2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one Derivatives as Potent and Selective Histamine-3 Receptor Antagonists

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• 作者：Dahui Zhou ; Jonathan L. Gross ; Adedayo B. Adedoyin ; Suzan B. Aschmies ; Julie Brennan ; Mark Bowlby ; Li Di ; Katie Kubek ; Brian J. Platt ; Zheng Wang ; Guoming Zhang ; Nicholas Brandon ; Thomas A. Comery ; Albert J. Robichaud
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：March 8, 2012
• 年：2012
• 卷：55
• 期：5
• 页码：2452-2468
• 全文大小：576K
• 年卷期：v.55,no.5(March 8, 2012)
• ISSN：1520-4804

文摘

On the basis of the previously reported benzimidazole 1,3鈥?bipyrrolidine benzamides (1), a new class of 2-(pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives (3鈥?b>50) were synthesized and evaluated as potent H₃ receptor antagonists. In particular, compound 39 exhibited potent in vitro binding and functional activities at the H₃ receptor, good selectivities against other neurotransmitter receptors and ion channels, acceptable pharmacokinetic properties, and a favorable in vivo profile.