110691-01-5Relevant academic research and scientific papers
New, non-adenosine, high-potency agonists for the human adenosine A 2B receptor with an improved selectivity profile compared to the reference agonist N-ethylcarboxamidoadenosine
Beukers, Margot W.,Chang, Lisa C. W.,Von Frijtag Drabbe Künzel, Jacobien K.,Mulder-Krieger, Thea,Spanjersberg, Ronald F.,Brussee, Johannes,Ijzerman, Ad P.
, p. 3707 - 3709 (2004)
The adenosine A2B receptor is the least well characterized of the four known adenosine receptor subtypes because of the absence of potent, selective agonists. Here, we present five non-adenosine agonists. Among them, 2-amino-4-(4-hydroxyphenyl)
Cascade synthesis of thieno[2,3-b]pyridines by using intramolecular cyclization reactions of 3-cyano-2-(organylmethylthio)pyridines
Alinaghizadeh, Fatemeh,Zahedifar, Mahboobeh,Seifi, Mohammad,Sheibani, Hassan
, p. 663 - 669 (2016)
2-Amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitriles as starting materials have been prepared by reducing of 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitrile derivatives which were synthesized on stepwise one-pot three component reaction of malon
Design, synthesis, characterization and biological evaluation of Thieno[2,3?b]pyridines?chitosan nanocomposites as drug delivery systems for colon targeting
Elghanam, Amal E.,Elsiginy, Samia M.,Khodair, Ahmed I.,Mansour, Hanaa
, (2020/04/15)
Thieno[2,3?b]pyridine derivatives DATPa?c have been synthesized based on Thorpe?Ziegler Cyclization. The reaction of arylidene malononitrile derivatives (Ia?c) with thiocyanoacetamide (II) in basic medium (piperidine) followed by alkylation using ethyl chloroacetate and finally, cyclization in sodium ethoxide yielded DATPa?c. Thieno[2,3?b]pyridine?chitosan nanocomposites CS?DATPa?c were prepared from the DATPa?c and CS nanoparticles using sodium tripolyphosphate (TPP). CS?DATPa?c nanocomposites were characterized using FTIR, TEM and XRD techniques and showed a relatively narrow size distribution of monodispersed nanoparticles with the average size of 14–78 nm. The in vitro release studies of CS?DAΤPa?c nanocomposites were investigated and showed that the drug release rate is pH-dependent and the trend is as follows: basic > neutral > acidic. The faster release rate in basic medium effectively prolongs drug delivery in gastric pH. Additionally, the antibacterial investigation showed that DATPa?c and CS?DATPa?c nanocomposites exhibited antibacterial activity against both Gram-positive and Gram-negative bacteria but CS?DATPa?c nanocomposites showed much higher antibacterial activity compared to the DATPa?c, which in agreement with the particle size measurements as DATPa?c are in the bulky structure whereas, CS?DATPa?c are in the nanostructure. The results may have applications of drug design for colon targeting.
Amino-3, 5-dicyanopyridines targeting the adenosine receptors ranging from pan ligands to combined A1/A2B partial agonists
Catarzi, Daniela,Varano, Flavia,Varani, Katia,Vincenzi, Fabrizio,Pasquini, Silvia,Dal Ben, Diego,Volpini, Rosaria,Colotta, Vittoria
, (2019/11/05)
The amino-3,5-dicyanopyridine derivatives belong to an intriguing series of adenosine receptor (AR) ligands that has been developed by both academic researchers and industry. Indeed, the studies carried out to date underline the versatility of the dicyanopyridine scaffold to obtain AR ligands with not only a wide range of affinities but also with diverse degrees of efficacies at the different ARs. These observations prompted us to investigate on the structure–activity relationships (SARs) of this series leading to important previously reported results. The present SAR study has helped to confirm the 1H-imidazol-2-yl group at R2 position as an important feature for producing potent AR agonists. Moreover, the nature of the R1 substituent highly affects not only affinity/activity at the hA1 and hA2B ARs but also selectivity versus the other subtypes. Potent hA1 and hA2B AR ligands were developed, and among them, the 2-amino-6-[(1H-imidazol-2-ylmethyl)sulfanyl]-4-[4-(prop-2-en-1-yloxy)phenyl]pyridine-3,5-dicarbonitrile (3) is active in the low nanomolar range at these subtypes and shows a good trend of selectivity versus both the hA2A and hA3 ARs. This combined hA1/hA2B partial agonist activity leads to a synergistic effect on glucose homeostasis and could potentially be beneficial in treating diabetes and related complications.
