New 4-phenyl- and 4-(4-substituted-phenyl)-n-butane-1-hydroxy-1,1-diphosphonic acids and per(trimethylsilyl) esters and known analogs are useful as targeted cytostatic drugs

摘要

The invention relates to a method of producing the 1-hydroxy-1,1-diphosphonic acid compounds of general formula (I), and/or the pharmacologically acceptable salts thereof, in which formula R<1> represents hydrogen, OH, NO2, Cl, F, Br, C1-C6 alkyl that may be substituted with halogen, amine and/or aminoalkyl, C1-6 alkoxy, aryl, heteroaryl, a group NR<3>R<4>, wherein R<3> and R<4> may be the same or different and represent hydrogen, C1-C6 alkyl, halogen-substituted alkyl, hydroxy-C1-alkyl; R<2> represents hydrogen, halogen, amine that may be substituted, C1-C6 alkyl that may be substituted with halogen, amine and/or aminoalkyl, C1-C6 alkoxy, aryl, heteroaryl; Y represents O, S or NH; Z represents C1-C5 alkylene that may be substituted with amine groups, and m and n are 0 or 1, with the proviso that if n=1, m=1. According to the inventive method, a compound of formula (II), wherein R<1>, R<2>, Y, Z, m and n are defined as above, is reacted with a compound of the formula P(OSiR<5>3)3-pR<6>p, wherein R<5> represents a C1-C4 alkyl group, R<6> represents a C1-C6 alkyloxy group, and p is 0, 1 or 2. The reaction product is hydrolyzed in a manner known pre se and is optionally converted to the corresponding salts.