✦ LIBER ✦
Rational design of a novel peripherally-restricted, orally active CB1 cannabinoid antagonist containing a 2,3-diarylpyrrole motif
✍ Scribed by Laurent Hortala; Murielle Rinaldi-Carmona; Christian Congy; Laurent Boulu; Freddy Sadoun; Gérard Fabre; Olivier Finance; Francis Barth
- Publisher
- Elsevier Science
- Year
- 2010
- Tongue
- English
- Weight
- 681 KB
- Volume
- 20
- Category
- Article
- ISSN
- 0960-894X
No coin nor oath required. For personal study only.
✦ Synopsis
A new series of 2,3-diarylpyrroles have been prepared and evaluated as CB 1 antagonists. Modulation of the topological polar surface area allowed the identification of high affinity peripherally-restricted CB 1 antagonists. Compound 11, obtained after further optimization of the metabolic profile displayed very low brain penetration, yet was able to reverse CP55940-induced gastrointestinal transit inhibition following oral administration.