Claims
- 1. A compound of Formula (I):
- 2. The compound according to claim 1, wherein
X is N; Y is C—Q2; Z1 is C—Q3; Z2 is C—Q4; and Z3 is CH; or a pharmaceutically acceptable salt thereof.
- 3. The compound according to claim 2, wherein
A is phenyl; and Q3 and Q4 are both —H; or a pharmaceutically acceptable salt thereof.
- 4. The compound according to claim 1, which is a compound of Formula (II):
- 5. The compound according to claim 4, wherein
Z1 is CH; Q2 is
(1) —H, (2) —C1-4 alkyl, (3) —(CH2)0-2CF3, (4) —O—C1-4 alkyl, (5) —O—(CH2)0-2CF3, (6) halo selected from —F, —Cl and —Br, (7) —CN, (8) —(CH2)1-3ORa, (9) —(CH2)0-2C(═O)Ra, (10) —(CH2)0-2CO2Ra, (11) —(CH2)0-2SRa, (12) —N(Ra)2, (13) —(CH2)1-3N(Ra)2, (14) —(CH2)0-2C(═O)N(Ra)2, (15) —G—(CH2)1-2—C(═O)N(Ra)2, wherein G is O, S, N(Ra), or N(SO2Ra), (16) —N(Ra)—C(Ra)═O, (17) —(CH2)1-2—N(Ra)—C(Ra)═O, (18) —C(═O)—N(Ra)—(CH2)1-3—[C(═O)]0-1—N(Ra)2, (19) —C(═O)—N(Ra)—(CH2)1-2H substituted with 1 or 2-ORa, (20) —SO2Ra, (21) —N(Ra)SO2Ra, (22) —CH═CH—(CH2)0-1—C(═O)—N(Ra)2, (23) —C≡C—CH2ORa, (24) —C≡C—CH2SRa, (25) —C≡C—CH2SO2Ra279(27) —N(Ra)—(CH2)1-4SRa, (28) —N(Ra)—(CH2)1-4ORa, (29) —N(Ra)—(CH2)1-4—N(Ra)2, (30) —N(Ra)—(CH2)1-4N(Ra)—C(Ra)═O, (31) —N(Ra)—(CH2)0-2—[C(═O)]1-2N(Ra)2, (32) —N(Ra)—(CH2)1-4—CO2Ra, (33) —N(Ra)C(═O)N(Ra)—(CH2)1-4—C(═O)N(Ra)2, (34) —N(Ra)C(═O)—(CH2)1-4—N(Ra)2, (35) —N(Ra)—SO2—N(Ra)2, (36) Rk, (37) —(CH2)1-4Rk, (38) —C≡C—CH2R (39) —O—Rk, (40) —S(O)n—Rk, (41) —N(Rc)—Rk, (42) —N(Rc)—(CH2)1-4H substituted with one or two Rk groups, (43) —N(Rc)—(CH2)1-4ORk, (44) —C(═O)—Rk, (45) —C(═O)N(Ra)—Rk, (46) —N(Ra)C(═O)—Rk, or (47) —C(═O)N(Ra)—(CH2)1-4Rk; and (48) —N(Ra)—S(O)nRk; Q4 is —H; each of R1 and R2 is independently:
(1) —H, (2) —C1-4 alkyl, (3) —(CH2)0-2CF3, (4) —O—C1-4 alkyl, (5) —O—(CH2)0-2CF3, (6) —OH, (7) halo selected from —F, —Cl and —Br, (8) —CN, (9) —(CH2)1-3ORa, (10) —(CH2)0-2C(═O)Ra, (11) —(CH2)0-2CO2Ra, (12) —(CH2)0-2SRa, (13) —N(Ra)2, (14) —(CH2)1-3N(Ra)2, (15) —(CH2)0-2C(═O)N(Ra)2, (16) —C1-4 alkyl-N(Ra)—C(Ra)═O, (17) —SO2Ra, (18) —N(Ra)SO2Ra, (19) —O—(CH2)1-4ORa, (20) —O—(CH2)1-4SRa, (21) —O—(CH2)1-4NH—CO2Ra, (22) —O—(CH2)2-4N(Ra)2, (23) —N(Ra)—(CH2)1-4SRa, (24) —N(Ra)—(CH2)1-4ORa, (25) —N(Ra)—(CH2)1-4N(Ra)2, (26) —N(Ra)—(CH2)1-4N(Ra)—C(Ra)═O, (27) —Rk, (28) —(CH2)1-4H substituted with 1 or 2 Rk groups, (29) —O—Rk, (30) —O—(CH2)1-4Rk, (31) —S(O)n—Rk, (32) —S(O)n—(CH2)1-4Rk, (33) —O—(CH2)1-4ORk, (34) —O—(CH2)1-4—O—(CH2)1-4Rk, (35) —O—(CH2)1-4SRk, or (36) —(CH2)0-4N(Rb)(Rk); each of R3 and R4 is independently
(1) —H, (2) halo selected from —F, —Cl and —Br, (3) —CN, (4) —OH, (5) C1-4 alkyl, (6) —(CH2)0-2CF3, (7) —O—C1-4 alkyl, or (8) —O(CH2)0-2CF3; and R5 is
(1) —H, (2) —C1-4 alkyl, (3) —(CH2)1-4N(Ra)2, (4) —(CH2)1-4CO2Ra, (5) phenyl optionally substituted with from 1 to 3 substituents independently selected from halogen, C1-4 alkyl, —(CH2)0-2CF3, —O—C1-4 alkyl, —O(CH2)0-2CF3, —S—C1-4 alkyl, —CN, and —OH, or (6) —(CH2)1-4-phenyl; or a pharmaceutically acceptable salt thereof.
