1082954-71-9 Usage
Uses
A 987306 is an H4 receptor antagonist and has been studied as an H4 modulator towards the potential treatment of diseases.
Biological Activity
a987306,cis-4-(piperazin-1-yl)-5,6,7a,8,9,10,11,11a-octahydrobenzofuro[2,3-h]quin- azolin-2-amine[1], is a selective and potent h4 receptor antagonist [2].h4r is one of 4 known g-protein-coupled receptors (h1, h2, h3 and h4 receptors) of histamine. it is for mediating some physiological functions of histamine [3].in a cell-based ca2+-flux functional assay, a 987306 had no activation to the receptor, but blocked the h4r activation induced by endogenous histamine. a 987306 potently decreased histamine-mediated binding between rat h4-receptor-containing membranes and gtp-γ-[35s] with a kb of 6 nm [3].in sprague-dawley rats, after ip injection, a 987306 had a favorable fractional bioavailability (fip/iv =72%), a half-life of 4.7 h and a cmax of 1.73 μm at a tmax of 0.25 h after dosing. after oral dosing, a 987306 had a moderate fractional oral bioavailability (fpo/iv =26%) with a half-life of 3.7 h and a cmax of 0.30 μm at a tmax of 1.5 h after dosing. the plasma protein binding of a 987306 measured in rats was found to be 59% [3].to human h4r and rat h4r, the ki values of a 987306 are 5.8 nm and 3.4 nm, respectively. a 987306 reduced scratch responses in mice with an ed50 of 0.36 μmol/kg. a 987306 was found to be selective and bear an ic50 > 810 nm for over 100 kinases [3].
references
[1]. vanina a. medina and elena s. rivera. histamine receptors and cancer pharmacology. british journal of pharmacology, 2010, 161:755-767.[2]. m.i. strakhova, c.a. cuff, a.m. manelli, et al. in vitro and in vivo characterization of a-940894: a potent histamine h4 receptor antagonist with anti-inflammatory properties. british journal of pharmacology, 2009, 157:44-54.[3]. huaqing liu, robert j. altenbach, tracy l. carr, et al. 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. j. med. chem., 2008, 51:7094-7098.
Check Digit Verification of cas no
The CAS Registry Mumber 1082954-71-9 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,8,2,9,5 and 4 respectively; the second part has 2 digits, 7 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 1082954-71:
(9*1)+(8*0)+(7*8)+(6*2)+(5*9)+(4*5)+(3*4)+(2*7)+(1*1)=169
169 % 10 = 9
So 1082954-71-9 is a valid CAS Registry Number.
1082954-71-9Relevant articles and documents
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
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.
, p. 7094 - 7098 (2008)
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.
