Structure-activity studies of a novel series of isoxazole-3-carboxamide derivatives as TRPV1 antagonists

Autor:	Michael Ohlmeyer, Yajing Rong, Katy Everett, Robert Swanson, Nasrin Ansari, Duncan McArthur, Kenneth S. Cameron, Quynhchi Pham, Irina Neagu, Heather Tracey, Darren Edwards, John Maclean, Maureen Dempster, Thomas R. Clarkson, Hazel McLuskey, Koc-Kan Ho, Helen Feilden, Paul Ratcliffe, David A. Dunn, Andrew Laird Roughton, S.A. Neale, Steve Kultgen, Glenn Walker, Littlewood Peter Thomas Albert, Melanie Sammons, Ronald Palin, Lynn Abernethy, Anna-Marie Easson, Deborah McGregor, Lesley-Anne Nisbet
Rok vydání:	2010
Předmět:	Stereochemistry medicine.drug_class Clinical Biochemistry TRPV1 Pharmaceutical Science Mechanism based TRPV Cation Channels Carboxamide Biochemistry chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Structure–activity relationship Potency Animals Isoxazole Solubility Rats Wistar Molecular Biology Antihypertensive Agents Organic Chemistry Hyperthermia Induced Isoxazoles Cyclohexanols Amides Rats chemistry Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 21(3)
ISSN:	1464-3405
Popis:	Optimisation of a screening hit incorporating both TRPV1 activity and solubility was conducted. Substitution of the isoxazole-3-carboxamide with the bespoke 1S, 3R-3-aminocyclohexanol motif afforded the requisite balance of potency and solubility. Compounds 32 and 40 were found to have antihyperalgesic effects in the rat CFA Hg assay and induce a mechanism based hyperthermia.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f76a2109a2b4a6f8968b66029d3564f8 https://pubmed.ncbi.nlm.nih.gov/21236666 Zobrazit plný text záznamu Full Text from ScienceDirect