公开号/公开日

WO2013132376 A1 2013-09-12 [WO2013132376] / 2013-09-12

申请号/申请日

2013WO-IB51391 / 2013-02-20

发明人

BAILEY SIMON;BURKE BENJAMIN JOSEPH;COLLINS MICHAEL RAYMOND;CUI JINGRONG JEAN;DEAL JUDITH GAIL;HOFFMAN ROBERT LOUIS;HUANG QINHUA;JOHNSON TED WILLIAM;KANIA ROBERT STEVEN;KATH JOHN CHARLES;LE PHUONG THI QUY;MCTIGUE MICHELE ANN;PALMER;

申请人

PFIZER;

主分类号

IPC分类号

A61K-031/4353A61P-035/00C07D-491/08C07D-491/18C07D-498/08C07D-498/18C07D-498/22C07D-513/18

摘要

(WO2013132376) The invention relates to compounds of formula (Phi) as further defined herein and to the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to the uses thereof.  The compounds and salts of the present invention inhibit anaplastic lymphoma kinase (ALK) and/or EML4-ALK and are useful for treating or ameliorating abnormal cell proliferative disorders, such as cancer.

机翻摘要

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地址

代理人

代理机构

;

优先权号

2012US-61607485 2012-03-06 2013US-61759307 2013-01-31

主权利要求

(WO2013132376) 1. A compound of the formula (I) wherein: X is selected from the group consisting of -(CR(5)R(6))[q]O(CR(5)R(6))[r], -(CR(5)R(6))[q]N(R(1))(CR(5)R(6))[r], -(CR(5)R(6))[q]C(0)N(R(1))(CR(5)R(6))[r]- and -(CR(5)R(6))[q]N(R(1))C(0)(CR(5)R(6))[r]; Y and Z are each independently N or CH, with the proviso that when Y is N, Z is CH and when Z is N, Y is CH; A is a ring selected from C[6]-Ci[2] aryl and 5-6 membered heteroaryl; R(1) is selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-C[12] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(2) is independently selected from the group consisting of halogen, C-|-C[6] alkyl, C[2]- C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -S(0)[t]R(7), -S(0)[2]NR(7)R(8), -S(0)[2]OR(7), -N0[2], -(CR(5)R(6))[q]NR(7)R(8), - N(CR(5)R(6))(CR(5)R(6))[q]NR(7)R(8), -OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]R(7), -CN, -C(0)R(7), -OC(0)R(7), -0(CR(5)R(6))[q]R(7), -NR(7)C(0)R(8), -(CR(5)R(6))[q]C(0)OR(7), -(CR(5)R(6))[q]NR(7)R(8), -C(=NR(7))NR(7)R(8), -NR(7)C(0)NR(7)R(8), -NR(7)S(0)[2]R(8) and -(CR(5)R(6))[q]C(0)NR(7)R(8); wherein each hydrogen on said C C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); R(3) and R(4) are each independently selected from hydrogen, Ci-C[6] alkyl and C[3]-C[6] cycloalkyi, wherein each hydrogen on Ci-C[6] alkyl and C[3]-C[6] cycloalkyi may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(5) and R(6) is independently selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) and -C(0)NR(9)R(10); wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, Cs- Ce cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(7) and R(8) is independently selected from the group consisting of hydrogen, C-|-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(9) and R(10) is independently selected from hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]- C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; p is 0, 1, 2, 3 or 4; each q is independently 0, 1, 2 or 3; each r is independently 0, 1, 2 or 3; and each t is independently 0, 1 or 2; or a pharmaceutically acceptable salt thereof. 