62774-58-7Relevant academic research and scientific papers
Design, synthesis, and biological activity of novel semicarbazones as potent Ryanodine receptor1 inhibitors of Alzheimer's disease
Dai, Baozhu,Ma, Xingxing,Tang, Yadong,Xu, Le,Guo, Su,Chen, Xinyan,Lu, Shitong,Wang, Guangjie,Liu, Yajing
, (2020/12/09)
Ryanodine receptors (RyRs) are important ligand-gated Ca2+ channels; their excessive activation leads to Ca2+ leakage in the sarcoplasmic reticulum that may cause neurological diseases. In this study, three series of novel potent RyR1 inhibitors based on dantrolene and bearing semicarbazone and imidazolyl moieties were designed and synthesized, and their biological activity was evaluated. Using a single-cell calcium imaging method, the calcium overload inhibitory activities of 26 target compounds were tested in the R614C cell line, using dantrolene as a positive control. The preliminary investigation showed that compound 12a suppressed Ca2+ release as evidenced by store overload-induced Ca2+release (SOICR) (31.5 ± 0.1%, 77.2 ± 0.1%, 93.7 ± 0.2%) at 0.1 μM, 3 μM and 10 μM, respectively. Docking simulation results showed that compound 12a could bind at the active site of the RyR1 protein. The Morris water-maze test showed that compound 12a significantly improved the cognitive behavior of AD-model mice. Further studies on the structural optimization of this series of derivatives are currently underway in our laboratory.
Synthesis and biological potentials of some new 1,3,4-oxadiazole analogues
Jawed Ahsan, Mohamed,Meena, Rachana,Dubey, Swati,Khan, Vasim,Manda, Sunita,Singh Jadav, Surender,Sharma, Piush,Geesi, Mohammed H.,Hassan, Mohd. Zaheen,Afroz Bakht, Mohammad,Riadi, Yassine,Akhter, Md. Habban,Salahuddin,Gundla, Rambabu
, p. 864 - 883 (2017/11/23)
In continuation of our research to explore new antiproliferative agents, we report herein the synthesis and antiproliferative activity of two new series of N-(substituted phenyl)-5-aryl-1,3,4-oxadiazol-2-amine (4a–j) and N-{[5-aryl-1,3,4-oxadiazol-2-yl]me
N6-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA), a very selective agonist with high affinity for the human adenosine A1 receptor
Beukers, Margot W.,Wanner, Martin J.,Von Frijtag Drabbe Künzel, Jacobien K.,Klaasse, Elisabeth C.,IJzerman, Adriaan P.,Koomen, Gerrit-Jan
, p. 1492 - 1503 (2007/10/03)
Four subtypes of adenosine receptors are currently known, that is, A1, A2A, A2B, and A3 receptors. Interestingly, quite substantial species differences exist especially between human and rat A3 receptors. As a result, ligands such as CCPA, which are very selective for the rat A1 receptor versus the human A3 receptor, are substantially less selective when the human A1 and A3 receptors are compared. New 2-substituted and 2,N6-disubstituted adenosines were synthesized, and their affinities for the human adenosine A1, A2A, A2B, and A3 receptors were determined. Although large substituents on the C2-position are generally thought to yield adenosine A2A receptor selective ligands, the reported series of 2-triazeno-substituted adenosines had a very high affinity for the A1 receptor. For example, 2-(3-phenylaminocarbonyltriazene-1-yl)adenosine had an affinity of 6.1 ± 1.3 nM for the human adenosine A1 receptor. Introduction of a diphenethyl substituent at the N6-position of this compound resulted in a high-affinity agonist, 3.1 ± 0.9 nM, for the human adenosine A1 receptor with 316- and 45-fold selectivity versus the human A2A and human A3 receptors, respectively. The most selective, high-affinity human adenosine A1 receptor agonist was the disubstituted compound N6-cyclopentyl-2-(3-phenylaminocarbonyltriazene-1-yl)adenosine (TCPA). TCPA had an affinity of 2.8 ± 0.8 nM for the human adenosine A1 receptor and was 75-fold and 214-fold selective versus the human A2A and human A3 receptors, respectively. In addition, TCPA was a full agonist and inhibited the forskolin-induced cAMP production of CHO cells stably transfected with the human adenosine A1 receptor with an IC50 of 1.5 ± 0.5 nM.
