Synthesis and pharmacological activity of fluorescent histamine H2 receptor antagonists related to potentidine.
Fluorescently labeled histamine H(2) receptor antagonists were synthesized starting from N-cyano-N'-[3-(3-piperidin-1-ylmethylphenoxy)propyl]guanidines with an additional N"-omega-aminoalkyl substituent (chain lengths 2-8 methylene groups) or from 3-(3-piperidin-1-ylmethylphenoxy)propylamine. The primary amino group was derivatized with various fluorophores (fluorescein, acridine, dansyl, nitrobenzoxadiazole (NBD), indolo[2,3-a]quinolizine). On the isolated spontaneously beating guinea pig right atrium most of the fluorescent probes were only weakly active, however, the NBD-labeled substances proved to be potent histamine H(2) receptor antagonists achieving pA(2) values in the range of 7.5-8.0, comparable to the activity of famotidine.
College of Pharmaceutical Sciences, Peking University, 100083, Beijing, China.
Liantao
L
Li
Julia
J
Kracht
Shiqi
S
Peng
Günther
G
Bernhardt
Sigurd
S
Elz
Armin
A
Buschauer
D000818:Animals; D005456:Fluorescent Dyes; D006146:Guanidines / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D011437:Propylamines / Q000138:chemical synthesis / Q000494:pharmacology; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship
D005456:Fluorescent Dyes; D006146:Guanidines; D006635:Histamine H2 Antagonists; D011437:Propylamines