5-sulfonamide benzimidazoles: A class of cannabinoid receptors agonists with potent in vivo antinociception activity

Letters in Drug Design and Discovery

Volumn 7, Issue 3, 2010, Pages 208-213

  Pagé, Daniel ^a   Wei, Zhongyong ^a,b   Liu, Ziping ^a   Tremblay, Maxime ^a   Desfossés, Hélène ^a   Milburn, Claire ^a   Srivastava, Sanjay ^a   Yang, Hua ^a,b   Brown, William ^a   Walpole, Christopher ^a   Tomaszewski, Mirek ^a   St Onge, Stéphane ^a   Lessard, Etienne ^a   Payza, Kemal ^a   Panetta, Rosemarie ^a   Yu, Xiao Hong ^a   Groblewski, Thierry ^a  

^a ASTRAZENECA   (United Kingdom)

^b Pharmaron Beijing Co Ltd   (China)

Author keywords

Antinociception; Benzimidazoles; Cannabinoid agonists

Indexed keywords

5 SULFONAMIDE BENZIMIDAZOLE DERIVATIVE; BENZIMIDAZOLE DERIVATIVE; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CANNABINOID RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ANALGESIA; ANTINOCICEPTION; ARTICLE; BINDING AFFINITY; BIOLOGICAL ACTIVITY; DISTRIBUTION VOLUME; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; HUMAN; IN VIVO STUDY; INFLAMMATION; NEUROPATHIC PAIN; NONHUMAN; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

EID: 77949762384     PISSN: 15701808     EISSN: None     Source Type: Journal    
DOI: 10.2174/157018010790596669     Document Type: Article

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27. 1H NMR (METHANOL-D4) δ ppm 1.22 (m, 5 H) 1.61 (m, 2 H) 1.64 (s, 9 H) 1.67 (m, 1 H) 1.74 (m, J=2.34 Hz, 2 H) 2.08 (m, 1 H) 3.29 (s, 3 H) 4.43 (d, J=7.62 Hz, 2 H) 7.15 (dd, J=5.08, 3.71 Hz, 1 H) 7.33 (dd, J=8.98, 1.95 Hz, 1 H) 7.40 (dd, J=3.71, 1.37 Hz, 1 H) 7.55 (d, J=1.56 Hz, 1 H) 7.81 (dd, J=5.08, 1.37 Hz, 1 H) 7.85 (d, J=8.98 Hz, 1 H); 446.1 (MH+ monoisot.); compound 67: 1H NMR (METHANOL-D4) δ ppm 1.29 (t, J=7.42 Hz, 3 H) 1.48-1.60 (m, 2 H) 1.64 (s, 9 H) 1.66 - 1.72 (m, 2 H) 1.73-1.82 (m, 2 H) 1.99-2.09 (m, 2 H) 2.18-2.28 (m, 1 H) 3.11 (q, J=7.29 Hz, 2 H) 4.50 (d, J=7.62 Hz, 2 H) 7.38 (dd, J=9.08, 2.05 Hz, 1 H) 7.72 (d, J=2.15 Hz, 1 H) 7.85 (d, J=8.98 Hz, 1 H); 414.0 (MH+ monoisot.).
28. H) for ligands in displacing specifically bound radioligand are calculated in Activity base with ExcelFit. The concentration of compounds to use and dilutions are also calculated with Activity base. The radioactivity (cpm) is counted in a TopCount (Packard) after adding 65 μL/well of MS-20 scintillation liquid.
29. max and Hill slope (nH) parameters.
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31. max = 110%).
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