| 主权项 |
1. A method of treating a disease, disorder, or condition associated with insufficient neurogenesis or unwanted neuronal cell death in a subject in need thereof, comprising administering an effective amount of a compound having formula (III), or a pharmaceutically acceptable salt thereof: wherein: each of R1, R2, R3, R4, R5, R6, R7, and R8 is independently selected from hydrogen, halo, hydroxyl, sulfhydryl, C1-C6 alkoxy, C1-C6 thioalkoxy, C1-C6 haloalkoxy, C1-C6 thiohaloalkoxy, C1-C6 alkyl, C1-C6 haloalkyl, cyano, —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, —NHC(O)(C1-C6 alkyl), and nitro; 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 hydrogen, halo, OR9 or C1-C3 alkyl; wherein R9 is C1-C3 alkyl that is optionally substituted with hydroxyl or C1-C3 alkoxy; Z is:
(i) —NR10R11;(ii) —OR12; or(iii) —S(O)nR13, wherein n is 0, 1, or 2; each of R10 and R11 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; (d) C1-C6 alkyl or C1-C6 haloalkyl, each of which is optionally substituted with from 1-3Rd;
(e) —C(O)(C1-C6 alkyl), —C(O)(C1-C6 haloalkyl), or —C(O)O(C1-C6 alkyl);(f) C2-C6 alkenyl or C2-C6 alkenyl;wherein one of R10and R11is (b) or (c); R12 1s: (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; R13is:
(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(C13 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 alkenyl;—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; (cc) C3-C6 cycloalkyl or heterocyclyl containing from 5-6 ring atoms, wherein from 1-2 of the ring atoms of the heterocyclyl is independently selected from N, NH, N(C1-C6 alkyl), NC(O)(C1-C6 alkyl), O, and S; and (dd) phenyl or heteroaryl containing from 5-6 ring atoms, wherein from 1-2 of the ring atoms of the heteroaryl is independently selected from N, NH, N(C1-C3 alkyl), O, and S; wherein each of said phenyl and heteroaryl is optionally substituted with from 1-3 substituents independently selected from halo; hydroxyl; cyano; nitro; —NH2; —NH(C1-C6 alkyl), N(C1-C6 alkyl)2, —NHC(O)(C1-C6 alkyl), C1-C6 alkoxy; C1-C6 haloalkoxy; C1-C6 thioalkoxy; C1-C6 thiohaloalkoxy; C1-C6 alkyl, and C1-C6 haloalkyl; 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)22n-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 —NCH1C(O)—, and Cy is a saturated, partially unsaturated or aromatic carbocyclic or heterocyclic ring system. |
