Pgf .beta.-prostaglandins and process for their preparation

C - Chemistry – Metallurgy – 07 – C

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260/235.01

C07C 405/00 (2006.01) C07D 257/04 (2006.01) C07D 309/12 (2006.01)

Patent

CA 1056376

A B S T R A C T New therapeutically useful PGF.beta. prostaglandins having the formula (I) Image (I) wherein R is a tetrazolyl or a -CH2-OH group or a -COOR"' group, wherein R " ' is an amino group or an-ORIV radical, wherein RIV is hydrogen, C1-C12 alkyl, trihaloalkyl or a pharmaceutically acceptable cation; R1 may be hydrogen or a CORb acyl, wherein Rb may be hydrogen or C1-C10 alkyl, a ? -(CH2)n1 -radical,wherein n1 may be zero or an integer number of 1 to 5 and ? is a phenyl radical which may be unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, alkoxy, trifluoromethyl, phenyl and cycoalkyl-alkyl, or Rb may be the following radical: Image wherein m is an integer number of 1 to 4, X is -CH2- or an oxygen or a sulphur atom and n1 is s above defined; one of R2 and R3 is hydroxy and the other is hydrogen or C1-C6 alkyl R4 and R5 are independently hydrogen or C1-C6 alkyl; n is zero or n integer of 1 to S; R6 is hydrogen or a Image group, wherein X and m are as above defined; A may be -CH2-CH2- or cis-CH=CH-, and wherein - when at the same time R is -COR" ', wherein R " ' is an ORIV radical, n is 3 or 4, A is cis-CH=CH-, R1 and R6 are hydrogen and one of R4 and R5 is hydrogen - the other is a 165- or 16R- C1-C6 alkyl. Also described is an im- proved process for the preparation of PGF.beta. prostaglandins and their 9-acyloxy derivatives comprising the selective esterification with s carboxylic acid of the 9.alpha.-hydroxy group of a PGF.beta. prostaglandin, in prusence of a compound of compound of formula MV Y3, wherein MV is a metalloid of the V group and Y is an alkyl, a dialkylamino or an aryl group, and of a hydrogen-acceptor agent, so as to obtain directly a PGF.beta.-9-acyloxy derivative which may be converted into the desired PGF.beta. prostaglandin by conventional methods.

234843

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