Multiple Binding Sites for Small Molecule Antagonists at the Chemokine Receptor CCR2

Autor: Maarten L. J. Doornbos, Annelien J.M. Zweemer, Dean Stamos, Hilde Vrieling, Jeffrey Abt, John Saunders, Indira Nederpelt, Sarah Hafith, Henk de Vries, Laura H. Heitman, Martine J. Smit, Raymond S. Gross, Adriaan P. IJzerman

Publikováno v: Molecular Pharmacology, 2013(84), 551-561. American Society for Pharmacology and Experimental Therapeutics
Zweemer, A J, Nederpelt, I, Vrieling, H, Hafith, S, Doornbos, M L, de Vries, H, Abt, J, Gross, R, Stamos, D, Saunders, J, Smit, M J, IJzerman, A P & Heitman, L H 2013, ' Multiple Binding Sites for Small Molecule Antagonists at the Chemokine Receptor CCR2 ', Molecular Pharmacology, vol. 2013, no. 84, pp. 551-561 . https://doi.org/10.1124/mol.113.086850

The chemokine receptor CCR2 is a G protein-coupled receptor that is activated primarily by the endogenous CC chemokine ligand 2 (CCL2). Many different small-molecule antagonists have been developed to inhibit this receptor, as it is involved in a var

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::876056dc6ab3615ab4c65f282a968413
https://doi.org/10.1124/mol.113.086850

2,6-Diaryl-4-acylaminopyrimidines as potent and selective adenosine A2A antagonists with improved solubility and metabolic stability

Autor: Marion Lanier, Xiaohu Zhang, John E. Tellew, Zhiyong Luo, Mark Santos, Raymond S. Gross, Deborah H. Slee, Emily Lin, Sandra M. Lechner, Jaimie K. Rueter, María I. Crespo, Jose-Luis Diaz, Yongsheng Chen, Siobhan Malany, Manisha Moorjani, John Saunders, John P. Williams, Binh G. Vong

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 18:5402-5405

In this report, the strategy and outcome of expanding SAR exploration to improve solubility and metabolic stability are discussed. Compound 35 exhibited excellent potency, selectivity over A(1) and improved solubility of >4 mg/mL at pH 8.0. In additi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::799d40e0876b3b15e810f1648d5b9dc2
https://doi.org/10.1016/j.bmcl.2008.09.048

Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists

Autor: Yongsheng Chen, Mark Santos, Emily Lin, Stacy Markison, John E. Tellew, Sandra M. Lechner, Maria Prat, Xiaohu Zhang, John Saunders, Silvia Gual, Marion Lanier, Marı´a I. Crespo, John P. Williams, Raymond S. Gross, Tanya Joswig, Jaimie K. Rueter, Deborah H. Slee, Siobhan Malany, Jose-Luis Diaz, Manisha Moorjani, Julio C. Castro-Palomino

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 18:1778-1783

A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-indu

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26dca2261358c58ec30c26ccccacb9f1
https://doi.org/10.1016/j.bmcl.2008.02.032

Design and Synthesis of Tricyclic Imidazo[4,5-b]pyridin-2-ones as Corticotropin-Releasing Factor-1 Antagonists

Autor: Said Zamani-Kord, Brian Dyck, Zhiqiang Guo, Robert W. Sullivan, Zhiyong Luo, Raymond S. Gross, Manisha Moorjani, Bin-Feng Li, Mustapha Haddach, John E. Tellew, Mehrak Kiankarimi, Marion Lanier, John P. Williams, James R. McCarthy, Dimitri Grigoriadis, Ta Kung Chen, Paul D. Crowe, John Saunders, Xiaohu Zhang, Jonathan Grey

Publikováno v: Journal of Medicinal Chemistry. 48:5104-5107

The synthesis and SAR studies of tricyclic imidazo[4,5-b]pyridin-2-ones as human corticotropin-releasing factor receptor (CRF(1)) antagonists are discussed herein. Compound 16g was identified as a functional antagonist that inhibited CRF-stimulated c

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::815355c45c4d5367cde1ab00c4dece95
https://doi.org/10.1021/jm050384+

When structure-affinity relationships meet structure-kinetics relationships: 3-((Inden-1-yl)amino)-1-isopropyl-cyclopentane-1-carboxamides as CCR2 antagonists

Autor: Laura H. Heitman, Henk de Vries, Johannes Brussee, Dean Stamos, Anouk M F van der Gracht, Adriaan P. IJzerman, Raymond S. Gross, Paul Krenitsky, Dave C.T. Bleeker, Farhana Barmare, Maris Vilums, John Saunders, Zhiyi Yu, Jeremy J. Clemens, Annelien J.M. Zweemer

Publikováno v: European journal of medicinal chemistry. 93

Chemokine ligand 2 (CCL2) mediates chemotaxis of monocytes to inflammatory sites via interaction with its G protein–coupled receptor CCR2. Preclinical animal models suggest that the CCL2-CCR2 axis has a critical role in the development and maintena

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e786a6e43028abb6d68684f0da2a22ac
https://pubmed.ncbi.nlm.nih.gov/25666912