title: 7-Phenyl-pyrido[2,3-d]pyrimidine-2,4-diamines: novel and highly selective protein tyrosine phosphatase 1B inhibitors.
abstract: High throughput screening of the Roche compound collection led to the identification of diaminopyrroloquinazoline series as a novel class of PTP1B inhibitors. Structural modification of diaminopyrroloquinazoline series resulted in pyrido[2,3-d]pyrimidine-2,4-diamine series which was further optimized to give compounds 5 and 24 as potent, selective (except T-cell phosphatase) PTP1B inhibitors with good mouse PK properties.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA. adriancheungdr@gmail.com
authors.forename: Adrian Wai-Hing
authors.initials: AW
authors.lastname: Cheung
authors.forename: Bruce
authors.initials: B
authors.lastname: Banner
authors.forename: Jolly
authors.initials: J
authors.lastname: Bose
authors.forename: Kyungjin
authors.initials: K
authors.lastname: Kim
authors.forename: Shiming
authors.initials: S
authors.lastname: Li
authors.forename: Nicholas
authors.initials: N
authors.lastname: Marcopulos
authors.forename: Lucja
authors.initials: L
authors.lastname: Orzechowski
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sergi
authors.forename: Kshitij C
authors.initials: KC
authors.lastname: Thakkar
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Wang
authors.forename: Weiya
authors.initials: W
authors.lastname: Yun
authors.forename: Catherine
authors.initials: C
authors.lastname: Zwingelstein
authors.forename: Steven
authors.initials: S
authors.lastname: Berthel
authors.forename: Andrée R
authors.initials: AR
authors.lastname: Olivier
mesh_terms: D000818:Animals; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C581074:7-phenyl-pyrido(2,3-d)pyrimidine-2,4-diamine; D003959:Diamines; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1