摘要:
The invention relates to antiinflammatory compounds of the formula (I), ##STR1## wherein A stands for hydrogen, hydroxyl or trifluoroacetoxy group;X stands for hydrogen or halogen with the proviso that if A is hydrogen, then X also means hydrogen;R stands for hydrogen, benzoyl or C.sub.1-8 alkanoyl group; and represents a single or double bond between two adjacent carbon atoms,as well as pharmaceutical compositions containing these compounds and a process for their preparation.
摘要:
The invention relates to antiinflammatory compounds of the formula (I), ##STR1## wherein A stands for hydrogen or hydroxyl group;X stands for hydrogen or halogen with the proviso that if A is hydrogen, then X also means hydrogen;R stands for hydrogen, benzoyl or C.sub.1-8 alkanoyl group;R.sup.1 and R.sup.2, which are the same or different, stand for hydrogen or a C.sub.1-4 alkyl group; or one of R.sup.1 and R.sup.2 is hydrogen and the other is phenyl group; or R.sup.1 and R.sup.2 together form a C.sub.4-5 alkylene group;means a single or double bond between two adjacent carbon atoms,as well as pharmaceutical compositions containing these compounds and a process for their preparation.
摘要:
The present invention relates to a new industrial process for the synthesis of solvate-free 17α-acetoxy-11β-[4-(N,N-dimethyl-amino)-phenyl]-19-norpregna-4,9-diene-3,20-dione [CDB-2914] of formula (I) which is a strong antiprogestogene and antiglucocorticoid agent. The invention also relates to compounds of formula (VII) and (VIII) used as intermediates in the process.The process according to the invention is the following:i) 3-(ethylene-dioxy)-estra-5(10),9(11)-diene-17-one of formula (X) is reacted with potassium acetilyde formed in situ in dry tetrahydrofuran by known method,ii) the obtained 3-(ethylene-dioxy)-17α-ethynyl-17β-hydroxy-estra-5(10),9(11)-diene of formula (IX) is reacted with phenylsulfenyl chloride in dichloromethane in the presence of triethylamine and acetic acid,iii) the obtained isomeric mixture of 3-(ethylene-dioxy)-21-(phenyl-sulfinyl)-19-norpregna-5(10),9(11),17(20),20-tetraene of formula (VIII) is reacted first with sodium methoxide in methanol, then with trimethyl phosphite,iv) the obtained 3-(ethylene-dioxy)-17α-hydroxy-20-methoxy-19-norpregna-5(10),9(11),20-triene of formula (VII) is reacted with hydrogen chloride in methanol, thenv) the obtained 3-(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11)-diene-20-one of formula (VI) is reacted with ethylene glycol in dichloromethane in the presence of trimethyl orthoformate and p-toluenesulfonic acid by known method,vi) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-19-norpregna-5(10),9(11)-diene of formula (V) is reacted with hydrogen peroxide in a mixture of pyridine and dichloromethane in the presence of hexachloroacetone by known method,vii) the obtained 3,3,20,20-bis(ethylene-dioxy)-17α-hydroxy-5,10-epoxy-19-norpregn-9(11)-ene of formula (IV), containing approximately a 1:1 mixture of 5α,10α- and 5β,10β-epoxides, is isolated from the solution and reacted with a Grignard reagent obtained from 4-bromo-N,N-dimethyl-aniline in tetrahydrofuran in the presence of copper(I) chloride catalyst without separation of the isomers by known method,viii) the obtained 3,3,20,20-bis(ethylene-dioxy)-5α,17α-dihydroxy-11β-[4-(N,N-dimethylamino)-phenyl]-19-norpregn-9(11)-ene of formula (III) is reacted with potassium hydrogensulfate in water by known method,ix) the obtained 11β-[4-(N,N-dimethylamino)-phenyl]-17α-hydroxy-19-norpregn-4,9-diene-3,20-dione of formula (II) is acetylated with acetic anhydride in the presence of perchloric acid by known method, finallyx) the solvate-free compound of formula (I) is liberated from the obtained solvate containing compound of formula (I) in a 1:1 mixture of ethanol and water at 70° C.