Patent GB-1373461-A (GB)
Title: Tetrazoyl derivatives of naturally occuring prostaglandins
IPC: C07D309/12
Filed: 1972-01-06
Abstract: 1373461 Tetrazole derivatives of prostaglandins PFIZER Inc 6 Jan 1972 [1 Sept 1971] 673/72 Heading C2C The invention comprises 2-decarboxy-2-(tetrazol-5-yl)prostaglandins, wherein the said prostaglandins are PGF 1 α, PGE 1 , PGA 1 , 13,14- dihydro-PGF 1 α, 13,14-dihydro-PGE 1 , 13,14-dihydro-PGA 1 , PGF 2 α, PGE 2 , PGA 2 , 13,14-dihydro-PGF 2 α, 13,14-dihydro-PGE 2 , 13,14-dihydro-PGA 2 , the 15#-C 1-3 -alkyl derivatives of the prostaglandins, PGF 3 α, PGE 3 , PGA 3 , the 9,15-bis-(tetrahydropyran-2-yl)ethers of 2-decarboxy-2-(tetrazol-5-yl)PGF 2 α, 2-decarboxy-2- (tetrazol-5-yl)-15#-(C 1-3  alkyl)-PGF 2 α, 2-decarboxy-2-(tetrazol-5-yl)-PGF 1 α, 2-decarboxy-15#- (C 1-3  alkyl)-PGF 1 α, 2-decarboxy-2-(tetrazol-5- yl)-13,14-dihydro-PGF 1 α, 2-decarboxy-2-(tetrazol-5-yl)-15#-(C 1-3  alkyl)-13,14-dihydro-PGF 1 α, 2 - decarboxy - 2 - (tetrazol - 5 - yl) - 13,14- dihydro-PGF 2 α, 2-decarboxy-2-(tetrazol-5-yl)- 15#-(C 1-3  alkyl)-13,14-dihydro-PGF 2 α, and 2- decarboxy-2-(tetrazol-5-yl)-PGF 3 α, and their preparation. The PGA derivatives are prepared by dehydrating the corresponding PGE derivatives, which are obtained by hydrolysing the 11,15-bis-(tetrahydropyran-2-yl)ether of the corresponding 2-decarboxy-2-tetrazol-5-yl)-PGE, resulting from the oxidation of the ethers of the corresponding 2-decarboxy-2-(tetrazol-5-yl)- PGF compounds. The PGF compounds are prepared by hydrolysing the corresponding 11,15-bis-(tetrahydropyran-2-yl)ethers. The 11, 15-bis(tetrahydropyran-2-yl)ether of 2-decarboxy-2-(tetrazol-5-yl)-PGF 2 α and the 15#-alkyl derivative thereof are obtained by reacting 4- (tetrazol-5-yl)butyltriphenylphosphonium bromide with 2-hydroxy-3,3α#,4,5,6,6α#-hexahydro-5α-(tetrahydropyran-2-yloxy)-4#-(3α-tetrahydropyran-2<SP>1</SP>-yloxyoct-trans-1-enyl)-2H-cyclopenta(b)furan or 2-hydroxy-3,3a#,4,5,6,6a#- hexahydro-4#-(3#-methyl-3α-tetrahydropyran- 2<SP>1</SP>-yloxyoct-trans-1-enyl)-5α-(tetetrahydropyran 2-yloxy)-2H-cyclopenta(b)furan; the PGF 2 α compound thus obtained may be hydrogenated to the corresponding PGF 1 α and 13,14-dihydro- PGF 1 α compounds. The 11,15-bis-(tetrahydropyran-2-yl)ethers of 13,14-dihydro-PGF 2 α and the 15#-alkyl derivatives thereof and PGF 3 α compounds are prepared by reacting the above mentioned phosphonium compound with 2- hydroxy - 3,3α#,4,5,6,6α#-hexahydro - 5α- (tetrahydropyran - 2 - yloxy) - 4# - (3α - tetrahydropyran - 2<SP>1</SP>- yloxyoctyl) - 2H - cyclopenta- (b)furan, 2 - hydroxy - 3,3a#,4,5,6,6a#-hexahydro - 4# - (3# - methyl - 3α - tetrahydropyran- 2<SP>1</SP> - yl - oxyoctyl - 5α - (tetrahydropyran - 2- yloxy) - 2H - cyclopenta(b)furan and 2- hydroxy - 3,3a#,4,5,6,6a# - hexahydro - 5α- (tetrahydropyran - 2 - yloxy) - 4# - (3α - tetrahydropyran - 2<SP>1</SP> - yloxyocta-trans - 1,cis - 5- dienyl)-2H-cyclopenta(b)furan. Pharmaceutical compositions, suitable for topical, oral, intravenous, intravaginal and intranasal administration, contain the above novel 2-decarboxy-2-(tetrazol-5-yl)prostaglandins or acid addition salts thereof and inert physiologically acceptable carriers. The compounds possess activities similar to natural prostaglandins.