IP Library › Patent Application 12519789

Patent Application

App. No. 12/519,789

IMIDAZOPYRIDINE ANALOGS AS CB2 RECEPTOR MODULATORS, USEFUL IN THE TREATMENT OF PAIN, RESPIRATORY AND NON-RESPIRATORY DISEASES

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Patent No.: US None
App. No.: 12/519,789

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Abstract

The present invention relates to compounds represented by Formula (I) and Formula (II): (I) (II) or pharmaceutically acceptable salts thereof. The present invention also provides pharmaceutical compositions comprising the instant compounds. This invention further provides methods to treat and prevent pain, respiratory and non-respiratory diseases.

Claims (187)

1 . A compound of Formula (I) or Formula (II):

or a pharmaceutically acceptable salt thereof, wherein

R 1 is selected from the group consisting of:

(1) —NH—R 4 ,

(2) —O—R 4 ,

(3) —CH2-C(O)—R 4 , and

(4) —R 4 ;

R 2 is selected from the group consisting of:

(1) H,

(2) halo,

(3) —CN,

(4) —CF 3 ,

(5) —C1-6alkyl,

(6) —C(O)—NH—C 1-3 alkyl-CF 3 ,

(7) —C(O)—NH—C 1-3 alkyl-heteroaryl, wherein the heteroaryl is optionally mono, di or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(8) —C(O)-heteroaryl, wherein the heteroaryl is optionally mono, di or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —O 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl-C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 and —C(O)-heteroaryl optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(9) —C(O)-heterocycle, wherein the heterocycle is optionally mono, di- or tri-substituted with substituents selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and oxo, wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(10) —NR 5 R 6 ,

(11) —C 1-4 alkyl-NR 5 R 6 ,

(12) —C 1-4 alkyl-heterocycle, wherein the alkyl is optionally substituted with hydroxyl and wherein the heterocycle is optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and —C(O)-heteroaryl, wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(13) —C 1-4 alkyl-heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(14) heterocycle, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(15) heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(16) aryl, optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of wherein the aryl is optionally mono or di-substituted with substituents selected from —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(17) O-aryl, optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(18) —O-heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —O—C 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—N(CH 3 )2, —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl,

(19) —NH-heteroaryl, wherein the heteroaryl is optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl, and

(20) —C 3-6 cycloalkyl, optionally mono, di- or tri-substituted with substituents selected —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , oxo, C(O)—O—C(CH 3 ) 3 , —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN;

R 3 is selected from the group consisting of

(1) H,

(2) halo,

(3) —C 1-4 alkyl, optionally substituted with hydroxyl,

(4) —CF 3 , and

(5) —OC 1-6 alkyl;

(6) —CN,

(7) —CHF 2 ,

(8) —O—CF 3 ,

(9) hydroxy,

(10) —S(O) 2 —CH 3 ,

(11) —C(O)—O—C 1-6 alkyl,

(12) —C(O)—NHC 1-6 alkyl,

(13) —C(O)—N(C 1-6 alkyl) 2 ,

(14) —C(O)—O—C(CH 3 ) 3 ,

(15) —C(O)-heteroaryl,

(16) —C 3-6 cycloalkyl,

(17) —NH 2 ,

(18) —NH 2 —C(O)—CF 3 ,

(19) —NH 2 —C(O)—N(CH 3 ) 2 ,

(20) —NC(O)—NH 2 ,

(21) —NH—S(O) 2 —CH 3 ,

(22) heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl, and

(23) aryl, optionally mono, di- or tri-substituted with substituents selected from the group consisting of wherein the aryl is optionally mono or di-substituted with substituents selected from —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, wherein the heteroaryl portion of —C(O)-heteroaryl, is optionally mono or di-substituted with substituents independently selected from halo, —CH 3 , —CF 3 , —CN and —OC 1-6 alkyl;

R 4 is selected from the group consisting of:

(1) adamantane, optionally mono and di-substituted with substituents independently selected from —CH 3 and hydroxyl,

(2) aryl, optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(3) heteroaryl, optionally mono, di- or tri-substituted with a substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—CH 3 , —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) heterocycle, optionally mono, di-, tri- or tetra substituted with a substituent selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and aryl, and wherein aryl and the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(5) C 3-6 cycloalkyl, optionally mono, di-, tri- or tetra substituted with substituents independently selected from the group consisting of hydroxyl, halo, phenyl,

