title: Design and synthesis of piperazine-indole p38 alpha MAP kinase inhibitors with improved pharmacokinetic profiles.
abstract: Derivatives of the 4-fluorobenzyl dimethylpiperazine-indole class of p38alpha MAP kinase inhibitors are described. Biological evaluation of these compounds focused on maintaining activity while improving pharmacokinetic (PK) properties. Improved properties were observed for structures bearing substitutions on the benzylic methylene.
authors.affiliation: Department of Medicinal Chemistry and Biology, Scios inc, 6500 Paseo Padre Parkway, Fremont, CA 94555, United States. Xuefei827@gmail.com
authors.forename: Xuefei
authors.initials: X
authors.lastname: Tan
authors.forename: Richland W
authors.initials: RW
authors.lastname: Tester
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Luedtke
authors.forename: Sarvajit
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Babu J
authors.initials: BJ
authors.lastname: Mavunkel
authors.forename: John J
authors.initials: JJ
authors.lastname: Perumattam
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Imad
authors.initials: I
authors.lastname: Nashashibi
authors.forename: Joon
authors.initials: J
authors.lastname: Jung
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Albert
authors.initials: A
authors.lastname: Liclican
authors.forename: Ramona
authors.initials: R
authors.lastname: Almirez
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Tabora
authors.forename: Vinh
authors.initials: V
authors.lastname: Tran
authors.forename: Maureen
authors.initials: M
authors.lastname: Laney
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Levy
authors.forename: Sundeep
authors.initials: S
authors.lastname: Dugar
mesh_terms: D000818:Animals; D004285:Dogs; D015195:Drug Design; D000882:Haplorhini; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D017433:Protein Structure, Secondary; D051381:Rats
chemical_list: D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D000077489:Piperazine; D048308:Mitogen-Activated Protein Kinase 14