Route scouting and optimization of a potent sulfoximine-based inverse agonist of RORγt. Issue 40 (4th October 2018)

• Record Type: Journal Article
• Authors: Lafitte, Guillaume; Parnet, Veronique; Pierre, Romain; Raffin, Catherine; Vatinel, Rodolphe; Musicki, Branislav; Tomas, Loic; Bouix-Peter, Claire; Ouvry, Gilles; Daver, Sebastien; Arlabosse, Jean-Marie; Boiteau, Jean-Guy; Gerfaud, Thibaud; Harris, Craig S.
• Is Part Of: Tetrahedron. Volume 74:Issue 40(2018)
• Page Start: 5974
• Page End: 5986
• Publication Date: 2018-10-04
• Subjects: RORγt inverse agonist -- Psoriasis -- Sulfoximine -- SNAr -- Route scouting; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.08.043
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: During our research looking for novel inverse agonists of RORγt, we identified a potent sulfoximine-based modulator as one of our pre-clinical candidates for the topical treatment for psoriasis. Herein, we describe the various routes we evaluated during the lead generation and optimization phases and the final route chosen for scale-up to deliver the first 100 g of API. Graphical abstract: