216686-60-1Relevant academic research and scientific papers
Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H
Kankanala, Jayakanth,Kirby, Karen A.,Huber, Andrew D.,Casey, Mary C.,Wilson, Daniel J.,Sarafianos, Stefan G.,Wang, Zhengqiang
, p. 149 - 161 (2017)
Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have s
Temperature-Controlled Thiation of α-Cyano-β-Alkynyl Carbonyl Derivatives for de Novo Synthesis of 2-Aminothiophenes and Thieno[2,3- c]isothiazoles
Kao, Tzu-Ting,Peng, Bo-Kai,Liang, Min-Chieh,Lee, Chia-Jui,Chen, I-Chia,Shia, Kak-Shan,Wu, Yen-Ku
, p. 14688 - 14697 (2018/10/24)
Making use of temperature-controlled thiation as a key operation, a simple route to 2-aminothiophenes or thieno[2,3-c]isothiazoles has been newly developed wherein the 2-aminothiophene nucleus was formed through an initial formation of thioamide followed
A Thieno[2,3- d]pyrimidine Scaffold Is a Novel Negative Allosteric Modulator of the Dopamine D2 Receptor
Fyfe, Tim J.,Zarzycka, Barbara,Lim, Herman D.,Kellam, Barrie,Mistry, Shailesh N.,Katrich, Vsevolod,Scammells, Peter J.,Lane, J. Robert,Capuano, Ben
, p. 174 - 206 (2018/05/14)
Recently, a novel negative allosteric modulator (NAM) of the D2-like dopamine receptors 1 was identified through virtual ligand screening. This ligand comprises a thieno[2,3-d]pyrimidine scaffold that does not feature in known dopaminergic ligands. Herein, we provide pharmacological validation of an allosteric mode of action for 1, revealing that it is a NAM of dopamine efficacy and identify the structural determinants of this allostery. We find that key structural moieties are important for functional affinity and negative cooperativity, while functionalization of the thienopyrimidine at the 5- and 6-positions results in analogues with divergent cooperativity profiles. Successive compound iterations have yielded analogues exhibiting a 10-fold improvement in functional affinity, as well as enhanced negative cooperativity with dopamine affinity and efficacy. Furthermore, our study reveals a fragment-like core that maintains low μM affinity and robust negative cooperativity with markedly improved ligand efficiency.
Synthesis of classical and nonclassical 2-amino-4-oxo-6-benzylthieno-[2,3- d]pyrimidines as potential thymidylate synthase inhibitors
Gangjee, Aleem,Qiu, Yibin,Kisliuk, Roy L.
, p. 941 - 946 (2007/10/03)
A series of seven nonclassical 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines 2-8 and one classical N-[4-(2-amino-4-oxo-3,4- dihydrothieno[2,3-d]pyrimidin-6-ylmethyl)benzoyl]-L-glutamic acid 9 (Table I) were designed as the first in a series of 6-substituted 6-5 fused ring analogs as potential thymidylate synthase (TS) inhibitors and as antitumor agents. The target compounds were synthesized via a Heck coupling of appropriately substituted iodobenzenes and allyl alcohol followed by cyclization using cyanoacetate and sulfur powder to afford substituted thiophenes. The resulting thiophenes were then cyclocondensed with chloroformamidine hydrochloride to afford 2-amino-4-oxo-6-substituted thieno[2,3-d]pyrimidines 2-8 and 26. Hydrolysis of 26 followed by coupling with diethyl L-glutamate afforded 28. The classical analog 9 was obtained by hydrolysis of 28. None of the target compounds inhibited human recombinant thymidylate synthase at 23 μM except 9 for which the IC50 value was 100 μM.
