O-1269

O-1269 is a drug that is a diarylpyrazole derivative, related to potent cannabinoid antagonist drugs such as rimonabant and surinabant. However O-1269 and several related drugs were unexpectedly found to act as full or partial agonists at the cannabinoid receptors rather than antagonists, and so produce the usual effects expected of cannabinoid agonists in animal tests, such as sedation and analgesic effects. The N-heptyl homolog O-1270 and the N-propyl homolog O-1399 also act as cannabinoid agonists with similar potency in vivo, despite weaker binding affinity at cannabinoid receptors compared to the pentyl homolog O-1269.[1][2][3] Agonist-like and atypical cannabinoid activity has also been observed with a number of related compounds.[4][5]

O-1269
Identifiers
IUPAC name
  • 5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-pentylpyrazole-3-carboxamide
CAS Number
PubChem CID
ChemSpider
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H22Cl3N3O
Molar mass450.79 g·mol−1
3D model (JSmol)
SMILES
  • CCCCCNC(=O)c2nn(c(c2C)-c(cc3)ccc3Cl)-c1ccc(Cl)cc1Cl
InChI
  • InChI=1S/C22H22Cl3N3O/c1-3-4-5-12-26-22(29)20-14(2)21(15-6-8-16(23)9-7-15)28(27-20)19-11-10-17(24)13-18(19)25/h6-11,13H,3-5,12H2,1-2H3,(H,26,29)
  • Key:JDBOTXIRNSWBCG-UHFFFAOYSA-N
 NY (what is this?)

References
  1. US 6509367, Billy R. Martin, Raj K. Razdan, Anu Mahadevan, "Pyrazole cannabinoid agonist and antagonists", published 2003-01-21
  2. Shim JY, Welsh WJ, Cartier E, Edwards JL, Howlett AC (March 2002). "Molecular interaction of the antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1- (2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide with the CB1 cannabinoid receptor". Journal of Medicinal Chemistry. 45 (7): 1447–59. doi:10.1021/jm010267o. PMID 11906286.
  3. Francisco ME, Seltzman HH, Gilliam AF, Mitchell RA, Rider SL, Pertwee RG, et al. (June 2002). "Synthesis and structure-activity relationships of amide and hydrazide analogues of the cannabinoid CB(1) receptor antagonist N-(piperidinyl)- 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716)". Journal of Medicinal Chemistry. 45 (13): 2708–19. doi:10.1021/jm010498v. PMID 12061874.
  4. Thomas BF, Francisco ME, Seltzman HH, Thomas JB, Fix SE, Schulz AK, et al. (September 2005). "Synthesis of long-chain amide analogs of the cannabinoid CB1 receptor antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716) with unique binding selectivities and pharmacological activities". Bioorganic & Medicinal Chemistry. 13 (18): 5463–74. doi:10.1016/j.bmc.2005.06.005. PMID 15994087.
  5. Wiley JL, Selley DE, Wang P, Kottani R, Gadthula S, Mahadeven A (February 2012). "3-Substituted pyrazole analogs of the cannabinoid type 1 (CB₁) receptor antagonist rimonabant: cannabinoid agonist-like effects in mice via non-CB₁, non-CB₂ mechanism". The Journal of Pharmacology and Experimental Therapeutics. 340 (2): 433–44. doi:10.1124/jpet.111.187815. PMC 3263966. PMID 22085649.
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