- 6. The compound according to claim 5, which is a compound of Formula (III):
- 7. The compound according to claim 6, wherein
L is
(i) a single bond; (ii) —(CH2)1-3—, which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of —F, —Cl, —Br, —OH, methyl, ethyl, —CO2CH3, —CO2CH2-phenyl, phenyl, benzyl, —(CH2)1-2OH, —CH(OH)-phenyl, and —CH(NH2)-phenyl; or (iii) 281, wherein u and v are each integers having a value of from 0 to 3, provided that the sum of u+v is 1, 2, 3 or 4; each of R1 and R2 is independently:
(1) —H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7) —OCF3 (8) halo selected from —F, —Cl and —Br, (9) —CN, (10) —CH2ORa, (11) —CO2Ra, (12) —SRa, (13) —N(Ra)2, (14) —(CH2)1-3N(Ra)2, (15) —SO2Ra, (16) —(CH2)1-2N(Ra)—C(Ra)═O, (17) —Rk, (18) —(CH2)1-3H substituted with 1 or 2 Rk groups, (19) —O—Rk, or (20) —O—(CH2)1-3Rk; R5 is
(1) —H, (2) methyl, (3) —(CH2)1-2N(Ra)2, (4) —(CH2)1-2CO2CH3, or (5) —(CH2)1-2CO2CH2CH3; (6) phenyl, or (7) benzyl; each Ra is independently —H or —C1-4 alkyl; each Rc is independently
(1) —H, (2) —C1-4 alkyl, (3) —(CH2)1-4N(Ra)2, or (4) —(CH2)1-4-phenyl, wherein the phenyl is optionally substituted with 1 to 3 substituents independently selected from halogen, C1-4 alkyl, C1-4 fluoroalkyl, —O—C1-4 alkyl, —O—C1-4 fluoroalkyl, —S—C1-4 alkyl, —CN, and —OH; and each Rk is independently:
(1) aryl selected from phenyl and naphthyl, wherein aryl is unsubstituted or substituted with from 1 to 4 substituents independently selected from:
(a) halogen, (b) C1-4 alkyl, (c) C1-4 fluoroalkyl, (d) —O—C1-4 alkyl, (e) —O—C1-4 fluoroalkyl, (f) phenyl, (g) —S—C1-4 alkyl, (h) —CN, (i) —OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from:
(i) halogen, (ii) C1-4 alkyl, (iii) C1-4 fluoroalkyl, and (iv) —OH, (k) —N(Ra)2, (l) —C1-4 alkyl-N(Ra)2, (m) —Rt, (p) —(CH2)0-3C(═O)N(Ra)2, and (q) —(CH2)0-3C(═O)Ra; (2) —C3-6 cycloalkyl, unsubstituted or substituted with from 1 to 3 substituents independently selected from:
(a) halogen, (b) C1-4 alkyl, (c) —O—C1-4 alkyl, (d) C1-4 fluoroalkyl, (e) —O—C1-4 fluoroalkyl, (f) —CN, (h) phenyl, and (j) —OH; (3) —C3-6 cycloalkyl fused with a phenyl ring, unsubstituted or substituted with from 1 to 4 substituents independently selected from:
(a) halogen, (b) C1-4 alkyl, (c) —O—C1-4 alkyl, (d) C1-4 fluoroalkyl, (e) —O—C1-4 fluoroalkyl, (f) —CN, and (g) —OH; (4) a 5- or 6- membered heteroaromatic ring selected from thienyl, pyridyl, imidazolyl, pyrrolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, pyrazinyl, pyrimidinyl, triazolyl, tetrazolyl, furanyl, and pyridazinyl, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with from 1 to 4 substituents independently selected from:
(a) halogen, (b) C1-4 alkyl, (c) C1-4 fluoroalkyl, (d) —O—C1-4 alkyl, (e) —O—C1-4 fluoroalkyl, (f) phenyl, (g) —S—C1-4 alkyl, (h) —CN, (i) —OH, (j) phenyloxy, unsubstituted or substituted with from 1 to 3 substituents independently selected from:
(i) halogen, (ii) C1-4 alkyl, (iii) C1-4 fluoroalkyl, and (iv) —OH, (k) —N(Ra)2, (l) —C1-4 alkyl-N(Ra)2, (m) —Rt, (n) oxo, (o) —(CH2)0-3C(═O)N(Ra)2, and (p) —(CH2)0-3C(═O)Ra; (5) a 5- or 6- or 7- membered saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, pyrazolidinyl, hexahydropyrimidinyl, thiazinanyl, thiazepanyl, azepanyl, thiadiazepanyl, dithiazepanyl, diazepanyl, and thiadiazinanyl, and wherein the heterocyclic ring is unsubstituted or substituted with from 1 to 4 substituents independently selected from:
(a) halogen, (b) C1-6 alkyl, (c) —O—C1-6 alkyl, (d) C1-6 fluoroalkyl, (e) —O—C1-6 fluoroalkyl, (f) —CN, (g) oxo, (h) phenyl (i) benzyl, (j) phenylethyl, (k) —OH, (l) —(CH2)0-3C(═O)N(Ra)2, (m) —(CH2)0-3C(═O)Ra, (n) —N(Ra)—C(═O)Ra, (o) —N(Ra)—CO2Ra, (p) —(CH2)1-3N(Ra)—C(═O)Ra, (q) —N(Ra)2, (r) —(CH2)1-3N(Ra)2, (s) —(CH2)1-3—ORa, (t) —(CH2)0-3CO2Ra, (u) —(CH2)0-3—O—(CH2)1-3—ORa, (v) —SO2Ra, (w) —SO2N(Ra)2, (x) —(CH2)0-3C(═O)O(CH2)1-2CH═CH2, (y) —Rt, (z) —(CH2)0-3C(═O)Rt, (aa) —N(Ra)Rt, and (bb) —(CH2)1-3Rt; or (6) an 8- to 10- membered heterobicyclic ring selected from indolyl, benzotriazolyl, benzoimidazolyl, imidazo[4,5-b]pyridinyl, dihydroimidazo[4,5-b]pyridinyl, pyrazolo[4,3-c]pyridinyl, dihydropyrazolo[4,3-c]pyridinyl, tetrahydropyrazolo[4,3-c]pyridinyl, pyrrolo[1,2-a]pyrazinyl, dihydropyrrolo[1,2-a]pyrazinyl, tetrahydropyrrolo[1,2-a]pyrazinyl, octahydropyrrolo[1,2-a]pyrazinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromanyl, isochromanyl, hexahydropyrazolo[4,3-c]pyridinyl, hexahydropurinyl, hexahydrooxazolo[3,4a]pyrazinyl, and 1,2,3,4-tetrahydro-1,8-naphthyridinyl; and wherein the bicyclic ring is unsubstituted or substituted with from 1 to 3 substituents independently selected from:
(a) halogen, (b) C1-4 alkyl, (c) —O—C1-4 alkyl, (d) C1-4 fluoroalkyl, (e) —O—C1-4 fluoroalkyl, (f) —CN, (g) ═O, and (h) —OH; Rt is naphthyl or a 5- or 6-membered heteromonocylic ring selected from pyrrolidinyl, pyrazolidinyl, imidazolinyl, piperidinyl, piperazinyl, pyrrolyl, pyridyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyrazinyl, pyrimidinyl, and pyradizinyl; and wherein the naphthyl or the heteromonocyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, oxo, C1-4 alkyl, and —O—C1-4 alkyl; or a pharmaceutically acceptable salt thereof.
