Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Repository Antimalarial Drugs : N,N′-Diacetyl-4,4′-diaminodiphenylsulphone and Related 4-Acylaminodiphenylsulphones

Nature volume 206, pages 630–631 (1965)Cite this article

Abstract

A SUSTAINED effort to develop antimalarial substances with prolonged action was initiated in these laboratories more than seven years ago. Recently, we reported the synthesis of cycloguanil pamoate (‘CamolarR’, CI-501) (refs. 1 and 2), a pamoic acid salt of 4,6-diamino-1-(p-chlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine (DHT), and various other dihydrotriazine1,3 and pyrimethamine3,4 salts that exhibit remarkable repository antimalarial properties2,4,5. A single intramuscular dose of cycloguanil pamoate has an unusual capacity to protect man for many months against challenges with susceptible strains of Plasmodium vivax and P. falciparum6. Cycloguanil pamoate has so far not shown a liability to induce rapid resistance during numerous observations on P. cynomolgi in monkeys2,5, although parasites known to be resistant to proguanil, DHT, or pyrimethamine are less susceptible to it7,8. A systematic search has been continued for a well-tolerated repository preparation that would destroy both normal and DHT-resistant parasites and simultaneously block the emergence of resistance denovo. Efforts were directed toward the synthesis of long-acting antimalarials possessing a different mode of action from DHT or pyrimethamine, both of which apparently inhibit the conversion of folic acid to folinic acid9.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Elslager, E. F., and Worth, D. F., South African Patents 257/62 (April 17, 1962) and 1680/63 (September 25, 1963); U.S. Patent 3,074,947 (January 22, 1963).

  2. Thompson, P. E., Olszewski, B. J., Elslager, E. F., and Worth, D. F., Amer. J. Trop. Med. Hyg., 12, 481 (1963).

    Article  CAS  Google Scholar 

  3. Elslager, E. F., and Thompson, P. E., Abst., ninth Nat. Med. Chem. Symp. Amer. Chem. Soc., Minneapolis, Minnesota, 6a (June 22, 1964).

  4. Elslager, E. F., and Worth, D. F., South African Patents 256/62 (April 17, 1962) and 1679/63 (September 25, 1963).

  5. Schmidt, L. H., Rossan, R. N., and Fisher, K. F., Amer. J. Trop. Med. Hyg., 12, 494 (1963).

    Article  CAS  Google Scholar 

  6. Coatney, G. R., Contacos, P. G., Lunn, J. S., Kilpatrick, J. W., and Elder, H. A., Amer. J. Trop. Med. Hyg., 12, 504 (1963); Contacos, P. G., Coatney, G. R., Lunn, J. S., and Kilpatrick, J. W., Amer. J. Trop. Med. Hyg., 13, 386 (1964).

    Article  CAS  Google Scholar 

  7. Thompson, P. E., Olszewski, B., and Waitz, J. A., Amer. J. Trop. Med. Hyg., 14, (1965).

  8. Thompson, P. E., Bayles, A., Olszewski, B., and Waitz, J. A., Amer. J. Trop. Med. Hyg., 14, 198 (1965).

    Article  CAS  Google Scholar 

  9. Hill, J., Experimental Chemotherapy, edit. by Schnitzer, R. J., and Hawking, F., 1, 547 (Academic Press, New York, 1963).

    Google Scholar 

  10. Coggeshall, L. T., Maier, J., and Best, C. A., J. Amer. Med. Assoc., 117, 1077 (1941).

    Article  Google Scholar 

  11. Archibald, H. M., and Ross, C. M., J. Trop. Med. and Hyg., 63, 25 (1960).

    CAS  Google Scholar 

  12. Greenberg, J., J. Pharmacol. Exp. Therap., 97, 238 (1949).

    CAS  Google Scholar 

  13. Ramakrishnan, S. P., Basu, P. C., Singh, H., and Singh, N., Bull. Wld. Hlth. Org., 27, 213 (1962).

    CAS  Google Scholar 

  14. Bishop, A., Paratisol., 53, 10 (1963).

    Google Scholar 

  15. Shonle, H. A., and Van Arendonk, A. M., J. Amer. Chem. Soc., 65, 2375 (1943); Heymann, H., and Heidelberger, C., J. Amer. Chem. Soc., 67, 1986 (1945).

    Article  CAS  Google Scholar 

  16. Coatney, G. R., Contacos, P. G., Lunn, J. S., Kilpatrick, J. W., and Elder, H. A., Amer. J. Trop. Med. Hyg., 12, 504 (1963); Contasoc, P. G., Coatney, G. R., Lunn, J. S., and Kilpatrick, J. W., Amer. J. Trop. Med. Hyg., 13, 386 (1964).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Laboratories, Parke, Davis and Co., Ann Arbor, Michigan

    E. F. ELSLAGER & D. F. WORTH

Authors
  1. E. F. ELSLAGER
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. F. WORTH
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

ELSLAGER, E., WORTH, D. Repository Antimalarial Drugs : N,N′-Diacetyl-4,4′-diaminodiphenylsulphone and Related 4-Acylaminodiphenylsulphones. Nature 206, 630–631 (1965). https://doi.org/10.1038/206630a0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/206630a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing