Linked Life Data

18574849

Source:http://linkedlifedata.com/resource/pubmed/id/18574849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-7-1
pubmed:abstractText
The cannabinoid-1 receptor (CB1R) has emerged as one of the most important targets for the treatment of obesity. Pioneering studies with rimonabant helped to validate animal models of food intake reduction and weight loss and made the connection to weight loss in the clinic. A novel, acyclic amide was identified from a high throughput screen (HTS) of the Merck sample collection and found to be a potent and selective CB1R inhibitor. Further optimization led to more potent compounds that were orally active in reducing food intake and weight loss in diet-induced obese (DIO) rats. However, many of these analogues exhibited a high potential for bioactivation and the formation of reactive intermediates and covalent protein binding. Identification of the products of oxidative metabolism guided medicinal chemistry efforts to minimize the formation of these unwanted products. These efforts resulted in the identification of the CB1R inverse agonist, taranabant, which is currently in Phase-III clinical studies for the treatment of obesity. This mini-review will describe some of the medicinal chemistry strategies that were followed from the original high throughput screen hit to the discovery of taranabant.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0365-6233
pubmed:author
pubmed:issnType
Print
pubmed:volume
341
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
405-11
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The discovery of taranabant, a selective cannabinoid-1 receptor inverse agonist for the treatment of obesity.
pubmed:affiliation
Merck Research Laboratories, Rahway, NJ 07065-0090, USA. william_hagmann@merck.com
pubmed:publicationType
Journal Article, Review