Linked Life Data

18006322

Source:http://linkedlifedata.com/resource/pubmed/id/18006322

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-3
pubmed:abstractText
In this study, a novel series of CB(2) receptor agonist imine derivatives, 1-6, was synthesized and evaluated for activity against the CB(2) receptor. In a previous paper we reported the synthesis and SARs of thiazole derivative 1, a potent CB(2) receptor agonist, but we had not assessed chemical modifications of the 5-membered heteroring of 1. In the present study, we therefore tried chemically modifying the 5-membered heteroring of 1 in an attempt to further improve binding affinity for the CB(2) receptor. In the course of making the structural modifications, we discovered that a novel pyrazole derivative 6b (CBS0550) had high affinity for the CB(2) receptor (IC(50)=2.9 nM, EC(50)=1.8 nM, E(max)=85%), high selectivity for CB(2) (CB(1) IC(50)/CB(2) IC(50)=1400), and good physicochemical properties (solubility in water: 5.9 mg/100mL at 25 degrees C). Oral administration of 6b to rats at a dose of 10mg/kg resulted in significant plasma concentrations, and orally administered compound 6b significantly reversed mechanical hyperalgesia in the Randall-Selitto model of inflammatory pain in rats.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1464-3391
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1111-24
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Imine derivatives as new potent and selective CB2 cannabinoid receptor agonists with an analgesic action.
pubmed:affiliation
Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, Saitama-shi, Saitama 331-9530, Japan. hiroshi.ohta@po.rd.taisho.co.jp
pubmed:publicationType
Journal Article