cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine (A-987306), A New Histamine H4R Antagonist that Blocks Pain Responses against Carrageen

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• 作者：Huaqing Liu ; Robert J. Altenbach ; Tracy L. Carr ; Prasant Chandran ; Gin C. Hsieh ; La Geisha R. Lewis ; Arlene M. Manelli ; Ivan Milicic ; Kennan C. Marsh ; Thomas R. Miller ; Marina I. Strakhova ; Timothy A.
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：November 27, 2008
• 年：2008
• 卷：51
• 期：22
• 页码：7094-7098
• 全文大小：140K
• 年卷期：v.51,no.22(November 27, 2008)
• ISSN：1520-4804

文摘

cis-4-(Piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quinazolin-2-amine, 4 (A-987306) is a new histamine H₄ antagonist. The compound is potent in H₄ receptor binding assays (rat H₄, K_i = 3.4 nM, human H₄ K_i = 5.8 nM) and demonstrated potent functional antagonism in vitro at human, rat, and mouse H₄ receptors in cell-based FLIPR assays. Compound 4 also demonstrated H₄ antagonism in vivo in mice, blocking H₄-agonist induced scratch responses, and showed anti-inflammatory activity in mice in a peritonitis model. Most interesting was the high potency and efficacy of this compound in blocking pain responses, where it showed an ED₅₀ of 42 μmol/kg (ip) in a rat post-carrageenan thermal hyperalgesia model of inflammatory pain.