, or —NH—.
7. A compound according to claim 6 , wherein
R 1 is C 2 -C 6 alkynyl, phenyl, thienyl, pyridyl, triazolyl, imidazolyl, pyrazinyl, benzofuranyl, 3,4-dihydropyrimidin-2(1H)-onyl, each of which is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CN, CO 2 H, phenyl, wherein the phenyl is optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, —OC(O)—C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, —C(O)R 10 , or, NR 6 R 7 , —(C 1 -C 4 alkyl)-NR 6 R 7 , —C(O)NR 6 R 7 , wherein
each R 6 and R 7 is independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, 2, or 3, groups that are independently halogen, OH, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 alkyl) or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl); and
R 10 is phenyl, pyridyl, or C 3 -C 8 cycloalkyl, wherein the cyclic portions are optionally substituted with halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, OH, CO 2 H, CN, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy.
8. A compound according to claim 7 , wherein
R 4 and R 5 are independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxy C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, piperidinyl, pyrrolidinyl, morpholinyl, morpholinyl C 1 -C 6 alkyl, piperidinyl C 1 -C 6 alkyl, pyrrolidinyl C 1 -C 6 alkyl, piperidinyl C 2 -C 6 alkenyl, pyrrolidinyl C 2 -C 6 alkenyl, morpholinyl C 2 -C 6 alkenyl, piperidinyl C 2 -C 6 alkynyl, pyrrolidinyl C 2 -C 6 alkynyl, morpholinyl C 2 -C 6 alkynyl, phenyl, furanyl, pyridyl, pyrazinyl C 1 -C 6 alkyl, pyridyl C 1 -C 6 alkyl, imidazolyl C 1 -C 6 alkyl, furanyl C 1 -C 6 alkyl, thienyl C 1 -C 6 alkyl, phenyl C 1 -C 6 alkyl, phenyl C 2 -C 6 alkenyl, phenyl C 2 -C 6 alkynyl, wherein the cyclic portion of each of the above is unsubstituted or substituted with one or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —SO 2 —(C 1 -C 6 ) alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NO 2 , CN, OH, phenyl C 1 -C 6 alkyl wherein the phenyl is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, CN, halogen, OH, and alkanoyl, C 1 -C 6 alkoxy C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 7 R 8 , or —C(O)NR 7 R 8 ,
wherein R 7 and R 8 are independently H or C 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkoxycarbonyl, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkanoyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl) or CO 2 H;
wherein the heterocycloalkyl and the cycloalkyl portions of R 4 and R 5 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 .
9. A compound according to claim 8 , wherein
Z is —NH— or —CH 2 —;
R 1 is C 2 -C 6 alkynyl, phenyl, thienyl, pyridyl, triazolyl, imidazolyl, pyrazinyl, benzofuranyl, 3,4-dihydropyrimidin-2(1H)-onyl, each of which is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CN, CO 2 H, phenyl, wherein the phenyl is optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , CF 3 , OCF 3 , —OC(O)—C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 6 R 7 , —(C 1 -C 4 alkyl)-NR 6 R 7 , or —C(O)NR 6 R 7 , wherein
each R 6 and R 7 is independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, 2, or 3, groups that are independently halogen, OH, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, NH 2 , NH(C 1 -C 6 alkyl) or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl); and
and
R 4 and R 5 are independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxy C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, piperidinyl, pyrrolidinyl, morpholinyl, morpholinyl C 1 -C 6 alkyl, piperidinyl C 1 -C 6 alkyl, pyrrolidinyl C 1 -C 6 alkyl, phenyl, furanyl, pyridyl, pyrazinyl C 1 -C 6 alkyl, pyridyl C 1 -C 6 alkyl, imidazolyl C 1 -C 6 alkyl, furanyl C 1 -C 4 alkyl, thienyl C 1 -C 6 alkyl, phenyl C 1 -C 6 alkyl, wherein the cyclic portion of each of the above is unsubstituted or substituted with one or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —SO 2 —(C 1 -C 6 ) alkyl, CF 3 , OCF 3 , NO 2 , CN, OH, phenyl C 1 -C 6 alkyl wherein the phenyl is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, CN, halogen, OH, and alkanoyl, C 1 -C 6 alkoxy C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 7 R 8 , or —C(O)NR 7 R 8 ,
wherein R 7 and R 8 are independently H or C 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl is optionally substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkoxycarbonyl, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkanoyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl) or CO 2 H;
wherein the heterocycloalkyl and the cycloalkyl portions of R 4 and R 5 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 .
