Synthesis and antitumor properties of new spiro(benzo[h]quinazoline-7,1′-cyclohexane) derivatives
4-Amino-3-cyano-1,2-dihydrospiro(naphathaline-2,1′-cyclohexane) (aminonitrile) was converted by interaction with p-tolyl acid chloranhydride into 4-(4-methylbenzoyl)amino-3-cyano-1,2-dihydrospiro(naphthaline-2,1′-cyclohexane) (II), which was subjected to cyclization to form 2-(p-tolyl)-4-oxo-3,4,5,6-tetrahydrospiro(benzo[h]quinazoline-5,1′-cyclohexane) (III). This aminonitrile was converted, using a known method, to 4-ethoxymethyleneimino-3-cyano-1,2-dihydrospiro(naphthaline-2,1′-cyclohexane) (IV). Compound IV was condensed with hydrazides of aromatic, alkylaromatic, and alkoxyaromatic acids in dimethylformamide, producing 5-substituted 7,8-dihydrospiro(benzo[h]triazolo[2,3-c]quinazolines) (Va-v) at high yield. The antitumor properties of the resulting compounds were studied using two models of grafted mouse tumors-Ehrlich ascites carcinoma (EAC) and sarcoma 180. Anumber of the newly synthesized compounds had, along with moderate acute toxicity, marked antitumor activity in experimental conditions.
KeywordsHydrazide Maximum Tolerate Dose Quinazolines Hydrogen Chloride Ehrlich Ascites Carcinoma
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- 2.K. Takaji, H. Hideki, T. Hirota, et al., Chem. Pharm. Bull., 23, 2015–2018 (1975); Chem. Abstr., 84, 5232w (1976).Google Scholar
- 4.K. Sasaki, Y.-X. Zhang, H. Yamamoto, et al., J. Chem. Res., (S), 92–93 (1999).Google Scholar
- 6.R. A. Kuroyan, A. I. Markosyan, M. G. Oganisyan, et al., USSR Patent 1672728.Google Scholar
- 7.I. A. Dzhagatspanyan, A. B. Asryan, R. S. Sukasyan, et al., Proceedings of the IX All-Russian Conf. Chemical Informatics [in Russian], Chernogolovka (1992), p. 205.Google Scholar
- 8.A. I. Markosyan, S. V. Dilanyan, R. A. Kuroyan, et al., Khim.-Farm. Zh., 29(4), 32–34 (1995).Google Scholar
- 9.A. I. Markosyan, R. A. Kuroyan, M. G. Oganisyan, et al., Khim.-Farm. Zh., 30(8), 10–13 (1996).Google Scholar
- 10.R. A. Kuroyan, A. I. Markosyan, A. K. Mkrtchyan, et al., Interaction of Chemical Structure and Biological Activity [in Russian], Erevan (1998), pp. 154–164.Google Scholar
- 11.R. A. Kuroyan, A. I. Markosyan, A. Sh. Oganisyan, and M. G. Oganisyan, Arm. Khim. Zh., 42(8), 527–529 (1989).Google Scholar
- 12.A. I. Markosyan, R. A. Kuroyan, M. G. Oganisyan, et al., Khim.-Farm. Zh., 25(6), 18–21 (1991).Google Scholar
- 13.G. N. Pershin, Methods in Experimental Chemotherapy [in Russian], Medgiz, Moscow (1971).Google Scholar
- 14.Z. R. Sofina, A. B. Sarkin, et al., Experimental Assessment of Antitumor Agents in the USSR and USA [in Russian], Meditsina, Moscow (1980).Google Scholar