Pharmaceutically active ornithine derivatives, ammonium salts thereof and methods of making same

摘要

In one embodiment, the present invention relates to a new class of ammonium salts of N^delta-acyl derivatives of N^alpha-(4-amino-4-deoxypteroyl)-L-ornithine compounds having a structure according to formula II-IV. Formula II has the structure of: wherein: R² represents up to four groups independently selected at each occurrence of R² from the group consisting of hydrogen, C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl, C_3-8 cycloalkyl, C_1-6 alkoxy, chloro, fluoro, hydroxy, and -COOH; R³, R⁴, and R⁵ are each independently selected from hydrogen and C_1-6 alkyl; or NR³R⁴ taken combination can form a 5 to 7 member heterocycle having at least one nitrogen ring atom; and x is a real number greater than 0 and less than about 4. The ammonium salts provided by the invention exhibit high inhibitory activity against the growth o methotrexate-resistant cells, and also exhibit superior chemical stability than corresponding acidic N^delta-acyl derivatives of N^delta-acyl derivatives of N^alpha(4-amino-4-deoxypteroyl)-L-ornithine compounds.