Total synthesis of human chymase inhibitor methyllinderone and structure--activity relationships of its derivatives.
Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of the active compound against human chymase using calculations.
Aoyama
Y
Y
Shionogi Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, 553-0002, Osaka, Japan. yasunori.aoyama@shionogi.co.jp
Konoike
T
T
Kanda
A
A
Naya
N
N
Nakajima
M
M
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053818:Chymases; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D012697:Serine Endopeptidases / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000475:Alkenes; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; C434647:methyllinderone; D012697:Serine Endopeptidases; D053818:Chymases