- 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 carrageenan-induced hyperalgesia
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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 H 4, Ki = 3.4 nM, human H4 Ki = 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 H 4-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.
- Liu, Huaqing,Altenbach, Robert J.,Carr, Tracy L.,Chandran, Prasant,Hsieh, Gin C.,Lewis, La Geisha R.,Manelli, Arlene M.,Milicic, Ivan,Marsh, Kennan C.,Miller, Thomas R.,Strakhova, Marina I.,Vortherms, Timothy A.,Wakefield, Brian D.,Wetter, Jill M.,Witte, David G.,Honore, Prisca,Esbenshade, Timothy A.,Brioni, Jorge D.,Cowart, Marlon D.
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- SUBSTITUTED PYRIMIDINE DERIVATIVES
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The present application describes substituted pyrimidine compounds of formula (I) wherein X, A1, R1, R2, R3, R4, R5, R6, R7, R8, R9, p, q, r, v,
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(2009/10/31)
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