[Synthesis and antineoplastic action of iso-piritrexim, a lipophilic folic acid antagonist].
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.
Troschütz
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Institut für Pharmazie und Lebensmittelchemie, Universität Erlangen-Nürnberg, FRG.
Zink
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Dennstedt
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D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008352:Mannich Bases; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D008352:Mannich Bases; D011743:Pyrimidines; C095639:iso-piritrexim
Synthese und Antitumorwirkung von Iso-Piritrexim, einem lipophilen Folatantagonisten.