title: Ring-fused pyrazole derivatives as potent inhibitors of lymphocyte-specific kinase (Lck): Structure, synthesis, and SAR.
abstract: We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as well as excellent cellular activity against mixed lymphocyte reaction (MLR) (IC(50)s <1nM).
authors: Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd, 403, Yoshino-Cho 1-Chome, Kita-Ku, Saitama-Shi, Saitama 331-9530, Japan. tetsuo.takayama@po.rd.taisho.co.jp
authors: Tetsuo
authors: T
authors: Takayama
authors: Hiroki
authors: H
authors: Umemiya
authors: Hideaki
authors: H
authors: Amada
authors: Tetsuya
authors: T
authors: Yabuuchi
authors: Takeshi
authors: T
authors: Koami
authors: Fumiyasu
authors: F
authors: Shiozawa
authors: Yusuke
authors: Y
authors: Oka
authors: Akiko
authors: A
authors: Takaoka
authors: Akie
authors: A
authors: Yamaguchi
authors: Mayumi
authors: M
authors: Endo
authors: Masakazu
authors: M
authors: Sato
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000255:Adenosine Triphosphate; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)