Patent GB-1466724-A (GB)
Title: Thiaprostaglandins process for their manufacture and pharmaceu tical preparations containing them
IPC: C07D317/30
Filed: 1974-05-14
Abstract: 1466724 9-Thiaprostaglandins CIBA-GEIGY AG 14 May 1974 [18 May 1973] 21251/74 Heading C2C The invention comprises 9-thiaprostaglandins of the Formula I wherein R is H or an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic, araliphatic or aromatic radical; A is ethylene, cis- or trans-vinylene; R 2  is H or C 1-7  alkyl; R 3  is an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical; Y is -C#C-, cis- or trans-CH=CR 1  or -CH 2 CHR 1 , wherein R 1  is H or C 1-7  alkyl; and x is 0, 1 or 2 and salts thereof when R is H and their preparation. The compounds are prepared by (1) the carbonyl reduction of compounds of the Formula III wherein R 2  is R 2  or R 3 ; R 8  is a free or esterified or etherified hydroxy group; and R 9  is a free or esterified carboxy group, CN or CONH 3  or a salt thereof when R 9  is COOH; with zinc borohydride or alkali metal borohydrides; or (2) reacting compounds of Formula III above in which R 8  is etherified hydroxy and R 9  is esterified carboxy with R 7 MgHal, and (3) hydrolysing any esterified or etherified hydroxy groups in the compounds resulting from (1) or (2) in a basic or acidic media or any resulting carbamoyl or nitrile groups in strongly basic media and, if desired, (4) carrying out any one or more of the following procedures on the compounds resulting from (1), (2) or (3): oxidizing compounds in which x is 0; esterifying or salifying any resulting acids or hydrolysing any resulting esters; hydrogenating double or triple bonds; resolving mixtures of isomers or racemates into single isomers or racemates; and/or resolving racemates into optical antipodes. The following intermediates and starting materials are also prepared: compounds of Formula III above; compounds of Formula I above in which the COOR group is replaced by a -CN group; 9-cyano-3-(2,2-diethoxyethylthio) - nonaxial; 16 - cyano - 10 - (2,2 - diethoxyethylthio) - 7 - hexadecen - 6 - one; 16 - cyano - 10 - formylmethylmercapto - 7- hexadecen-6-one bis-(ethylene acetal); ethyl 9- cyano - 2 - nonenoate; ethyl 2 - (6 - cyanohexyl) - 4 - oxo - tetrahydrothiophene - 3- carboxylate; ethyl 2-(6-cyanohexyl)-4-(2-tetrahydropyronyloxy) - tetrahydrothiophene - 3- carboxylate; 7 - [3α - hydroxymethyl - 4#- (2 - tetrahydropyranyloxy) - tetrahydro - 2#- thienyl] - heptanenitrile; 7 - (3α - hydroxymethyl - 4# - (2 - tetrahydropyranyloxy)- tetrahydro - 2# - thienyl] - heptanoic acid and the methyl ester thereof; methyl 7-[1,1- dioxo - 3α - hydroxymethyl - 4# - (2 - tetrahydropyranyloxy) - tetrahydro - 2# - thienyl]- heptanoate; methyl 7 - [1,1 - dioxo - 3α- formyl - 4# - (2 - tetrahydropyranyloxy) - tetrahydro - 2# - thienyl]heptanoate; methyl 7 - [3α - formyl - 4# - (2 - tetrahydropyranyloxy)- tetrahydro - 2# - thienyl]heptanoate; ethyl 2- diethoxymethyl - 4 - oxotetrahydrothiophene- 3 - carboxylate; ethyl 2 - diethoxymethyl - 4- hydroxytetrahydrothiophene - 3 - carboxylate; 2 - diethoxymethyl - 4 - hydroxy - 3 - hydroxymethyltetrahydrothiophene; 2 - diethoxymethyl - 4 - benzoyloxy - 3 - benzoyloxymethyltetrahydrothiophene; 4-benzoyloxy-3-benzoyloxymethyltetrahydrothiophene - 2 - carboxaldehyde; 4 - benzoyloxy - 3 - benzoyloxymethyl - 2 - hydroxymethyltetrahydrothiophene; 4 - benzoyloxy - 3 - benzoyloxymethyl- 2 - bromomethyltetrahydrothiophene; α- (4 - benzoyloxy - 3 - benzoyloxymethyltetrahydro - 2 - thienyl)acetonitrile; α - (4 - hydroxy- 3 - hydroxymethyltetrahydro - 2 - thienyl)- acetonitrile, its acetonide with 2,2-dimethoxypropane, and the dioxide of said acetonide; the acetonide of α-(4-hydroxy-3-hydroxymethyl- 1,1 - dioxotetrahydro - 2 - thienyl)acetaldehyde; the acetonide of 7-(4-hydroxy-3-hydroxymethyl - 1,1 - dioxotetrahydro - 2 - thienyl) - 5 - cisheptenoic acid; methyl 7-(4-hydroxy-3-hydroxymethyl - 1,1 - dioxotetrahydro - 2 - thienyl) - 5 - cis - heptenoate; methyl 7 - (4- hydroxy - 3 - (p - nitrobenzoyloxymethyl) - 1,1- dioxotetrahydro - 2 - thienyl] - 5 - cis - heptenoate and the 2-tetrahydropyranyl ether thereof; methyl 7 - [1,1 - dioxo - 3 - hydroxymethyl- 4 - (2 - tetrahydropyranyloxy) - tetrahydro - 2- thienyl] - 5 - cis - heptenoate; methyl 7 - [1,1- dioxo - 3 - formyl - 4 - (2 - tetrahydropyranyloxy) - tetrahydro - 2 - thienyl] - 5 - cis - heptenoate; methyl 7 - [1,1 - dioxo - 3α - (2,2- di - bromovinyl) - 4# - (2 - tetrahydropyranyloxy) - tetrahydro - 2# - thienyl]heptanoate; methyl 7 - [1,1 - dioxo - 3α - ethynyl - 4# - (2- tetrahydropyranyloxy) - tetrahydro - 2#- thienyl]heptanoate; and methyl 7-[1,1-dioxo- 3α - (3# - hydroxy - 1 - octynyl) - 4# - (2 - tetrahydropyranyloxy) - tetrahydro - 2# - thienyl]- heptanoate. Pharmaceutical compositions, suitable for oral, parenteral and rectal administration, contain the above thiaprostaglandins in conjunction or admixture with pharmaceutically suitable carriers. The compounds possess prostaglandinlike pharmacological properties.