title: Design and synthesis of Rho kinase inhibitors (I).
abstract: 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.
authors.affiliation: Pharmaceutical Research Laboratories, Kirin Brewery Co. Ltd, 3 Miyhara-cho, Takasaki-shi, Gunma 370-1295, Japan.
authors.forename: Atsuya
authors.initials: A
authors.lastname: Takami
authors.forename: Masayuki
authors.initials: M
authors.lastname: Iwakubo
authors.forename: Yuji
authors.initials: Y
authors.lastname: Okada
authors.forename: Takehisa
authors.initials: T
authors.lastname: Kawata
authors.forename: Hideharu
authors.initials: H
authors.lastname: Odai
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Shindo
authors.forename: Kaname
authors.initials: K
authors.lastname: Kimura
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Tagami
authors.forename: Mika
authors.initials: M
authors.lastname: Miyake
authors.forename: Kayoko
authors.initials: K
authors.lastname: Fukushima
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
authors.forename: Mutsuki
authors.initials: M
authors.lastname: Amano
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iijima
mesh_terms: D000595:Amino Acid Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization; D054460:rho-Associated Kinases
chemical_list: D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases