ACS Medicinal Chemistry Letters
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(2014CB541906), and the Zhejiang Technology Office (Qianjiang
Talents Project 2010R10048).
9. Aghazadeh Tabrizi, M.; Baraldi, P. G.; Borea, P. A.; Varani,
1
2
3
4
5
6
7
8
K. Medicinal chemistry, pharmacology, and potential
therapeutic benefits of cannabinoid CB2 receptor agonists.
Chem. Rev. 2016, 116, 519ꢀ560.
ABBREVIATIONS
10. Muccioli, G.; Lambert, D. Current knowledge on the
antagonists and inverse agonists of cannabinoid receptors.
Curr. Med. Chem. 2005, 12, 1361ꢀ1394.
11. Riether, D. Selective cannabinoid receptor 2 modulators: a
patent review 2009ꢀpresent. Expert Opin. Ther. Pat. 2012, 22,
495ꢀ510.
12. Mugnaini, C.; Brizzi, A.; Ligresti, A.; Allarà, M.; Lamponi,
S.; Vacondio, F.; Silva, C.; Mor, M.; Di Marzo, V.; Corelli, F.
Investigations on the 4ꢀquinoloneꢀ3ꢀcarboxylic acid motif. 7.
CB1, cannabinoid receptor type 1; CB2, cannabinoid receptor type
2; CNS, central nervous system; SAR, structureꢀactivity
relationship
REFERENCES
1. Howlett, A. B., F.; Bonner, T.; Cabral, G.; Casellas, P.;
Devane, W.; Felder, C.; Herkenham, M.; Mackie, K.; Martin,
B. International Union of Pharmacology. XXVII.
Classification of cannabinoid receptors. Pharmacol. Rev.
2002, 54, 161ꢀ202.
2. Henness, S.; Robinson, D. M.; LysengꢀWilliamson, K. A.
Rimonabant. Drugs 2006, 66, 2109ꢀ2119.
3. Huffman, J. W.; Liddle, J.; Yu, S.; Aung, M. M.; Abood, M.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis
and
pharmacological
evaluation
of
4ꢀquinoloneꢀ3ꢀcarboxamides
and
4ꢀhydroxyꢀ2ꢀquinoloneꢀ3ꢀcarboxamides as high affinity
cannabinoid receptor 2 (CB2R) ligands with improved
aqueous solubility J. Med. Chem. 2016, 59, 1052ꢀ1067.
13. Ellsworth, B. A.; Sher, P. M.; Wu, X.; Wu, G.; Sulsky, R. B.;
Gu, Z.; Murugesan, N.; Zhu, Y.; Yu, G.; Sitkoff, D. F.;
Carlson, K. E.; Kang, L.; Yang, Y.; Lee, N.; Baska, R. A.;
Keim, W. J.; Cullen, M. J.; Azzara, A. V.; Zuvich, E.;
Thomas, M. A.; Rohrbach, K. W.; Devenny, J. J.; Godonis, H.
E.; Harvey, S. J.; Murphy, B. J.; Everlof, G. G.; Stetsko, P. I.;
Gudmundsson, O.; Johnghar, S.; Ranasinghe, A.; Behnia, K.;
Pelleymounter, M. A.; Ewing, W. R. Reductions in log P
improved protein binding and clearance predictions enabling
the prospective design of cannabinoid receptor (CB1)
antagonists with desired pharmacokinetic properties. J. Med.
Chem. 2013, 56, 9586ꢀ9600.
E.;
Wiley,
J.
L.;
Martin,
B.
R.
related
3ꢀ(1',1'ꢀdimethylbutyl)ꢀ1ꢀdeoxyꢀꢁ8ꢀTHC
and
compounds: synthesis of selective ligands for the CB2
receptor. Bioorg. Med. Chem. Lett. 1999, 7, 2905ꢀ2914.
