Patent EA-000025-B1 (EA)
Title: Oxaindene derivatives, process for production thereof (variants), pharmaceutical composition on their base, administering and medical treatment
Inventor: SZANTAY CSABA
IPC: A61P29/00
Filed: 1996-06-26
Abstract: 1. Oxaindene derivatives of general formula (I)     wherein  R1 represents lower C1-4 alkyl, lower C1-4 alkoxy or lower C3-6 cycloalkyl, R2 represents hydrogen, lower C1-4 alkyl or lower C3-6 cycloalkyl, R3 represents hydrogen, lower C1-4 alkyl, lower C1-4 alkoxy or benzyloxy, X represents hydrogen, an aliphatic C1-4-acyl or benzoyl or naphthoyl group, optionally substituted by one or more nitro or C1-4-alkoxy group(s) or a group of the formula R<5>R<6>=N-R<7> wherein R<5>, R<6> and R<7> each represent lower C1-4 alkylene, or R<5> and R<6> together with the nitrogen atom to which they are attached form a piperidyl or morpholinyl group, A and B together form an ethylene or a vinylene group, and n is 1, 2 or 3, stereoisomers and pharmaceutically acceptable acid addition salts thereof. 2. Compounds as claimed in Claim I, wherein R<1>, R<2> and R<3> represent independently hydrogen, lower alkyl, X stands for hydrogen, A and B together represent vinylene and n is 1 or 2. 3. Compounds as claimed in Claim I, wherein R<1> stands for lower alkyl, R<2> and R<3> represent independently hydrogen, lower alkyl, X stands for hydrogen, A and B together represent ethylene and n is 1 or 3. 4. Compounds of general formula (I): cis-4,6,7-trimethyl-2,3,3a,8a-tetrahydro-1H-8-oxa-cyclopenta[a]indene-5-ol, l,2,4-trimethyl-4b,6,7,8,9,9a-hexahydro-5H-10-oxabenzo[a]azulene-3-ol and cis-4,6,7-trimethyl-3a,8a-dihydro-3H-8-oxacyclopenta[a]indene-5-ol. 5. A process for the preparation of the compounds of general formula (I) wherein X represents hydrogen and A and B together form a vinylene group, reacting a hydroquinone derivative of general formula (II),     wherein R<1>, R<2> and R<3> are as stated in Claim 1 and R<4> represents hydrogen or lower alkoxy, with a cycloalkene derivative of general formula (III),     wherein n is as stated in Claim 1, in a solvent, in the presence of the catalytic amount of a strong acid. 6. A process according to Claim 5 characterized in, that catalytic hydrogenation of final products is additionally carried out for the preparation of compounds of general formula (1) wherein A and B together form an ethytelene group. 7. A process for preparation of compounds of general formula (I) (variant),wherein X stands for hydrogen, A and B form an ethylene group characterized in, that reacting a hydroquinone derivatives of general formula (II), wherein R<1>, R<2> and R<3> as stated in Claim 1 and R<4> represent hydrogen with cycloalkadiene derivatives of general formula (IV) in the presence of the catalytic amount of a strong acid.   8. A process according to Claims 5 and 7 characterized in, that the final product is subjected to acylation and dialkylaminoalkylation. 9. A process according to Claim 5, which comprises carrying out the reaction in an aprotic olvent,preferably in an aromatic hydrocarbon. 10. A process according to Claims 5 or 9, which comprises using as strong acid p-toluenesulfonic acid, camphor-10-sulfonic acid or benzenesulfonic acid. 11. A process according to Claims 5, 9 and10, which comprises carrying out the reaction at an elevated temperature, preferably between 60 degree C and 110 degree C. 12. A process according to Claim 6 which comprises carrying out the catalytic hydrogenation in a polar solvent. 13. A process according to Claim 12 which comprises using palladium as catalyst for the hydrogenation. 14. A process according to Claims 6, 12 and 13, which comprises carrying out the reaction at room temperature. 15. A process according to Claim 7 which comprises using as strong acid p-toluenesulfonic acid, camphor-10-sulfonic acid or benzenesulfonic acid. 16. A process according to Claims 7 or 15, which comprises carrying out the reaction in an anhydrous aprotic solvent. 17. A process according to Claims 7 or 15-16, which comprises carrying out the reaction at an elevated temperature, preferably between 30 degree C and 90 degree C. 18. Pharmaceutical compositions comprising as active ingredient a compound of general formula (I) or a pharmaceutically acceptable acid addition salt thereof in admixture with suitable inert solid or liquid pharmaceutical carriers. 19. Use of the compounds of general formula (I) or pharmaceutically acceptable acid addition salts thereof for the preparation of pharmaceutical compositions suitable particularly for the treatment of diseases of allergy, diseases of the joints, asthma, diseases of the gastro-intestinal tract and skin disorders. 20. Method of antiallergic, antiarticular, antiulceric and antiasthmatic treatment, which comprises administering to a patient an effective amount of a compound of general formula (1) or a pharmaceutically acceptable acid addition salt thereof.