139181-27-4Relevant academic research and scientific papers
NON BRAIN PENETRANT A2A INHIBITORS AND METHODS FOR USE IN THE TREATMENT OF CANCERS
-
, (2020/04/24)
The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention further relates to the use of the compounds of Formula (I) as A2A inhibitors. The invention also relates to the use of the compounds of F
triAZOLOtriAZINE DERIVATIVES AS A2A RECEPTOR ANTAGONISTS
-
, (2020/01/24)
The present invention provides triazolotriazine derivatives of formula (1) as A2A receptor antagonists. Compounds of formula (1) and pharmaceutical compositions including the compounds can be used for the treatment of disorders related to A2A receptor hyperfunctioning, such as certain types cancers. Compounds of formula (1) and methods of preparing the compounds are disclosed in the invention.
TRIAZOLOTRIAZINE DERIVATIVES AS A2A RECEPTOR ANTAGONISTS
-
, (2020/01/24)
The present invention provides triazolotriazine derivatives of formula (1) as A2A receptor antagonists. Compounds of formula (1) and pharmaceutical compositions including the compounds can be used for the treatment of disorders related to A2A receptor hyp
An Fc–Small Molecule Conjugate for Targeted Inhibition of the Adenosine 2A Receptor
Hsiao, Po-Yuan,Kalin, Jay H.,Sun, Im-Hong,Amin, Mohammed N.,Lo, Ying-Chun,Chiang, Meng-Jung,Giddens, John,Sysa-Shah, Polina,Gabrielson, Kathleen,Wang, Lai-Xi,Powell, Jonathan D.,Cole, Philip A.
, p. 1951 - 1960 (2016/10/24)
The adenosine A2A receptor (A2AR) is expressed in immune cells, as well as brain and heart tissue, and has been intensively studied as a therapeutic target for multiple disease indications. Inhibitors of the A2AR have the
Synthesis and pharmacological evaluation of dual acting ligands targeting the adenosine A2A and dopamine D2 receptors for the potential treatment of parkinsons disease
J?rg, Manuela,May, Lauren T.,Mak, Frankie S.,Lee, Kiew Ching K.,Miller, Neil D.,Scammells, Peter J.,Capuano, Ben
supporting information, p. 718 - 738 (2015/01/30)
A relatively new strategy in drug discovery is the development of dual acting ligands. These molecules are potentially able to interact at two orthosteric binding sites of a heterodimer simultaneously, possibly resulting in enhanced subtype selectivity, higher affinity, enhanced or modified physiological response, and reduced reliance on multiple drug administration regimens. In this study, we have successfully synthesized a series of classical heterobivalent ligands as well as a series of more integrated and drug-like dual acting molecules, incorporating ropinirole as a dopamine D2 receptor agonist and ZM 241385 as an adenosine A2A receptor antagonist. The best compounds of our series maintained the potency of the original pharmacophores at both receptors (adenosine A2A and dopamine D2). In addition, the integrated dual acting ligands also showed promising results in preliminary blood-brain barrier permeability tests, whereas the classical heterobivalent ligands are potentially more suited as pharmacological tools.
Binding kinetics of ZM241385 derivatives at the human adenosine A 2A receptor
Guo, Dong,Xia, Lizi,Van Veldhoven, Jacobus P. D.,Hazeu, Marc,Mocking, Tamara,Brussee, Johannes,Ijzerman, Adriaan P.,Heitman, Laura H.
supporting information, p. 752 - 761 (2014/05/06)
Classical drug design and development rely mostly on affinity- or potency-driven structure-activity relationships (SAR). Thus far, a given compound's binding kinetics have been largely ignored, the importance of which is now being increasingly recognized. In the present study, we performed an extensive structure-kinetics relationship (SKR) study in addition to a traditional SAR analysis at the adenosine A2A receptor (A 2AR). The ensemble of 24 A2AR compounds, all triazolotriazine derivatives resembling the prototypic antagonist ZM241385 (4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino) ethyl)phenol), displayed only minor differences in affinity, although they varied substantially in their dissociation rates from the receptor. We believe that such a combination of SKR and SAR analyses, as we have done with the A 2AR, will have general importance for the superfamily of G protein-coupled receptors, as it can serve as a new strategy to tailor the interaction between ligand and receptor. Above and beyond: Insight into the binding kinetics of ZM241385 derivatives at the human adenosine A2A receptor has provided additional information beyond a traditional structure-activity relationship (SAR) analysis. The strategy, combining a structure-kinetics relationship investigation and SAR, can serve as an important tool for more directed medicinal chemistry efforts in the future.
Novel adenosine A2A receptor ligands: A synthetic, functional and computational investigation of selected literature adenosine A2A receptor antagonists for extending into extracellular space
J?rg, Manuela,Shonberg, Jeremy,Mak, Frankie S.,Miller, Neil D.,Yuriev, Elizabeth,Scammells, Peter J.,Capuano, Ben
supporting information, p. 3427 - 3433 (2013/06/26)
Growing evidence has suggested a role in targeting the adenosine A 2A receptor for the treatment of Parkinson's disease. The literature compounds KW 6002 (2) and ZM 241385 (5) were used as a starting point from which a series of novel ligands targeting the adenosine A2A receptor were synthesized and tested in a recombinant human adenosine A2A receptor functional assay. In order to further explore these molecules, we investigated the biological effects of assorted linkers attached to different positions on selected adenosine A2A receptor antagonists, and assessed their potential binding modes using molecular docking studies. The results suggest that linking from the phenolic oxygen of selected adenosine A2A receptor antagonists is relatively well tolerated due to the extension towards extracellular space, and leads to the potential of attaching further functionality from this position.
Synthesis, molecular structure, NMR spectroscopic and computational analysis of a selective adenosine A2A antagonist, ZM 241385
Joerg, Manuela,Agostino, Mark,Yuriev, Elizabeth,Mak, Frankie S.,Miller, Neil D.,White, Jonathan M.,Scammells, Peter J.,Capuano, Ben
, p. 1241 - 1251 (2013/08/23)
Herein, we describe the synthesis of the adenosine A2A antagonist ZM 241385 (9) starting from commercially available 2-furanhydrazide (1) and including a comprehensive structural characterization of all the intermediates and the final product.
2-furyl-triazalo [1,5-a]-[1,3,5]triazines and pyrazolo [2,3-a][1,3,5]triazines
-
, (2008/06/13)
Compounds of the formula I: STR1 wherein: X is O, S or NH;n is O or an integer of from 1 to 3;R 1 is hydrogen, (1-6C)alkyl, or (1-4C)alkanoyl;R 2 is CH 2 R 3, NHR 4, SO 2 NR 5 YNR 6 R 7 or R 8, in which R 3 is hydroxy, (1-4C)alkoxy or (1-4C)alkylsulphonyl
Adenine isosteres with bridgehead nitrogen. Part 1. Two independent syntheses of the triazolotriazine ring system leading to a range of substituents in the 2, 5 and 7 positions
Caulkett, Peter W. R.,Jones, Geraint,McPartlin, Mary,Renshaw, Nigel D.,Stewart, Sarah K.,Wright, Brian
, p. 801 - 808 (2007/10/02)
Condensation of a 3-substituted 5-amino-1,2,4-triazole with an N-cyanocarbonimidate (RX)2C=NCN, yields the title compounds, in most cases as a mixture of isomers; separation and elaboration then gives triazolotriazines bearing a range
