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Discovery of novel, potent, selective, and orally active human glucagon receptor antagonists containing a pyrazole core.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Jan 01; Vol. 21 (1), pp. 76-81. Date of Electronic Publication: 2010 Nov 21. - Publication Year :
- 2011
-
Abstract
- A novel class of 1,3,5-pyrazoles has been discovered as potent human glucagon receptor antagonists. Notably, compound 26 is orally bioavailable in several preclinical species and shows selectivity towards cardiac ion channels, other family B receptors such hGIP and hGLP1, and a large panel of enzymes and additional receptors. When dosed orally, compound 26 is efficacious in suppressing glucagon induced plasma glucose excursion in rhesus monkey and transgenic murine pharmacodynamic models at 1 and 10 mpk, respectively.<br /> (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Subjects :
- Administration, Oral
Animals
Blood Glucose metabolism
Dogs
Drug Evaluation, Preclinical
Humans
Macaca mulatta
Mice
Mice, Transgenic
Pyrazoles chemical synthesis
Pyrazoles pharmacokinetics
Rats
Receptors, Glucagon metabolism
Structure-Activity Relationship
Pyrazoles chemistry
Receptors, Glucagon antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 21
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 21147532
- Full Text :
- https://doi.org/10.1016/j.bmcl.2010.11.074