| 摘要 |
<p>The invention comprises carbocyclic hydroxyamines of the formula <FORM:1023214/C2/1> in which R1 is H, alkyl containing at least 2 carbon atoms, R2 is H, alkyl containing at least 2 carbon atoms, hydroxy alkyl, alkoxy alkyl, cycloalkyl, alkenyl, aralkyl or haloalkyl, n is 1 or 2 and in which the carbocyclic nucleus may optionally bear one or more halogen, hydroxy, alkyl or alkoxy substituents, their carboxylic esters and salts thereof. The esters are preferably those of acids of formula R3COOH in which R3 is an alkyl, alkenyl or aryl radical of not more than 20 carbon atoms. The hydroxyamines may be made as follows:-(a) by reacting a halogeno compound of formula <FORM:1023214/C2/2> in which X is a halogen, with an amino of formula NHR1R2; (b) by reacting an epoxide of formula <FORM:1023214/C2/3> with an amine of formula NHR1R2; (c) by reactin a compound of formula <FORM:1023214/C2/4> with a compound of formula XCH2.CHOH.CH2.NR1R2 or <FORM:1023214/C2/5> (d) when R1 is H and R2 is a radical of formula -CHR4R5 in which R4 is H or alkyl and R5 is alkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, aralkyl, or haloalkyl, by reacting a compound of formula <FORM:1023214/C2/6> with a carbonyl compound of formula R4COR5 under reducing conditions, e.g. in the presence of hydrogen and a hydrogenation catalyst; (e) when n is 2, by the reduction of a naphthalene derivative of formula <FORM:1023214/C2/7> or (f) when R1 is hydrogen by the hydrogenolysis of a compound of formula <FORM:1023214/C2/8> in which R6 is a radical capable of being removed by hydrogenolysis. The carboxylic esters of these compounds may be produced by treatment with acylating agents, e.g. acetic anhydride, acetyl chloride or benzoyl chloride. The salts may be acid addition salts of inorganic acids, e.g. hydrochlorides, hydrobromides, phosphates and sulphates or of organic acids, e.g. oxalates, lactates, tartrates, acetates, salicylates, citrates, benzoates, naphthoates, o-acetoxybenzoates, adipates, maleates and 1,11-methylene - bis - (2 - hydroxy - 3 - naphthoates), or of acidic synthetic resins. Starting materials of formulae <FORM:1023214/C2/9> or <FORM:1023214/C2/100> are prepared by reacting the corresponding hydroxy substituted carbocyclic compound with epichlorhydrin in the presence of piperidine or caustic soda. The new carbocyclic hydroxyamines referred to above may be incorporated into pharmaceutical compositions for the treatment of coronary artery disease. The active compounds may be used in association with a pharmaceutically-acceptable diluent or carrier and may be administered orally or by injection.</p> |
