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.
Similar content being viewed by others
References
Ammon, H. L., and Wheeler, C. L. (1975)J. Am. Chem. Soc. 97, 2326.
Bergin, R., and Carlstrom, D. (1968)Acta Cryst. B 24, 1506.
Byre, G., Mostad, A., and Romming, C. (1976)Acta Chem. Scand. Ser. B 30, 843.
Carlstrom, D. (1973)Acta Cryst. B 29, 161.
Carlstrom, D., and Bergin, R. (1967)Acta Cryst. 23, 313.
Cody, V. (1974)American Crystallographic Association Meeting, Vol. 2, p. 209.
Cody, V., and Mukherjee, R. (1975)Acta Cryst. B 31 2168.
Cromer, D. T., and Waber, J. T. (1974)International Tables for X-Ray Crystallography, Vol. IV (Kynoch Press, Birmingham).
Goodman, L. S., and Gilman, A. (1970)The Pharmacological Basis of Therapeutics, 4th edn. (Macmillan, Toronto), p. 735.
Griffith, E. A. H., Chandler, W. D., and Robertson, B. E. (1972)Can. J. Chem. 50, 2979.
Haas, D. J., Harris, D. R., and Mills, H. H. (1975)Acta Cryst. 19, 676.
Jackman, L. M., and Jen, T. (1974)J. Am. Chem. Soc. 97, 2811.
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.
Mostad, A., and Romming, C. (1971)Acta Chem. Scand. Ser. B 28, 1161.
Pook, K. H., Stahle, H., and Daniel, H. (1974)Chem. Ber. 107, 2644.
Pullman, B., Coubeils, J. L., Courriere, Ph., and Gervois, J. P. (1972)J. Med. Chem. 15, 17.
Rouot, B., Leclerc, G., and Wermuth, C. (1973)Chim. Ther. 5, 545.
Stewart, R. F., Davidson, E. R., and Simpson, W. T. (1965)J. Chem. Phys. 42, 3175.
Stout, G. H., and Jensen, L. H. (1965)X-Ray Structure Determination, A Practical Guide (Macmillan, Toronto).
Timmermans, P. B. M. W. M. (1976) Clonidine and structurally related imidazolidines, Ph.D. Thesis, University of Amsterdam, Academische Pers, Amsterdam.
Author information
Authors and Affiliations
Additional information
Presented in part at the American Crystallographic Association Meeting, Clemson, South Carolina, January 1976.
Rights and permissions
About this article
Cite this article
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
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01370924