Diamine derivatives containing imidazolidinylidene propanedinitrile as a new class of histamine H(3) receptor antagonists: conformationally restricted derivatives.
Novel conformationally restricted diamine derivatives containing imidazolidinylidene propanedinitrile were synthesized and evaluated for human and rat histamine H(3) receptor (H(3)R) binding affinities. Among them, compounds 2b, 2c, 2j, 2k and 2m were found to be potent ligands for both H(3)Rs with K(i) values in the sub-nanomolar range, and showed potent H(3) receptor antagonism.
Sasho
Setsuya
S
Medicinal Chemistry Research Laboratories, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd, Sunto-gun, Shizuoka 411-8731, Japan. setsuya.sasho@kyowa-kirin.co.jp
Seishi
Takashi
T
Kawamura
Mariko
M
Tomuro
Misato
M
Hirose
Ryo
R
Toki
Shinichiro
S
Shimada
Junich
J
D000818:Animals; D003959:Diamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D018100:Receptors, Histamine H3 / Q000378:metabolism*
D003959:Diamines; D054828:Histamine H3 Antagonists; D048289:Imidazolidines; D009570:Nitriles; D018100:Receptors, Histamine H3; C539543:imidazolidinylidene propanedinitrile