Identification, Synthesis, and Biological Evaluation of 6-[(6R)-2-(4-Fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one (AS1940477), a Potent p38 MAP Kinase Inhibitor

2012 ◽  
Vol 55 (17) ◽  
pp. 7772-7785 ◽  
Author(s):  
Toru Asano ◽  
Hitoshi Yamazaki ◽  
Chiyoshi Kasahara ◽  
Hirokazu Kubota ◽  
Toru Kontani ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitor ◽  
Biological Evaluation ◽  
P38 Map Kinase ◽  
Synthesis And Biological Evaluation

scholarly journals Design, Synthesis, and Biological Evaluation of Chromone-Based p38 MAP Kinase Inhibitors

2011 ◽  
Vol 54 (20) ◽  
pp. 7427-7431 ◽  
Author(s):  
Christine Dyrager ◽  
Linda Nilsson Möllers ◽  
Linda Karlsson Kjäll ◽  
John Patrick Alao ◽  
Peter Dinér ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Biological Evaluation ◽  
P38 Map Kinase ◽  
Design Synthesis ◽  
P38 Map Kinase Inhibitors ◽  
Synthesis And Biological Evaluation

Structure‐Based Design, Synthesis, and Biological Evaluation of Imidazo[4,5‐ b ]Pyridin‐2‐one‐Based p38 MAP Kinase Inhibitors: Part 2

ChemMedChem ◽  
2019 ◽  
Vol 14 (24) ◽  
pp. 2093-2101
Author(s):  
Akira Kaieda ◽  
Masashi Takahashi ◽  
Hiromi Fukuda ◽  
Rei Okamoto ◽  
Shinji Morimoto ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Biological Evaluation ◽  
P38 Map Kinase ◽  
Design Synthesis ◽  
P38 Map Kinase Inhibitors ◽  
Synthesis And Biological Evaluation

Structure‐Based Design, Synthesis, and Biological Evaluation of Imidazo[4,5‐ b ]pyridin‐2‐one‐Based p38 MAP Kinase Inhibitors: Part 1

ChemMedChem ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. 1022-1030 ◽  
Author(s):  
Akira Kaieda ◽  
Masashi Takahashi ◽  
Hiromi Fukuda ◽  
Rei Okamoto ◽  
Shinji Morimoto ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Biological Evaluation ◽  
P38 Map Kinase ◽  
Design Synthesis ◽  
P38 Map Kinase Inhibitors ◽  
Synthesis And Biological Evaluation

Structure-based design, synthesis, and biological evaluation of imidazo[1,2-b]pyridazine-based p38 MAP kinase inhibitors

2018 ◽  
Vol 26 (3) ◽  
pp. 647-660 ◽  
Author(s):  
Akira Kaieda ◽  
Masashi Takahashi ◽  
Takafumi Takai ◽  
Masayuki Goto ◽  
Takahiro Miyazaki ◽  
...  
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Biological Evaluation ◽  
P38 Map Kinase ◽  
Design Synthesis ◽  
P38 Map Kinase Inhibitors ◽  
Synthesis And Biological Evaluation

p38 MAP kinase inhibitor reverses stress-induced cardiac myocyte dysfunction

2005 ◽  
Vol 98 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Hong Kan ◽  
Dale Birkle ◽  
Abnash C. Jain ◽  
Conard Failinger ◽  
Sherry Xie ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cardiac Myocyte ◽  
Kinase Inhibitor ◽  
Ventricular Myocytes ◽  
Myocardial Dysfunction ◽  
P38 Map Kinase ◽  
Border Detection ◽  
Rat Ventricular Myocytes ◽  
Adult Rat ◽  
Fractional Shortening

Stress is gaining increasing acceptance as an independent risk factor contributing to adverse cardiovascular outcomes. Potential mechanisms responsible for the deleterious effects of stress on the development and progression of cardiovascular disease remain to be elucidated. An established animal model of stress in humans is the prenatally stressed (PS) rat. We stressed rats in their third trimester of pregnancy by daily injections of saline and moving from cage to cage. Male offspring of these stressed dams (PS) and age-matched male control offspring (control) were further subjected to restraint stress (R) at 6 and 7 wk of age. Echocardiography revealed a significant decrease in fractional shortening in PS + R vs. controls + R (45.8 ± 3.9 vs. 61.9 ± 2.4%, PS + R vs. controls + R; P < 0.01; n = 12). Isolated adult rat ventricular myocytes from PS + R also revealed diminished fractional shortening (6.7 ± 0.8 vs. 12.7 ± 1.1%, PS + R vs. controls + R; P < 0.01; n = 24) and blunted inotropic responses to isoproterenol ( P < 0.01; n = 24) determined by automated border detection. The p38 mitogen-activated protein (MAP) kinase inhibitor SB-203580 blocked p38 MAP kinase phosphorylation, reversed the depression in fractional shortening, and partially ameliorated the blunted adrenergic signaling seen in adult rat ventricular myocytes from PS + R. Phosphorylation of p38 MAP kinase in cardiac myocytes by stress may be sufficient to lead to myocardial dysfunction in animal models and possibly humans.

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