[Synthesis and antineoplastic action of iso-piritrexim, a lipophilic folic acid antagonist].

Abstract

Two strategies towards the synthesis of Iso-Piritrexim (12) are described. A) The Mannich-reaction of ketone 2 yields the bases 4-HCl and 5-HCl. By means of LC base 4 is separated and treated with in situ generated 3,3-diaminoacrylonitrile (9) to yield the 2-aminonicotinonitrile 11. The cyclocondensation of 11 with guanidine provides Iso-PTX (12). B) Reduction and oxidation of the beta-ketoester 15 leads to the beta-ketoaldehyde 17, which is cyclocondensed with 2,4,6-triaminopyrimidine (18) to yield Iso-PTX (12). In the NCl-tumor-test Iso-PTX (12) shows a moderate activity against some leukemia and lung cancer cell lines.

• Authors: R Troschütz, M Zink, T Dennstedt
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 328 Issue 6 Pg. 535-40 (Jun 1995) ISSN: 0365-6233 [Print] Germany
• Vernacular Title: Synthese und Antitumorwirkung von Iso-Piritrexim, einem lipophilen Folatantagonisten.
• PMID: 7677569 (Publication Type: English Abstract, Journal Article)

Chemical References

• Antineoplastic Agents
• Folic Acid Antagonists
• Mannich Bases
• Pyrimidines
• iso-piritrexim

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Drug Screening Assays, Antitumor
• Folic Acid Antagonists (chemical synthesis, pharmacology)
• Humans
• Mannich Bases
• Pyrimidines (chemical synthesis, pharmacology)
• Tumor Cells, Cultured