Advertisement

Pharmaceutical Chemistry Journal

, Volume 42, Issue 2, pp 56–59 | Cite as

Synthesis and antitumor properties of new spiro(benzo[h]quinazoline-7,1′-cyclohexane) derivatives

  • I. I. Markosyan
  • S. A. Gabrielyan
  • G. A. Panosyan
  • F. G. Arsenyan
  • B. T. Garibdzhanyan
The Search for New Therapeutic Agents

Abstract

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.

Keywords

Hydrazide Maximum Tolerate Dose Quinazolines Hydrogen Chloride Ehrlich Ascites Carcinoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    K. Sasaki, Y. Sekiya, H. Fujiwara, et al., J. Heterocyclic Chem., 30, 993–995 (1993).CrossRefGoogle Scholar
  2. 2.
    K. Takaji, H. Hideki, T. Hirota, et al., Chem. Pharm. Bull., 23, 2015–2018 (1975); Chem. Abstr., 84, 5232w (1976).Google Scholar
  3. 3.
    T. Hirota, K. Kawanishi, K. Sasaki, et al., J. Het. Chem., 23(3), 685–688 (1986).CrossRefGoogle Scholar
  4. 4.
    K. Sasaki, Y.-X. Zhang, H. Yamamoto, et al., J. Chem. Res., (S), 92–93 (1999).Google Scholar
  5. 5.
    H. Morita, Y. Sato, K.-T. Chan, et al., J. Nat. Prod., 63(12), 1707–1708 (2000).PubMedCrossRefGoogle Scholar
  6. 6.
    R. A. Kuroyan, A. I. Markosyan, M. G. Oganisyan, et al., USSR Patent 1672728.Google Scholar
  7. 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. 8.
    A. I. Markosyan, S. V. Dilanyan, R. A. Kuroyan, et al., Khim.-Farm. Zh., 29(4), 32–34 (1995).Google Scholar
  9. 9.
    A. I. Markosyan, R. A. Kuroyan, M. G. Oganisyan, et al., Khim.-Farm. Zh., 30(8), 10–13 (1996).Google Scholar
  10. 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. 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. 12.
    A. I. Markosyan, R. A. Kuroyan, M. G. Oganisyan, et al., Khim.-Farm. Zh., 25(6), 18–21 (1991).Google Scholar
  13. 13.
    G. N. Pershin, Methods in Experimental Chemotherapy [in Russian], Medgiz, Moscow (1971).Google Scholar
  14. 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

Copyright information

© Springer Science+Business Media, Inc. 2008

Authors and Affiliations

  • I. I. Markosyan
    • 1
  • S. A. Gabrielyan
    • 1
  • G. A. Panosyan
    • 1
  • F. G. Arsenyan
    • 1
  • B. T. Garibdzhanyan
    • 1
  1. 1.Institute of Fine Organic ChemistryNational Academy of Sciences of the Republic of ArmeniaErevanArmenia

Personalised recommendations