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Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'.
J Med Chem. 2003 Jul 17; 46(15):3221-9.JM

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.

Authors+Show Affiliations

Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vass. Constantinou, Athens 116-35 Greece. dpapah@eie.grNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12852753

Citation

Papahatjis, Demetris P., et al. "Pharmacophoric Requirements for the Cannabinoid Side Chain. Probing the Cannabinoid Receptor Subsite at C1'." Journal of Medicinal Chemistry, vol. 46, no. 15, 2003, pp. 3221-9.
Papahatjis DP, Nikas SP, Kourouli T, et al. Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'. J Med Chem. 2003;46(15):3221-9.
Papahatjis, D. P., Nikas, S. P., Kourouli, T., Chari, R., Xu, W., Pertwee, R. G., & Makriyannis, A. (2003). Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'. Journal of Medicinal Chemistry, 46(15), 3221-9.
Papahatjis DP, et al. Pharmacophoric Requirements for the Cannabinoid Side Chain. Probing the Cannabinoid Receptor Subsite at C1'. J Med Chem. 2003 Jul 17;46(15):3221-9. PubMed PMID: 12852753.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacophoric requirements for the cannabinoid side chain. Probing the cannabinoid receptor subsite at C1'. AU - Papahatjis,Demetris P, AU - Nikas,Spyros P, AU - Kourouli,Therapia, AU - Chari,Ravi, AU - Xu,Wei, AU - Pertwee,Roger G, AU - Makriyannis,Alexandros, PY - 2003/7/11/pubmed PY - 2003/8/19/medline PY - 2003/7/11/entrez SP - 3221 EP - 9 JF - Journal of medicinal chemistry JO - J Med Chem VL - 46 IS - 15 N2 - 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. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/12852753/Pharmacophoric_requirements_for_the_cannabinoid_side_chain__Probing_the_cannabinoid_receptor_subsite_at_C1'_ L2 - https://doi.org/10.1021/jm020558c DB - PRIME DP - Unbound Medicine ER -