ACS Chemical Neuroscience p. 1565 - 1574 (2016)
Update date:2022-08-10
Topics:
Alix, Katie
Khatri, Shailesh
Mosier, Philip D.
Casterlow, Samantha
Yan, Dong
Nyce, Heather L.
White, Michael M.
Schulte, Marvin K.
Dukat, Ma?gorzata
Introduction of minor variations to the substitution pattern of arylguanidine 5-hydroxytryptamine-3 (5-HT3) receptor ligands resulted in a broad spectrum of functionally-active ligands from antagonist to superagonist. For example, (i) introduction of an additional Cl-substituent(s) to our lead full agonist N-(3-chlorophenyl)guanidine (mCPG, 2; efficacy % = 106) yielded superagonists 7-9 (efficacy % = 186, 139, and 129, respectively), (ii) a positional isomer of 2, p-Cl analog 11, displayed partial agonist actions (efficacy % = 12), and (iii) replacing the halogen atom at the meta or para position with an electron donating OCH3 group or a stronger electron withdrawing (i.e., CF3) group resulted in antagonists 13-16. We posit based on combined mutagenesis, crystallographic, and computational analyses that for the 5-HT3 receptor, the arylguanidines that are better able to simultaneously engage the primary and complementary subunits, thus keeping them in close proximity, have greater agonist character while those that are deficient in this ability are antagonists.
View MoreContact:86-311-67265101
Address:203 Lianmeng Road, Qiaoxi District
Shanghai Haoyuan Chemexpress Co., Ltd.
Contact:86-21-51870955;58998985;58999585
Address:Room 601, No. 2 BLD, NO. 720, Cailun Road, Zhangjiang, Shanghai, China
Contact:+86 21 5017 5386
Address:No 999,Jiangyue Rd, Minhang Dist ,201114,Shanghai ,China
chengdu firsterchem Pharmaceutical Co., Ltd.
Contact:028-66825849
Address:chengdu
Shijiazhuang Sdyano Fine Chemical Co., Ltd
Contact:+86-311-89830448
Address:NO.48 Ta Nan Road,Yuhua District,Shijiazhuang,Hebei,China
Doi:10.1002/aoc.4352
(2018)Doi:10.1139/v72-246
(1972)Doi:10.1016/j.tetlet.2011.01.047
(2011)Doi:10.1002/jps.2600740124
(1985)Doi:10.1016/S0040-4039(99)00724-8
(1999)Doi:10.1039/cc9960002029
(1996)