Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists

Takao Kiyoi, Mark York, Stuart Francis, Darren Edwards, Glenn Walker, Andrea K Houghton, Jean E Cottney, James Baker, Julia M Adam

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.

LanguageEnglish
Pages4918-4921
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number16
DOIs
Publication statusPublished - 15 Aug 2010

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Cannabinoid Receptor Agonists
Structure-Activity Relationship
Lead compounds
Indoles
Enantiomers
Amides
indole
Lead

Keywords

  • amides
  • animals
  • drug design
  • humans
  • indoles
  • mice
  • microsomes
  • receptor, Cannabinoid, CB1
  • structure-activity relationships

Cite this

Kiyoi, Takao ; York, Mark ; Francis, Stuart ; Edwards, Darren ; Walker, Glenn ; Houghton, Andrea K ; Cottney, Jean E ; Baker, James ; Adam, Julia M. / Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 16. pp. 4918-4921.
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Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists. / Kiyoi, Takao; York, Mark; Francis, Stuart; Edwards, Darren; Walker, Glenn; Houghton, Andrea K; Cottney, Jean E; Baker, James; Adam, Julia M.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 16, 15.08.2010, p. 4918-4921.

Research output: Contribution to journalArticle

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AU - Francis, Stuart

AU - Edwards, Darren

AU - Walker, Glenn

AU - Houghton, Andrea K

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AU - Baker, James

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KW - amides

KW - animals

KW - drug design

KW - humans

KW - indoles

KW - mice

KW - microsomes

KW - receptor, Cannabinoid, CB1

KW - structure-activity relationships

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