HETEROCYCLIC COMPOUNDS AND USE THEREOF

摘要

Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury, cancer, inflammatory disease, and autoimmune disease with the heterocyclic compounds.

主权项

1. A compound of formula (I):wherein
each of R1 and R2, independently, is H, halo, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl; or R1 and R2, together with the two carbon atoms to which they are bonded, are C5-10 cycloalkyl, C3-10 heterocycloalkyl, aryl, or heteroaryl, each of C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, C5-10 cycloalkyl, C3-10 heterocycloalkyl, aryl, and heteroaryl being optionally substituted with halo, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxyl, aryl, heteroaryl, or C(O)ORa, in which Ra is H, C1-10 alkyl, C3-10 cycloalkyl, C3-10 heterocycloalkyl, aryl, or heteroaryl; and each of R3 and R4, independently, is NRbRc, in which
each of Rb and Rc, independently, is H or C1-6 alkyl;R5 is H, C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl alkyl, heteroaryl alkyl, aryl, or heteroaryl, each of C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl alkyl, heteroaryl alkyl, aryl, and heteroaryl being optionally substituted with halo, nitro, cyano, amino, C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl;R6 is H, C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl;L1 is heteroaryl, C1-10 heterocycloalkyl, NH, or NRd, in which Rd is C(O)(CH2)2CHNH2CO2Re, Re being H, C1-6 alkyl, C3-10 cycloalkyl, C3-10 heterocycloalkyl, aryl, or heteroaryl;R7 is H, C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl, each of C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl being optionally substituted with hydroxy, hydroxy C1-6 alkyl, halo, nitro, cyano, amino, amino C1-6 alkyl, amino C3-10 cycloalkyl, amino C1-10 heterocycloalkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl;m is 1-6;n is 1-6;each of R8 and R9, independently, is H, C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, or heteroaryl, each of C1-6 alkyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, and heteroaryl being optionally substituted with C(O)ORf, in which Rf is H, C1-10 alkyl, C3-20 cycloalkyl, C3-20 heterocycloalkyl, aryl, or heteroaryl; or R8 and R9, together with the nitrogen atoms to which they are bonded, are C3-10 heterocycloalkyl;L2 is C1-6 alkyl; or L2, together with R8 or R9 and the nitrogen atom to which they are bonded, is C4-10 heterocycloalkyl or heteroaryl; andR10 is H, C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, heteroaryl, aryl alkyl, heteroaryl alkyl, C(O)ORg, C(S)NRhRi, C(O)NRjRk, or C(O)Rp, each of C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, heteroaryl, aryl alkyl, and heteroaryl alkyl being optionally substituted with hydroxy, halo, nitro, cyano, amino, C(O)OR11, or P(O)(OR12)2, in which each of R11 and R12, independently, is H or C1-6 alkyl; or R10, together with R9 and the nitrogen atom to which they are bonded, is C4-10 heterocycloalkyl or heteroaryl; each of Rg, Rh, Ri, Rj, and Rk, independently, being H, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkyl, aryl alkyl, heteroaryl alkyl, aryl, or heteroaryl; and Rp being H, C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, heteroaryl, aryl alkyl, heteroaryl alkyl, orin which each of C1-6 alkyl, C1-6 alkoxyl, C3-10 cycloalkyl, C1-10 heterocycloalkyl, aryl, heteroaryl, aryl alkyl, heteroaryl alkyl is optionally substituted with halo, P(O)(OH)2, or P(O)(O—C1-6 alkyl)2; o is 0-2; D1 is OH or NR14R15, each of R14 and R15, independently, being H, C(O)CH(NH2)CH2OH, or C(NH)NH2; D2 is O or NR16, R16 being H, C1-6 alkyl, S(O)2Rq, NHRr, or CH2CO2Rs, in which each of Rq and Rr, independently, is aryl optionally substituted with halo or alkoxyl, and Rs is H, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkyl, aryl alkyl, heteroaryl alkyl, aryl, or heteroaryl; R13 is H, C1-6 alkyl, C3-10 cycloalkyl, C3-10 heterocycloalkyl, aryl alkyl, heteroaryl alkyl, aryl, or heteroaryl, each of C1-6 alkyl, C3-10 cycloalkyl, C3-10 heterocycloalkyl, aryl alkyl, heteroaryl alkyl, aryl, and heteroaryl being optionally substituted with hydroxy, C1-6 alkyl, C3-10 cycloalkyl, C3-10 heterocycloalkyl, aryl alkyl, heteroaryl alkyl, aryl, heteroaryl, P(O)(OH)2, P(O)(O—C1-6 alkyl)2, hydroxy, or C(O)ORt, in which Rt is H, C1-6 alkyl, C1-6 alkoxyl, C1-6 alkyl, aryl alkyl, heteroaryl alkyl, aryl, or heteroaryl; and X is ═O or -aryl.