NEW PROSTAGLANDIN ANALOGUES

摘要

1509781 Prostaglandins ONO PHARMACEUTICAL CO Ltd 28 April 1976 [30 April 1975 20 Oct 1975] 18039/75 and 43041/75 Heading C2C [Also in Division C3] The invention comprises prostaglanins of the formula wherein X is ethylene or cis-vinylene; Y is ethylene or trans-vinylene; R1 is H, methyl or ethyl; R2 and R3 each are H 2 trifluoromethyl, C 1-3 alkyl or halogen; R4 is H or C 1-12 alkyl; one A is a grouping of the formula cyclodextrin clathrates of such acids and ethers, and non-toxic salts therof when R4 is H and their preparation by reacting aldehydes of the Formula VIII wherein Z is x=O or with the appropriate 2-lithio-acetophenones, hydrolysing the resulting organo-lithium complex and optionally separating the mixture of 15α- and 15#-hydroxy epimers. 31 - Chloroacetophenone is obtaine by reacting methyllithium with 3-chlorobenzoic acid. Methyl 7 - [2# - (2 - formyl - trans - vinyl)- 3α - hydroxy - 5 - oxo - 1α - cyclopentyl] - cis - 5 heptenoate is prepared by hydrolysing methyl 7 - [2# - (2 - formyl - trans - vinyl) - 5 - oxo - 3α- (2 - tetrahydropyronyloxy) - 1α - cyclopentyl]- cis - 5 - heptenoate, obtained by esterifying the corresponding acid, which is made by oxidizing 7 - [5α - hydroxy - 2# - (3 - hydroxyprop - trans- 1 - enyl) - 3α - (2 - tetrahydropyranyloxy)- 1α-cyclopentyl]-cis-5-heptenoic acid. Pharmaceutical compositions, suitable for oral, parenteral, rectal or vaginal administration, contain the above prostaglandins, cyclodextrin clathrates thereof or non-toxic salts thereof, together with pharmaceutical carriers or coatings. The compounds possess pharmacological properties similar to those of the naturally occurring prostaglandins.