10. A compound according to claim 9 , wherein
R 1 is phenyl, thienyl, pyridyl, imidazolyl, pyrazinyl, benzofuranyl, each of which is unsubstituted or substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CN, CO 2 H, phenyl, wherein the phenyl is optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , CF 3 , OCF 3 , —OC(O)—C 1 -C 6 alkyl, C 1 -C 6 alkoxycarbonyl, C 1 -C 6 alkanoyl, NR 6 R 7 , —(C 1 -C 4 alkyl)-NR 6 R 7 , or —C(O)NR 6 R 7 , wherein
each R 6 and R 7 is independently H, C 1 -C 6 alkyl, or C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, 2, or 3, groups that are independently halogen, OH, CF 3 , OCF 3 , NH 2 , NH(C 1 -C 6 alkyl) or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl); and
and
R 4 and R 5 are independently H, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, piperidinyl, pyrrolidinyl, morpholinyl C 1 -C 4 alkyl, piperidinyl C 1 -C 4 alkyl, phenyl, furanyl, pyridyl, pyrazinyl C 1 -C 4 alkyl, pyridyl C 1 -C 4 alkyl, imidazolyl C 1 -C 4 alkyl, furanyl C 1 -C 4 alkyl, thienyl C 1 -C 4 alkyl, phenyl C 1 -C 4 alkyl, wherein the cyclic portion of each of the above is unsubstituted or substituted with one or more groups that are independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, halogen, —SO 2 —(C 1 -C 4 ) alkyl, CF 3 , OCF 3 , NO 2 , CN, OH, NR 7 R 8 , or —C(O)NR 7 R 8 ,
wherein R 7 and R 8 are independently H or C 1 -C 6 alkyl, wherein the C 1 -C 6 alkyl is optionally substituted with 1, or 2 groups that are independently C 1 -C 6 alkoxycarbonyl, halogen, C 1 -C 6 alkoxy, C 1 -C 6 alkanoyl, NH 2 , NH(C 1 -C 6 alkyl), N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl) or CO 2 H;
wherein the heterocycloalkyl and the cycloalkyl portions of R 4 and R 5 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 .
11. A compound according to claim 10 , wherein
R 4 is H or methyl; and
R 5 is —CH 2 -furanyl.
12. A compound according to claim 11 , wherein
R 1 is phenyl, thienyl, pyridyl, or pyrazinyl, each of which is unsubstituted or substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CF 3 , OCF 3 , NR 6 R 7 , —(C 1 -C 2 alkyl)-NR 6 R 7 , or —C(O)NR 6 R 7 , wherein
each R 6 and R 7 at each occurrence are independently H, C 1 -C 6 alkyl, or C 1 -C 4 alkoxycarbonyl.
13. A compound according to claim 6 , wherein
R 4 and R 5 and the nitrogen to which they are attached form a piperazinyl, morpholinyl, piperidinyl, imidazolidinyl, or pyrrolidinyl ring, each of which is unsubstituted or substituted with 1 or more groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, phenyl C 1 -C 4 alkyl, C 1 -C 6 alkanoyl, OH, pyridyl, pyrimidyl, pyrazinyl, pyrimidyl C 1 -C 4 alkyl, pyrazinyl C 1 -C 4 alkyl, phenyl, —OCH 2 CH 2 O—, —OCH 2 O—,
wherein the pyridyl, pyrimidyl, pyrazinyl, pyrimidyl C 1 -C 6 alkyl, and phenyl groups are unsubstituted or substituted with 1 or more groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, CF 3 or OCF 3 .