- 8. A compound of Formula (IV):
- 9. The compound according to claim 8, wherein
Q2 is
(1) —H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7) —OCF3 (8) halo selected from —F, —Cl and —Br, (9) —CN, (10) —CH2OH, (11) —CH2OCH3, (12) —(CH2)0-2C(═O)CH3, (13) —(CH2)0-2CO2CH3, (14) —SRa, (15) —N(Ra)2, (16) —(CH2)1-2N(Ra)2, (17) —(CH2)0-2C(═O)N(Ra)2, (18) —S—CH2—C(═O)N(Ra)2, (19) —O—CH2—C(═O)N(Ra)2, (20) —N(SO2Ra)—CH2—C(═O)N(Ra)2, (21) —N(Ra)—C(Ra)═O, (22) —C(═O)—N(Ra)—(CH2)1-2—C(═O)N(Ra)2, (23) —C(═O)—N(Ra)—(CH2)1-2ORa, (24) —C(═O)—N(Ra)—(CH2)1-3—N(Ra)2, (25) —SO2Ra, (26) —N(Ra)SO2Ra, (27) —CH═CH—C(═O)—N(Ra)2, (28) —C≡C—CH2ORa, (29) —C≡C—CH2SRa, (30) —C≡C—CH2SO2R 284(32) —N(Ra)—(CH2)1-3 SRa, (33) —N(Ra)—(CH2)1-3ORa, (34) —N(Ra)—(CH2)1-3N(Ra)2, (35) —N(Ra)—(CH2)1-3N(Ra)—C(Ra)═O, (36) —N(Ra)CH2—C(═O)N(Ra)2, (37) —N(Ra)—C(═O)—C(═O)—N(Ra)2, (38) —N(Ra)—C(═O)—N(Ra)2, (39) —N(Ra)—(CH2)1-2—CO2Ra, (40) —N(Ra)—C(═O)—N(Ra)—(CH2)1-2—C(═O)—N(Ra)2, (41) —N(Ra)—C(═O)—(CH2)1-2—C(═O)—N(Ra)2, (42) —N(Ra)—SO2—N(Ra)2, (43) Rk, (44) —(CH2)1-4Rk, (45) —C≡C—CH2Rk, (46) —O—Rk, (47) —S—Rk, (48) —SO2—Rk, (49) —N(Rc)—Rk, (50) —N(Rc)—(CH2)1-4H substituted with one or two Rk groups, (51) —N(Rc)—(CH2)1-4ORk, (52) —C(═O)—Rk, (53) —C(═O)N(Ra)—Rk, (54) —N(Ra)—C(═O)—Rk, (55) —C(═O)N(Ra)—(CH2)1-4Rk, or (56) —N(Ra)—SO2Rk, each of R1 and R2 is independently:
(1) —H, (2) methyl, (3) ethyl, (4) CF3, (5) methoxy, (6) ethoxy (7) —OCF3 (8) halo selected from —F and —Cl, (9) —CN, (10) —CH2ORa, (11) —CO2Ra, (12) —SRa, (13) —N(Ra)2, (14) —(CH2)1-3N(Ra)2, (15) —SO2Ra, (16) —Rk, (17) —(CH2)1-3Rk, (18) —O—Rk, or (19) —O—(CH2)1-3Rk; each Ra is independently —H or —C1-4 alkyl; each Rc is independently —H, —C1-4 alkyl, or —(CH2)1-3N(Ra)2; each Rk is independently:
(1) phenyl which is unsubstituted or substituted with from 1 to 4 substituents independently selected from:
(a) halogen selected from —F, —Cl, and —Br, (b) methyl or ethyl, (c) —CF3, (d) methoxy, (e) —OCF3, (f) phenyl, (g) —S—CH3, (h) —CN, (i) —OH, (j) phenyloxy (k) —N(Ra)2, (l) —(CH2)1-3N(Ra)2, (m) —Rt, (p) —(CH2)0-3C(═O)N(Ra)2, and (q) —(CH2)0-3C(═O)Ra; (2) —C3-6 cycloalkyl, (3) a 5- or 6- membered heteroaromatic ring selected from thienyl, pyridyl, imidazolyl, pyrrolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, pyrazinyl, pyrimidinyl, triazolyl, tetrazolyl, furanyl, and pyridazinyl, wherein the heteroaromatic ring is unsubstituted or substituted on nitrogen or carbon with 1 or 2 substituents independently selected from:
(a) halogen selected from —F, —Cl, and —Br, (b) methyl or ethyl, (c) —CF3, (d) methoxy, (e) —OCF3, (f) —S—C1-6 alkyl, (g) —CN, (h) —OH, (i) —N(Ra)2, (j) —C1-6 alkyl-N(Ra)2, (k) —Rt, (l) oxo, (m) —(CH2)0-3C(═O)N(Ra)2, and (n) —(CH2)0-3C(═O)Ra; (4) a 5- or 6- or 7- membered saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, pyrazolidinyl, hexahydropyrimidinyl, thiazinanyl, thiazepanyl, azepanyl, thiadiazepanyl, dithiazepanyl, diazepanyl, and thiadiazinanyl; and wherein the heterocyclic ring is unsubstituted or substituted with 1 to 4 substituents independently selected from:
