NESS-0327

NESS-0327
Identifiers
CAS Number	494844-07-4;
PubChem CID	10435654;
ChemSpider	8611079 ;
UNII	X1BQI2J97I;
CompTox Dashboard (EPA)	DTXSID00439851 ;
Chemical and physical data
Formula	C24H23Cl3N4O
Molar mass	489.83 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Clc3cc(Cl)ccc3-n4c2-c1ccc(Cl)cc1CCCc2c(n4)C(=O)NN5CCCCC5;
	InChI InChI=1S/C24H23Cl3N4O/c25-16-7-9-18-15(13-16)5-4-6-19-22(24(32)29-30-11-2-1-3-12-30)28-31(23(18)19)21-10-8-17(26)14-20(21)27/h7-10,13-14H,1-6,11-12H2,(H,29,32) ; Key:NCXBPZJQQSNIRA-UHFFFAOYSA-N ;
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NESS-0327 is a drug used in scientific research which acts as an extremely potent and selective antagonist of the cannabinoid receptor CB₁. It is much more potent an antagonist, and more selective for the CB₁ receptor over CB₂, than the more commonly used ligand rimonabant, with a K_i at CB₁ of 350fM (i.e. 0.00035nM) and a selectivity of over 60,000x for CB₁ over CB₂.[1] Independently, two other groups have described only modest nanomolar CB₁ affinity for this compound (125nM[2] and 18.4nM[3]). Also unlike rimonabant, NESS-0327 does not appear to act as an inverse agonist at higher doses, instead being a purely neutral antagonist which blocks the CB₁ receptor but does not produce any physiological effect of its own.[4]

References

Ruiu S, Pinna GA, Marchese G, Mussinu JM, Saba P, Tambaro S, et al. (July 2003). "Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor". The Journal of Pharmacology and Experimental Therapeutics. 306 (1): 363–70. doi:10.1124/jpet.103.049924. PMID 12663689. S2CID 32018707.
Stoit AR, Lange JH, Hartog AP, Ronken E, Tipker K, Stuivenberg HH, et al. (August 2002). "Design, synthesis and biological activity of rigid cannabinoid CB1 receptor antagonists". Chemical & Pharmaceutical Bulletin. 50 (8): 1109–13. doi:10.1248/cpb.50.1109. PMID 12192147.
Zhang Y, Burgess JP, Brackeen M, Gilliam A, Mascarella SW, Page K, et al. (June 2008). "Conformationally constrained analogues of N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716): design, synthesis, computational analysis, and biological evaluations". Journal of Medicinal Chemistry. 51 (12): 3526–39. doi:10.1021/jm8000778. PMID 18512901.
Tambaro S, Mongeau R, Dessi C, Pani L, Ruiu S (November 2005). "Modulation of ATP-mediated contractions of the rat vas deferens through presynaptic cannabinoid receptors". European Journal of Pharmacology. 525 (1–3): 150–3. doi:10.1016/j.ejphar.2005.09.058. PMID 16271359.

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[1] Ruiu S, Pinna GA, Marchese G, Mussinu JM, Saba P, Tambaro S, et al. (July 2003). "Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor". The Journal of Pharmacology and Experimental Therapeutics. 306 (1): 363–70. doi:10.1124/jpet.103.049924. PMID 12663689. S2CID 32018707.

[2] Stoit AR, Lange JH, Hartog AP, Ronken E, Tipker K, Stuivenberg HH, et al. (August 2002). "Design, synthesis and biological activity of rigid cannabinoid CB1 receptor antagonists". Chemical & Pharmaceutical Bulletin. 50 (8): 1109–13. doi:10.1248/cpb.50.1109. PMID 12192147.

[3] Zhang Y, Burgess JP, Brackeen M, Gilliam A, Mascarella SW, Page K, et al. (June 2008). "Conformationally constrained analogues of N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716): design, synthesis, computational analysis, and biological evaluations". Journal of Medicinal Chemistry. 51 (12): 3526–39. doi:10.1021/jm8000778. PMID 18512901.

[4] Tambaro S, Mongeau R, Dessi C, Pani L, Ruiu S (November 2005). "Modulation of ATP-mediated contractions of the rat vas deferens through presynaptic cannabinoid receptors". European Journal of Pharmacology. 525 (1–3): 150–3. doi:10.1016/j.ejphar.2005.09.058. PMID 16271359.

NESS-0327

See also

References