title: Identification of highly potent and selective PI3Kδ inhibitors.
abstract: Selective PI3Kδ inhibitors have recently been hypothesized to be appropriate immunosuppressive agents for the treatment of immunological disorders such as rheumatoid arthritis. However, few reports have highlighted molecules that are highly selective for PI3Kδ over the other PI3K isoforms. In this letter, isoform and kinome selective PI3Kδ inhibitors are presented. The Structural Activity Relationship leading to such molecules is outlined.
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States. Electronic address: david.marcoux@bms.com.
authors.forename: David
authors.initials: D
authors.lastname: Marcoux
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Lan-Ying
authors.initials: LY
authors.lastname: Qin
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Zheming
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ruan
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Weigelt
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Gary
authors.initials: G
authors.lastname: Schieven
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: John
authors.initials: J
authors.lastname: Hynes
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Bhide
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Poss
authors.affiliation: Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Tino
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors
keywords: Autoimmune diseases; PI3Kδ; Phosphoinositide 3-kinases; Pyrrolotriazine; Rheumatoid arthritis