Preclinical Evaluation of the First Adenosine A1 Receptor Partial Agonist Radioligand for Positron Emission Tomography Imaging
Guo, Min,Gao, Zhan-Guo,Tyler, Ryan,Stodden, Tyler,Li, Yang,Ramsey, Joseph,Zhao, Wen-Jing,Wang, Gene-Jack,Wiers, Corinde E.,Fowler, Joanna S.,Rice, Kenner C.,Jacobson, Kenneth A.,Kim, Sung Won,Volkow, Nora D.
, p. 9966 - 9975 (2018/11/23)
Central adenosine A1 receptor (A1R) is implicated in pain, sleep, substance use disorders, and neurodegenerative diseases, and is an important target for pharmaceutical development. Radiotracers for A1R positron emission t
Structure-kinetics relationships of Capadenoson derivatives as adenosine A1 receptor agonists
Louvel, Julien,Guo, Dong,Soethoudt, Marjolein,Mocking, Tamara A.M.,Lenselink, Eelke B.,Mulder-Krieger, Thea,Heitman, Laura H.,Ijzerman, Adriaan P.
, p. 681 - 691 (2015/08/03)
Abstract We report the synthesis and biological evaluation of new derivatives of Capadenoson, a former drug candidate that was previously advanced to phase IIa clinical trials. 19 of the 20 ligands show an affinity below 100 nM at the human adenosine A1 receptor (hA1AR) and display a wide range of residence times at this target (from approx. 5 min (compound 10) up to 132 min (compound 5)). Structure-affinity and structure-kinetics relationships were established, and computational studies of a homology model of the hA1AR revealed crucial interactions for both the affinity and dissociation kinetics of this family of ligands. These results were also combined with global metrics (Ligand Efficiency, cLogP), showing the importance of binding kinetics as an additional way to better select a drug candidate amongst seemingly similar leads.
SUBSTITUTED DICYANOPYRIDINES AND USE THEREOF
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Paragraph 0434, (2013/08/28)
The present application relates to novel substituted dicyanopyridines, to processes for their preparation, to their use for the treatment and/or prophylaxis of diseases and to their use for preparing medicaments for the treatment and/or prophylaxis of diseases, preferably for the treatment and/or prophylaxis of cardiovascular disorders.
Structure-activity relationship study of prion inhibition by 2-aminopyridine-3,5-dicarbonitrile-based compounds: Parallel synthesis, bioactivity, and in vitro pharmacokinetics
May, Barnaby C. H.,Zorn, Julie A.,Witkop, Juanita,Sherrill, John,Wallace, Andrew C.,Legname, Giuseppe,Prusiner, Stanley B.,Cohen, Fred E.
, p. 65 - 73 (2007/10/03)
2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We identify compounds with significantly improved bioactivity (approximately 40-fold) against replication of the infectious prion isoform (PrPSc) and suitable pharmacokinetic profiles to warrant evaluation in animal models of prion disease.
Studies with polyfunctionally substituted heteroaromatics: The reaction of heterocyclic enaminonitriles with α-β-unsaturated nitrites
Hussein,Abdel Hafez,Elnagdi
, p. 347 - 350 (2007/10/03)
5-Amino-4-cyano-3-phenylpyrazole (1) reacts with cinnamonitriles (2) to yield the pyrazolo[1,5-a]pyrimidines (3). Also, 5-amino-4-cyano-l-phenylpyrazole (4) reacts with cinnamonitriles (2) to yield the pyrazolo[3,4-6]pyridine derivatives (5). In contrast
Pyrolysis, photolysis and mass spectra of pyran and thiopyran derivatives
Atalla,Hussein,Badr
, p. 163 - 170 (2007/10/03)
Pyrolysis and photolysis of 2-amino-3,5-dicyano-6-phenyl-4H-pyran (1) afford HNCO, acrylonitrile, cinnamonitrile and 2-hydroxy-3,5-dicyano-6-phenylpyridine. Pyrolysis of 2-carboxyimino-3,5-dicyano-6-phenyl-4H-pyran (2) gives HCN, acrylonitrile, cinnamonitrile and 2-hydroxy-3,5-dicyano-6-phenylpyridine. Furthermore both pyrolysis and photolysis of 2,6-diamino-3,5-dicyanothiopyran (3) gives rise to HNCS, acrylonitrile and 6-amino-3,5-dicyano-6-mercaptopyridine. Moreover, comparative studies of pyrolysis, photolysis and mass spectra of 2,6-diamino-3,5-dicyano-4-arylthiopyran derivatives 4a-c revealed similar results as HNCS, cinnamonitrile derivatives and pyridinethione derivatives. The mass spectral fragmentation patterns of these compounds were recorded and studied to determine the homolysis fission involved in the rearrangements. Partial similarity of products obtained from pyrolysis and photolysis, and the mechanistic implications of these data are discussed.
