	US 7,612,060 B2
	Triazoles and methods of use
Toshihiro Aya, Thousand Oaks, Calif. (US); Guolin Cai, Thousand Oaks, Calif. (US); Jian J. Chen, Newbury Park, Calif. (US); Derin D'Amico, Newbury Park, Calif. (US); Thomas Nguyen, Thousand Oaks, Calif. (US); and Wenyuan Qian, Camarillo, Calif. (US)
Assigned to Amgen Inc., Thousand Oaks, Calif. (US)
Filed on Oct. 11, 2005, as Appl. No. 11/247,046.
Claims priority of provisional application 60/618893, filed on Oct. 13, 2004.
Prior Publication US 2006/0100213 A1, May 11, 2006
Int. Cl. C07D 403/00 (2006.01); C07D 401/00 (2006.01); C07D 413/00 (2006.01); A01N 43/46 (2006.01); A61K 31/535 (2006.01); A61K 31/497 (2006.01)

U.S. Cl. 514—217.08 [544/366; 544/360; 544/370; 544/363; 544/359; 544/369; 514/235.5; 514/252.17; 514/254.04; 514/254.05]

8 Claims

1. A compound of Formula (I):

wherein:

t is 1;

X is selected from —NH— or —NR^d— where R^dis C_1-8alkyl or C_1-4haloalkyl;

is:

A is a group of formula (a):

where:

R¹is a 5-, 6-, 7-, or 8-membered saturated, partially saturated or unsaturated monocyclic, a saturated, partially saturated or unsaturated 8-, 9-, 10- or 11-membered bicyclic, or 12-, 13-, 14- or 15-membered tricyclic hydrocarbon ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, wherein the carbon and sulfur atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from R⁶, R⁷or R⁸independently selected from basic moieties, and additionally substituted by 0, 1, 2 or 3 substituents selected from R⁶, R₇and R⁸which are selected from R^g, C_1-8alkyl, C_1-4haloalkyl, hydroxyalkyl, cyano, nitro, —C(═O)R^b, —C(═O)OR^b, —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)R^b, —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂R^b, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)R^b, —S(═O)₂R^b, —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)R^b, —S(═O)₂N(R^a)C(═O)OR^b, —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)R^b, —N(R^a)C(═O)OR^b, —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂R^b, —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^aand —NR^aC_2-6alkylOR^a, and the ring is additionally substituted by 0, 1, 2, 3, 4 or 5 substituents selected from R⁶, R₇, R⁸, R⁹and R¹⁰which are independently selected from Br, Cl, F and I;

R²is a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic hydrocarbon ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from R^e, R^g, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)R^b, —C(═O)OR^b, —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)R^b, —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂R^b, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)R^b, —S(═O)₂R^b, —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)R^b, —S(═O)₂N(R^a)C(═O)OR^b, —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)R^b, —N(R^a)C(═O)OR^b, —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S (═O)₂R^b, —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^aand —NR^aC_2-6alkylOR^a, and the ring is additionally substituted by 0, 1, 2, 3, 4 or 5 substituents independently selected from Br, Cl, F and I;

R³, R^3a, R⁴and R⁵are independently in each instance selected from H, C_1-3alkyl, C_1-3haloalkyl, —OH, F, Cl, Br and I; or

R³and R^3atogether form oxo;

R^xis selected from H, F, Cl, (C₁-C₃)haloalkyl, and (C₁-C₃)alkyl;

R^ais independently, at each instance, H or R^b;

R^bis independently, at each instance, phenyl, benzyl or C_1-6alkyl, the phenyl, benzyl and C_1-6alkyl being substituted by 0, 1, 2 or 3 substituents selected from halo, C_1-4alkyl, C_1-3haloalkyl, —OC_1-4alkyl, —NH₂, —NHC_1-4alkyl, —N(C_1-4alkyl)C_1-4alkyl.

