Design and synthesis of Rho kinase inhibitors (I)

Atsuya Takami, Masayuki Iwakubo, Yuji Okada, Takehisa Kawata, Hideharu Odai, Nobuaki Takahashi, Kazutoshi Shindo, Kaname Kimura, Yoshimichi Tagami, Mika Miyake, Kayoko Fukushima, Masaki Inagaki, Mutsuki Amano, Kozo Kaibuchi, Hiroshi Iijima

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2115-2137
Number of pages23
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number9
DOIs
Publication statusPublished - 01-05-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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