دورية
Difluoromethylene at the γ-Lactam α-Position Improves 11-Deoxy-8-aza-PGE1Series EP4Receptor Binding and Activity: 11-Deoxy-10,10-difluoro-8-aza-PGE1Analog (KMN-159) as a Potent EP4Agonist
| العنوان: | Difluoromethylene at the γ-Lactam α-Position Improves 11-Deoxy-8-aza-PGE1Series EP4Receptor Binding and Activity: 11-Deoxy-10,10-difluoro-8-aza-PGE1Analog (KMN-159) as a Potent EP4Agonist |
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| المؤلفون: | Barrett, Stephen D., Holt, Melissa C., Kramer, James B., Germain, Bradlee, Ho, Chi S., Ciske, Fred L., Kornilov, Andrei, Colombo, Joseph M., Uzieblo, Adam, O’Malley, James P., Owen, Thomas A., Stein, Adam J., Morano, Maria I. |
| المصدر: | Journal of Medicinal Chemistry; April 2019, Vol. 62 Issue: 9 p4731-4741, 11p |
| مستخلص: | A series of small-molecule full agonists of the prostaglandin E2type 4 (EP4) receptor have been generated and evaluated for binding affinity and cellular potency. KMN-80 and its gem-difluoro analog KMN-159 possess high selectivity relative to other prostanoid receptors. Difluoro substitution is positioned alpha to the lactam ring carbonyl and results in KMN-159’s fivefold increase in potency versus KMN-80. The two analogs exhibit electronic and conformational variations, including altered nitrogen hybridization and lactam ring puckering, that may drive the observed difluoro-associated increased potency within this four-compound series. |
| قاعدة البيانات: | Supplemental Index |
Find this issue from the American Chemical Society | تدمد: | 00222623 15204804 |
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| DOI: | 10.1021/acs.jmedchem.9b00336 |