| 主权项 |
1. A compound having formula Ior a pharmaceutically acceptable salt, hydrate, N-oxide, isotopically enriched or enantiomerically enriched version or a rotamer thereof, wherein
each of ring vertices Xa, Xb and Xc is independently selected from the group consisting of N, NH, N(R2), O, CH and C(R2); the subscript n is 0, 1 or 2; Z is selected from the group consisting of (i) monocyclic or fused-bicyclic aryl and heteroaryl, wherein the heteroaryl group has from 1-4 heteroatoms as ring members selected from N, O and S; and wherein said aryl and heteroaryl groups are optionally substituted with from 1 to 5 R5 substituents; (ii) monocyclic four-, five-, six- or seven-membered ring selected from the group consisting of cycloalkane, and heterocycloalkane, wherein the heterocycloalkane rings have from 1-3 heteroatoms as ring members selected from N, O and S; and wherein each of said monocyclic Z rings are optionally substituted with from 1 to 3 R5 substituents; R1 is a member selected from the group consisting of H and C1-8 alkyl, wherein the alkyl portion is optionally substituted with halogen, —NRaRb, —ORa, —CO2Ra, and —CONRaRb; each R2 is independently selected from the group consisting of H, halogen, CN, C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —ORa, —CO2Ra, —X—CO2Ra, —NRaRb, —CONRaRb and —X—CONRaRb; R3 is a member selected from the group consisting of H, C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —CO2Ra, —X—CO2Ra, —CONRaRb and —X—CONRaRb; each R4, when present, is a member independently selected from the group consisting of C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —CO2Ra, —X—CO2Ra, —NRaRb, —CONRaRb and —X—CONRaRb; each R5 is a member independently selected from the group consisting of halogen, CN, —X—CN, C1-8 alkyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, C3-5 spirocycloalkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —ORa, —CO2Ra, —X—CO2Ra, —NRaRb, —CONRaRb, —X—CONRaRb, aryl, 5- or 6-membered heteroaryl, and 3-, 4-, 5- or 6-membered heterocyclic wherein the heteroatoms present as ring vertices of the heteroaryl and heterocyclic rings are selected from N, O and S, and wherein the aryl, heteroaryl and hetereocyclic portions of R5 are optionally further substituted with 1-3 Ra; each Ra and Rb is independently selected from the group consisting of hydrogen, hydroxyl, halogen, cyano, C1-8 alkyl, C1-8 alkoxy, C1-8 haloalkyl, C3-6 cycloalkyl, C3-6 cycloalkylalkyl, amino, C1-8 alkylamino, di C1-8 alkylamino, carboxamide, carboxy C1-4 alkyl ester, carboxylic acid, and —SO2—C1-8 alkyl; each X is a C1-4 alkylene linking group or a linking group having the formula —(CH2)mO(CH2)p—, wherein the subscripts m and p are integer of from 0 to 5, and m+p is from 0 to 6, wherein any of the methylene portions of X are optionally substituted with one or two methyl groups.
|
