Patent GB-1431871-A (GB)
Title: 10-aza-11,12-secoprostaglandins and their production
IPC: C07C401/00
Filed: 1974-01-21
Abstract: 1431871 11,12-Secoprostaglandins MERCK & CO Inc 21 Jan 1974 [26 Jan 1973] 02667/74 Heading C2C The invention comprises 11,12-secoprostaglandins of the Formula I: in which R is COOY, wherein Y is H, a pharmaceutically acceptable cation or C 1-10  alkyl, CONHNH 2  or CONR<SP>6</SP>R<SP>7</SP>, wherein R<SP>6</SP> and R<SP>7</SP> each are H, C 1-4  alkyl or C 4-7  dialkylaminoalkyl; A is ethylene, trimethylene, α-methylethylene, #-methylethylene, α,α-dimethylethylene, #,#-dimethylethylene or oxymethylene; R<SP>1</SP> is H or CH 3 ; R<SP>2</SP> is H or C 1-3  alkyl; R<SP>3</SP> is H or CH 3  ; R<SP>4</SP> is H or C 1-5  alkanoyl; and R<SP>5</SP> is C 3-7  alkyl, 4- pentenyl or 5,5,5-trifluoropentyl; except that when R<SP>3</SP> is CH 3 , R<SP>5</SP> is not 4-pentenyl; and their preparation. Compounds of the above formula in which R<SP>3</SP> is H and R is COOH are obtained by reacting compounds of the Formula III: wherein R<SP>9</SP> is C 1-5  alkyl, with compounds of the formula R<SP>1</SP>(R<SP>2</SP>)NH, and subjecting the compound then obtained to basic hydrolysis and acidification. Compounds of the above Formula I in which R<SP>3</SP> is CH 3 , R<SP>6</SP> is C 3-7  alkyl or 5,5,5-trifluoropentyl and R is COOH are prepared by reacting compounds of the Formula IV: in which R<SP>10</SP> is C 3-7  alkyl or 5,5,5-trifluoropentyl with compounds of the formula R<SP>1</SP>(R<SP>2</SP>)NH, hydrating the product with mercuric oxide in aqueous tetrahydrofuran, followed by treatment with sodium borohydride, and subjecting the resulting compounds to basic hydrolysis and acidification. The compound in which R<SP>4</SP> is C 1-5  alkanoyl are made by acylating the corresponding compounds in which R<SP>4</SP> is H. The esters, amides and hydrazides of the above Formula I are prepared by standard methods. The following intermediates are also prepared: 3(S and R) - 3 - (2 - tetrahydropyranyloxy) - 1 - octyne; 4(S and R) - 1,1 - diethoxy- 4 - (2 - tetrahydropyranyloxyl - 2 - octyne; 4(S and R) - 4 - hydroxy - 2 - nonynal; 4(S and R) - 4 - (2 - tetrahydropyranyloxy - 2 - nonynal; 4(S and R) - 4 - (2 - tetrahydropyranyloxy)- nonanal; (4S and R) - 4 - (2 - tetrahydropyranyloxy) - 1 - nonanol; (4S and R) - 1- methylsulphonyloxy - 4 - (2 - tetrahydropyranyloxy)nonane; di-tert. - butyl 2 - [4(S and R) - (2 - tetrahydropyranyloxy)nonyl] - 2 - (6- ethoxycarbonylhexyl)malonate; di-tert.-butyl 2 - [4(S and R) - hydroxynonyl] - 2 - (6 - ethoxycarbonylhexyl)malonate; di-tert.-butyl 2-[4(S and R) - acetoxynonyl] - 2 - (6 - ethoxycarbonylhexyl)malonate; N - t - butyl - 3 - (8- carbamoyl - 12 - hydroxyheptadecanoyloxy)- crotonamide; compounds of the formulµ XIV, XV, XVI and XVII: acid chlorides of the Formulµ III and IV above; and compounds of the formula Pharmaceutical compositions, suitable for oral, parenteral, rectal or topical administration, contain the above compounds together with pharmaceutically acceptable carriers. The compounds are used to improve renal function, for treatment of hypertension, for fertility control and prevention of thrombus formation.