title: Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.
abstract: The design and synthesis of isoxazole 3 is described, a potent JNK inhibitor with two fold selectivity over p38. Optimization of this scaffold led to compounds 27 and 28 which showed greatly improved selectivity over p38 by maintaining the JNK3 potency of compound 3. Extensive SAR studies will be described as well as preliminary in vivo data of the two lead compounds.
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Yuanjun
authors: Y
authors: He
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Derek
authors: D
authors: Duckett
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Weimin
authors: W
authors: Chen
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Yuan Yuan
authors: YY
authors: Ling
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Michael D
authors: MD
authors: Cameron
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Li
authors: L
authors: Lin
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Claudia H
authors: CH
authors: Ruiz
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Philip V
authors: PV
authors: Lograsso
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors: Theodore M
authors: TM
authors: Kamenecka
authors: Department of Molecular Therapeutics, and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA. Electronic address: marcelk@scripps.edu.
authors: Marcel
authors: M
authors: Koenig
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D007555:Isoxazoles; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Isoxazole; JNK; Kinase; c-Jun