| 主权项 |
1. A method of treating a disease or disorder dependent on CXCR7 activity in a human subject, said disease or disorder selected from the group consisting of breast cancer, prostate cancer, lung cancer, glioblastoma, rheumatoid arthritis, pulmonary hypertension, and atherosclerosis, comprising administering to said subject a therapeutically effective amount of a compound having formula Ior a pharmaceutically acceptable salt, hydrate, N-oxide, isotopically enriched or enantiomerically enriched version thereof, wherein
the subscript n is an integer of from 0 to 2; each R1, when present, is independently selected from the group consisting of C1-4 alkyl, —CO2Ra, —X—CO2Ra, —CONRaRb and —X—CONRaRb; R2 and R3 are each members independently selected from the group consisting of H, —Ra, —XRa, —XNRaRb, —XNHCONRaRb, —XNHCORa, —X—O—CONRaRb, —XNHSO2Ra, —CO2Ra, —X—CO2Ra, —CONRaRb and —X—CONRaRb; or taken together are oxo; C1 is phenyl or quinolin-8-yl optionally substituted with from 1 to 3 R4 substituents; C2 is selected from the group consisting of pyrrolidine, piperidine, thiazole, pyrazole, oxazole and benzene, each of which is optionally substituted with from 1 to 2 R5 substituents; C3 is selected from the group consisting of C3-8 alkyl, cyclopropyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl and phenyl, wherein each of said cyclopropyl, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl and phenyl groups are optionally substituted with from 1 to 2 R6 substituents each R4 is independently selected from the group consisting of halogen, —CN, —NO2, —Rc, —CO2Ra, —NRaRb, —ORa, —X—CO2Ra, —CONRaRb and —X—CONRaRb; wherein within each of R1, R2, R3 and R4, each Ra and Rb is independently selected from hydrogen, C1-8 alkyl, C3-7 cycloalkyl, C1-8 haloalkyl, and four- to six-membered heterocycloalkyl, or when attached to the same nitrogen atom can be combined with the nitrogen atom to form a four-, five- or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O or S; each Rc is independently selected from the group consisting of C1-8 alkyl, C1-8 haloalkyl, C3-6 cycloalkyl, aryl and heteroaryl, and wherein the aliphatic and cyclic portions of Ra, Rb and Rc are optionally further substituted with from one to three halogen, hydroxy, methyl, alkoxy, amino, alkylamino, dialkylamino, carboxamide, carboxy alkyl ester, carboxylic acid, heteroaryl, and four- to six-membered heterocycloalkyl groups; and wherein the heterocycloalkyl portions of R2, R3 and R4 are optionally substituted with oxo; and optionally when two R4 substituents are on adjacent atoms, are combined to form a fused five or six-membered ring having carbon and oxygen atoms as ring members; each R5 is independently selected from the group consisting of halogen, —CN, —NO2, —Rf, —CO2Rd, —CORd, —NRdRe, —ORd, —X—CO2Rd, —CONRdRe and —X—CONRdRe; wherein each Rd and Re is independently selected from hydrogen, C1-8 alkyl, C1-8 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkylalkyl, and four- to six-membered heterocycloalkyl or when attached to the same nitrogen atom can be combined with the nitrogen atom to form a five or six-membered ring having from 0 to 2 additional heteroatoms as ring members selected from N, O or S; each Rf is independently selected from the group consisting of C1-8 alkyl, C1-8 haloalkyl, and C3-6 cycloalkyl, and wherein the aliphatic and cyclic portions of Rd, Re and Rf are optionally further substituted with from one to three halogen, hydroxy, methyl, alkoxy, amino, alkylamino, dialkylamino, carboxamide, carboxy alkyl ester, carboxylic acid, heteroaryl, four- to six-membered heterocycloalkyl groups; each R6 is independently selected from the group consisting of halogen, —CN, —NO2, —Ri, —CO2Rg, —CORg, —NRgRh, —ORg, —X—CO2Rg, —X—CORg, —CONRgRh and —X—CONRgRh, wherein each Rg and Rh is independently selected from hydrogen, C1-8 alkyl and C1-8 haloalkyl; each Ri is independently selected from the group consisting of C1-8 alkyl and C1-8 haloalkyl; and each X is independently selected from the group consisting of —OCH2—, —CH2—, —C(CH3)2— and —CH2CH2—;
for a period of time sufficient to treat said disease or disorder. |