(a) halogen selected from —F, —Cl, and —Br, (b) methyl or ethyl, (c) —CF3, (d) methoxy, (e) —OCF3, (f) —CN, (g) ═O, (h) phenyl, (i) benzyl, (j) phenylethyl, (k) —OH, (l) —(CH2)0-3C(═O)N(Ra)2, (m) —(CH2)0-3C(═O)Ra, (n) N(Ra)—C(═O)Ra, (o) N(Ra)—CO2Ra, (p) (CH2)1-3N(Ra)—C(═O)Ra, (q) N(Ra)2, (r) (CH2)1-3N(Ra)2, (s) SO2Ra, (t) —(CH2)0-3C(═O)Rt, (u) —Rt, (v) —N(Ra)Rt, and (w) —(CH2)1-3Rt; and (5) an 8- to 10- membered heterobicyclic ring selected from indolyl, benzotriazolyl, benzoimidazolyl, imidazo[4,5-b]pyridinyl, dihydroimidazo[4,5-b]pyridinyl, pyrazolo[4,3-c]pyridinyl, dihydropyrazolo[4,3-c]pyridinyl, tetrahydropyrazolo[4,3-c]pyridinyl, pyrrolo[1,2-a]pyrazinyl, dihydropyrrolo[1,2-a]pyrazinyl, tetrahydropyrrolo[1,2-a]pyrazinyl, octahydropyrrolo[1,2-a]pyrazinyl, isoindolyl, indazolyl, indolinyl, isoindolinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, chromanyl, isochromanyl, and 1,2,3,4-tetrahydro-1,8-naphthyridinyl, wherein the bicyclic ring is unsubstituted or substituted with 1 or 2 substituents independently selected from:
(a) halogen selected from —F, —Cl, and —Br, (b) methyl or ethyl, (c) —CF3, (d) methoxy, (e) —OCF3, (f) —CN, (g) ═O, and (h) —OH; Rt is selected from pyrrolidinyl, pyrazolidinyl, imidazolinyl, piperidinyl, piperazinyl, pyrrolyl, pyridyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, pyrazinyl, pyrimidinyl, and pyradizinyl; any one of which is unsubstituted or substituted with 1 or 2 substituents independently selected from —F, —Cl, —Br, oxo, methyl, and methoxy; or a pharmaceutically acceptable salt thereof.
- 10. The compound according to claim 9, which is a compound of Formula (VI):
- 11. A compound of Formula (V-A):
- 12. The compound according to claim 11, wherein R1 is H or F, and R2 is H or —SO2CH3, with the proviso that R1 and R2 are not both H;
or a pharmaceutically acceptable salt thereof.
- 13. The compound according to claim 12, which is a compound of Formula (VIII):
- 14. The compound according to claim 12, wherein
Q2 is:
(1) —C(═O)N(Ra)2, (2) —CH2C(═O)N(Ra)2, (3) —CH2CH2C(═O)N(Ra)2, (4) —S—CH2—C(═O)N(Ra)2, (5) —O—CH2—C(═O)N(Ra)2, (6) —N(Ra)—C(Ra)═O, (7) —N(SO2Ra)—CH2—C(═O)N(Ra)2, (8) —N(Ra)—C(═O)—C(═O)—N(Ra)2, (9) —N(Ra)SO2Ra, (10) —CH═CH—C(═O)—N(Ra)2, (11) —N(Ra)CH2—C(═O)N(Ra)2, (12) —N(Ra)—C(═O)—N(Ra)2, (13) —Rk, (14) —(CH2)1-3Rk, or (15) —N(Rc)—(CH2)1-3Rk, each Ra is independently —H or —C1-4 alkyl; each Rc is independently —H or —C1-4 alkyl; and Rk is a saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, pyrazolidinyl, hexahydropyrimidinyl, 1,2-thiazinanyl, 1,4-thiazepanyl, 1,2,5-thiadiazepanyl, 1,5,2-dithiazepanyl, 1,4-diazepanyl, and 1,2,6-thiadiazinanyl, wherein the heterocyclic ring is unsubstituted or substituted with 1 to 4 substituents independently selected from:
(a) methyl or ethyl, (b) ═O, (c) —C(═O)N(Ra)2, (d) —CH2C(═O)N(Ra)2, (e) —C(═O)Ra, or (f) —SO2Ra; or a pharmaceutically acceptable salt thereof.
- 15. The compound according to claim 14, wherein
Q2 is:
(1) —C(═O)N(Ra)2, (2) —CH2C(═O)N(Ra)2, (3) —CH2CH2C(═O)N(Ra)2, (4) —S—CH2—C(═O)N(Ra)2, (5) —O—CH2—C(═O)N(Ra)2, (6) —N(SO2Ra)—CH2—C(═O)N(Ra)2, (7) —N(Ra)—C(═O)—C(═O)—N(Ra)2, (8) —N(Ra)SO2Ra, (9) —CH═CH—C(═O)—N(Ra)2, (10) —N(Ra)CH2—C(═O)N(Ra)2, (11) —N(Ra)—C(═O)—N(Ra)2, (12) —Rk, (13) —(CH2)1-2Rk, or (14) —NH—(CH2)1-2Rk; each Ra is independently methyl, ethyl, or isopropyl; and Rk is a saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, pyrazolidinyl, hexahydropyrimidinyl, 1,2-thiazinanyl, 1,4-thiazepanyl, 1,2,5-thiadiazepanyl, 1,5,2-dithiazepanyl, 1,4-diazepanyl, and 1,2,6-thiadiazinanyl, wherein the heterocyclic ring is unsubstituted or substituted with 1 to 4 substituents independently selected from:
(a) methyl or ethyl, (b) ═O, (c) —C(═O)NH2, (d) —C(═O)CH3, or (e) —SO2CH3; or a pharmaceutically acceptable salt thereof.
