A long-standing collaboration with Dr. Wolff Arzneimittel has resulted in a nice paper in the Journal of Medicinal Chemistry.
This project aimed at the development of novel κ agonists restricted to the periphery.
In the discovery stage of the project, a diastereo- and enantioselective synthesis of (4aR,5S,8aS)-configured decahydroquinoxalines was developed. Fine-tuning of physicochemical and pharmacological properties was executed by a team of medicinal chemists at Mercachem.
Anita Wegert, Project Manager in Medicinal Chemistry, explains “The methanesulfonamide 2a containing the (S)-configured hydroxypyrrolidine ring was investigated in two mouse models of dermatitis. The compound was identified as a potent (Ki = 0.63 nM) and highly selective κ agonist (EC50 = 1.8 nM), selective for the periphery, with dose-dependent anti-inflammatory activity in acute and chronic skin inflammation.”
In a joint effort, three different Mercachem business units cracked the challenging synthesis (Discovery Chemistry), optimized the synthetic route (Process Research), and performed lead optimization (Medicinal Chemistry).
This is what we mean by seamless integration of chemistry services!