Substituted aryl pyrimidines as potent and soluble TRPV1 antagonists
| Autor: | Mqhele Ncube, Lillian Liao, Rami Tamir, Yunxin Bo, Narender R. Gavva, James J. S. Treanor, Partha P. Chakrabarti, Markian Stec, Nuria A. Tamayo, Mark H. Norman |
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| Rok vydání: | 2008 |
| Předmět: |
Stereochemistry
Clinical Biochemistry TRPV Cation Channels Pharmaceutical Science Biochemistry Chemical synthesis Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Animals Combinatorial Chemistry Techniques Potency Structure–activity relationship Benzothiazoles Solubility Molecular Biology Molecular Structure Bicyclic molecule Aryl Organic Chemistry Antagonist Rats Bioavailability Pyrimidines chemistry Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 18:5118-5122 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2008.07.112 |
| Popis: | Clinical candidate AMG 517 (1) is a potent antagonist toward multiple modes of activation of TRPV1; however, it suffers from poor solubility. Analogs with various substituents at the R region of 3 were prepared to improve the solubility while maintaining the potent TRPV1 activity of 1. Compounds were identified that maintained potency, had good pharmacokinetic properties, and improved solubility relative to 1. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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