Chinese Science Bulletin

, Volume 46, Issue 4, pp 303–306 | Cite as

3D-QSAR study on phenoxyalkylamine compounds of α1-adrenoceptor antagonist



The study of three-dimensional quantitative structure-activity relationship (3D-QSAR) of DDPH and its derivatives that have been known with their activity parameters has been developed using the comparative molecular field analysis (CoMFA) method. Here, (+)-DDPH crystal structure was selected as the active conformation model and comparisons between the influences of different charge calculation methods and grid setup were conducted. The coefficients of cross-validation (q 2) and regression (r 2) are 0.481 and 0.997, respectively. The standard error (SE) is 0.102. The research result suggests that the steric field makes more contributions to the activity than the electrostatic field. This model can help us not only in improving our understanding of the receptor-ligand interactions, but also in predicting the activity of derivatives and designing new compounds with better potency.


CoMFA α1-adrenoceptor antagonist 


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  1. 1.
    Xia, L., Ni, P. Z., Qian, J. Q. et al., Preparation of phenoxyalkylamine compounds as antihypertensive agents, China Patent, CN 1070623.1Google Scholar
  2. 2.
    Cramer, R. D., Patterson, D. E., Bunce, J. D., Comparative molecular field analysis (CoMFA) (I)—Effect of shape on binding of steroids to carrier proteins, J. Am. Chem. Soc., 1988, 110(18): 59.CrossRefGoogle Scholar
  3. 3.
    Beuerle, G., Kovar, K. A., Schulze-Alexandru, M. et al., Three-dimensional quantitive structure-activity relationship of hallucinogenic phenylalkanime and tryptamine derivatives studies using comparative molecular field analysis (CoMFA), Quant. Struct-Act. Relat., 1997, 16(6): 447.CrossRefGoogle Scholar
  4. 4.
    Matter, H., Schwab, W., Barbier, D. et al., Quantitative structure-activity relationship of human neutropil collagenase (MMP-8) inhibitors using comparative molecular field analysis and X-ray structure analysis, J. Med. Chem., 1999, 42 (11): 1908.CrossRefGoogle Scholar
  5. 5.
    Liu, J., Li, Z. M., Wang, X. et al., Comparative molecular field analysis (CoMFA) of new herbicial sulfonylurea compounds, Sci. in China, Ser. B, 1998, 48(1): 50.CrossRefGoogle Scholar
  6. 6.
    Song, W., Zhang, Y. J., Xia, L. et al., Effects of some mexiletine derivatives on α1-adrenoceptors, Acta Pharmaceutica Sinica (in Chinese), 1998, 33(2): 102.Google Scholar
  7. 7.
    Xu, J. Y., Xia, L., Ni, P. Z. et al., Synthesis and cardiovascular activity of some benzylethylamine derivatives, Journal of China Pharmaceutical University (in Chinese), 1992, 23(4): 203.Google Scholar
  8. 8.
    Ni, P. Z., Sun, H. B., Pen, J. H. et al., Resolution of (±)DDPH and α1-adrenoceptor antagonsign activities of both (±) and (-) DDPH, Journal of China Pharmaceutical University (in Chinese), 1996, 27(8): 462Google Scholar
  9. 9.
    Song, S. Y., Lin, X. Y., Xia, L. et al., Crystal structure of new drug DDPH and absolute configuration of (+)DDPH, Chinese Journal of Structural Chemistry (in Chinese), 1997, 16(2): 102.Google Scholar
  10. 10.
    Wang, R. X., Liu, G., Lai, L. H. et al., Role of compound orientation in CoMFA studies, Acta Physicochimica Sinca (in Chinese), 1998, 14(1): 1.CrossRefGoogle Scholar

Copyright information

© Science in China Press 2001

Authors and Affiliations

  1. 1.Department of Medicinal ChemistryChina Pharmaceutical UniversityNanjingChina
  2. 2.State Key Laboratory of Natural and Biomimetic DrugsBeijing Medical UniversityBeijingChina

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