Skip to main content
SpringerLink
Log in

PAF inhibitory activity of diketopiperazines: Structure-activity relationships

  • PAF Receptor and Antagonists
  • Published:
Lipids

Abstract

FR900452, a natural product isolated from the culture broth ofStreptomyces phaeofaciens No. 7739, was found to inhibit PAF-induced rabbit platelet aggregation with an IC50 of 3.7×10−7M. FR900452, 1-methyl-3-[1-[5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-ylidene)-2-piperazinyl]ethyl]-2-indoline, has an oxocylopentylidene group incorporated as a vinylogous amide in a diketopiperazine skeleton. This unique structure led us to synthesize diketopiperazine derivatives, 3-arylalkyl-6-substituted-piperazine-2,5-diones. their observed PAF inhibitory activity suggest that the D-D configuration of diketopiperazine is an important factor for anti-PAF activity and that the hydrophobic aromatic portion may play a specific role in the binding of the diketopiperazine to the PAF receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

IC50 :

concentration required to inhibit the platelet aggregation response by 50%

PAF:

platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine

PRP:

platelet-rich plasma

References

  1. Handley, D.A. (1988)Trends Pharmacol. Sci. 13, 137–152.

    Google Scholar 

  2. Braquet, P., Touqui, L., Shen, T.Y., and Vargafting, B.B. (1987)Pharmacol. Rev. 39, 97–145.

    PubMed  CAS  Google Scholar 

  3. Braquet, P., and Godfroid, J.J. (1986)Trends Pharmacol. Sci. 8, 397–403.

    Article  Google Scholar 

  4. Okamoto, M., Yoshida, K., Uchida, I., Nishikawa, M., Kohsaka, M., and Aoki, H. (1986)Chem. Pharm. Bull. 34, 340–344.

    PubMed  CAS  Google Scholar 

  5. Okamoto, M., Yoshida, K., Uchida, I., Kohsaka, M., and Aoki, H. (1986)Chem. Pharm. Bull. 34, 345–348.

    PubMed  CAS  Google Scholar 

  6. Shimazaki, N., Shima, I., Hemmi, K., Tsurumi, Y., and Hashimoto, M. (1987)Chem. Pharm. Bull. 35, 3527–3530.

    PubMed  CAS  Google Scholar 

  7. Okamoto, M., Yoshida, K., Nishikawa, M., Ando, T., Iwami, M., Kohsaka, M., and Aoki, H. (1986)Chem. Pharm. Bull. 34, 3005–3010.

    PubMed  CAS  Google Scholar 

  8. Takase, S., Shigematsu, N., Shima, I., Uchida, I., Hashimoto, M., Toda, T., Koda, S., and Morimoto, Y. (1987)J. Org. Chem. 52, 3485–3487.

    Article  CAS  Google Scholar 

  9. Shimazaki, N., Hemmi, K., Nakaguchi, O., Miyazaki, Y., and Hashimoto, M., European Patent No. EP 243122 (1987).

  10. Shimazaki, N., Shima, I., Hemmi, K., and Hashimoto, M. (1987)J. Med. Chem. 30, 1706–1709.

    Article  PubMed  CAS  Google Scholar 

  11. Shima, I., Shimazaki, N., Imai, K., Hemmi, K., and Hashimoto, M. (1990)Chem. Pharm. Bull. 38, 564–566.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, 300-26, Tsukuba, Ibaraki, Japan

    Norihiko Shimazaki, Ichiro Shima, Masanori Okamoto, Keizo Yoshida, Keiji Hemmi & Masashi Hashimoto

Authors
  1. Norihiko Shimazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ichiro Shima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masanori Okamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keizo Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Keiji Hemmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masashi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Shimazaki, N., Shima, I., Okamoto, M. et al. PAF inhibitory activity of diketopiperazines: Structure-activity relationships. Lipids 26, 1175–1178 (1991). https://doi.org/10.1007/BF02536526

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02536526

Keywords

Search

Navigation