Synthesis of dammarane-type triterpenoids with anti-inflammatory activity in vivo.
The 17-alpha-substituted triterpene 1 [(17alpha)-23-(E)-dammara-20,23-diene-3beta,25-diol] showed promising activity in animal models of immunosuppression and inflammation. Using a mouse model for inflammatory skin diseases (oxazolone-induced allergic contact dermatitis, ACD) as the directing in vivo test system, Structure-activity-relationship studies with the aim to understand the necessary structural requirements for the biological activity of 1 were conducted. Furthermore, we anticipated to identify biologically active compounds with the 17beta configuration, which are thermodynamically more stable and much easier to synthesize. This was achieved by identifying the 17-beta substituted dammarane 5B and its analogues.
Scholz
Dieter
D
Novartis Institute for Biomedical Research, A-1230 Vienna, Austria. dieter.scholz@pharma.novartis.com
Baumann
Karl
K
Grassberger
Max
M
Wolff-Winiski
Barbara
B
Rihs
Grety
G
Walter
Hansrudolf
H
Meingassner
Josef G
JG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013552:Swine; D014315:Triterpenes / Q000138:chemical synthesis / Q000494:pharmacology*; D000097669:Dammaranes
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D014315:Triterpenes; D000097669:Dammaranes