2. A compound of the formula (V) A is a ring selected from C[6]-Ci[2] aryl and 5-6 membered heteroaryl; R(1) is selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(2) is independently selected from the group consisting of halogen, Ci-C[6] alkyl, C[2]- C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -S(0)[t]R(7), -S(0)[2]NR(7)R(8), -S(0)[2]OR(7), -N0[2], -(CR(5)R(6))[q]NR(7)R(8), - N(CR(5)R(6))(CR(5)R(6))[q]NR(7)R(8), -OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]R(7), -CN, -C(0)R(7), -OC(0)R(7), -0(CR(5)R(6))[q]R(7), -NR(7)C(0)R(8), -(CR(5)R(6))[q]C(0)OR(7), -(CR(5)R(6))[q]NR(7)R(8), -C(=NR(7))NR(7)R(8), -NR(7)C(0)NR(7)R(8), -NR(7)S(0)[2]R(8) and -(CR(5)R(6))[q]C(0)NR(7)R(8); wherein each hydrogen on said C C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); R(3) and R(4) are each independently selected from hydrogen, Ci-C[6] alkyl and C[3]-C[6] cycloalkyi, wherein each hydrogen on Ci-C[6] alkyl and C[3]-C[6] cycloalkyi may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(5) and R(6) is independently selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) and -C(0)NR(9)R(10); wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]- C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(7) and R(8) is independently selected from the group consisting of hydrogen, C-|-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(9) and R(10) is independently selected from hydrogen, C^Ce alkyl, C[2]-C[6] alkenyl, C[2]- C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl; p is 0, 1, 2, 3 or 4; each q is independently 0, 1, 2 or 3; each r is independently 0, 1, 2 or 3; and each t is independently 0, 1 or 2; or a pharmaceutically acceptable salt thereof. 3. A compound of the formula (VI) (VI) wherein: A is a ring selected from C[6]-Ci[2] aryl and 5-6 membered heteroaryl; R(1) is selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(2) is independently selected from the group consisting of halogen, C Ce alkyl, C[2]- C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -S(0)[t]R(7), -S(0)[2]NR(7)R(8), -S(0)[2]OR(7), -N0[2], -(CR(5)R(6))[q]NR(7)R(8), - N(CR(5)R(6))(CR(5)R(6))[q]NR(7)R(8), -OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]R(7), -CN, -C(0)R(7), -OC(0)R(7), -0(CR(5)R(6))[q]R(7), -NR(7)C(0)R(8), -(CR(5)R(6))[q]C(0)OR(7), -(CR(5)R(6))[q]NR(7)R(8), -C(=NR(7))NR(7)R(8), -NR(7)C(0)NR(7)R(8), -NR(7)S(0)[2]R(8) and -(CR(5)R(6))[q]C(0)NR(7)R(8); wherein each hydrogen on said C C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); R(3) and R(4) are each independently selected from hydrogen, C-|-C[6] alkyl and C[3]-C[6] cycloalkyi, wherein each hydrogen on C Ce alkyl and C[3]-C[6] cycloalkyi may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(5) and R(6) is independently selected from the group consisting of hydrogen, CrC[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) and -C(0)NR(9)R(10); wherein each hydrogen on said CrC[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, Cs- Ce cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(7) and R(8) is independently selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(9) and R(10) is independently selected from hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]- C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl; p is 0, 1, 2, 3 or 4; each q is independently 0, 1, 2 or 3; each r is independently 0, 1, 2 or 3; and each t is independently 0, 1 or 2; or a pharmaceutically acceptable salt thereof. 8), -S(0)[2]OR(7), -N0[2], -(CR(5)R(6))[q]NR(7)R(8), - N(CR(5)R(6))(CR(5)R(6))[q]NR(7)R(8), -OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]R(7), -CN, -C(0)R(7), -OC(0)R(7), -0(CR(5)R(6))[q]R(7), -NR(7)C(0)R(8), -(CR(5)R(6))[q]C(0)OR(7), -(CR(5)R(6))[q]NR(7)R(8), -C(=NR(7))NR(7)R(8), -NR(7)C(0)NR(7)R(8), -NR(7)S(0)[2]R(8) and -(CR(5)R(6))[q]C(0)NR(7)R(8); wherein each hydrogen on said C C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); R(3) is Ci-C[6] alkyl or C[3]-C[6] cycloalkyi and R(4) is hydrogen, wherein each hydrogen on said Ci-C[6] alkyl or C[3]-C[6] cycloalkyi may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(5) and R(6) is independently selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(1).deg., -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) and -C(0)NR(9)R(10); wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]- C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(7) and R(8) is independently selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said C-|-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-C[12] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(9) and R(10) is independently selected from hydrogen, C-|-C[6] alkyl, C[2]-C[6] alkenyl, C[2]- C[6] alkynyl, C[3]-C[6] cycloalkyl, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl; p is 0, 1, 2, 3 or 4; each q is independently 0, 1, 2 or 3; each r is independently 0, 1, 2 or 3; and each t is independently 0, 1 or 2; or a pharmaceutically acceptable salt thereof. R(1) is selected from the group consisting of hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl, wherein each hydrogen on said Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(2) is independently selected from the group consisting of halogen, Ci-C[6] alkyl, C[2]- C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -S(0)[t]R(7), -S(0)[2]NR(7)R(8), -S(0)[2]OR(7), -N0[2], -(CR(5)R(6))[q]NR(7)R(8), - N(CR(5)R(6))(CR(5)R(6))[q]NR(7)R(8), -OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]OR(7), -0(CR(5)R(6))(CR(5)R(6))[q]R(7), -CN, -C(0)R(7), -OC(0)R(7), -0(CR(5)R(6))[q]R(7), -NR(7)C(0)R(8), -(CR(5)R(6))[q]C(0)OR(7), -(CR(5)R(6))[q]NR(7)R(8), -C(=NR(7))NR(7)R(8), -NR(7)C(0)NR(7)R(8), -NR(7)S(0)[2]R(8) and -(CR(5)R(6))[q]C(0)NR(7)R(8); wherein each hydrogen on said C C[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-C[12] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); R(3) is C Ce alkyl or C[3]-C[6] cycloalkyi and R(4) is hydrogen, wherein each hydrogen on said Ci-C[6] alkyl or C[3]-C[6] cycloalkyi may be independently optionally substituted by halogen, -OH, - NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(5) and R(6) is independently selected from the group consisting of hydrogen, C Ce alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) and -C(0)NR(9)R(10); wherein each hydrogen on said CrC[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, Cs- Ce cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(7) and R(8) is independently selected from the group consisting of hydrogen, CrC[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl, wherein each hydrogen on said CrC[6] alkyl, C[2]-C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic and 5-6 membered heteroaryl may be independently optionally substituted by halogen, -OH, -NH[2], -S(0)[t]R(9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -NO[2], -OR(9), -CN, -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(1).deg. or -C(0)NR(9)R(10); each R (9) and R(10) is independently selected from hydrogen, Ci-C[6] alkyl, C[2]-C[6] alkenyl, C[2]- C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, and 5-6 membered heteroaryl; p is 0, 1, 2, 3 or 4; each q is independently 0, 1, 2 or 3; each r is independently 0, 1, 2 or 3; and each t is independently 0, 1 or 2; or a pharmaceutically acceptable salt thereof. 9), -S(0)[2]NR(9)R(10), -S(0)[2]OR(9), -N0[2], -CN, -OR(9), -C(0)R(9), -OC(0)R(9), -NR(9)C(0)R(10), -C(0)OR(9), -C(=NR(9))NR(9)R(10), -NR(9)C(0)NR(9)R(10), -NR(9)S(0)[2]R(10) or -C(0)NR(9)R(10); each R(2) is independently selected from the group consisting of halogen, C Ce alkyl, C[2]- C[6] alkenyl, C[2]-C[6] alkynyl, C[3]-C[6] cycloalkyi, C[6]-Ci[2] aryl, 3-12 membered heteroalicyclic, 5-6 membered heteroaryl, -S(0)[t]R(7), -S(0)[2]NR(7)R(

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