Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'

D P Papahatjis, S P Nikas, T Kourouli, R Chari, W Xu, R G Pertwee, A Makriyannis

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Earlier work from our laboratories has provided evidence for the existence of a subsite within the CB1 and CB2 cannabinoid receptor binding domain corresponding to substituents at the benzylic side chain position of classical cannabinoids. The existence and stereochemical features of this subsite have now been probed through the synthesis of a novel series of (-)-Delta(8)-tetrahydrocannabinol analogues bearing C1'-ring substituents. Of the compounds described here, those with C1'-dithiolane (1c), C1'-dioxolane (2d), and cyclopentyl (2a) substituents exhibited the highest affinities for CB1 and CB2. We used molecular modeling approaches to better define the stereochemical limits of the putative subsite. In vitro pharmacological testing found 1c to be a potent CB1 agonist.

Original languageEnglish
Pages (from-to)3221-3229
Number of pages9
JournalJournal of Medicinal Chemistry
Volume46
DOIs
Publication statusPublished - 2003

Keywords

  • ANALOGS
  • BRAIN
  • PHARMACOLOGY
  • DELTA(8)-TETRAHYDROCANNABINOLS
  • EXPRESSION
  • INHIBITION
  • ANANDAMIDE
  • HASHISH
  • LIGAND
  • BINDS

Cite this

Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'. / Papahatjis, D P ; Nikas, S P ; Kourouli, T ; Chari, R ; Xu, W ; Pertwee, R G ; Makriyannis, A .

In: Journal of Medicinal Chemistry, Vol. 46, 2003, p. 3221-3229.

Research output: Contribution to journalArticle

Papahatjis, D P ; Nikas, S P ; Kourouli, T ; Chari, R ; Xu, W ; Pertwee, R G ; Makriyannis, A . / Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'. In: Journal of Medicinal Chemistry. 2003 ; Vol. 46. pp. 3221-3229.
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AU - Chari, R

AU - Xu, W

AU - Pertwee, R G

AU - Makriyannis, A

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KW - HASHISH

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