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D‐Amino Acid Homopiperazine Amides: Discovery of A‐320436, a Potent and Selective Non‐Imidazole Histamine H 3 ‐Receptor Antagonist
Author(s) -
Curtis Michael P.,
Dwight Wesley,
Pratt John,
Cowart Marlon,
Esbenshade Timothy A.,
Krueger Kathy M.,
Fox Gerard B.,
Pan Jia Bao,
Pagano Thomas G.,
Hancock Arthur A.,
Faghih Ramin,
Bennani Youssef L.
Publication year - 2004
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200300844
Subject(s) - chemistry , imidazole , antagonist , stereochemistry , histamine , antagonism , in vivo , in vitro , chemical synthesis , carboxamide , receptor , pharmacology , biochemistry , biology , microbiology and biotechnology
Structure‐activity relationships of homopiperazine‐containing alkoxybiaryl nitriles employing various D‐amino acid moieties and their N ‐furanoyl analogues were undertaken. This led to A‐320436, a potent and selective non‐imidazole H 3 ‐receptor antagonist possessing balanced affinity for both rat and human H 3 ‐receptors. This compound was shown to demonstrate in vitro and in vivo functional antagonism and is non‐neurotoxic at doses (i.p.) up to 163 mg/kg in a general observation test.