- 16. The compound according to claim 4, which is a compound of Formula (IX):
- 17. The compound according to claim 16, which is a compound of Formula (X):
- 18. The compound according to claim 17, which is a compound of Formula (XI):
- 19. The compound according to claim 18, which is a compound of Formula (XII):
- 20. The compound according to claim 19, wherein
R6 is:
(1) —H (2) methyl, (3) ethyl (4) —CF3, (4) —(CH2)1-3—ORa, (5) —(CH2)1-3—SRa, (6) —(CH2)1-3—SO2Ra, (7) —(CH2)1-3—N(Ra)2, (8) —(CH2)1-3—C(═O)—N(Ra)2, or (9) —(CH2)1-3—CO2Ra; R9 is:
(1) —H (2) methyl, (3) ethyl, (4) —CF3, (4) —(CH2)1-3—ORa, (5) —(CH2)1-3—SRa, (6) —(CH2)1-3—SO2Ra, (7) —(CH2)1-3—N(Ra)2, (8) —(CH2)1-3—C(═O)—N(Ra)2, (9) —(CH2)1-3—CO2Ra, or (10) —(CH2)1-3-Rk; each Ra is independently —H, methyl, or ethyl; Rk is a saturated heterocyclic ring selected from piperidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, isothiazolidinyl, oxazolidinyl, isooxazolidinyl, pyrrolidinyl, imidazolidinyl, piperazinyl, tetrahydrofuranyl, and pyrazolidinyl; and wherein the heterocyclic ring is unsubstituted or substituted with from 1 to 3 substituents independently selected from:
(a) halogen selected from —F, —Cl, and —Br, (b) methyl, (c) —CF3, (d) methoxy, (e) —OCF3, (f) —CN, and (g) ═O; or a pharmaceutically acceptable salt thereof.
- 21. A compound according to claim 1, which is a compound selected from the group consisting of
N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-[(1R,S)-2,3-dihydro-1H-inden-1-yl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-[2-(3-chlorophenyl)ethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-[2-(2-chlorophenyl)ethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-[2-(1,1′-biphenyl-4-yl)ethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-[2-(4-phenoxyphenyl)ethyl]-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(3-phenylpropyl)-1,6-naphthyridine-7-carboxamide; N-(1,1′-biphenyl-2-ylmethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(1,1′-biphenyl-3-ylmethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-phenyl-1,6-naphthyridine-7-carboxamide; 8 N-(2-chlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-benzyl-8-hydroxy-N-methyl-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(1-methyl-1-phenylethyl)-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(2-phenylethyl)-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(1-naphthylmethyl)-1,6-naphthyridine-7-carboxamide; N-benzyl-8-hydroxy-N-phenyl-1,6-naphthyridine-7-carboxamide; N-(3-chlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-chlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; Methyl (2S)-{[(8-hydroxy-1,6-naphthyridin-7-yl)carbonyl]amino}(phenyl)ethanoate; Ethyl N-benzyl-N-[(8-hydroxy-1,6-naphthyridin-7-yl)carbonyl]glycinate; N-benzyl-8-hydroxy-N-(2-phenylethyl)-1,6-naphthyridine-7-carboxamide; N-(1,2-diphenylethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2,3-dihydro-1H-inden-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-benzyl-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2-anilinoethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2,2-diphenylethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,3-diphenylpropyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2-chloro-6-phenoxybenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; Methyl (2R)-{[(8-hydroxy-1,6-naphthyridin-7-yl)carbonyl]amino}(phenyl)ethanoate; 8-hydroxy-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-1,6-naphthyridine-7-carboxamide; N-(2,3-dihydro-1H-inden-1-ylmethyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(6,7,8,9-tetrahydro-5H-benzo [a][7]annulen-6-ylmethyl)-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-[2-(1′-naphthylamino)ethyl]-1,6-naphthyridine-7-carboxamide; N-(2,3-dihydro-1H-inden-2-yl methyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-[(R)-1-phenylethyl]-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-[(1S)-1-phenylethyl]1-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(3-hydroxy-1-phenylpropyl)-1,6-naphthyridine-7-carboxamide; N-[2-(4-chlorophenyl)ethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-[(1R)-2-hydroxy-1-phenylethyl]-1,6-naphthyridine-7-carboxamide; N-[(1S)-1-benzyl-2-hydroxyethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-[(1R)-1-benzyl-2-hydroxyethyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(2-hydroxy-2-phenylethyl)-1,6-naphthyridine-7-carboxamide; 5-chloro-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-piperidin-1-yl-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-phenyl-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(1H-imidazol-1-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-morpholin-4-yl-1,6-naphthyridine-7-carboxamide; (±)-8-hydroxy-N-[(cis)-3-phenyl-2,3-dihydro-1H-inden-1-yl]-1,6-naphthyridine-7-carboxamide 5-bromo-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(benzyl)-8-hydroxy-5-phenyl-1,6-naphthyridine-7-carboxamide; N-(2,3-dihydro-1H-inden-1-yl)-8-hydroxy-5-phenyl-1,6-naphthyridine-7-carboxamide; 8-hydroxy-N-(1-naphthylmethyl)-5-phenyl-1,6-naphthyridine-7-carboxamide; N-(2,5-dichlorobenzyl)-8-hydroxy-5-phenyl-1,6-naphthyridine-7-carboxamide; N-(3-chlorobenzyl)-8-hydroxy-5-phenyl-1,6-naphthyridine-7-carboxamide; N-[(1S)-2,3-dihydro-1H-inden-1-yl]-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-phenoxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4-methylpiperazin-1-yl)-1,6-naphthyridine-7-carboxamide; 5-(4-benzylpiperazin-1-yl)-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-{4-[2-(formylamino)ethyl]piperazin-1-yl}-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4-pyridin-2-ylpiperazin-1-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4-pyrrolidin-1-ylpiperidin-1-yl)-1,6-naphthyridine-7-carboxamide; 5-anilino-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-{[3-(formylamino)propyl]amino}-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-{[2-(dimethylamino)ethyl]amino}-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-morpholin-4-ylethyl)amino]-1,6-naphthyridine-7-carboxamide; 5-[(1-benzylpiperidin-4-yl)amino]-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-[[2-(dimethylamino)ethyl](methyl)amino]-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-Hydroxy-5-phenylsulfanyl-[1,6]naphthyridine-7-carboxylic acid 3,5-dichlorobenzylamide; 5-benzenesulfonyl-8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 3,5-dichlorobenzylamide; tert-butyl 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)pyrrolidin-3-ylcarbamate; 5-(3-aminopyrrolidin-1-yl)-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide trifluoroacetate; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4H-1,2,4-triazol-4-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(1H-1,2,4-triazol-1-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(3-hydroxypyrrolidin-1-yl)-1,6-naphthyridine-7-carboxamide; 5-[3-(acetylamino)pyrrolidin-1-yl]-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-(4-formylpiperazin-1-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)piperazine; 8-Hydroxy-5-(3-hydroxy-prop-1-ynyl)-[1,6]naphthyridine-7-carboxylic