Discovery of MDV6058 (PF-06952229), a selective and potent TGFβR1 inhibitor: Design, synthesis and optimization

Autor:	Brahmam Pujala, Sreekanth A. Ramachandran, Mukesh Sonawane, Maruti M. Kamble, Dayanand Panpatil, Swati Adhikari, Sanjeev Soni, Venkata Subbareddy, Bharat U. Shinde, Anjan K. Nayak, Chandni Bansal, Ashu Gupta, Kakoli Mukherjee, Anil K. Agarwal, Javier Guerrero, Francisco J. Herrera, Sebastian Bernales, Mausumee Guha, Sarvajit Chakravarty, Son M. Pham, Roopa Rai
Rok vydání:	2022
Předmět:	Mice Organic Chemistry Clinical Biochemistry Drug Discovery Solvents Pharmaceutical Science Molecular Medicine Animals Molecular Biology Biochemistry Receptors Transforming Growth Factor beta
Zdroj:	Bioorganicmedicinal chemistry letters. 75
ISSN:	1464-3405
Popis:	Compound 1 is a potent TGF-β receptor type-1 (TGFβR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::284f050e012e992686c32f90ce8a56e0 https://pubmed.ncbi.nlm.nih.gov/36089110 Zobrazit plný text záznamu Full Text from ScienceDirect