14. A compound according to claim 13 , wherein
R 1 is phenyl, thienyl, furanyl, pyridyl, pyrazinyl, triazolyl, imidazolyl, oxazolyl, benzofuranyl, each of which is unsubstituted or substituted with 1, 2, 3, 4, or 5 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, CN, CO 2 H, phenyl, wherein the phenyl group is optionally substituted with 1 or more groups that are independently selected from C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, OH, CF 3 , and OCF 3 , CF 3 , OCF 3 , —OC(O)—C 1 -C 4 alkyl, C 1 -C 4 alkoxycarbonyl, or C 1 -C 4 alkanoyl.
15. A compound according to claim 13 , wherein
R 1 is phenyl, thienyl, pyridyl, pyrazinyl, triazolyl, imidazolyl, benzofuranyl, each of which is unsubstituted or substituted with 1, 2, or 3 groups that are independently C 1 -C 6 alkyl, halogen, C 1 -C 6 alkoxy, OH, —C(O)R 10 , NR 6 R 7 , —(C 1 -C 4 alkyl)-NR 6 R 7 , or —C(O)NR 6 R 7 , wherein
each R 6 and R 7 is independently H, C 1 -C 6 alkyl, C 1 -C 4 alkoxyalkyl, C 1 -C 6 alkoxycarbonyl, wherein the alkyl portion of each is unsubstituted or substituted with 1, or 2 groups that are independently halogen, OH, CF 3 , OCF 3 , NH 2 , NH(C 1 -C 6 alkyl) or N(C 1 -C 6 alkyl) (C 1 -C 6 alkyl);
R 10 is phenyl, naphthyl, pyridyl, quinolinyl, pyrimidyl, furanyl, indolyl, or C 3 -C 8 cycloalkyl, each of which is optionally substituted with halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, OH, CO 2 H, CN, NO 2 , C 1 -C 4 haloalkyl, or C 1 -C 4 haloalkoxy;
wherein the heterocycloalkyl and the cycloalkyl portions of R 1 and R 10 are further optionally substituted with ═O, ═N—OH, or ═N—OCH 3 .
16. A compound according to claim 15 , wherein
R 4 and R 5 and the nitrogen to which they are attached form a piperazinyl, morpholinyl, piperidinyl, imidazolidinyl, or pyrrolidinyl ring, which is unsubstituted or substituted with 1 or more groups that are independently C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen, phenyl C 1 -C 2 alkyl, C 1 -C 6 alkanoyl, OH, pyridyl, pyrimidyl C 1 -C 2 alkyl, phenyl, —OCH 2 CH 2 O—, or —OCH 2 O—; and
R 2 and R 3 are both H.
17. A compound according to claim 1 which is
8-[5-(2-Dimethylamino-ethylcarbamoyl)-thiophen-2-yl]-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-[5-(2-Diethylamino-ethylcarbamoyl)-thiophen-2-yl]-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-[5-(2-Dimethylamino-ethylcarbamoyl)-thiophen-2-yl]-[1,6]naphthyridine-2-carboxylic acid cyclopropylamide;
8-[5-(2-Diethylamino-ethylcarbamoyl)-thiophen-2-yl]-[1,6]naphthyridine-2-carboxylic acid cyclopropylamide;
5-(2-Methylcarbamoyl-[1,6]naphthyridin-8-yl)-thiophene-2-carboxylic acid amide;
5-(2-Methylcarbamoyl-[1,6]naphthyridin-8-yl)-thiophene-2-carboxylic acid methylamide;
8-[5-(3-Morpholin-4-yl-propylcarbamoyl)-thiophen-2-yl]-[1,6]naphthyridine-2-carboxylic acid methylamide;
8-Thiophen-3-yl[1,6]-naphthyridine-2-carboxylic acid;
8-Thiophen-3-yl[1,6]-naphthyridine-2-carboxylic acid (2-oxo-cyclohexyl)amide;
8-Thiophen-3-yl-[1,6]naphthyridine-2-carboxylic acid amide;
8-Phenyl[1,6]-naphthyridine-2-carboxylic acid;
8-Phenyl[1,6]-naphthyridine-2-carboxylic acid amide;
