Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists

Takao Kiyoi, Julia M Adam, John K Clark, Keneth Davies, Anna-Marie Easson, Darren Edwards, Helen Feilden, Ruth Fields, Stuart Francis, Fiona Jeremiah, Duncan McArthur, Angus J Morrison, Alan Prosser, Paul D Ratcliffe, Jurgen Schulz, Grant Wishart, James Baker, Robert Campbell, Jean E Cottney, Maureen Deehan & 2 others Ola Epemolu, Louise Evans

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Novel 3-(1H-indol-3-yl)-1,2,4-oxadiazoles and -thiadiazoles were synthesized and found to be potent CB1 cannabinoid receptor agonists. The oral bioavailability of these compounds could be dramatically improved by optimization studies of the side chains attached to the indole and oxadiazole cores, leading to identification of a CB1 receptor agonist with good oral activity in a range of preclinical models of antinociception and antihyperalgesia.

LanguageEnglish
Pages1748-1753
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number6
DOIs
Publication statusPublished - 15 Mar 2011

Fingerprint

Oxadiazoles
Cannabinoid Receptor Agonists
Cannabinoid Receptor CB1
Thiadiazoles
Biological Availability
indole

Keywords

  • administration, oral
  • animals
  • biological availability
  • drug discovery
  • heterocyclic compounds
  • rats
  • receptor, cannabinoid, CB1

Cite this

Kiyoi, T., Adam, J. M., Clark, J. K., Davies, K., Easson, A-M., Edwards, D., ... Evans, L. (2011). Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists. Bioorganic and Medicinal Chemistry Letters, 21(6), 1748-1753. https://doi.org/10.1016/j.bmcl.2011.01.082
Kiyoi, Takao ; Adam, Julia M ; Clark, John K ; Davies, Keneth ; Easson, Anna-Marie ; Edwards, Darren ; Feilden, Helen ; Fields, Ruth ; Francis, Stuart ; Jeremiah, Fiona ; McArthur, Duncan ; Morrison, Angus J ; Prosser, Alan ; Ratcliffe, Paul D ; Schulz, Jurgen ; Wishart, Grant ; Baker, James ; Campbell, Robert ; Cottney, Jean E ; Deehan, Maureen ; Epemolu, Ola ; Evans, Louise. / Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 6. pp. 1748-1753.
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Kiyoi, T, Adam, JM, Clark, JK, Davies, K, Easson, A-M, Edwards, D, Feilden, H, Fields, R, Francis, S, Jeremiah, F, McArthur, D, Morrison, AJ, Prosser, A, Ratcliffe, PD, Schulz, J, Wishart, G, Baker, J, Campbell, R, Cottney, JE, Deehan, M, Epemolu, O & Evans, L 2011, 'Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists' Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 6, pp. 1748-1753. https://doi.org/10.1016/j.bmcl.2011.01.082

Discovery of potent and orally bioavailable heterocycle-based cannabinoid CB1 receptor agonists. / Kiyoi, Takao; Adam, Julia M; Clark, John K; Davies, Keneth; Easson, Anna-Marie; Edwards, Darren; Feilden, Helen; Fields, Ruth; Francis, Stuart; Jeremiah, Fiona; McArthur, Duncan; Morrison, Angus J; Prosser, Alan; Ratcliffe, Paul D; Schulz, Jurgen; Wishart, Grant; Baker, James; Campbell, Robert; Cottney, Jean E; Deehan, Maureen; Epemolu, Ola; Evans, Louise.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 6, 15.03.2011, p. 1748-1753.

Research output: Contribution to journalArticle

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AU - Clark, John K

AU - Davies, Keneth

AU - Easson, Anna-Marie

AU - Edwards, Darren

AU - Feilden, Helen

AU - Fields, Ruth

AU - Francis, Stuart

AU - Jeremiah, Fiona

AU - McArthur, Duncan

AU - Morrison, Angus J

AU - Prosser, Alan

AU - Ratcliffe, Paul D

AU - Schulz, Jurgen

AU - Wishart, Grant

AU - Baker, James

AU - Campbell, Robert

AU - Cottney, Jean E

AU - Deehan, Maureen

AU - Epemolu, Ola

AU - Evans, Louise

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KW - receptor, cannabinoid, CB1

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