THIAZOLE-SUBSTITUTED AMINOPYRIMIDINES AS SPLEEN TYROSINE KINASE INHIBITORS

摘要

The invention provides certain thiazole-substituted aminopyrimidine compounds of the Formula (I) (I), or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R5, R6, and the subscripts r, s, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk).;

主权项

1. A compound of the Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 is selected from the group consisting of:
(i) C1-C3 alkyl; and(ii) C1-C3 fluoroalkyl; R2 is selected from the group consisting of
(i) ring CB, wherein ring CB is selected from the group consisting of:
(a) a 5- or 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from the group consisting of N, O, and S;(b) phenyl; and(c) cyclohexenyl;wherein ring CB is unsubstituted or substituted with 1 to 3 R7, wherein each R7 is independently C1-C6 alkyl, C1-C6 alkoxy, halo, —CN, —CH2—O—C1-C3 alkyl, —S(O)—C1-C3 alkyl, —S(O)2—C1-C3 alkyl, amino, —N(H)—C1-C3 alkyl, —N(C1-C3 alkyl)2, —C(O)NH2, —C(O)N(H)—C1-C3 alkyl, —C(O)N(C1-C3 alkyl)2, or —C(O)N(H)-cyclopropyl;(ii) C1-C3 alkoxy;(iii) —CN(iv) —S(O)xC1-C3 alkyl;(v) C2-C6 alkenyl, wherein said alkenyl is unsubstituted or substituted by 1 cyclopropyl;(vi) Cl; R3 is selected from the group of H and halo; R5 is —C(O)ORA or —C(O)NH2; R6 is C1-C3 alkyl the subscript r is 0, 1, or 2; the subscript s is 0 or 1; the subscript t is 0, 1, 2, 3, 4, or 5; the subscript x is 0, 1, or 2; RA is independently selected from the group consisting of:
(a) H;(b) C1-C8 alkyl;(c) a group of the formula -M-RCH, wherein
M is a bond or —(CH2)n1—, wherein the subscript n1 is 1 or 2;RCH is (a) aryl or C3-C6 cycloalkyl optionally substituted with 1-3 groups independently selected from halo, C1-C4 alkyl, or C1-C4 alkoxy; or (b) a 5- to 6-membered monocyclic heterocycle containing 1 or 2 heteroatoms independently selected from the group consisting of N and O, wherein said heterocycle of RCH is optionally substituted with 1 or 2 groups independently selected from the group consisting of oxo and C1-3 alkyl;(d) a group of the formula —(CH2)n1—Rm or —(CH2)2—O—(CH2)2—Rm wherein Rm is —CO2Rm, —C(O)N(Rm2)2, or —O(CO)Rm1;
Rm1 is C1-C4 alkyl; andRm2 is H or C1-C4 alkyl;(e) a group of the formula —(CH2)2—Rn,
Rn is —OH, —O—(C1-C4 alkyl), —O—(CH2)2—O—(C1-C4 alkyl), —NH2, —N(H)(C1-C4 alkyl) or —N(C1-C4 alkyl)2; (f) a group of the formulawherein
 Ro is H or C1-C4 alkyl; and  Rp is C1-C4 alkyl, C3-C6 cycloalkyl, or phenyl; and, (g) a group of the formulawherein Ro and Rp are as set forth above.