title: Novel and orally bioavailable inducible nitric oxide synthase inhibitors: synthesis and evaluation of optically active 4,5-dialkyl-2-iminoselenazolidine derivatives.
abstract: We have previously reported that (4R,5R)-5-ethyl-2-imino-4-methylthiazolidine (3) strongly inhibits inducible nitric oxide synthase (iNOS). In a successive search for strong and selective iNOS inhibitors, we, herein, describe the synthesis of the selenium analogue of 3 (4: ES-2133) and its related optically active compounds and examine their in vitro and in vivo inhibitory activity against iNOS. In addition, an alternative synthetic method to the selected compound 4 and its pharmacokinetic profile is also reported.
authors.affiliation: Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, Enoki-cho 33-94, Suita, Osaka 564-0053, Japan. shigeo-ueda@dainippon-pharm.co.jp
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ueda
authors.forename: Hideo
authors.initials: H
authors.lastname: Terauchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yano
authors.forename: Masashi
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Taeko
authors.initials: T
authors.lastname: Kubo
authors.forename: Hisao
authors.initials: H
authors.lastname: Minato
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Arai
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Tsuji
authors.forename: Nobuhide
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D001120:Arginine / Q000037:antagonists & inhibitors; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D007700:Kinetics; D008968:Molecular Conformation; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D012643:Selenium / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D016566:Organoselenium Compounds; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D012643:Selenium