Discovery and process development of a novel TACE inhibitor for the topical treatment of psoriasis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Bioorganic and Medicinal Chemistry Année : 2018

Discovery and process development of a novel TACE inhibitor for the topical treatment of psoriasis

Jean-Guy Boiteau
Audrey Beillard
Yushma Bhurruth-Alcor

Résumé

Targeting the TNFα pathway is a validated approach to the treatment of psoriasis. In this pathway, TACE stands out as a druggable target and has been the focus of in-house research programs. In this article, we present the discovery of clinical candidate 26a. Starting from hits plagued with poor solubility or genotoxicity, 26a was identified through thorough multiparameter optimisation. Showing robust in vivo activity in an oxazolone-mediated inflammation model, the compound was selected for development. Following a polymorph screen, the hydrochloride salt was selected and the synthesis was efficiently developed to yield the API in 47% overall yield.

Domaines

Médicaments
Fichier non déposé

Dates et versions

hal-04554515 , version 1 (22-04-2024)

Identifiants

Citer

Jean-Guy Boiteau, Gilles Ouvry, Jean-Marie Arlabosse, Stéphanie Astri, Audrey Beillard, et al.. Discovery and process development of a novel TACE inhibitor for the topical treatment of psoriasis. Bioorganic and Medicinal Chemistry, 2018, 26 (4), pp.945-956. ⟨10.1016/j.bmc.2017.07.054⟩. ⟨hal-04554515⟩

Collections

RIIP UNIV-LILLE
8 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More