1147271-23-5Relevant academic research and scientific papers
Targeting promoter G-quadruplex DNAs by indenopyrimidine-based ligands
Diveshkumar,Sakrikar, Saaz,Harikrishna,Dhamodharan,Pradeepkumar
, p. 2754 - 2765 (2015/02/02)
The formation of G-quadruplex structures can regulate telomerase activity and the expression of oncogenes at the transcriptional and translational levels. Therefore, stabilization of G-quadruplex DNA structures by small molecules has been recognized as a promising strategy for anticancer drug therapy. One of the major challenges in this field is to impart stabilizing molecules with selectivity toward quadruplex structures over duplex DNAs, and to maintain specificity toward a particular quadruplex topology. Herein we report the synthesis and binding interactions of indenopyrimidine derivatives, endowed with drug-like properties, with oncogenic promoters of c-myc and c-kit, telomeric and duplex DNAs. The results show specific stabilization of promoter over telomeric quadruplexes and duplex DNAs. Molecular modeling studies support the experimental observations by unraveling the dual binding mode of ligands by exploiting the top and bottom quartets of a G-quadruplex structure. This study underscores the potential of the indenopyrimidine scaffold, which can be used to achieve specific G-quadruplex-mediated anticancer activity.
Design and characterization of optimized adenosine A2A/A 1 receptor antagonists for the treatment of Parkinson's disease
Shook, Brian C.,Rassnick, Stefanie,Wallace, Nathaniel,Crooke, Jeffrey,Ault, Mark,Chakravarty, Devraj,Barbay, J. Kent,Wang, Aihua,Powell, Mark T.,Leonard, Kristi,Alford, Vernon,Scannevin, Robert H.,Carroll, Karen,Lampron, Lisa,Westover, Lori,Lim, Heng-Keang,Russell, Ronald,Branum, Shawn,Wells, Kenneth M.,Damon, Sandra,Youells, Scott,Li, Xun,Beauchamp, Derek A.,Rhodes, Kenneth,Jackson, Paul F.
experimental part, p. 1402 - 1417 (2012/04/04)
The design and characterization of two, dual adenosine A 2A/A1 receptor antagonists in several animal models of Parkinson's disease is described. Compound 1 was previously reported as a potential treatment for Parkinson's disease. Fu
Optimization of arylindenopyrimidines as potent adenosine A2A/A1 antagonists
Shook, Brian C.,Rassnick, Stefanie,Chakravarty, Devraj,Wallace, Nathaniel,Ault, Mark,Crooke, Jeffrey,Barbay, J. Kent,Wang, Aihua,Leonard, Kristi,Powell, Mark T.,Alford, Vernon,Hall, Daniel,Rupert, Kenneth C.,Heintzelman, Geoffrey R.,Hansen, Kristen,Bullington, James L.,Scannevin, Robert H.,Carroll, Karen,Lampron, Lisa,Westover, Lori,Russell, Ronald,Branum, Shawn,Wells, Kenneth,Damon, Sandra,Youells, Scott,Beauchamp, Derek,Li, Xun,Rhodes, Kenneth,Jackson, Paul F.
scheme or table, p. 2868 - 2871 (2010/07/06)
Two reactive metabolites were identified in vivo for the dual A2A/A1 receptor antagonist 1. Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1. Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro and in vivo activity.
ARYLINDENOPYRIMIDINES AND THEIR USE AS ADENOSINE A2a
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Page/Page column 3; 4, (2009/05/29)
This invention relates to novel arylindenopyrimidines A, B, and C, and their therapeutic and prophylactic uses. Disorders treated and/or prevented using these compounds include Parkinson's Disease.
