| 主权项 |
1. A compound for promoting post-natal mammalian neurogenesis and/or reducing neuronal cell death in a subject in need thereof, the compound having formula (I) or a pharmaceutically acceptable salt thereof: wherein: each of R1, R2, R3, and R4 is independently selected from hydrogen, halo, C1-C6 alkoxy, C1-C6 alkyl, and cyano; R and R′ are defined according to (1), (2), or (3) below: (1) R and R′ together with C2 and C3, respectively, form a fused phenyl ring having formula (II): wherein each of R5, R6, R7, and R8 is independently selected from hydrogen, halo, C1-C6 alkoxy, C1-C6 alkyl, and cyano; (2) R and R′ together with C2 and C3, respectively, form a fused heterocyclic ring containing from 5-6 ring atoms, wherein from 1-2 of the ring atoms is independently selected from N, NH, N(C1-C6 alkyl), NC(O)(C1-C6 alkyl), O, and S; or (3) R and R′ together with C2 and C3, respectively, form a fused heteroaryl ring containing from 5-6 ring atoms, wherein from 1-2 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S; and wherein said heteroaryl ring is optionally substituted with from 1-3 independently selected Rb; each of L1 and L2 is CH2; A is CRA1RA2, wherein one of RA1 and RA2 is halo or OR9, and the other of RA1 and RA2 is halo, hydrogen or C1-C3 alkyl; Z is:
(i) —NR10R11;(ii) —OR12; or(iii) —S(O)nR13, wherein n is 0, 1, or 2; R9 is hydrogen; or C1-C3 alkyl that is optionally substituted with hydroxyl or C1-C3 alkoxy; each of R10 and R1 is independently selected from:
(a) hydrogen;(b) C6-C10 aryl that is optionally substituted with from 1-4 Rb;(c) heteroaryl containing from 5-14 ring atoms, wherein from 1-6 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S, wherein said heteroaryl is optionally substituted with from 1-4 Rb;wherein one of R10 and R1 is (b) or (c); R12 is:
(i) C6-C10 aryl that is optionally substituted with from 1-4 Rb; or(ii) heteroaryl containing from 5-14 ring atoms, wherein from 1-6 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S; and wherein said heteroaryl is optionally substituted with from 1-4 Rb; R13 is:
(i) C6-C10 aryl that is optionally substituted with from 1-4 Rb; or(ii) heteroaryl containing from 5-14 ring atoms, wherein from 1-6 of the ring atoms is independently selected from N, NH, N(C1-C3 alkyl), O, and S; and wherein said heteroaryl is optionally substituted with from 1-4 Rb; Rb at each occurrence is independently selected from:
(aa) C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 thioalkoxy; C1-C6 thiohaloalkoxy; C1-C6 alkyl; C1-C6 haloalkyl; —NH(C1-C6 alkyl); N(C1-C6 alkyl)2; —NHC(O)(C1-C6 alkyl); wherein the alkyl portion of each is optionally substituted with from 1-3 independently selected Re;(bb) halo; hydroxyl; cyano; nitro; —NH2; azido; sulfhydryl; C2-C6 alkenyl; C2-C6 alkynyl; —C(O)H; —C(O)(C1-C6 alkyl); —C(O)(C1-C6 haloalkyl); C(O)OH; —C(O)O(C1-C6 alkyl); —C(O)NH2; —C(O)NH(C1-C6 alkyl); C(O)N(C1-C6 alkyl)2; —SO2(C1-C6 alkyl); —SO2NH2; —SO2NH(C1-C6 alkyl); —SO2N(C1-C6 alkyl)2; and Re at each occurrence is, independently selected from hydroxyl, C1-C6 alkoxy; C1-C6 thioalkoxy; C1-C6 haloalkoxy; C1-C6 thiohaloalkoxy; —NH2; —NH(C1-C6 alkyl); N(C1-C6 alkyl)2; —NHC(O)(C1-C6 alkyl); cyano; —C(O)H; —C(O)(C1-C6 alkyl); —C(O)(C1-C6 haloalkyl); C(O)OH; —C(O)O(C1-C6 alkyl); —C(O)NH2; —C(O)NH(C1-C6 alkyl); C(O)N(C1-C6 alkyl)2; —SO2(C1-C6 alkyl); —SO2NH2; —SO2NH(C1-C6 alkyl); —SO2N(C1-C6 alkyl)2; and L3-(C1-C6 alkylene)-Cy, where in L3 is a —O—, —NH—, —NCH3—, —C(O)—, —C(O)NH—, —C(O)NCH3—, —NHC(O)—, or —NCH3C(O)—, and Cy is a saturated, partially unsaturated or aromatic carbocyclic or heterocyclic ring system. |