R^dis independently at each instance C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)R^b, —C(═O)OR^b, —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)R^b, —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂R^b, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)R^b, —S(═O)₂R^b, —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)R^b, —S(═O)₂N(R^a)C(═O)OR^b, —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)R^b, —N(R^a)C(═O)OR^b, —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂R^b, —N(R^a)S(═O)₂NR^aR^a, —NR_aC_2-6-alkylNR^aR^aor —NR_aC_2-6alkylOR^a;

R^eis independently at each instance C_1-6alkyl substituted by 0, 1, 2 or 3 substituents independently selected from R^dand additionally substituted by 0 or 1 substituents selected from R^g; and

R^gis independently at each instance a saturated, partially saturated or unsaturated 5-, 6- or 7-membered monocyclic or 6-, 7-, 8-, 9-, 10- or 11-membered bicyclic hydrocarbon ring containing 0, 1, 2, 3 or 4 atoms selected from N, O and S, wherein the carbon atoms of the ring are substituted by 0, 1 or 2 oxo groups and the ring is substituted by 0, 1, 2 or 3 substituents selected from C_1-8alkyl, C_1-4haloalkyl, halo, cyano, nitro, —C(═O)R^b—C(═O)OR^b, —C(═O)NR^aR^a, —C(═NR^a)NR^aR^a, —OR^a, —OC(═O)R^b, —OC(═O)NR^aR^a, —OC(═O)N(R^a)S(═O)₂R^b, —OC_2-6alkylNR^aR^a, —OC_2-6alkylOR^a, —SR^a, —S(═O)R^b, —S(═O)₂R^b, —S(═O)₂NR^aR^a, —S(═O)₂N(R^a)C(═O)R^b, —S(═O)₂N(R^a)C(═O)OR^b, —S(═O)₂N(R^a)C(═O)NR^aR^a, —NR^aR^a, —N(R^a)C(═O)R^b, —N(R^a)C(═O)OR^b, —N(R^a)C(═O)NR^aR^a, —N(R^a)C(═NR^a)NR^aR^a, —N(R^a)S(═O)₂R^b, —N(R^a)S(═O)₂NR^aR^a, —NR^aC_2-6alkylNR^aR^aand —NR^aC_2-6alkylOR^a, and the ring is additionally substituted by 0, 1, 2, 3, 4 or 5 substituents independently selected from Br, Cl, F and I; or

a pharmaceutically-acceptable salt thereof;

wherein the basic moieties are independently selected from amino, cycloalkylaminoC_1-6alkyl, cycloalkylC_1-6alkylamino-C_1-6alkyl, heterocyclylaminoC_1-6alkyl, heterocyclylC_1-6alkylaminoC_1-6alkyl, arylaminoC_1-6alkyl, arylC_1-6alkylaminoC_1-6alkyl, C_1-6-alkylamino-C_1-6-alkoxy, C_1-6-alkylamino-C_1-6-alkoxy-C_1-6-alkoxy, aminoC_1-6alkoxy, aminoC_1-6alkyl, C_1-6alkylaminoC_1-6alkyl, C_1-4-alkylamino-C_2-6-alkenyl, 5-8 membered nitrogen-containing heterocyclyl-C_2-6-alkenyl, heterocyclyl-C_1-6alkylamino-C_2-6alkyl, 5-6 membered heterocyclyloxy, 4-6 membered nitrogen-containing heterocyclyl and 5-7 membered nitrogen-containing heterocyclyl-alkyl; and wherein each of said basic moieties is substituted by 0, 1, 2 or 3 groups independently selected from halo, —NH₂, hydroxyl, cyano, —CF₃, C_1-6alkylamino, oxo, C_1-6alkoxy, C_2-6alkenyl, C_2-6alkynyl, diC_1-6alkylamino, C_1-6alkyl, substituted C_1-6alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, substituted saturated or partially saturated heterocyclyl and unsubstituted saturated or partially saturated heterocyclyl, wherein each substituted C_1-6alkyl, substituted aryl, substituted heteroaryl, and substituted saturated or partially saturated heterocyclyl is substituted by 0, 1, 2 or 3 groups independently selected from halo, —NH₂, hydroxyl, cyano, C_1-6alkylamino, C_1-6haloalkyl, oxo, C_1-6alkoxy, C_1-6alkoxyC_1-6alkyl, C_1-6alkyl, C_2-6alkenyl, C_2-6alkynyl, or diC_1-6alkylamino.