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Discovery of potent, soluble and orally active TRPV1 antagonists. Structure-activity relationships of a series of isoxazoles.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Aug 01; Vol. 21 (15), pp. 4652-7. Date of Electronic Publication: 2011 Jan 26. - Publication Year :
- 2011
-
Abstract
- Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted. Substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties. Compound 21a was found to be efficacious in the rat Capsaicin Hargreaves assay following oral administration.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Amides chemistry
Amides pharmacokinetics
Amides therapeutic use
Animals
Capsaicin toxicity
Cyclohexanols pharmacokinetics
Cyclohexanols therapeutic use
Disease Models, Animal
Drug Evaluation, Preclinical
Humans
Hyperalgesia chemically induced
Hyperalgesia drug therapy
Isoxazoles pharmacokinetics
Isoxazoles therapeutic use
Microsomes, Liver metabolism
Rats
Structure-Activity Relationship
TRPV Cation Channels metabolism
Cyclohexanols chemistry
Isoxazoles chemistry
TRPV Cation Channels antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 21
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 21723725
- Full Text :
- https://doi.org/10.1016/j.bmcl.2011.01.051