Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III

Yongchun Shen; Roch Boivin; Naoki Yoneda; Hong Du; Shawn Schiller; Tomohiro Matsushima; Masaki Goto; Hiroshi Shirota; Fabian Gusovsky; Charles Lemelin; Yimin Jiang; Zhiyi Zhang; Robert Pelletier; Megumi Ikemori-Kawada; Yoshiyuki Kawakami; Atsushi Inoue; Matthew Schnaderbeck; Yuan Wang

doi:10.1016/j.bmcl.2010.03.087

Discovery of anti-inflammatory clinical candidate E6201, inspired from resorcylic lactone LL-Z1640-2, III

Bioorg Med Chem Lett. 2010 May 15;20(10):3155-7. doi: 10.1016/j.bmcl.2010.03.087. Epub 2010 Mar 30.

Authors

Yongchun Shen¹, Roch Boivin, Naoki Yoneda, Hong Du, Shawn Schiller, Tomohiro Matsushima, Masaki Goto, Hiroshi Shirota, Fabian Gusovsky, Charles Lemelin, Yimin Jiang, Zhiyi Zhang, Robert Pelletier, Megumi Ikemori-Kawada, Yoshiyuki Kawakami, Atsushi Inoue, Matthew Schnaderbeck, Yuan Wang

Affiliation

¹ Eisai Inc., Andover, MA 01810, USA.

PMID: 20399648
DOI: 10.1016/j.bmcl.2010.03.087

Abstract

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.

MeSH terms

Administration, Oral
Animals
Anti-Inflammatory Agents / chemical synthesis
Anti-Inflammatory Agents / chemistry*
Anti-Inflammatory Agents / pharmacokinetics
Drug Discovery
Lactones / chemical synthesis
Lactones / chemistry*
Lactones / pharmacokinetics
Mice
Structure-Activity Relationship

Substances

14-(ethylamino)-8,9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
Anti-Inflammatory Agents
LL Z1640-2
Lactones