| 主权项 |
1. A compound having formula I or a pharmaceutically acceptable salt thereof, wherein R1 is C1-4alkyl, C1-4fluoroalkyl, C3-6cycloalkyl or C1-4alkoxy; R2 is H or halogen; R3 is H, halogen, NRbRc, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl or C1-4hydroxyalkyl; R4 is H or halogen; one of X1 and X2 is N, and the other is C—F, C-Q or C—Y—Z; Q is selected from (a) C1-4alkyl optionally substituted with 1 to 2 groups independently selected from ORa and CO2Ra, and (b) NH—C1-4alkyl optionally substituted with CO2Ra; Y is selected from the group consisting of (a) a bond, (b)—O(CH2)0-1—, (c) —NH(CH2)0-1, (d) —C(R5)(R6), and (e) —C(O)—; R5 is H, OH, C1-4alkoxy or halogen; R6 is H, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl or C1-4hydroxyalkyl; Z is (a) aryl or a carbocycle each optionally substituted with 1-5 groups independently selected from C1-4alkyl, ORa, CO2Ra, and CONRbRc, or (b) heteroaryl or a 4- to 10-membered mono- or bicyclic heterocycle each optionally substituted with 1 or 2 groups independently selected from oxo, ORa, CO2Ra, CONRbRc, CORd, NRbRc, NHC(O)ORa, NHCORd, NHCONRbRc, and cyclohexyl optionally substituted with CO2Ra; Ra is selected from the group consisting of:
(i) H;(ii) C1-8 alkyl;(iii) a group of the formula -M-RCH, wherein
M is a bond or —(CH2)1-2—;RCH is (a) aryl or carbocycle optionally substituted with 1-3 groups independently selected from halo, C1-4alkyl, or C1-4alkoxy; 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;(iv) a group of the formula —(CH2)1-2—Re or —(CH2)2—O—(CH2)2—Re wherein
Re is CO2Re1, C(O)N(Re2)2, or —(CO)Re1;
Re1 is C1-4alkyl; andRe2 is H or C1-4alkyl;(v) a group of the formula —(CH2)2—Rf,
Rf is OH, —OC1-4alkyl, NH2, —N(H)(C1-4alkyl) or N(C1-4alkyl)2;(vi) a group of the formula wherein
Rg is H or C1-4alkyl; andRh is C1-4alkyl, C3-6cycloalkyl, or phenyl; and,(vii) a group of the formulawherein Rg and Rh are as set forth above;
Rb and Rc are each independently selected from H and C1-4alkyl; or Rb, Re and the nitrogen atom to which they are attached together form a 4- to 6-membered ring optionally having an additional heteroatom selected from N—Ra, O and S, wherein said ring is optionally substituted with a group selected from CO2Ra and oxo; Rd is (a) C1-4alkyl optionally substituted with NRbRc, O-aryl, aryl, heteroaryl, or V—W, (b) aryl, (c) heteroaryl, (d) V—W, or (e) a group selected from 1-isoindolinone, 2-indolinone, fluorenyl (optionally substituted with oxo), tetrahydrocarbazolyl, and dibenzo[b,d]furanyl; wherein V and W are each independently selected from aryl and heteroaryl, and aryl and heteroaryl in (a) through (d) are each optionally substituted with 1-3 groups independently selected from (i) C1-4alkyl, (ii) C1-4haloalkyl, (iii) CN, (iv) halogen, (v) ORa, (vi) phenoxy, (vii) CH2-aryl, (viii) CH2-heteroaryl, (ix) NRbRc, (x) CONRbRc, (xi) NHCOC1-4alkyl, and (xii) SO2C1-4alkyl. |
