TY - JOUR
T1 - Design and synthesis of Rho kinase inhibitors (I)
AU - Takami, Atsuya
AU - Iwakubo, Masayuki
AU - Okada, Yuji
AU - Kawata, Takehisa
AU - Odai, Hideharu
AU - Takahashi, Nobuaki
AU - Shindo, Kazutoshi
AU - Kimura, Kaname
AU - Tagami, Yoshimichi
AU - Miyake, Mika
AU - Fukushima, Kayoko
AU - Inagaki, Masaki
AU - Amano, Mutsuki
AU - Kaibuchi, Kozo
AU - Iijima, Hiroshi
PY - 2004/5/1
Y1 - 2004/5/1
N2 - Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure-activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1H-indazole, isoquinoline, and phthalimide.
AB - Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure-activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1H-indazole, isoquinoline, and phthalimide.
UR - http://www.scopus.com/inward/record.url?scp=11144355930&partnerID=8YFLogxK
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U2 - 10.1016/j.bmc.2004.02.025
DO - 10.1016/j.bmc.2004.02.025
M3 - Article
C2 - 15080913
AN - SCOPUS:11144355930
SN - 0968-0896
VL - 12
SP - 2115
EP - 2137
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 9
ER -