Peripherally selective diphenyl purine antagonist of the CB1 receptor.
Peripherally selective diphenyl purine antagonist of the CB1 receptor.
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DOI：
10.1021/jm401129n
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发表时间：
2013-10-24
影响因子：
7.3
通讯作者：
Maitra R
中科院分区：
文献类型：
--
作者：
Fulp A;Bortoff K;Zhang Y;Snyder R;Fennell T;Marusich JA;Wiley JL;Seltzman H;Maitra R
Antagonists of the CB1 receptor can be useful in the treatment of several diseases including obesity, diabetes, and liver disease. However, to date, the only clinically approved CB1 receptor antagonist, rimonabant, was withdrawn due to adverse CNS related side effects such as depression and suicidal ideation. Since rimonabant’s withdrawal, several groups have begun pursuing peripherally selective CB1 antagonists. These compounds are expected to be devoid of undesirable CNS related effects but maintain efficacy through antagonism of peripherally expressed CB1 receptors within target tissues. Reported here are our latest results toward development of a peripherally selective analog of the diphenyl purine CB1 antagonist otenabant 1. Compound 9 (N-{1-[8-(2-Chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}pentanamide) is a potent, orally absorbed antagonist of the CB1 receptor that is >50-fold selective for CB1 over CB2, highly selective for the periphery in a rodent model, and without efficacy in a series of in vivo assays designed to evaluate its ability to mitigate the central effects of Δ9-THC through the CB1 receptor.
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影响因子：
7.3
作者：
Pulp, Alan;Bortoff, Katherine;Zhang, Yanan;Seltzman, Herbert;Mathews, James;Snyder, Rodney;Fennell, Tim;Maitra, Rangan
通讯作者：
Maitra, Rangan
影响因子：
5.7
作者：
Chugh, Brige P.;Lerch, Jason P.;Sled, John G.
通讯作者：
Sled, John G.
影响因子：
5
作者：
Wiley, JL;Martin, BR
通讯作者：
Martin, BR
影响因子：
4.8
作者：
Bouaboula, M;Perrachon, S;Casellas, P
通讯作者：
Casellas, P
DOI：
10.1111/j.1476-5381.1959.tb00928.x
发表时间：
1959-01-01
期刊：
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子：
--
作者：
ARUNLAKSHANA, O;SCHILD, HO
通讯作者：
SCHILD, HO