Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III.
Inspired by natural product, LL-Z1640-2, clinical candidate, E6201 (22) was discovered in a medicinal chemistry effort through total synthesis. The modification on C14-position to N-alkyl substitution showed to be potent in vitro and orally active in vivo in anti-inflammatory assays.
Shen
Yongchun
Y
Eisai Inc., Andover, MA 01810, USA.
Boivin
Roch
R
Yoneda
Naoki
N
Du
Hong
H
Schiller
Shawn
S
Matsushima
Tomohiro
T
Goto
Masaki
M
Shirota
Hiroshi
H
Gusovsky
Fabian
F
Lemelin
Charles
C
Jiang
Yimin
Y
Zhang
Zhiyi
Z
Pelletier
Robert
R
Ikemori-Kawada
Megumi
M
Kawakami
Yoshiyuki
Y
Inoue
Atsushi
A
Schnaderbeck
Matthew
M
Wang
Yuan
Y
D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D055808:Drug Discovery; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D013329:Structure-Activity Relationship
C545120:14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione; D000893:Anti-Inflammatory Agents; C118715:LL Z1640-2; D007783:Lactones