Thrombomodulin induction in cultured human endothelial cells by 9-cis-locked retinoic acid analogues.
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.
Ikegami
Shiro
S
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan. shi-ike@pharm.teikyo-u.ac.jp
Iimori
Takamasa
T
Sudo
Minoru
M
Kitsukawa
Maroka
M
Foroumadi
Alireza
A
Yonemura
Takeshi
T
Takahashi
Hideyo
H
Kizaki
Keiichiro
K
Ishii
Hidemi
H
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*
D018180:Thrombomodulin; D000077556:Alitretinoin; D014212:Tretinoin; D010165:Palladium