8-Phenyl[1,6]-naphthyridine-2-carboxylic acid (2-oxo-cyclohexyl)amide;
8-(3-Hydroxy-prop-1-ynyl-[1,6]naphthyridine-2-carboxylic acid cyclopropylamide;
8-(3-Hydroxy-prop-1-ynyl-[1,6]naphthyridine-2-carboxylic acid amide;
8-(3-Hydroxy-prop-1-ynyl-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)amide;
(3-{2-[(Furan-2-ylmethyl)-carbamoyl]-[1,6]naphthyridin-8-yl}-prop-2-ynyl)-carbamic acid tert-butyl ester;
8-Phenylethynyl-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-Ethynyl-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(4-Methoxy-phenylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-para-Tolylamino-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-Phenylamino-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(3-Trifluoromethyl-phenylamino0-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(4-Trifluoromethyl-phenylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(Pyridin-3-ylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(Pyridin-4-ylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(Pyrazin-2-ylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(3,5-Dichloro-phenylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(4-Methoxy-phenylamino)-[1,6]naphthyridine-2-carboxylic acid cyclopropylamide;
8-(3,5-Dichloro-phenylamino)-[1,6]naphthyridine-2-carboxylic acid cyclopropylamide;
8-(4-Methoxy-phenylamino)-[1,6]naphthyridine-2-carboxylic acid amide;
8-[(Furan-2-ylmethyl)-amino]-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-[(Pyridin-4-ylmethyl)-amino]-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-[(Pyridin-2-ylmethyl)-amino]-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-[(Pyridin-3-ylmethyl)-amino]-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(3-Methoxy-benzylamino)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-Cyclopropylamino-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-Prop-2-ynylamino-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(2-Oxo-pyrrolidin-1-yl)-[1,6]naphthyridine-2-carboxylic acid (furan-2-ylmethyl)-amide;
8-(3-thienyl)-1,6-naphthyridine-2-carboxylic acid;
N-cyclopropyl-8-[5-({[2-(diethylamino)ethyl]amino}carbonyl)-2-thienyl]-1,6-naphthyridine-2-carboxamide;
8-phenyl-1,6-naphthyridine-2-carboxylic acid;
N-(2-furylmethyl)-8-{[4-(trifluoromethyl)phenyl]amino}-1,6-naphthyridine-2-carboxamide;
N-(2-furylmethyl)-8-[(4-methylphenyl)amino]-1,6-naphthyridine-2-carboxamide;
8-anilino-N-(2-furylmethyl)-1,6-naphthyridine-2-carboxamide;
N-(2-furylmethyl)-8-{[3-(trifluoromethyl)phenyl]amino}-1,6-naphthyridine-2-carboxamide;
N-(2-furylmethyl)-8-[(4-methoxyphenyl)amino]-1,6-naphthyridine-2-carboxamide;
N-(2-furylmethyl)-8-(3-hydroxyprop-1-yn-1-yl)-1,6-naphthyridine-2-carboxamide;
8-(5-carboxy-2-thienyl)-1,6-naphthyridine-2-carboxylic acid;
N-(2-furylmethyl)-8-(pyridin-3-ylamino)-1,6-naphthyridine-2-carboxamide;
tert-butyl [3-(2-{[(2-furylmethyl)amino]carbonyl}-1,6-naphthyridin-8-yl)prop-2-yn-1-yl]carbamate;
N-(2-furylmethyl)-8-(pyridin-4-ylamino)-1,6-naphthyridine-2-carboxamide;
8-[5-({[2-(diethylamino)ethyl]amino}carbonyl)-2-thienyl]-N-(2-furylmethyl)-1,6-naphthyridine-2-carboxamide;
8-[5-({[2-(dimethylamino)ethyl]amino}carbonyl)-2-thienyl]-N-(2-furylmethyl)-1,6-naphthyridine-2-carboxamide;
N-cyclopropyl-8-[5-({[2-(dimethylamino)ethyl]amino}carbonyl)-2-thienyl]-1,6-naphthyridine-2-carboxamide;
N-(2-furylmethyl)-8-(pyrazin-2-ylamino)-1,6-naphthyridine-2-carboxamide;
N-(2-oxocyclohexyl)-8-(3-thienyl)-1,6-naphthyridine-2-carboxamide;
N-(2-oxocyclohexyl)-8-phenyl-1,6-naphthyridine-2-carboxamide;
8-(3-hydroxyprop-1-yn-1-yl)-1,6-naphthyridine-2-carboxamide;
N-cyclopropyl-8-(3-hydroxyprop-1-yn-1-yl)-1,6-naphthyridine-2-carboxamide;
N-(2-furylmethyl)-8-(phenylethynyl)-1,6-naphthyridine-2-carboxamide;
8-ethynyl-N-(2-furylmethyl)-1,6-naphthyridine-2-carboxamide;
N-cyclopropyl-8-[(4-methoxyphenyl)amino]-1,6-naphthyridine-2-carboxamide;
2-[(4-benzylpiperazin-1-yl)carbonyl]-8-(4-methoxyphenyl)-1,6-naphthyridine;
N-[4-(methylsulfonyl)benzyl]-8-(3-thienyl)-1,6-naphthyridine-2-carboxamide;
1-{[8-(3-thienyl)-1,6-naphthyridin-2-yl]carbonyl}piperidin-4-ol;
N-(2-methoxyethyl)-8-(3-thienyl)-1,6-naphthyridine-2-carboxamide;
8-(4-methoxyphenyl)-2-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]-1,6-naphthyridine;
N-(1-benzylpiperidin-4-yl)-8-(4-methoxyphenyl)-1,6-naphthyridine-2-carboxamide;
8-(4-methoxyphenyl)-N-[4-(methylsulfonyl)benzyl]-1,6-naphthyridine-2-carboxamide;
2-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-8-phenyl-1,6-naphthyridine;
8-phenyl-2-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]-1,6-naphthyridine;
2-[(4-benzylpiperazin-1-yl)carbonyl]-8-phenyl-1,6-naphthyridine;
N-(1-benzylpiperidin-4-yl)-8-phenyl-1,6-naphthyridine-2-carboxamide;
N-[4-(methylsulfonyl)benzyl]-8-phenyl-1,6-naphthyridine-2-carboxamide;
2-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-8-(3-thienyl)-1,6-naphthyridine;
2-[(4-pyridin-2-ylpiperazin-1-yl)carbonyl]-8-(3-thienyl)-1,6-naphthyridine;
2-[(4-benzylpiperazin-1-yl)carbonyl]-8-(3-thienyl)-1,6-naphthyridine;
N-(1-benzylpiperidin-4-yl)-8-(3-thienyl)-1,6-naphthyridine-2-carboxamide;
2-({4-[(4,6-dimethoxypyrimidin-2-yl)methyl]piperazin-1-yl}carbonyl)-8-(3-thienyl)-1,6-naphthyridine;
1-{[8-(1-benzofuran-2-yl)-1,6-naphthyridin-2-yl]carbonyl}piperidin-4-ol;
8-(1-benzofuran-2-yl)-N-(2-methoxyethyl)-1,6-naphthyridine-2-carboxamide;
1-[(8-phenyl-1,6-naphthyridin-2-yl)carbonyl]piperidin-4-ol;
N-(2-methoxyethyl)-8-phenyl-1,6-naphthyridine-2-carboxamide;
8-(1-benzofuran-2-yl)-2-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-1,6-naphthyridine;
8-(1-benzofuran-2-yl)-2-[(4-benzylpiperazin-1-yl)carbonyl]-1,6-naphthyridine;
8-(1-benzofuran-2-yl)-N-(1-benzylpiperidin-4-yl)-1,6-naphthyridine-2-carboxamide;
8-(1-benzofuran-2-yl)-N-[4-(methylsulfonyl)benzyl]-1,6-naphthyridine-2-carboxamide;
or a pharmaceutically acceptable salt thereof.
18. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable solvent, carrier, excipient, adjuvant or a combination thereof.
19. A method of treating a disease or condition selected from inflammation and arthritis comprising administering a therapeutically effective amount of a compound of claim 1 to a patient in need of such treatment.