acid 3,5-dichloro-benzylamide; 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazine; 8-Hydroxy-5-(3-piperidin-1-yl-prop-1-ynyl)-[1,6]naphthyridine-7-carboxylic acid 3,5-dichloro-benzylamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-thiomorpholin-4-yl-1,6-naphthyridine-7-carboxamide; 5-[3-(aminocarbonyl)piperidin-1-yl]-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-4-(2-phenylethyl)piperazine; 4-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]pyridine; 5-[(cyclopropylmethyl)amino]-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-{[2-(formylamino)ethyl]amino}-8-hydroxy-1,6-naphthyridine-7-carboxamide; 2-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]ethanamine; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-methoxyethyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-{[2-(methylthio)ethyl]amino}-1,6-naphthyridine-7-carboxamide; 1-{2-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]ethyl}pyrrolidine; 1 N-(3,5-dichlorobenzyl)-8-hydroxy-5-pyrrolidin-1-yl-1,6-naphthyridine-7-carboxamide; 3-{2-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]ethyl}pyridine; 1-{3-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]propyl}-1H-imidazoline; 1-{3-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]propyl}pyrrolidine; 1-(2-aminoethyl)-4-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)piperazine; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-phenoxyethyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-{[3-(2-oxopyrrolidin-1-yl)propyl]amino}-1,6-naphthyridine-7-carboxamide; 2-[benzyl(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]ethanamine; 1-{3-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)amino]propyl}-4-methylpiperazine; 1:1 mixture of 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-1H-imidazo[4,5-b]pyridine and 3-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-3H-imidazo[4,5-b]pyridine; N-(3,5-dichlorobenzyl)-8-hydroxy-5-{[4-(3-methyl-2-oxoimidazolidin-1-yl)phenyl]amino}-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-({[(2R)-5-oxopyrrolidin-2-yl]methyl}amino)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-{[(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]amino}-1,6-naphthyridine-7-carboxamide; 2-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)octahydropyrrolo[1,2-a]pyrazine; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[4-(pyrimidin-2-ylamino)piperidin-1-yl]-1,6-naphthyridine-7-carboxamide 2-{2-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)(methyl)amino]ethyl}pyridine; N-(3,5-dichlorobenzyl)-5-(dimethylamino)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-Hydroxy-5-(3-morpholin-4-yl-prop-1-ynyl)-[1,6]naphthyridine-7-carboxylic acid 3,5-dichloro-benzylamide; N-(3,5-difluorobenzyl)-8-hydroxy-5-(methylsulfonyl)-1,6-naphthyridine-7-carboxamide; 5-cyano-N-(2,3-dimethoxybenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxyamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-thien-2-yl-1,6-naphthyridine-7-carboxamide; 8-hydroxy-5-phenylsulfanyl-[1,6]naphthyridine-7-carboxylic acid 2-methylsulfanylbenzylamide; N-(2,3-dimethoxybenzyl)-8-hydroxy-5-(methylsulfonyl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-hydroxyethyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(propylamino)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(1H-imidazol-4-ylethyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(3-phenylprop-1-yl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(3-morpholin-4-ylpropyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[4-(pyridin-2-ylmethyl)piperazin-1-yl]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-morpholin-4-yl-2-pyridin-3-ylethyl)amino]-1,6-naphthyridine-7-carboxamide; N-(2,3-dimethoxybenzyl)-5-{[4-(dimethylamino)phenyl]thio}-8-hydroxy-1,6-naphthyridine-7-carboxamide; 8-hydroxy-6-methyl-[1,6]naphthyridine-7-carboxylic acid 3,5-dichloro-benzylamide; 8-hydroxy-6-methyl-[1,6]naphthyridine-7-carboxylic acid 4-fluoro-benzylamide; 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 1-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-4-methylpiperazine; 1-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)piperazine; 5-[[2-(dimethylamino)-2-oxoethyl](methyl)amino]-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-1-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-N-1-,N-2-,N-2-trimethylethanediamide; N-(4-fluorobenzyl)-5-(2,6-dioxohexahydropyrimidin-4-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; 5-(1,3-dimethyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-8-hydroxy[1,6]-naphthyridine-7-carboxamide; 5-(1-methyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-8-hydroxy[1,6]-naphthyridine-7-carboxamide; 5-(3-methyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-8-hydroxy[1,6]-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(5-oxo-1,4-thiazepan-7-yl)[1,6]naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(1-oxido-5-oxo-1,4-thiazepan-7-yl)-[1,6]naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(1,1-dioxido-5-oxo-1,4-thiazepan-7-yl)[1,6]-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-{[2-(dimethylamino)-2-oxoethyl]sulfanyl}-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(dimethylamino)-2-oxoethoxy]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-{[2-(dimethylamino)-2-oxoethyl](methylsulfonyl)amino}-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[3-(dimethylamino)-3-oxopropyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[(1E)-3-(dimethylamino)-3-oxo-1-propenyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(3-oxo-1-piperazinyl)ethyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(2-oxo-1-imidazolidinyl)ethyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(2-oxo-1-piperazinyl)ethyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; 5-(1,1-dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 5-(1,1-dioxidoisothiazolidin-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-[methyl(methylsulfonyl)amino]-1,6-naphthyridine-7-carboxamide; 5-[acetyl(methyl)amino]-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 5-[[(dimethylamino)carbonyl](methyl)amino]-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-6-hydroxy-3-methyl-1-(2-morpholin-4-ylethyl)-2-oxo-2,3-dihydro-1H-pyrimido[4,5,6-de]-1,6-naphthyridine-5-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-thiomorpholin-4-yl-1,6-naphthyridine-7-carboxamide; 5-(1,1-dioxidothiomorpholin-4-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(4-methyl-3-oxopiperazin-1-yl)-1,6-naphthyridine-7-carboxamide; 1-(7-{[4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl-L-prolinamide; N-(4-fluorobenzyl)-8-hydroxy-5-(2-oxotetrahydropyrimidin-1 (2H)-yl)-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(2-oxoimidazolidin-1-yl)-1,6-naphthyridine-7-carboxamide; N-7-(4-fluorobenzyl)-8-hydroxy-N 5, N 5-dimethyl-1,6-naphthyridine-5,7-dicarboxamide; N-7-(4-fluorobenzyl)-8-hydroxy-N 5-isopropyl-N 5-methyl-1,6-naphthyridine-5,7-dicarboxamide; N-7-(4-fluorobenzyl)-8-hydroxy-N 5-(2-morpholin-4-ylethyl)-1,6-naphthyridine-5,7-dicarboxamide; N 5-[2-(dimethylamino)-2-oxoethyl]-N 