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The molecular conformation of clonidine hydrochloride, an α-adrenergic agonist

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Abstract

The molecular conformation of the antihypertensive drug clonidine hydrochloride [2-(2,6-dichlorophenylimino)-2-imidazole HCl] has been shown by crystallographic studies to have a nearly perpendicular arrangement of the phenyl and imidazole rings as described by the torsion angles C2-C1-N1-C2′= 76 ° and C1-N1-C2′-N′1 = 0 °. This conformation is not either of those suggested as the minimum energy form by CNDO/2 calculations for the protonated or free-base models. However, it is consistent with a nonplanar model proposed as the active conformer based on QSAR and spectral studies. The bonding about the imidazole carbon is similar to the guanidinium ion and the three C2′-N distances of the planar imidazole ring are nearly equal. The chloride ion forms strong hydrogen bonds with the amine hydrogen (2.3 Å) and the imidazole (N1′,) hydrogen (2.4 Å). Comparison with α-adrenergic agonists shows that this conformation of clonidine fits the proposed pharmacophore model and should compete effectively for the α-adrenergic receptors.

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References

  • Ammon, H. L., and Wheeler, C. L. (1975)J. Am. Chem. Soc. 97, 2326.

    Google Scholar 

  • Bergin, R., and Carlstrom, D. (1968)Acta Cryst. B 24, 1506.

    Google Scholar 

  • Byre, G., Mostad, A., and Romming, C. (1976)Acta Chem. Scand. Ser. B 30, 843.

    Google Scholar 

  • Carlstrom, D. (1973)Acta Cryst. B 29, 161.

    Google Scholar 

  • Carlstrom, D., and Bergin, R. (1967)Acta Cryst. 23, 313.

    Google Scholar 

  • Cody, V. (1974)American Crystallographic Association Meeting, Vol. 2, p. 209.

    Google Scholar 

  • Cody, V., and Mukherjee, R. (1975)Acta Cryst. B 31 2168.

    Google Scholar 

  • Cromer, D. T., and Waber, J. T. (1974)International Tables for X-Ray Crystallography, Vol. IV (Kynoch Press, Birmingham).

    Google Scholar 

  • Goodman, L. S., and Gilman, A. (1970)The Pharmacological Basis of Therapeutics, 4th edn. (Macmillan, Toronto), p. 735.

    Google Scholar 

  • Griffith, E. A. H., Chandler, W. D., and Robertson, B. E. (1972)Can. J. Chem. 50, 2979.

    Google Scholar 

  • Haas, D. J., Harris, D. R., and Mills, H. H. (1975)Acta Cryst. 19, 676.

    Google Scholar 

  • Jackman, L. M., and Jen, T. (1974)J. Am. Chem. Soc. 97, 2811.

    Google Scholar 

  • Meerman-van Benthem, C. M., van der Meer, K., Mulder, J. J. C., Timmermans, P. B. M. W. M., and van Zwieten, P. A. (1975)Mol. Pharmacol. II, 667.

    Google Scholar 

  • Mostad, A., and Romming, C. (1971)Acta Chem. Scand. Ser. B 28, 1161.

    Google Scholar 

  • Pook, K. H., Stahle, H., and Daniel, H. (1974)Chem. Ber. 107, 2644.

    Google Scholar 

  • Pullman, B., Coubeils, J. L., Courriere, Ph., and Gervois, J. P. (1972)J. Med. Chem. 15, 17.

    PubMed  Google Scholar 

  • Rouot, B., Leclerc, G., and Wermuth, C. (1973)Chim. Ther. 5, 545.

    Google Scholar 

  • Stewart, R. F., Davidson, E. R., and Simpson, W. T. (1965)J. Chem. Phys. 42, 3175.

    Google Scholar 

  • Stout, G. H., and Jensen, L. H. (1965)X-Ray Structure Determination, A Practical Guide (Macmillan, Toronto).

    Google Scholar 

  • Timmermans, P. B. M. W. M. (1976) Clonidine and structurally related imidazolidines, Ph.D. Thesis, University of Amsterdam, Academische Pers, Amsterdam.

    Google Scholar 

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Presented in part at the American Crystallographic Association Meeting, Clemson, South Carolina, January 1976.

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Cody, V., DeTitta, G.T. The molecular conformation of clonidine hydrochloride, an α-adrenergic agonist. Journal of Crystal and Molecular Structure 9, 33–43 (1979). https://doi.org/10.1007/BF01370924

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