In vitro Optimization of Structure Activity Relationships of Analogues of A‐331440 Combining Radioligand Receptor Binding Assays and Micronucleus Assays of Potential Antiobesity Histamine H3 Receptor Antagonists

• Published in: Basic & clinical pharmacology & toxicology Vol. 95; no. 3; pp. 144 - 152
• Main Authors: Hancock, Arthur A., Diehl, Marilyn S., Faghih, Ramin, Bush, Eugene N., Krueger, Kathleen M., Krishna, Gopala, Miller, Thomas R., Wilcox, Nguyen, Phong, Pratt, John K., Cowart, Marlon D., Esbenshade, Timothy A., Jacobson, Peer B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.09.2004; Blackwell
• Subjects: Animals; Anti-Obesity Agents - pharmacology; Biological and medical sciences; Biphenyl Compounds - pharmacology; Cell Line; Cricetinae; Cricetulus; Disease Models, Animal; Drug Design; Histamine Antagonists - chemical synthesis; Histamine Antagonists - pharmacology; Medical sciences; Mice; Mice, Inbred C57BL; Micronucleus Tests; Molecular Structure; Nitriles - pharmacology; Pharmacology. Drug treatments; Pyrrolidines - pharmacology; Radioligand Assay; Receptors, Histamine H3 - metabolism; Structure-Activity Relationship; Weight Loss - drug effects; H3 histamine receptor; Antagonist; In vitro; Biological receptor

: A‐331440 {4′‐[3‐(3(R)‐(dimethylamino)‐pyrrolidin‐1‐yl)‐propoxy]‐biphenyl‐4‐carbonitrile}, a potent and selective antagonist of histamine H3 receptors, yielded positive results in an in vitro micronucleus assay, predictive of genotoxicity in vivo. Because this compound has highly favourable propert...