(6) C 5-10 carbocycle, wherein the carbocycle is optionally mono, di- or tri-substituted with substituents independently selected from halo, hydroxyl, —OC 1-6 alkyl, CF 3 ,

(7) C 1-6 alkyl, optionally mono or di-substituted with substituents independently selected from the group consisting of CF 3 , hydroxyl, —CN, —CHF2,

(8) C 1-6 alkyl-C 3-6 cycloalkyl, wherein the cycloalkyl is optionally mono or di-substituted with substituents independently selected from hydroxyl, phenyl, —CH 2 OH, and —C 3-6 cycloalkyl,

(9) —C 1-6 alkyl-heteroaryl, wherein the heteroaryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and the C 1-6 alkyl is optionally mono or di-substituted with a substitutent selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(10) —C 1-6 alkyl-aryl, wherein the aryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and the C 1-6 alkyl is optionally mono or di-substituted with a substitutent selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl, and

(11) —C 1-6 alkyl-heterocycle, wherein the heterocycle is optionally mono, di- or tri-substituted with substitutents independently selected from the —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and aryl, and the C 1-6 alkyl is optionally mono or di-substituted with a substitutent selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl and wherein aryl and the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl;

R 5 is selected from the group consisting of hydrogen and methyl;

R 6 is selected from the group consisting of:

(1) C 1-4 alkyl, optionally mono or di-substituted, with substituents independently selected from the group consisting of C 3-6 cycloalkyl, —CF 3 , heteroaryl, —C 1-3 alkyl-CF 3 , CH 3 , tetrahydrofuran, and

(2) —C 1-3 alkyl-C 3-6 cycloalkyl, wherein the cycloalkyl is optionally mono or di-substituted with substituents independently selected from the group consisting of halo, CF 3 , CH 3 , C 1-3 alkyl, —OC 1-6 alkyl, or

R5 and R6 are joined together so that along with the nitrogen to which they are attached, there is formed a heterocycle, wherein said heterocycle is optionally mono, di or tri-substituted with substituents independently selected from the group consisting of —OC 1-6 alkyl, —NH—C(O)—O—C(CH 3 ) 3 , hydroxy, —CH 3 , —CF 3 , —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—N(CH 3 )2, oxo, —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH—C(O)—CF 3 , —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —S—CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono- di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN and —O—C 1-6 alkyl;

provided that when the compound is of Formula (II), and R 1 is optionally substituted aryl, then R 2 is other than hydrogen, halo, cyano, optionally substituted aryl, optionally substituted heteroaryl or NR 5 R 6 wherein both of R 5 and R 6 are hydrogen, or unsubstituted alkyl.

2 . A compound according to claim 1 wherein

R 1 is selected from the group consisting of:

(1) —NH—R 4 ,

(2) —O—R 4 , and

(3) —R 4 .

3 . A compound according to claim 2 wherein

R 1 is selected from the group consisting of:

(1) —NH—R 4 , and

(2) —R 4 .

4 . A compound according to claim 1 wherein

R 2 is selected from the group consisting of:

(1) H,

(2) halo,

(3) —CN,

(4) —CF3,

(5) —C1-6alkyl,

(6) —C(O)-heterocycle, wherein the heterocycle is optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(7) —NR 5 R 6 ,

(8) —C 1-4 alkyl-NR 5 R 6 ,

(9) —C 1-4 alkyl-heterocycle, wherein the alkyl is optionally substituted with hydroxyl and wherein the heterocycle is optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(10) —C 1-4 alkyl-heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(11) heterocycle, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(12) heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl

(13) aryl, optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of wherein the aryl is optionally mono or di-substituted with substituents selected from —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl, and

(14) —C 3-6 cycloalkyl, optionally mono or di-substituted with substituents independently selected from —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , oxo, C(O)—O—C(CH 3 ) 3 , —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN.

5 . A compound according to claim 4 wherein

R 2 is selected from the group consisting of:

(1) H,

(2) —CF3,

(3) —C(O)-heterocycle, wherein the heterocycle is optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) —NR 5 R 6 ,

(5) —C 1-4 alkyl-NR 5 R 6 ,

(6) —C 1-4 alkyl-heterocycle, wherein the alkyl is optionally substituted with hydroxyl and wherein the heterocycle is optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(7) heterocycle, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(8) heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl, and

(9) aryl, optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl.

