Novel tricyclic compounds having acetylene groups at C-8a and cyano enones in rings A and C: highly potent anti-inflammatory and cytoprotective agents.
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.
Honda
Tadashi
T
Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover, New Hampshire 03755, USA. th9@dartmouth.edu
Sundararajan
Chitra
C
Yoshizawa
Hidenori
H
Su
Xiaobo
X
Honda
Yukiko
Y
Liby
Karen T
KT
Sporn
Michael B
MB
Gribble
Gordon W
GW
D000480:Alkynes / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D019610:Cytoprotection; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C116817:2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid; D000480:Alkynes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D006575:Heterocyclic Compounds, 3-Ring; D009570:Nitriles; D009569:Nitric Oxide; D009828:Oleanolic Acid; D007371:Interferon-gamma