PHARMACEUTICALLY ACTIVE ORNITHINE DERIVATIVES, AMMONIUM SALTS THEREOF AND METHODS OF MAKING SAME

• Main Authors: LIN, MING-TEH, BADER, HENRY, ROSOWSKY, ANDRE, BLUMBERGS, PETER
• Format: Patent
• Language: English; French; German
• Published: 29.03.2006
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

In one embodiment, the present invention relates to a new class of ammonium salts of Ndelta-acyl derivatives of Nalpha-(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, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C1-6 alkoxy, chloro, fluoro, hydroxy, and -COOH; R3, R4, and R5 are each independently selected from hydrogen and C1-6 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 Ndelta-acyl derivatives of Ndelta-acyl derivatives of Nalpha(4-amino-4-deoxypteroyl)-L-ornithine compounds.