ANTITUMOR-ACTIVITY OF ETHYL 5-AMINO-1,2-DIHYDRO-2-METHYL-3-PHENYLPYRIDO[3,4-B]PYRAZIN-7-YLCARBAMATE, 2-HYDROXYETHANESULFONATE, HYDRATE (NSC-370147) AGAINST SELECTED TUMOR SYSTEMS IN CULTURE AND IN MICE

  • 1 June 1990
    • journal article
    • research article
    • Vol. 50  (11) , 3239-3244
Abstract
Ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7-ylcarbamate,2-hydroxyethanesulfonate, hydrate (NSC370147) was evaluated for antitumor activity against a spectrum of tumor systems in culture and in mice. NSC 370147 was cytotoxic to a variety of mouse and human cell lines at nanomolar concentrations. The compound exhibited good in vivo antitumor activity against several murine tumors (P388 and L1210 leukemia, colon 11/A and 36, mammary 16/C, and M5076 sarcoma). Activity was largely independent of route of administration but favored a prolonged treatment schedule. NSC 370147 was as active against murine leukemia sublines resistant to Adriamycin, amsacrine, vincristine, melphalan, cisplatin, methotrexate, and CI-920 (a topoisomerase II inhibitor) as against the corresponding parental lines. Only the 1-.beta.-D-arabinofuranosylcystosine-resistant P388 subline exhibited any cross-resistance to NSC 370147. NSC370147 has a spectrum of activity similar to that of vincristine and, unlike vincristine, is active against multidrug-resistant cell lines. Therefore, NSC 370147 is a candidate for clinical trial because of its favorable activity compared to vincristine, its effectiveness against multidrug-resistant cells, and its retention of activity for p.o. administration.