New boswellic acid derivatives are microsomal prostaglandin E-1 synthesis inhibitors, useful to treat e.g. rheumatoid arthritis, inflammatory bowel disease, asthma, feverish and painful conditions, cancers, emphysema and multiple sclerosis

摘要

Boswellic acid derivatives (I) are new. Boswellic acid derivatives of formula (I) are new. R 1>polar or anionic substituents, preferably OH or hydroxyalkyl, carboxyalkyl, hydroxyaryl, carboxyaryl, hydroxyheteroaryl, carboxyheteroaryl, hydroxyalkylaryl, carboxyalkylaryl, hydroxyalkylheteroaryl, carboxyalkylheteroaryl (which is attached over N, O or C to the residue molecule, where the hydroxyaryl, carboxyaryl, hydroxyheteroaryl, carboxyheteroaryl, hydroxyalkylaryl, carboxyalkylaryl, hydroxyalkylheteroaryl or carboxyalkylheteroaryl is further condensed with a ring system, and one or more H atoms are substituted by one or more halo, O, N, S, OH, NH 2, NO 2, SH, (1-10C)alkyl, (2-10C)alkenyl, (2-10C)alkynyl, OCF 3, (1-10C)alkoxy, (1-10C)alkylamine, (1-10C)alkylthio, (1-10C)alkylsilyl, (3-10)cycloalkyl, (3-10C)cycloalkenyl, (3-10C)cycloheteroalkyl, (3-10C)cycloheteroalkenyl, COOH or its corresponding acid addition salt), or phosphate or sulfate (which is connected with optionally substituted aryl, heteroaryl, alkylaryl or alkylheteroaryl); R1a : H or R 1>; R 2>2H, H, OH or O; and R 3>a carboxyl group, carboxylic acid salt with a counterion, (1-5C)carboxylic acid ester or (1-5C)carboxylic amide. [Image] ACTIVITY : Antiarthritic; Antirheumatic; Antiinflammatory; Gastrointestinal-Gen.; Antiasthmatic; Antipyretic; Cytostatic; Respiratory-Gen.; Vasotropic; Neuroprotective. MECHANISM OF ACTION : Microsomal prostaglandin E-1 synthesis inhibitor; Prostaglandin-E2 synthesis inhibitor; Cathepsin G inhibitor. The ability of (I) to inhibit microsomal prostaglandin E-1 synthesis inhibitor was tested in A549 cells. The results showed that 3-O-oxaloyl beta boswellic acid exhibited an IC 50value of approximately 0.03-20 mu M.