4. Hanuš, L.; Breuer, A.; Tchilibon, S.; Shiloah, S.; Goldenberg,
D.; Horowitz, M.; Pertwee, R. G.; Ross, R. A.; Mechoulam,
R.; Fride, E. HUꢀ308: a specific agonist for CB2, a peripheral
cannabinoid receptor. Proc. Natl. Acad. Sci. USA 1999, 96,
14228ꢀ14233.
5. Ibrahim, M. M.; Deng, H.; Zvonok, A.; Cockayne, D. A.;
Kwan, J.; Mata, H. P.; Vanderah, T. W.; Lai, J.; Porreca, F.;
Makriyannis, A. Activation of CB2 cannabinoid receptors by
AM1241 inhibits experimental neuropathic pain: pain
inhibition by receptors not present in the CNS. Proc. Natl.
Acad. Sci. USA 2003, 100, 10529ꢀ10533.
6. A randomized, doubleꢀblind study to evaluate the safety and
efficacy of 2 doses of Sꢀ777469 in patients with atopic
7. Giblin, G. M. P.; O'Shaughnessy, C. T.; Naylor, A.; Mitchell,
W. L.; Eatherton, A. J.; Slingsby, B. P.; Rawlings, D. A.;
Goldsmith, P.; Brown, A. J.; Haslam, C. P.; Clayton, N. M.;
Wilson, A. W.; Chessell, I. P.; Wittington, A. R.; Green, R.
14. Han, S.; Zhang, F.ꢀF.; Qian, H.ꢀY.; Chen, L.ꢀL.; Pu, J.ꢀB.;
Xie,
X.;
Chen,
J.ꢀZ.
Development
of
quinolineꢀ2,4(1H,3H)ꢀdiones as potent and selective ligands
of the cannabinoid type 2 receptor. J. Med. Chem. 2015, 58,
5751ꢀ5769.
15. Zhu, T.; Fang, L.ꢀY.; Xie, X. Development of a universal
highthroughput calcium assay for Gꢀproteinꢀcoupled
receptors with promiscuous Gꢀprotein Gα15/16. Acta
Pharmacol. Sin. 2008, 29, 507ꢀ516.
16. Giblin, G. M.; O'Shaughnessy, C. T.; Naylor, A.; Mitchell, W.
L.; Eatherton, A. J.; Slingsby, B. P.; Rawlings, D. A.;
Goldsmith, P.; Brown, A. J.; Haslam, C. P. Discovery of
2ꢀ[(2,4ꢀdichlorophenyl)amino]ꢀNꢀ[(tetrahydroꢀ2Hꢀpyranꢀ4ꢀyl
Discovery
of
2ꢀ[(2,4ꢀdichlorophenyl)amino]ꢀNꢀ[(tetrahydroꢀ2Hꢀpyranꢀ4ꢀyl
)methyl]ꢀ4ꢀ(trifluoromethyl)ꢀ5ꢀpyrimidinecarboxamide,
selective CB2 receptor agonist for the treatment of
inflammatory pain. J. Med. Chem. 2007, 50, 2597ꢀ2600.
8. Ostenfeld, T.; Price, J.; Albanese, M.; Bullman, J.; Guillard,
F.; Meyer, I.; Leeson, R.; Costantin, C.; Ziviani, L.; Nocini, P.
F.; Milleri, S. A randomized, controlled study to investigate
the analgesic efficacy of single doses of the cannabinoid
receptorꢀ2 agonist GW842166, ibuprofen or placebo in
patients with acute pain following third molar tooth
extraction. Clin. J. Pain 2011, 27, 668ꢀ676.
a
)methyl]ꢀ4ꢀ(trifluoromethyl)ꢀ5ꢀpyrimidinecarboxamide,
a
selective CB2 receptor agonist for the treatment of
inflammatory pain. J. Med. Chem. 2007, 50, 2597ꢀ2600.
17. Cheng, T.; Zhao, Y.; Li, X.; Lin, F.; Xu, Y.; Zhang, X.; Li,
Y.; Wang, R.; Lai, L. Computation of octanolꢀwater partition
coefficients by guiding an additive model with knowledge. J.
Chem. Inf. Model. 2007, 47, 2140ꢀ2148.
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