Synthesis and biological activity of N-(aminoiminomethyl)-1H-indole carboxamide derivatives as Na+/H+ exchanger inhibitors.
A series of N-(aminoiminomethyl)-1H-indole carboxamide derivatives were synthesized and their inhibitory potencies against the Na+/H+ exchanger were measured. Variation of the carbonylguanidine group at the 2- to 7-position of the indole ring system showed that a substitution at the 2-position improved the Na+/H+ exchanger inhibitory activity the most in vitro. This led to the synthesis and evaluation of an extensive series of N-(aminoiminomethyl)-1H-indole-2-carboxamide derivatives. Derivatives having an alkyl or substituted alkyl group at the 1-position of the indole ring system showed higher levels of in vitro activities. N-(aminoiminomethyl)- 1-(2-phenylethyl)-1H-indole-2-carboxamide (49) had the strongest activity.
Kitano
M
M
Research Center, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Kojima
A
A
Nakano
K
K
Miyagishi
A
A
Noguchi
T
T
Ohashi
N
N
D000818:Animals; D002478:Cells, Cultured; D006146:Guanidines / Q000737:chemistry* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013055:Spectrophotometry, Infrared
D006146:Guanidines; D007211:Indoles; C402800:N-(aminoiminomethyl)-1-(2-phenylethyl)-1H-indole-2-carboxamide; D017923:Sodium-Hydrogen Exchangers