7-(4-fluorobenzyl)-8-hydroxy-N 5-methyl-1,6-naphthyridine-5,7-dicarboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-5-ethyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-1,5,2-dithiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1,5,5-tetraoxido-1,5,2-dithiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,4-dimethyl-7-oxo-1,4-diazepan-5-yl)-8-hydroxy-[1,6]-napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1-methyl-7-oxo-1,4-diazepan-5-yl)-8-hydroxy-[1,6]-napthyridine-7-carboxamide; N-(4-Fluorobenzyl)-5-(7-oxo-1,4-diazepan-5-yl)-8-hydroxy-[1,6]-napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[4-(methylsulfonyl)thiomorpholin-2-yl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[4-(methylsulfonyl)-1-oxidothiomorpholin-2-yl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[4-(methylsulfonyl)-1,1-dioxidothiomorpholin-2-yl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(2-Acetyl-1-methylpyrazolidin-3-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-[5-(methylsulfonyl)-1,1-dioxido-1,2,5-thiadiazepan-2-yl]-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2yl)-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-{methyl[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}-1,6-naphthyridine-7-carboxamide; N-[4-fluoro-2-(methylsulfonyl)benzyl]-8-hydroxy-5-{methyl[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}-1,6-naphthyridine-7-carboxamide; N-7-[4-fluoro-2-(methylsulfonyl)benzyl]-8-hydroxy-N-5-,N-5-dimethyl-1,6-naphthyridine-5,7-dicarboxamide; N-[4-fluoro-2-(methylsulfonyl)benzyl]-8-hydroxy-5-(1,1-dioxido-1,2-thiazinan-2-yl)-1,6-naphthyridine-7-carboxamide N-(2-(methylsulfonyl)benzyl)-5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2-[(dimethylaminosulfonyl]-4-fluorobenzyl)-5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(1-methyl-5-oxopyrrolidin-3-yl)-1,6-naphthyridine-7-carboxamide; and pharmaceutically acceptable salts thereof.
- 22. A compound according to claim 21, which is a compound selected from the group consisting of
1-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-4-methylpiperazine; 1-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)piperazine; N-(3,5-dichlorobenzyl)-5-(4-formylpiperazin-1-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-5-{4-[2-(formylamino)ethyl]piperazin-1-yl}-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[4-(pyridin-2-ylmethyl)piperazin-1-yl]-1,6-naphthyridine-7-carboxamide; 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-4-(2-oxo-2-pyrrolidin-1-ylethyl)piperazine; 1-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)piperazine; 2-(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)octahydropyrrolo[1,2-a]pyrazine; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-{[4-(3-methyl-2-oxoimidazolidin-1-yl)phenyl]amino}-1,6-naphthyridine-7-carboxamide; 5-[3-(aminocarbonyl)piperidin-1-yl]-N-(3,5-dichlorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide;
N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4-pyrrolidin-1-ylpiperidin-1-yl)-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-morpholin-4-ylethyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4-methylpiperazin-1-yl)-1,6-naphthyridine-7-carboxamide; 8-hydroxy-6-methyl-[1,6]naphthyridine-7-carboxylic acid 3,5-dichloro-benzylamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[4-(pyrimidin-2-ylamino)piperidin-1-yl]-1,6-naphthyridine-7-carboxamide N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(3-morpholin-4-ylpropyl)amino]-1,6-naphthyridine-7-carboxamide; N-(3,5-dichlorobenzyl)-8-hydroxy-5-[(2-morpholin-4-yl-2-pyridin-3-ylethyl)amino]-1,6-naphthyridine-7-carboxamide; 2-{2-[(7-{[(3,5-dichlorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)(methyl)amino]ethyl}pyridine; N-(3,5-dichlorobenzyl)-8-hydroxy-5-(4-pyridin-2-ylpiperazin-1-yl)-1,6-naphthyridine-7-carboxamide; and pharmaceutically acceptable salts thereof.
- 23. A compound according to claim 21, which is a compound selected from the group consisting of
5-[[2-(dimethylamino)-2-oxoethyl](methyl)amino]-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-1-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl)-N-1-,N-2-,N-2-trimethylethanediamide; N-(4-fluorobenzyl)-5-(2,6-dioxohexahydropyrimidin-4-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; 5-(1,3-dimethyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-8-hydroxy[1,6]-naphthyridine-7-carboxamide; 5-(1-methyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-8-hydroxy[1,6]-naphthyridine-7-carboxamide; 5-(3-methyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-8-hydroxy[1,6]-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(5-oxo-1,4-thiazepan-7-yl) [1,6]naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(1-oxido-5-oxo-1,4-thiazepan-7-yl)-[1,6]naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(1,1-dioxido-5-oxo-1,4-thiazepan-7-yl)[1,6]-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-{[2-(dimethylamino)-2-oxoethyl]sulfanyl}-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(dimethylamino)-2-oxoethoxy]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-{[2-(dimethylamino)-2-oxoethyl](methylsulfonyl)amino}-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[3-(dimethylamino)-3-oxopropyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[(1E)-3-(dimethylamino)-3-oxo-1-propenyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(3-oxo-1-piperazinyl)ethyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(2-oxo-1-imidazolidinyl)ethyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[2-(2-oxo-1-piperazinyl)ethyl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; 5-(1,1-dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 5-(1,1-dioxidoisothiazolidin-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-[methyl(methylsulfonyl)amino]-1,6-naphthyridine-7-carboxamide; 5-[acetyl(methyl)amino]-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; 5-[[(dimethylamino)carbonyl](methyl)amino]-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-6-hydroxy-3-methyl-1-(2-morpholin-4-ylethyl)-2-oxo-2,3-dihydro-1H-pyrimido[4,5,6-de]-1,6-naphthyridine-5-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-thiomorpholin-4-yl-1,6-naphthyridine-7-carboxamide; 5-(1,1-dioxidothiomorpholin-4-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(4-methyl-3-oxopiperazin-1-yl)-1,6-naphthyridine-7-carboxamide; 1-(7-{[4-fluorobenzyl)amino]carbonyl}-8-hydroxy-1,6-naphthyridin-5-yl-L-prolinamide; N-(4-fluorobenzyl)-8-hydroxy-5-(2-oxotetrahydropyrimidin-1 (2H)-yl)-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(2-oxoimidazolidin-1-yl)-1,6-naphthyridine-7-carboxamide; N-7-(4-fluorobenzyl)-8-hydroxy-N 5, N 5-dimethyl-1,6-naphthyridine-5,7-dicarboxamide; N 7-(4-fluorobenzyl)-8-hydroxy-N 5-isopropyl-N 5-methyl-1,6-naphthyridine-5,7-dicarboxamide; N 7-(4-fluorobenzyl)-8-hydroxy-N 5-(2-morpholin-4-ylethyl)-1,6-naphthyridine-5,7-dicarboxamide; N 5-[2-(dimethylamino)-2-oxoethyl]-N 7-(4-fluorobenzyl)-8-hydroxy-N 5-methyl-1,6-naphthyridine-5,7-dicarboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; and pharmaceutically acceptable salts thereof.
