4-[6-(2-Aminoethyl)naphthalen-2-yl]benzonitriles are potent histamine H₃ receptor antagonists with high CNS penetration

详细信息    查看全文

• 作者：Lawrence A. Black ; Diana L. Nersesian ; Padam Sharma ; Yi-Yin Ku ; Youssef L. Bennani ; Kennan C. Marsh ; Thomas R. Miller ; Timothy A. Esbenshade ; Arthur A. Hancock ; Marlon Cowart
• 关键词：Histamine H3 receptor antagonists ; Naphthalene ; High CNS penetration
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：1 March 2007
• 年：2007
• 卷：17
• 期：5
• 页码：1443-1446
• 全文大小：143 K

文摘

4-[6-(2-Tertiaryaminoethyl)naphthalen-2-yl]benzonitriles are conformationally constrained histamine H₃ receptor antagonists with high potency and selectivity. The analogs were designed around a naphthalene core, with the goal of enhancing lipophilicity and CNS penetration, as compared to a previously reported benzofuran series. The SAR of the tertiary amine moiety is similar to that reported for the benzofuran series, with analogs bearing a 2-methylpyrrolidine substituent possessing the greatest rat and human H₃ receptor binding affinities.