6 . A compound according to claim 5 wherein

R 2 is selected from the group consisting of:

(1) —CF3,

(2) —C 1-4 alkyl-heterocycle, wherein the alkyl is optionally substituted with hydroxyl and wherein the heterocycle is optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(3) heterocycle, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl, and

(5) aryl, optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of wherein the aryl is optionally mono or di-substituted with substituents selected from —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl.

7 . A compound according to claim 1 wherein

R 3 is selected from the group consisting of

(1) H,

(2) halo,

(3) —C 1-4 alkyl, optionally substituted with hydroxyl,

(4) —CF 3 ,

(5) —OC 1-6 alkyl, and

(6) —CN.

8 . A compound according to claim 7 wherein

R 3 is selected from the group consisting of

(1) H, and

(2) halo.

9 . A compound according to claim 1 wherein

R 4 is selected from the group consisting of:

(1) adamantane, optionally mono and di-substituted with substituents independently selected from —CH 3 and hydroxyl,

(2) aryl, optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(3) heteroaryl, optionally mono or di-substituted with a substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—CH 3 , —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) heterocycle, optionally mono, di-, tri- or tetra substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and aryl, and wherein aryl and the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(5) C 1-6 alkyl-C 3-6 cycloalkyl, wherein the cycloalkyl is optionally mono or di-substituted with substituents selected from hydroxyl, phenyl, —CH 2 OH, —C 3-6 cycloalkyl,

(6) —C 1-6 alkyl-heteroaryl, wherein the heteroaryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(7) —C 1-6 alkyl-aryl, wherein the aryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and the C 1-6 alkyl is optionally mono or di-substituted with a substitutent selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl, and

(8) —C 1-6 alkyl-heterocycle, wherein the heterocycle is optionally mono, di- or tri-substituted with substitutents independently selected from the —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and aryl, and the C 1-6 alkyl is optionally mono or di-substituted with a substitutent selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein aryl and the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl.

10 . A compound according to claim 9 wherein

R 4 is selected from the group consisting of:

(1) aryl, optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)heteroaryl is optionally mono or di-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(2) heterocycle, optionally mono, di-, tri- or tetra substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and aryl, and wherein aryl and the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(3) —C 1-6 alkyl-heteroaryl, wherein the heteroaryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) —C 1-6 alkyl-aryl, wherein the aryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl.

11 . A compound according to claim 1 wherein

R5 and R6 are joined together so that along with the nitrogen to which they are attached, there is formed a heterocycle, wherein said heterocycle is optionally mono, di or tri-substituted with substituents independently selected from the group consisting of —OC 1-6 alkyl, —NH—C(O)—O—C(CH 3 ) 3 , hydroxy, —CH 3 , —CF 3 , —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—N(CH 3 ) 2 , oxo, —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH—C(O)—CF 3 , —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —S—CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono- or di-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN and —O—C 1-6 alkyl.

12 . A compound according to claim 1 wherein

R 1 is selected from the group consisting of:

(1) —NH—R 4 , and

(2) —R 4 ;

R 2 is selected from the group consisting of:

(1) —CF3,

(3) heterocycle, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , and oxo, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(5) aryl, optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl;

R 3 is selected from the group consisting of

(1) H, and

(2) halo; and

R 4 is selected from the group consisting of:

(1) aryl, optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(3) —C 1-6 alkyl-heteroaryl, wherein the heteroaryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) —C 1-6 alkyl-aryl, wherein the aryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl.

13 . A compound according to claim 1 wherein

R 1 is selected from the group consisting of:

(1) —NH—R 4 , and

(2) —R 4 ;

R 2 is selected from the group consisting of:

(1) —NR 5 R 6 ,

(2) —C 1-4 alkyl-NR 5 R 6 ,

(3) heteroaryl, optionally mono, di- or tri-substituted with substituents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF 3 , hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl and

(4) aryl, optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of wherein the aryl is optionally mono or di-substituted with substituents selected from —CH 3 , —O—C 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl;

R 3 is selected from the group consisting of

(1) H, and

(2) halo; and

R 4 is selected from the group consisting of:

(1) aryl, optionally mono, di- or tri-substituted with substituents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C3-6cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and wherein the heteroaryl portion of —C(o)-heteroaryl is optionally mono, di- or tri-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(2) heterocycle, optionally mono, di-, tri- or tetra substituted with a substituent independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 2 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , oxo and aryl, and wherein aryl and the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(3) —C 1-6 alkyl-heteroaryl, wherein the heteroaryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CN, —CH 3 , —CF 3 , —CHF 2 , —OC 1-6 alkyl, —O—CF3, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , and —NH—S(O) 2 —CH 3 , and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl,

(4) —C 1-6 alkyl-aryl, wherein the aryl is optionally mono, di- or tri-substituted with substitutents independently selected from —CH 3 , —OC 1-6 alkyl, hydroxy, —CH 3 —OH, halo, —S(O) 2 —CH 3 , —C(O)—O—C 1-6 alkyl, —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —C(O)—O—C(CH 3 ) 3 , C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH 2 —C(O)—CF 3 , —NH 2 —C(O)—N(CH 3 ) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —CF 3 and —CN, and the C 1-6 alkyl is optionally mono or di-substituted with substitutents independently selected from the group consisting of —CF 3 , —CHF 2 , hydroxyl and —OC 1-6 alkyl, and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono, di- or tri-substituted with substituents selected from the group consisting of halo, —CH 3 , —CF 3 , —CN, —OC 1-6 alkyl; and

R5 and R6 are joined together so that along with the nitrogen to which they are attached, there is formed a heterocycle, wherein said heterocycle is optionally mono, di or tri-substituted with substituents independently selected from the group consisting of —OC 1-6 alkyl, —NH—C(O)—O—C(CH 3 ) 3 , hydroxy, —CH 3 , —CF 3 , —CH 2 —OH, halo, —S(O) 2 —CH 3 , C(O)—O—C 1-6 alkyl, —C(O)—N(CH 3 )2, oxo, —C(O)—O—C(CH 3 ) 3 , —C(O)-heteroaryl, —C 3-6 cycloalkyl, —NH 2 , —NH—C(O)—CF 3 , —C(O)—NHC 1-6 alkyl, —C(O)—N(C 1-6 alkyl) 2 , —NC(O)—NH 2 , —NH—S(O) 2 —CH 3 , —O—CF 3 , —S—CH 3 , and wherein the heteroaryl portion of —C(O)-heteroaryl is optionally mono- di- or tri-substituted with substituents independently selected from the group consisting of halo, —CH 3 , —CF 3 , —CN and —O—C 1-6 alkyl.

14 . A compound according to claim 1 selected from the group consisting of

15 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

16 . A method of modulating the CB2 receptor in a patient in need of such modulation, comprising administering an effective amount of a compound according to claim 1 .

17 . A method of agonizing the CB2 receptor in a patient in need of such agonizing, comprising administering an effective amount of a compound according to claim 1 .

18 . A method of treating a disease mediated by agonizing the CB2 receptor in a patient in need of such treatment, comprising administering an effective amount of a compound according to claim 1 .

19 . A method of treating a disease selected from the group consisting inflammatory pain, osteoporosis, atheroschlerosis, immune disorders and arthritis comprising administering an effective amount of a compound according to claim 1 .

20 . A method according to claim 19 , for the treatment of the acute and chronic pain.

21 . A method according to claim 21 , for the treatment of the pain of rheumatoid arthritis or osteoarthritis.

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 15, 2010

From: BILODEAU, MARK T.; BURGEY, CHRISTOPHER S.; DENG, ZHENGWU JAMES; HARTNETT, JOHN C.; KETT, NATHAN R.; MELAMED, JEFFREY; MUNSON, PETER M.; NANDA, KAUSIK K.; THOMPSON, WAYNE; TROTTER, B. WESLEY; WU, ZHICAI

To: MERCK & CO., INC.

Reel/Frame 024689/0501 →

CHANGE OF NAME Recorded Jan 27, 2010

From: MERCK & CO., INC.

To: MERCK SHARP & DOHME CORP.

Reel/Frame 023852/0595 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 14, 2009

From: BILODEAU, MARK T.; BURGEY, CHRISTOPHER S.; DENG, ZHENGWU JAMES; HARTNETT, JOHN C.; KETT, NATHAN R.; MELAMED, JEFFREY; NANDA, KAUSIK K.; TROTTER, B. WESLEY; WU, ZHICAI

To: MERCK & CO., INC.

Reel/Frame 023518/0053 →