PROCESS FOR PREPARING NOVEL HYDROXY-4-CUMARIN DERIVATIVES

摘要

1,193,500. Coumarin derivatives. LIPHA, LYONNAISE INDUSTRIELLE PHARMACEUTIQUE. 12 Dec., 1967 [13 Dec., 1966; 13 Nov., 1967], No. 56507/67. Heading C2C. The invention comprises compounds of the general Formula I wherein R represents a thienyl radical optionally substituted by an alkyl group of 1-4 carbon atoms or a nitro group or a halogen atom, and R 1 represents an alkyl group of 1-4 carbon atoms or a phenyl or biphenyl radical optionally substituted by a halogen atom or a nitro group. They are prepared by reducing a ketone of the general formula wherein R and R 1 are as defined above, with aluminium isopropylate in isopropanol. 3 - (4SP1/SP - hydroxy - 3SP1/SP - coumarinyl) - 3 - (5SP11/SP - methyl - 2SP11 /SP- thienyl) - propiophenone is prepared by reacting 4-hydroxy coumarin with 1 - phenyl - 3 - (5SP11/SP - methyl - 2SP11/SP- thienyl - 1 - 2 - propen - 1 - one, which is prepared by reacting acetophenone with 5-methyl thenaldehyde. The 3 - (4SP1 /SP- hydroxy - 3SP1/SP - coumarinyl) - 3 - (5SP11/SP - halo - 2SP11/SP - thienyl) - p - halo - halophenyl)- propiophenones are prepared by reacting 4- hydroxy coumarin with the corresponding 1 - p - halo - (or p 1 - halophenyl) - phenyl - 3 - (5SP1/SP - halo 2SP1/SP- thienyl) - 2 - propen - 1 - one which is prepared by reacting the corresponding 5SP1/SP-halo- 2-thenaldehyde with the corresponding p-halo (or pSP11/SP-halophenyl) acetophenone. 3 - (4SP1/SP - hydroxy - 3SP1/SP- coumarinyl) - 3 - (2SP1/SP - thienyl) - p - nitropropiophenone is prepared from 4-hydroxy coumarin and 1-p-nitrophenyl- 3 - (2SP1/SP - thienyl) - 2 - propen - 1 - one. 3 - (4SP1 /SP- hydroxy - 3SP1/SP - coumarinyl) - 3 - (5SP11/SP- bromo - 2SP11 /SP- thienyl) - p- (4SP1/SP- nitrophenyl) - propiophenone is prepared by reacting 4-hydroxycoumarin with 51-bromo-thenylidene-p- (4SP1/SP-nitrophenyl) -acetophenone. Pharmaceutical compositions comprising as active ingredient a compound of Formula I together with a pharmaceutically acceptable carrier are administered orally and have anticoagulant activity of the anti-vitamin K type.