PROSTANOIC ACID DERIVATIVES

摘要

1494321 Prostaglandins IMPERIAL CHEMICAL INDUSTRIES Ltd 14 July 1975 [8 Aug 1974] 34995/74 Headings C2C and C2P [Also in Division C3] The invention comprises prostaglandins of the Formula I wherein R1 is H or C 1-10 alkyl, R2 is C 1-10 alkyl, R3, R4, R6 and R6 each are H or C 1-4 alkyl, and A is vinylene orα-hydroxyethylene, of which the CH 2 group is bonded to the carbon atom of the ring ketone group, and salts thereof when R1 is H and their preparation. The compounds are prepared by removing, at a pH of between 4 and 7, a hydroxy protecting group from compounds of the formula wherein B is vinylene or -CH 2 . CH(... OR7)-, where R7 is a hydroxy protecting group, and, if desired, esterifying the resulting acids. Compounds of Formula I above in which A is vinylene may also be obtained by dehydrating the corresponding compounds in which A isα-hydroxyethylene. The following intermediates are also prepared: 16,16 - ethylene - 11α,15 - bis(1 - methoxy - 1- methylethoxy) - 9 - oxo - 5 - cis, 13 - transprostadienoic acid; 16,16 - ethylene - 11α,15- bis(1 - methoxy - 1 - methylethoxy) - 9α- hydroxy - 5 - cis, 13 - trans - prostadienoic acid; methyl 3 - butyl - 1 - pyrazoline - 3- carboxylate; methyl 1 - butylcyclopropanecarboxylate, 4# - [4,4, - ethylene - 3 - oxo (or 3 - hydroxy) - 1 - trans - octenyl] - 3,3α#,4,- 5,6,6α# - hexahydro - 5α- (4 - phenylbenzoyloxy) 2H - cyclopenta[b]furan - 2 - one; 4# - [4,4- ethylene - 3 - hydroxy - 1 - trans - octenyl]- 3,3α#,4,5,6,6α# - hexahydro - 2H - cyclopenta- [b]furan - 2 - one; and, 4# - [4,4 - ethylene - 3- (1 - methoxy - 1 - methylethoxy) - 1 - transoctenyl] - 3,3α#,4,5,6,6α# - hexahydro - 5α- (1- methoxy - 1 - methylethoxy) - 2H - cyclopenta- [b]furan-2-one (and 2-ol). 16,16 - Ethylene - 11α- hydroxy - 9,15 - dioxo- 5 - cis, 13 - trans - prostadienoic acid is obtained as a by-product. Dimehyl 3,3 - ethylene - 2 - oxoheptylphosphonate is prepared by reacting dimethyl methylphosphonate with methyl 1-butylcyclopropanecarboxylate in the presence of butyllithium. Pharmaceutical compositions, suitable for oral administration, contain the above prostaglandins or salts thereof together with pharmaceutically or veterinarily acceptable carriers or diluents. The compounds inhibit the production of gastric acid in warm blooded animals.