Identification and synthesis of 2,7-diamino-thiazolo[5,4-d]pyrimidine derivatives as TRPV1 antagonists
| Autor: | Matthew L. Peterson, Bryan James Branstetter, Lin Luo, Alec D. Lebsack, Michael P. Maher, Sandra R. Chaplan, Michele C. Rizzolio, Anindya Bhattacharya, J. Guy Breitenbucher, Nadia Nasser, Hong Ao, Wei Xiao, Michael D. Hack, Mena Kansagara, Brian Scott, Alan D. Wickenden, Raymond Rynberg |
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| Rok vydání: | 2009 |
| Předmět: |
Pyrimidine
Stereochemistry Clinical Biochemistry Treatment outcome TRPV Cation Channels TRPV1 Administration Oral Pharmaceutical Science Thermal Hyperalgesia Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery medicine Animals Structure–activity relationship Molecular Biology Organic Chemistry Rats Thiazoles Pyrimidines Treatment Outcome chemistry Hyperalgesia Molecular Medicine medicine.symptom |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 19:40-46 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2008.11.024 |
| Popis: | We have identified and synthesized a series of 2,7-diamino-thiazolo[5,4-d]pyrimidines as TRPV1 antagonists. An exploration of the structure-activity relationships at the 2-, 5-, and 7-positions of the thiazolo[5,4-d]pyrimidine led to the identification of several potent TRPV1 antagonists, including 3, 29, 51, and 57. Compound 3 was orally bioavailable and afforded a significant reversal of carrageenan-induced thermal hyperalgesia with an ED(50)=0.5mg/kg in rats. |
| Databáze: | OpenAIRE |
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