Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR.
We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <10nM) for Lck kinase inhibition.
Takayama
Tetsuo
T
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
Umemiya
Hiroki
H
Amada
Hideaki
H
Yabuuchi
Tetsuya
T
Shiozawa
Fumiyasu
F
Katakai
Hironori
H
Takaoka
Akiko
A
Yamaguchi
Akie
A
Endo
Mayumi
M
Sato
Masakazu
M
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
D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000255:Adenosine Triphosphate; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)