Novel tricyclic compounds having acetylene groups at C-8a and cyano enones in rings A and C: highly potent anti-inflammatory and cytoprotective agents

  • J Med Chem. 2007 Apr 19;50(8):1731-4. doi: 10.1021/jm070141c.
Tadashi Honda  1 ,  Chitra Sundararajan ,  Hidenori Yoshizawa ,  Xiaobo Su ,  Yukiko Honda ,  Karen T Liby ,  Michael B Sporn ,  Gordon W Gribble
Affiliations
  • 1. Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, New Hampshire 03755, USA. [email protected]
PMID: 17367124 DOI: 10.1021/jm070141c
Abstract

Novel C-8a functionalized tricyclic compounds having cyano enones in rings A and C have been synthesized and biologically evaluated. Among them, compounds with acetylene groups at C-8a show extremely high potency in in vitro and in vivo bioassays for anti-inflammatory and cytoprotective activities. Both in vitro and in vivo potencies are markedly higher than those of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which is being evaluated as an Anticancer drug in phase I clinical trials.