Design of potent, orally effective, nonpeptidal antagonists of the peptide hormone cholecystokinin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 83 ·No. 13 ·1986-07-00 ·Pages 4918-22

Evans BE, Bock MG, Rittle KE, DiPardo RM, Whitter WL, Veber DF, Anderson PS, Freidinger RM

Abstract

We describe the design and synthesis of nonpeptidal antagonists of the peptide hormone cholecystokinin. Several of these compounds have high specificity and nanomolar binding affinity and are active after oral administration. To our knowledge, the design of such agents has not previously been accomplished for any peptide hormone. The structural similarities between these synthetic compounds and the anxiolytic 1,4-benzodiazepines are noted, and the potential of this structural feature for future design of ligands for other peptide hormone receptors is discussed.

MeSH Terms

Animals Benzodiazepines/chemical synthesis,pharmacology Binding, Competitive Cholecystokinin/antagonists & inhibitors Pancreas/metabolism Radioligand Assay Rats Receptors, Cell Surface/metabolism Receptors, Cholecystokinin Structure-Activity Relationship

Chemicals

Receptors, Cell Surface Receptors, Cholecystokinin Benzodiazepines Cholecystokinin

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Evans B E

Bock M G

Rittle K E

DiPardo R M

Whitter W L

Veber D F

Anderson P S

Freidinger R M

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26 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.83.13.4918

Published

1986-07-00

Pages

4918-22

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC323855

Subset

External Links

PubMed source DOI: 10.1073/pnas.83.13.4918 PMC Full Text View journal details

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Design of potent, orally effective, nonpeptidal antagonists of the peptide hormone cholecystokinin.

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