title: Structure-based de novo design of non-nucleoside adenosine deaminase inhibitors.
abstract: We searched for non-nucleoside inhibitors of adenosine deaminase by rational structure-based de novo design and succeeded in the discovery of 1-(1-hydroxy-4-phenyl-2-butyl)imidazole-4-carboxamide (FR221647: K(i)=5.9 microM to human ADA) as a novel inhibitor with moderate activity and good pharmacokinetics compared with the known inhibitors pentostatin and EHNA.
authors.affiliation: Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. isao_nakanishi@po.fujisawa.co.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terasaka
authors.forename: Isao
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Eikyu
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Nobuya
authors.initials: N
authors.lastname: Nishio
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sato
authors.forename: Masako
authors.initials: M
authors.lastname: Kuno
authors.forename: Nobuo
authors.initials: N
authors.lastname: Seki
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sakane
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D007274:Injections, Intraperitoneal; D051379:Mice; D008958:Models, Molecular; D015649:Pentostatin / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D058892:Adenosine Deaminase Inhibitors; D004791:Enzyme Inhibitors; D015649:Pentostatin; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine