Results 271 to 280 of about 121,181 (303)

The discovery of novel calcium sensing receptor negative allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2009
The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis.
Gayatri, Balan, Jonathan, Bauman, Samit, Bhattacharya, Mayda, Castrodad, David R, Healy, Michael, Herr, Paul, Humphries, Sandra, Jennings, Amit S, Kalgutkar, Brendon, Kapinos, Vishal, Khot, Kimberly, Lazarra, Mei, Li, Yan, Li, Constantin, Neagu, Robert, Oliver, David W, Piotrowski, David, Price, Hong, Qi, Holly A, Simmons, James, Southers, Liuqing, Wei, Yan, Zhang, Vishwas M, Paralkar   +23 more
openaire   +2 more sources

A negative allosteric modulator modulates GABAB-receptor signalling through GB2 subunits

Biochemical Journal, 2016
An γ-aminobutyric acid type B (GABAB)-receptor mediates slow and prolonged synaptic inhibition in the central nervous system, which represents an interesting target for the treatment of various diseases and disorders of the central nervous system.
Bing, Sun, Linhai, Chen, Lei, Liu, Zhixiong, Xia, Jean-Philippe, Pin, Fajun, Nan, Jianfeng, Liu   +6 more
openaire   +2 more sources

Structure optimization of positive allosteric modulators of GABAB receptors led to the unexpected discovery of antagonists/potential negative allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2020
Positive allosteric modulators (PAMs) of GABAB receptor represent an interesting alternative to receptor agonists such as baclofen, as they act on the receptor in a more physiological way and thus are devoid of the side effects typically exerted by the agonists.
Claudia Mugnaini, Antonella Brizzi, Rafaela Mostallino, Maria Paola Castelli, Federico Corelli   +4 more
openaire   +3 more sources

Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-(( trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1 H)-yl)ethyl)cyclohexyl)-1 H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor.

Journal of Medicinal Chemistry, 2018
SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of "second generation" analogues of 1 whereby subtle modifications to the indole-2-carboxamide motif ...
Anitha Kopinathan, C. Draper-Joyce, M. Szabó, A. Christopoulos, P. Scammells, J. R. Lane, B. Capuano   +6 more
semanticscholar   +1 more source

Nanobodies as negative allosteric modulators for human calcium sensing receptor

Biochemical and Biophysical Research Communications
Human calcium sensing receptor (CaSR) senses calcium ion concentrations in vivo and is an important class of drug targets. Mutations in the receptor can lead to disorders of calcium homeostasis, including hypercalcemia and hypocalcemia. Here, 127 CaSR-targeted nanobodies were generated from camels, and four nanobodies with inhibitory function were ...
Qianqian Cui, Lu Wang, Haonan Wang, Xiaochen Chen, Li Han, Tengjie Geng, Yongjun Kou, Wenqing Zhang, Mei Dai, Huarui Qiao, Zengchao Sun, Lingyun Li, Zhongyun Lan, Hongxi Xu, Jiaqiang Xu, Yuanyuan Dai, Yong Geng   +16 more
openaire   +2 more sources

In silico docking yields small molecule negative allosteric modulators targeting the core of Frizzled 7

Nature Communications
Targeting the Frizzled family (FZD1-10) of WNT receptors pharmacologically has, despite substantial therapeutic potential, proven difficult. Given an almost complete lack of validated, effective small molecules targeting FZDs, no putative ligand binding ...
Magdalena M. Scharf, Julia Kinsolving, Lukas Grätz, J. Voss, David Carrasco‐Busturia, Björn Forsberg, Peter Kolb, Gunnar Schulte   +7 more
semanticscholar   +1 more source

6-Aryl-3-pyrrolidinylpyridines as mGlu5 receptor negative allosteric modulators

Bioorganic & Medicinal Chemistry Letters, 2011
A series of 6-aryl-3-pyrrolidinylpyridine analogs was explored as structurally novel negative allosteric modulators of the mGlu5 receptor lacking an alkyne or oxadiazole moiety. Compounds in this series were characterized by tractable SAR, good in vitro potencies and brain penetration in rodents.
Jesse M, Weiss, Hermogenes N, Jimenez, Guiying, Li, Myriam, April, Michelle A, Uberti, Maria D, Bacolod, Robb M, Brodbeck, Darío, Doller   +7 more
openaire   +2 more sources

Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel

European Journal of Medicinal Chemistry, 2015
We synthesized and evaluated a series of compounds for their allosteric modulation at the Kv11.1 (hERG) channel. Most compounds were negative allosteric modulators of [(3)H]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly ...
Yu, Z., Veldhoven, J.P.D. van, Hart, I.M. 't, Kopf, A.H., Heitman, L.H., IJzerman, A.P.   +5 more
openaire   +3 more sources

Understanding the Allosteric Modulation of PTH1R by a Negative Allosteric Modulator

Cells, 2023
Mengrong Li, Yiqiong Bao, Lili Xi
exaly  

Elaboration and Design of α7 nAChR Negative Allosteric Modulators

2015
VCU Theses and ...
openaire   +1 more source