97374-49-7Relevant academic research and scientific papers
Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family
Borrmann, Thomas,Abdelrahman, Aliaa,Volpini, Rosaria,Lambertucci, Catia,Alksnis, Edgars,Gorzalka, Simone,Knospe, Melanie,Schiedel, Anke C.,Cristalli, Gloria,Müller, Christa E.
supporting information; scheme or table, p. 5974 - 5989 (2010/03/24)
Adenine derivatives bearing substituents in the 2-, N6-, 7-, 8-, and/or 9-position and a series of deazapurines were synthesized and investigated in [3H]adenine binding studies at the adenine receptor in rat brain cortical membrane preparations (rAde1R). Steep structure-activity relationships were observed. Substitution in the 8-position (amino, dimethylamino, piperidinyl, piperazinyl) or in the 9-position (2-morpholinoethyl) with basic residues or introduction of polar substituents at the 6-amino function (hydroxy, amino, acetyl) represented the best modifications. Functional evaluation of selected adenine derivatives in adenylate cyclase assays at 1321N1 astrocytoma cells stably expressing the rAde1R showed that all compounds investigated were agonists or partial agonists. A subset of compounds was additionally investigated in binding studies at human embryonic kidney (HEK293) cells, which also express a high-affinity adenine binding site. Structure-affinity relationships at the human cell line were similar to those at the rAde1R, but not identical. In particular, N 6-acetyladenine (25, Ki rat: 2.85 μM; Ki human: 0.515 μM) and 8-aminoadenine (33, Ki rat: 6.51 μM; Ki human: 0.0341 μM) were much more potent at the human as compared to the rat binding site. The new AdeR ligands may serve as lead structures and contribute to the elucidation of the functions of the adenine receptor family. 2009 American Chemical Society.
Inhibition of siderophore biosynthesis in Mycobacterium tuberculosis with nucleoside bisubstrate analogues: Structure-activity relationships of the nucleobase domain of 5′-O-[N-(salicyl)sulfamoyl]adenosine
Neres, Jo?o,Labello, Nicholas P.,Somu, Ravindranadh V.,Boshoff, Helena I.,Wilson, Daniel J.,Vannada, Jagadeshwar,Chen, Liqiang,Barry III, Clifton E.,Bennett, Eric M.,Aldrich, Courtney C.
experimental part, p. 5349 - 5370 (2009/07/01)
5′-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) is a prototype for a new class of antitubercular agents that inhibit the aryl acid adenylating enzyme (AAAE) known as MbtA involved in biosynthesis of the mycobactins. Herein, we report the structure-based design, synthesis, biochemical, and biological evaluation of a comprehensive and systematic series of analogues, exploring the structure-activity relationship of the purine nucleobase domain of Sal-AMS. Significantly, 2-phenyl-Sal-AMS derivative 26 exhibited exceptionally potent antitubercular activity with an MIC99 under iron-deficient conditions of 0.049 μM while the N-6-cyclopropyl-Sal-AMS 16 led to improved potency and to a 64-enhancement in activity under iron-deficient conditions relative to iron-replete conditions, a phenotype concordant with the designed mechanism of action. The most potent MbtA inhibitors disclosed here display in vitro antitubercular activity superior to most current first line TB drugs, and these compounds are also expected to be useful against a wide range of pathogens that require aryl-capped siderphores for virulence.
N-cycloalkyl derivatives of adenosine and 1-deazaadenosine as agonists and partial agonists of the A1 adenosine receptor
Vittori, Sauro,Lorenzen, Anna,Stannek, Christina,Costanzi, Stefano,Volpini, Rosaria,Ijzerman, Adriaan P.,Von Frijtag Drabbe Kunzel, Jakobien K.,Cristalli, Gloria
, p. 250 - 260 (2007/10/03)
A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'- deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A1 and A(
Dog Coronary Artery Adenosine Receptor: Structure of the N6-Alkyl Subregion
Kusachi, Shozo,Thompson, Robert D.,Bugni, William J.,Yamada, Nobuyuki,Olsson, R. A.
, p. 1636 - 1643 (2007/10/02)
The moderately potent and stereoselective coronary vasoactivity of N6-adenosine (1) is the basis for the present study that maps the N6 region of the coronary artery adenosine receptor by means of the structure-coronary vasoactivity relationships of 81 analogues of 1 in the open-thorax dog.Stereoselectivity is a general property of N6-substituted adenosines that have a chiral center adjacent to N6.The activity ratio of 1 to its S diastereomer is 10, the result of the positive interaction with the receptor of the propyl C-3 group of the Rdiastereomer in combination with the steric hindrance exerted by this group of the S diastereomer.Replacing the benzyl moiety of 1 by an ethyl, phenyl, phenethyl, or naphthyl group lowers potency of the R diastereomer and, accordingly, the R/S ratio.Propyl C-1 interacts with a receptor region large enough to accommodate three methylene residues and the propyl C-3 residue with a separate region large enough to accommodate two.The receptor subregion that interacts with the propyl C-1 of 1 is more tolerant of bulk and of polar substituents than the subregion that interacts with propyl C-3.Evidence bearing on the possible contribution of N6 to activity, e.g. through hydrogen bonding, is ambiguous.These results support a provisional model of the N6-alkyl subregion.
