PHOSPHORYLETHANOLAMINES

摘要

1488582 Pharmaceutically active phosphate diesters DAINIPPON PHARMACEUTICAL CO Ltd 8 Jan 1975 [12 Jan 1974 5 Dec 1974] 796/75 Headings C2P and C2C Novel compounds of Formula I where R is octadeca-9,12-dienoyl, octadeca- 9,12,15-trienoyl, 4-(41-chlorophenoxy)phenoxyacetyl or alpha-(4-(41-chlorophenoxy)phenoxy) propionyl and m is 2 or 2 and their pharmaceutically acceptable acid addition salts may be obtained by splitting off the protecting groups from a compound of Formula V where one of Z 1 and Z 2 is H and the other is a protecting group or both Z 1 and Z 2 are protecting groups or Z 1 and Z 2 together are a protecting group and optionally converting the product to a salt. The compounds of Formula V may be obtained (a) by reacting a compound of Formula II with a compound of Formula III where X 1 is halogen and X 2 is halogen or OY, where Y is a protecting group, or X 1 is OH and X 2 is OH or OY and hydrolysing the resulting product when X 2 is halogen or splitting off the protecting group when X 2 is OY or (b) by reacting a compound of Formula II with a phosphorus oxyhalide to give a compound of formula R-NH(CH 2 ) m O-P(O)(Hal) 2 , reacting this product with a compound of formula and hydrolysing the product. The following intermediates are isolated in examples: (octadeca - 9,12 - dienoylamino)ethyl and propyl 2 - (N - phthalimido)ethyl phosphates; 2 - (octadeca - 9,12 - dienoylamino)ethyl - 2 - (N - 2,2,2- trichloroethoxycarbonylamino)ethyl phosphate; (octadeca - 9,12,15 - trienoylamino)ethyl and propyl 2 - (N - phthalimido)ethyl phosphates; 2 - (octadeca - 9,12 - dienoylamino)ethyl 2 - (N- phthalimido)ethyl benzyl phosphate; 2 - (octadeca - 9,12,15 - trienoylamino)ethyl 2 - (tritylamino)ethyl phosphate; (4 - (41 - chlorophenoxy) phenoxyacetylamino)ethyl and propyl 2 - (N- phthalimido)ethyl phosphates; (alpha (4 - (41- chlorophenoxy)phenoxy)propionylamino)ethyl and propyl 2 - (N - phthalimido)ethyl phosphates; and 2 - (4 - (41 - chlorophenoxy)phenoxyacetylamino)ethyl dichlorophosphate. The compounds of Formula II may be prepared (a) when R is octa-deca-dienoyl or -trienoyl, by reacting an acid ROH or an alkyl ester thereof with a compound H 2 N(CH 2 ) m OH or (b) when R is a substituted phenoxy-acetyl or -propionyl, by reacting 4-(41-chlorophenoxy) phenol with an ester Hal-A-COOW where A is methylene or ethylidene and W is alkyl and reacting the resulting ester with a compound H 2 N(CH 2 ) m OH. The compounds of Formula I may be used as the active ingredients in conventional pharmaceutical compositions.