Expansion of SAR studies on triaryl bis sulfone cannabinoid CB2 receptor ligands

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 22, 2010, Pages 6785-6789

  Tong, Ling ^a   Shankar, B B ^a   Chen, Lei ^a   Rizvi, Razia ^a   Kelly, Joseph ^a   Gilbert, Eric ^a   Huang, Chunli ^a   Yang, De Yi ^a   Kozlowski, Joseph A ^a   Shih, N Y ^a   Gonsiorek, W ^a   Hipkin, R William ^a   Malikzay, Asra ^a   Lunn, Charles A ^a   Lundell, Daniel J ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Cannabinoid receptor; CB2; Inverse agonists; SAR

Indexed keywords

CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; SULFONE DERIVATIVE;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; DRUG DESIGN; DRUG EXPOSURE; DRUG OXIDATION; DRUG POTENCY; DRUG SELECTIVITY; NONHUMAN; RAT; REACTION OPTIMIZATION; STRUCTURE ACTIVITY RELATION;

ANIMALS; LIGANDS; RATS; RECEPTOR, CANNABINOID, CB2; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

RATTUS;

EID: 77958040363     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.08.126     Document Type: Article

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13. 3) δ 8.25 (d, J = 9.3 Hz, 1H), 8.03 (dt, J = 1.6 Hz, 7.0 Hz, 1H), 7.64 (d, J = 8 Hz, 1H), 7.51-7.60 (m, 2H), 7.47 (b, 1H), 7.37 (t, J = 7.7 Hz, 1H), 7.28 (t, J = 7.7 Hz, 1H), 7.05 (t, J = 9.6 Hz, 1H), 5.6 (b, 1H), 3.95 (d, J = 13 Hz, 2H), 3.19 (d, J = 6.6 Hz, 2H), 2.84 (t, J = 11.5 Hz, 2H), 1.81 (d, J = 13.3 Hz, 2H), 1.70 (m, 1H), 1.35 (dt, J = 4.0 Hz, 11.6 Hz, 2H).
14. 3) δ 8.23 (m, 1H), 8.02 (m, 1H), 7.58 (m, 1H), 7.42 (s, 1H), 7.25 (m, 3H), 7.04 (m, 1H), 5.17 (t, J = 6.6 Hz, 1H), 3.42 (m, 2H), 3.33 (m, 2H), 3.19 (d, J = 6.6 Hz, 2H), 1.54 (m, 4H), 1.42 (q, J = 7.0 Hz, 2H), 0.83 (t, J = 7.0 Hz, 3H).
15. 3) δ 8.5 (d, J = 4 Hz, 1H), 8.4 (d, J = 6 Hz, 1H), 8.2 (d, J = 6 Hz, 1H), 7.9 (m, 1H), 7.62 (d, 1H), 7.4-7.6 (m, 3H), 7.36 (m, 1H), 3.5 (m, 2H), 3.38 (m, 2H), 3.19 (d, J = 6.6 Hz, 2H), 1.58 (m, 4H), 1.38 (m, 2H), 1.2 (m, 4H).
16. 3) δ 8.40 (d, J = 7.0 Hz, 1H), 8.23 (m, 1H), 7.97 (d, J = 10 Hz, 1H), 7.58 (m, 1H), 7.30 (m, 1H), 7.22 (m, 1H), 7.02 (m, 1H), 5.40 (b, 1H), 3.70 (d, J = 15 Hz, 2H), 3.25 (m, 4H), 3.20 (s, 3H), 1.96 (d, J = 15 Hz, 2H), 1.66 (m, 2H).
17. 2 receptor to interact with β-arrestin. As expected, the agonist WIN55212-2 increases this interaction.
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