advances in the treatment and prevention of diseases artériosclérotiques.

摘要

The invention comprises steroids of the formula: FORM:0949256/C2/1 wherein R1 is an a - or b -OCO(CH2)nCOOM, -OCO(CH2)nNR2, -OCO(CH2)nNR2.HB, -OPO3M2, -OSO3M or -OCO(CH2)nX radical; R2 is a hydrogen atom; R3 is a =O; an a - or b -OH, an -OCOR or an -OCO(CH2)nX radical; n is 1, 2, 3, 4 or 5; R is hydrogen or C1-5 alkyl; X is halogen; M is a hydrogen atom, an alkali metal or one equivalent of an alkaline earth metal; and HB is a non-toxic mineral acid; with the proviso that R3 is not an acetate group when R1 is a chloroacetate group. Cholestane -3, 5, 6-triols and their esters can be prepared from cholesterol or its esters by oxidizing with a peracid or osmium tetroxide. The oxidation product, if obtained in the form of an ester or of the 5, 6-epoxide, can be hydrolysed by an acid to give the 5, 6-glycol. The triols may be esterified by conventional methods. Halo-acetic acid esters may be interconverted or may be converted to amino-acetic acid esters. Examples describe the preparation of the 3-hemisuccinate, 3-diethylaminoacetate, 3-chloroacetate, 3-iodoacetate, 3, 6-bis-chloroacetate, 3, 6-bis-iodoacetate, 3-hemisuccinate 6-formate, 3-hemisuccinate 6-acetate, 3-phosphate and 3-sulphate of cholestane -3b , 5a , 6b -triol, and alkali metal salts and acid-addition salts of some of these compounds. An intermediate in the preparation of the phosphate is the 3 b -phosphodichloride; and cholesterol 3-hemisuccinate is prepared from cholesterol and succinic anhydride. The preparation of other compounds of the above general formula, including ones where R1 may have the additional values of =O, a - or b -OH, -OCOR and OCOR4 (wherein R4 is C1-5 alkyl), R in -OCO(CH2)nNR2 may have the additional value of an acyl radical, R3 may have the additional values of -OCO(CH2)nNR2 (R having the extended definition given), -OCO(CH2)2NR2.HB, -OCO(CH2)nCOOM, -OSO3M and -OPO3M2; and R2 has the additional value of a C1-5 acyl radical, is also referred to.ALSO:Pharmaceutical compositions comprise a steroid of the formula FORM:0949256/A5-A6/1 (wherein R1 and R3 represent = O or an a - or b -OH, -OCOR, -OCOOR4, -OCO(CH2)nX, -OCO(CH2)nNR52, -OCO(CH2)nNR2.HB, -OCO(CH2)nCOOM -OSO3M or -OPO3M2 radical, R is hydrogen or C1-5 alkyl, R4 is C1-5 alkyl, R5 is hydrogen, C1-5 alkyl or acyl, X is halogen, M is hydrogen, an alkali metal or one equivalent of an alkaline earth metal, HB is a non-toxic mineral acid, n is 1, 2, 3, 4 or 5 and R2 is hydrogen or an aliphatic acyl radical of at most 5 carbon atoms) and a solid pharmaceutical carrier or a sterile diluent. They may be used for the treatment or prevention of atherosclerotic diseases. Suitable forms include powders, tablets, pills, solutions, emulsions, injections and suspensions, which may contain emulsifying agents and flavouring agents. A tablet containing cholestone-3b ,5a ,6b -triol 3,6-diformate is described.