Synthesis and evaluation of (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) analogs with anti-tuberculosis activity.
In order to identify new and potent candidate drugs to treat tuberculosis, a library of compounds was screened, and (S,S)-N,N'-bis-[3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxy-propyl]-ethylenediamine (S2824) was identified as a hit in the screen. This research discusses our efforts to synthesize and test 30 analogs of this hit for activity against Mycobacterium tuberculosis. Two compounds with homopiperazine ring possess high in vitro activity against drug sensitive and resistant M. tuberculosis with MICs 0.78-3.13 microg/mL (or 1.22-4.88 microM).
Zhang
Xuelian
X
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China.
Hu
Yanwei
Y
Chen
Shudan
S
Luo
Rusong
R
Yue
Jun
J
Zhang
Ying
Y
Duan
Wenhu
W
Wang
Honghai
H
D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D024881:Drug Resistance, Bacterial; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy*
D000995:Antitubercular Agents; D001381:Azepines; D001559:Benzhydryl Compounds; D005029:Ethylenediamines; C546149:N,N'-bis(3-(2,2',6,6'-tetramethylbenzhydryloxy)-2-hydroxypropyl)ethylenediamine; C546150:S 282429; C546151:S 282430