title: Thrombomodulin induction in cultured human endothelial cells by 9-cis-locked retinoic acid analogues.
abstract: 9-cis-Retinoic acid (RA) analogues devised to lock the 9-cis double bond by ring formation were synthesized using two stereoselective carbon-carbon bond formation reactions as key steps. The palladium-mediated Suzuki reaction was adopted to construct a 7E-double bond (RA numbering) and the Horner-Emmons olefination was employed for stereoselective 11E-double bond (RA numbering) formation. The synthesized 9-cis-RA analogues that are locked by five-membered ring systems (cyclopentene, dihydrofuran, and dihydrothiophene) were shown to have comparable thrombomodulin induction activities to that of 9-cis RA. Conformational analysis of these compounds showed their similarity to 9-cis RA in the spatial orientation of the side chain and the terminal carboxy group.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. shi-ike@pharm.teikyo-u.ac.jp
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegami
authors.forename: Takamasa
authors.initials: T
authors.lastname: Iimori
authors.forename: Minoru
authors.initials: M
authors.lastname: Sudo
authors.forename: Maroka
authors.initials: M
authors.lastname: Kitsukawa
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yonemura
authors.forename: Hideyo
authors.initials: H
authors.lastname: Takahashi
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kizaki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000077556:Alitretinoin; D002384:Catalysis; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D018180:Thrombomodulin / Q000096:biosynthesis*; D014212:Tretinoin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018180:Thrombomodulin; D000077556:Alitretinoin; D014212:Tretinoin; D010165:Palladium