Abstract
THE teratogenic activity of thalidomide is now well known, but the mechanism by which the drug produces foetal abnormalities is obscure. Recent investigations in this laboratory1 on the relationship between embryotoxic activity and chemical structure in a series of compounds related to thalidomide (α-phthalimidoglutarimide) suggested that the phthalimide portion of the molecule is important in determining teratogenic activity. Replacement of the phthalimide ring of thalidomide by other ring systems such as those of succinimide and hexahydrophthalimide was found to lead to the loss of embryotoxic activity in tho rabbit. However, replacement of the glutarimide ring of thalidomide by other groups did not in every case lead to complete loss of embryopathic activity, for 4-phthalimidobutyramide, phthalimidobenzene and 2-phthalimidoglutaric acid anhydride were still embryotoxic in rabbits but much less so than thalidomide. These observations suggested that an N-substituted phthalimide structure was essential for embryotoxic activity. However, the exact structural requirements in the N-substituent for embryotoxicity are not yet clear, but, so far as is known at present, optimum embryotoxic activity is found when the N-substituent is α-glutarimide as in thalidomide itself.
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References
Fabro, S., Schumacher, H., Smith, R. L., and Williams, R. T., Life Sci., 3, 987 (1964).
Fabro, S., Schumacher, H., Smith, R. L., Stagg, R. B. L., and Williams, R. T., Biochem. J., 90, 5–6P (1964).
Drew, H. D. K., and Hatt, H. H., J. Chem. Soc., 16 (1937).
Green, J. N., and Benson, B. C., J. Pharm. Pharmacol., 13, 117T (1961).
Schumacher, H., Smith, R. L., and Williams, R. T., Brit. J. Pharmacol., 25, 324 (1965).
Schumacher, H., Smith, R. L., Stagg, R. B. L., and Williams, R. T., Pharm. Act. Helv., 39, 394 (1964).
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FABRO, S., SMITH, R. & WILLIAMS, R. Thalidomide as a Possible Biological Acylating Agent. Nature 208, 1208–1209 (1965). https://doi.org/10.1038/2081208a0
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DOI: https://doi.org/10.1038/2081208a0
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