[Synthesis and bioactivity of N- [4- ( benzimidazole-2-thio) phenyl] -N'-alkyl guanidine derivatives].
In order to get some novel compounds with potent iNOS inhibitory activity, 12 target compounds of N-[ 4-( benzimidazole-2-thio) phenyl ] -N'-alkyl guanidine derivatives ( I1- I12 ) were synthesized from 1-benzoyl-3-[ 4-( benzimidazole-2-thio) phenyl] thioureas (4) by hydrolysis with 2. 0 mol x L(-1) sodium hydroxide solution containing tetrahydrofuran to form the corresponding N-[ 4-(benzimidazole-2-thio) phenyl] thioureas (5) which was S-ethylated with ethyl iodide, followed by amination with primary amines or secondary amines. The intermediate 4 was synthesized from 2-mercaptobenzimidazole (1) by reaction with 1-chloro-4-nitrobenzene to form 2-( 4-nitrophenylthio) benzimidazole (2) which was reduced by iron powder and hydrochloric acid, followed by reaction with benzoyl isothiocyanate. The structures of compounds I1 - I12 were confirmed by IR, MS,1H NMR and elemental analysis. The results of preliminary pharmacological test showed that the activities of three compounds (I 1, I8 and I10) were stronger than aminoguanidine, especially for compound I1.
Xu
Yun-gen
YG
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China. xyg64@126.com
Xing
Ai-min
AM
Hong
Min
M
Sun
Xiao-yu
XY
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D015394:Molecular Structure; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D006146:Guanidines; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine