Journal of Medicinal Chemistry p. 4786 - 4792 (1995)
Update date:2022-07-31
Topics:
Lebreton, Luc
Curet, Olivier
Gueddari, Salach
Mazouz, Fathi
Bernard, Suzanne
et al.
Twenty new 2-(cyanoalkyl)tetrazoles (15 and 16) and twenty new 2-(hydroxyalkyl)tetrazoles (17 and 18) were synthesized and investigated in vitro for their abilities to inhibit selectivity rat brain monoamine oxidase (MAO) B over MAO A.Most of then were MAO B inhibitors and those bearing a sunstituted 4-(arylmethoxy)phenyl group in the position 5 of the tetrazole ring had IC50 values between 8 νM for 18d and 2 nM for 16a (30 nM for lazabemide) with a selectivity toward MAO B of 37000 for 16a.The reversibility of their inhibitory activity was demonstrated by in vitro dialysis tests.The 5-<4-(phenylmethoxy)phenyl>-2-(2-cyanoethyl)-tetrazole (16a) its derivative 16h and the 5-<4-(phenylmethoxy)phenyl>-2-(2-hydroxyethyl)-tetrazole (18a) and its derivative 18h were found to be potent, in vitro selective, and competitive MAO B inhibitors.Tetrazole 16a can be considered one of the most active and selective competitive MAO B inhibitors known up to now.This compound was selected for ex vivo experiments and shown to be a strong and reversible MAO B inhibitor with a short duration of action after oral administration at 5 mg/kg.The structure-activity approach gives rise to the great inportance of lipophilicity over electronic effects of the compounds in these series.
View MoreSuzhou Chiral Pharmaceuticals Co., Ltd.
Contact:86-0512-63197058
Address:Building A, No. 2358, Chang'an Road, Wujiang Science Park
Contact:86-571-86737118-8689
Address:No.69, 12 Street, HEDA, Hangzhou, Zhejiang, China
Shandong Topscience Biotech Co., Ltd.
Contact:0633-2619278
Address:No. 98 Lanshan West Road, Lanshan District, Rizhao, Shandong Province, P.R. of China
Shanghai Bocimed Pharmaceutical Co., Ltd.
website:http://www.bocimed.com
Contact:+86-21-68861632
Address:Building 1, Lane 647, Songtao Road, Zhangjiang High-Tech Park, Shanghai
Xi'an Costrong Pharmaceutical Co., Ltd.
Contact:029- 68576496
Address:Room 2004,Shuibao Building,No.190,South Erhuan Rd, Yanta District,Xi'an,Shaan Xi,China
Doi:10.1039/c6cc08601b
(2016)Doi:10.1002/adsc.201000269
(2010)Doi:10.1016/j.tetasy.2010.04.029
(2010)Doi:10.1021/acs.orglett.9b04201
(2020)Doi:10.1007/BF00955433
(1989)Doi:10.1021/ic101068a
(2010)