AI Article Synopsis
- - A new series of pyridone-based drugs targeting the EP3 receptor was developed to improve their physical properties and ability to be taken orally by animals.
- - The promising compounds identified, specifically 3h, 3l, and 4d, showed decent performance in lab tests and moderate to good resistance to metabolism.
- - These compounds demonstrated favorable characteristics in rodents, including low clearance rates, high exposure when taken orally, and acceptable half-lives, indicating their potential for further development.
Article Abstract
A novel series of pyridone-based EP3 receptor antagonists was optimized for good physical properties and oral bioavailability in rodents. The lead compounds 3h, 3l and 4d displayed good in vitro profiles, moderate to good metabolic stability and good rodent PK profiles with low clearance, high oral exposure and acceptable half-life.
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| http://dx.doi.org/10.1016/j.bmcl.2021.128172 | DOI Listing |
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Erratum to "Optimization of physicochemical properties of pyridone-based EP3 receptor antagonists" [Bioorg. Med. Chem. Lett. 47 (2021) 128172].
Bioorg Med Chem Lett
September 2021
Discovery Sciences, Discovery Chemistry, Janssen Research & Development, LLC, 1400 McKean Road, Box 776, Spring House, PA 19477, United States.
Optimization of physicochemical properties of pyridone-based EP3 receptor antagonists.
Bioorg Med Chem Lett
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Discovery Sciences, Discovery Chemistry, Janssen Research & Development, LLC, 1400 McKean Road, Box 776, Spring House, PA 19477, United States.
Article Synopsis
- - A new series of pyridone-based drugs targeting the EP3 receptor was developed to improve their physical properties and ability to be taken orally by animals.
- - The promising compounds identified, specifically 3h, 3l, and 4d, showed decent performance in lab tests and moderate to good resistance to metabolism.
- - These compounds demonstrated favorable characteristics in rodents, including low clearance rates, high exposure when taken orally, and acceptable half-lives, indicating their potential for further development.
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Discovery Chemistry, Cardiovascular and Metabolic Research, Janssen Research & Development, LLC, 1400 McKean Roads, Box 776, Spring House, Pennsylvania 19477, United States.
A novel series of pyridones were discovered as potent EP3 antagonists. Optimization guided by EP3 binding and functional assays as well as by eADME and PK profiling led to multiple compounds with good physical properties, excellent oral bioavailability, and a clean in vitro safety profile. Compound was identified as a lead compound as evidenced by the reversal of sulprostone-induced suppression of glucose-stimulated insulin secretion in INS 1E β-cells in vitro and in a rat ivGTT model in vivo.
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