Patent GB-1431100-A (GB)
Title: 11,12-secoprostaglandins
IPC: C07C401/00
Filed: 1973-10-22
Abstract: 1431100 11,12-Secoprostaglandins MERCK & CO Inc 22 Oct 1973 [30 Oct 1972 23 Aug 1973] 49040/73 Headings C2C and C2P The invention comprises 11,12-secoprostaglandins of the Formula I in which R is -COOY, CONHNH 2  or where Y is H, C 1-10  alkyl or a pharmaceutically acceptable cation and each of R<SP>6</SP> and R<SP>7</SP> is H, C 1-4  alkyl or C 4-7  dialkylaminoalkyl; A is ethylene trimethylene, α-methylethylene, #- methylethylene, α,α-dimethylene, #,#-dimethylethylene or oxymethylene; R<SP>1</SP> is formyl, acetyl, propionyl or acryloyl and R<SP>3</SP> is H or C 1-6  alkanoyl, or R<SP>1</SP> is 3-hydroxypropionyl, glycoloyl, hydroxymethyl, 1 - hydroxyethyl, 1,2 - dihydroxyethyl, 1,3 - dihydroxypropyl or 1- hydroxy-1-methylethyl and R<SP>3</SP> is H; Z is methylene, ethylene, trimethylene, tetramethylene, vinylene or ethynylene; R<SP>2</SP> is H or (unless Z is vinylene) a methyl radical; each R<SP>4</SP> is independently H or methyl; and R<SP>5</SP> is H, C 1-4  alkyl or CH 2 CF 3 , or (unless Z is vinyl or ethynylene) a vinyl radical, or (unless Z is vinylene) R<SP>5</SP> and R<SP>2</SP> are joined together to form, with the intervening carbon atoms, a C 5-9  carbocyclic ring, and their preparation via actoacetic acid or malonic acid syntheses or Wittig reactions. The following intermediates are also prepared; compounds of the formulµ where R<SP>10</SP> and R<SP>11</SP> are C 1-5  alkyl where X is halogen and Z<SP>1</SP> is (CH 2 ) n  where n is 1 to 4, where R<SP>12</SP> is H, C 1-4  alkyl or CH 2 CF 3 ; where R<SP>52</SP> is H, C 1-4  alkyl or CH 2 CF 3  or R<SP>52</SP> and R<SP>3</SP> are joined together to form, with the intervening carbon atoms a C 5-9  carbocyclic ring; 1 - nonen - 4 - ol, 4 - acetoxy - 1 - nonene, 2 - methyl - 2 - hydroxy - 3 - (6 - carboxyhexyl) - 6 - hexyltetrahydropyran; where X<SP>1</SP> is Cl or OH; dimethyl 3-oxosebacoate, 1-chloro 3 -octanol; 3-chloromethoxy-1-chlorooctane; 3-benzyloxy-1-chlorooctane; methyl- 8 - oxo - 9 - methoxycarbonyl - 12 - benzyloxyheptadecanoate; 8-oxo-12-benzyloxyheptadecanoic acid; 3-chloromethoxy-1-bromopropane; 3-benzyloxy-1-bromopropane; 8-(3- benzyloxypropylidenyl) - 12 - benzyloxyheptadecanoic acid; 8-(4-benzyloxynonyl)-8,9-epoxy- 11-benzyloxyundecanoic acid; 8-(3-benzyloxypropionyl) - 12 - benzyloxyheptadecanoic acid; 5-acetoxypentyl chloride; diethyl 2-(5-acetoxypentyl) - 2 - methylmalonate; 7 - bromo - 2- methylheptanoic acid, and its methyl ester; 8- (3 - benzyloxy - 1 - hydroxypropyl) - 12 - benzyloxyheptadecanoic acid; 8-(3-methoxy-1-bydroxypropyl) - 12 - hydroxyheptadecanoic acid; 8,12 - dihydroxyheptadecanoic acid; ethyl ethyl 4-bromobutoxyacetate; N-t-butyl-3-(8- acetyl - 12 - hydroxyheptadecanoyloxy)crotonamide; ethyl 8-diazoacetyl-12-acetoxy-heptadecanoate; 3-acetoxy-1-octyne; 1-diethylamino - 4 - acetoxy - 2 - nonyne; 1-bromo- 4 - acetoxy - 2 - nonyne; diethyl 2 - acetyl- 2 - (4 - acetoxy - 2 - nonynyl)azelate; 8- acetyl - 12 - oxo - heptadecanoic acid; 1- acetoxy - 1 - ethynylcyclohexane, 1 - acetoxy- ] - ethynylcyclooctane; 1 - acetoxy - 1 - (3- diethylamino - 1 - propynyl)cyclohexane; 1- acetoxy - 1 - (3 - diethylamino - 1 - propynyl)-cyclooctane; 1 - acetoxy - 1 - (3- bromo - 1 - propynyl)cyclohexane; and 1- acetoxy - 1 - (3 - bromo - 1 - propynyl)cyclooctane. (3 - Benzyloxypropyl)triphenylphosphonium bromide is obtained by reacting 3-benzyloxy-1- bromopropane with triphenylphosphine. Pharmaceutical compositions suitable for oral, parenteral, rectal or topical administration, contain the above 11,12-secoprostaglandins and pharmaceutically acceptable carriers. The compositions are used to improve renal function, the treatment of hypertension and dwarfism, and prevention of thrombus formation.