Discovery of 1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-ones based novel, potent and PI3Kδ selective inhibitors

Autor:	Krishnarup Ghoshdastidar, Jeevan Kumar, Jogeswar Mahapatra, Ranjit C. Desai, Dipam Patel, Debdutta Bandyopadhyay, S. Sachchidanand, Purvi Vyas, Rajesh Bahekar, Radhika Funde, Abhijit Chatterjee, Poonam Giri, Shubhangi S. Soman, Bhushan N. Dave, Rajendra Chopade
Rok vydání:	2019
Předmět:	Gene isoform Dose-Response Relationship Drug Molecular Structure Class I Phosphatidylinositol 3-Kinases 010405 organic chemistry Chemistry Organic Chemistry Clinical Biochemistry Pharmaceutical Science Quinolones Pharmacology medicine.disease 01 natural sciences Biochemistry 0104 chemical sciences Structure-Activity Relationship 010404 medicinal & biomolecular chemistry Rheumatoid arthritis Drug Discovery medicine Humans Molecular Medicine Effective treatment Molecular Biology Phosphoinositide-3 Kinase Inhibitors
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 29:1313-1319
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2019.04.007
Popis:	PI3Kδ is implicated in various inflammatory and autoimmune diseases. For the effective treatment of chronic immunological disorders such as rheumatoid arthritis, it is essential to develop isoform selective PI3Kδ inhibitors. Structure guided optimization of an imidazo-quinolinones based pan-PI3K/m-TOR inhibitor (Dactolisib) led to the discovery of a potent and orally bioavailable PI3Kδ isoform selective inhibitor (10h), with an improved efficacy in the animal models.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de12126b0618081b11549b208238c51f https://doi.org/10.1016/j.bmcl.2019.04.007 Zobrazit plný text záznamu Full Text from ScienceDirect