- 24. A compound according to claim 21, which is a compound selected from the group consisting of
N-(4-fluorobenzyl)-5-(1,1-dioxido-5-methyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-5-ethyl-4-oxo-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-1,5,2-dithiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1,5,5-tetraoxido-1,5,2-dithiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,4-dimethyl-7-oxo-1,4-diazepan-5-yl)-8-hydroxy-[1,6]-napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1-methyl-7-oxo-1,4-diazepan-5-yl)-8-hydroxy-[1,6]-napthyridine-7-carboxamide; N-(4-Fluorobenzyl)-5-(7-oxo-1,4-diazepan-5-yl)-8-hydroxy-[1,6]-napthyridine-7-carboxamide N-(4-fluorobenzyl)-5-[4-(methylsulfonyl)thiomorpholin-2-yl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[4-(methylsulfonyl)-1-oxidothiomorpholin-2-yl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-[4-(methylsulfonyl)-1,1-dioxidothiomorpholin-2-yl]-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(2-Acetyl-1-methylpyrazolidin-3-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-5-(1,1-dioxido-1,2,5-thiadiazepan-2-yl)-8-hydroxy-[1,6]napthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-[5-(methylsulfonyl)-1,1-dioxido-1,2,5-thiadiazepan-2-yl]-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5(6-methyl-1,1-dioxido-1,2,6-thiadiazinan-2yl)-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-{methyl[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}-1,6-naphthyridine-7-carboxamide; N-[4-fluoro-2-(methylsulfonyl)benzyl]-8-hydroxy-5-{methyl[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}-1,6-naphthyridine-7-carboxamide; N-7-[4-fluoro-2-(methylsulfonyl)benzyl]-8-hydroxy-N-5-,N-5-dimethyl-1,6-naphthyridine-5,7-dicarboxamide; N-[4-fluoro-2-(methylsulfonyl)benzyl]-8-hydroxy-5-(1,1-dioxido-1,2-thiazinan-2-yl)-1,6-naphthyridine-7-carboxamide N-(2-(methylsulfonyl)benzyl)-5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(2-[(dimethylaminosulfonyl]-4-fluorobenzyl)-5-(1,1-dioxido-1,2-thiazinan-2-yl)-8-hydroxy-1,6-naphthyridine-7-carboxamide; N-(4-fluorobenzyl)-8-hydroxy-5-(1-methyl-5-oxopyrrolidin-3-yl)-1,6-naphthyridine-7-carboxamide; and pharmaceutically acceptable salts thereof.
- 25. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
- 26. A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.
- 27. A method for preventing or treating infection by HIV or for preventing, treating or delaying the onset of AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof.
- 28. The method according to claim 27, wherein the compound is administered in combination with a therapeutically effective amount of at least one HIV infection/AIDS treatment agent selected from the group consisting of HIV/AIDS antiviral agents, immunomodulators, and anti-infective agents.
- 29. The method according to claim 27, wherein the compound is administered in combination with a therapeutically effective amount of at least one antiviral selected from the group consisting of HIV protease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors and nucleoside HIV reverse transcriptase inhibitors.
- 30. A method of inhibiting HIV integrase in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition according to claim 25.
- 31. A method for preventing or treating infection by HIV or for preventing, treating, or delaying the onset of AIDS in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the composition according to claim 25.
- 32. A pharmaceutical composition which comprises the product prepared by combining an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
- 33. A combination useful for inhibiting HIV integrase, for treating or preventing infection by HIV, or for preventing, treating or delaying the onset of AIDS, which is a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of an HIV infection/AIDS treatment agent selected from the group consisting of HIV/AIDS antiviral agents, immunomodulators, and anti-infective agents.
- 34. The combination according to claim 33, wherein the HIV infection/AIDS treatment agent is an antiviral selected from the group consisting of IEV protease inhibitors, non-nucleoside HIV reverse transcriptase inhibitors and nucleoside HIV reverse transcriptase inhibitors.
- 35. A method of inhibiting HIV integrase, for preventing or treating infection by HIV or for preventing, treating or delaying the onset of AIDS in a subject in need thereof, which comprises administering to the subject a therapeutically effective amount of a compound of Formula (I-A):
- 36. The method according to claim 35, wherein the compound is selected from the group consisting of:
benzyl 8-hydroxyquinoline-7-carboxamide; 1-Methyl-3-phenylpropyl 8-hydroxyquinoline-7-carboxamide; 2-Phenylcyclopropyl 8-hydroxyquinoline-7-carboxamide; 1-Indanyl 8-hydroxyquinoline-7-carboxamide; N-[(2E)-3-Phenyl-2-propenyl]8-hydroxyquinoline-7-carboxamide; Benzyl 8-Hydroxyquinoline-7-carboxamide;
and pharmaceutically acceptable salts thereof.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application No. 60/239,707, filed Oct. 12, 2000, and U.S. Provisional Application No. 60/281,656, filed Apr. 5, 2001, the disclosures of which are hereby incorporated by reference in their entireties.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60239707 |
Oct 2000 |
US |
|
60281656 |
Apr 2001 |
US |
Patent Application
20030055071
