24237-44-3Relevant academic research and scientific papers
New P2X3 receptor antagonists. Part 1: Discovery and optimization of tricyclic compounds
Szántó, Gábor,Makó, Attila,Bata, Imre,Farkas, Bence,Kolok, Sándor,Vastag, Mónika,Cselenyák, Attila
, p. 3896 - 3904 (2016)
Purinergic P2X3 receptors are trimeric ligand-gated ion channels whose antagonism is an appealing yet challenging and not fully validated drug development idea. With the aim of identification of an orally active, potent human P2X3 receptor antagonist compound that can penetrate the central nervous system, the compound collection of Gedeon Richter was screened. A hit series of tricyclic compounds was subjected to a rapid, two-step optimization process focusing on increasing potency, improving metabolic stability and CNS penetrability. Attempts resulted in compound 65, a potential tool compound for testing P2X3 inhibitory effects in vivo.
Discovery of Thieno[2,3- d]pyrimidine-Based Hydroxamic Acid Derivatives as Bromodomain-Containing Protein 4/Histone Deacetylase Dual Inhibitors Induce Autophagic Cell Death in Colorectal Carcinoma Cells
Pan, Zhaoping,Li, Xiang,Wang, Yujia,Jiang, Qinglin,Jiang, Li,Zhang, Min,Zhang, Nan,Wu, Fengbo,Liu, Bo,He, Gu
, p. 3678 - 3700 (2020/04/30)
Bromodomain-containing protein 4 (BRD4) and histone deacetylases (HDAC) are both attractive epigenetic targets in cancer and other chronic diseases. Based on the integrated fragment-based drug design, synthesis, and in vitro and in vivo evaluations, a series of novel thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives are discovered as selective BRD4-HDAC dual inhibitors. Compound 17c is the most potent inhibitor for BRD4 and HDAC with IC50 values at nanomolar levels, as well as the expression level of c-Myc, and increases the acetylation of histone H3. Moreover, 17c presents inhibitory effects on the proliferation of colorectal carcinoma (CRC) cells via inducing autophagic cell death. It also has a good pharmacokinetic profile in rats and oral bioavailability of 40.5%. In the HCT-116 xenograft in vivo models, 17c displays potent inhibitory efficiency on tumor growth by inducing autophagic cell death and suppressing IL6-JAK-STAT signaling pathways. Our results suggest that the BRD4-HDAC dual inhibition might be an attractive therapeutic strategy for CRC.
Efficient three-component Gewald reactions under Et3N/H 2O conditions
Abaee, M. Saeed,Cheraghi, Somayeh
, p. 261 - 269 (2014/04/03)
In a medium consisting of triethylamine and water, methylene ketones undergo room temperature Gewald reactions with elemental sulfur and ethyl cyanoacetate (or malononitrile) to yield 2 aminothiophene derivatives efficiently within short time periods. Because of the high polarity of the medium, products precipitate in the reaction mixtures spontaneously. This makes isolation of the products easy by simple filtration and avoids cumbersome chromatographic separations. Mechanistic studies suggest that the reactions proceed via a Knoevenagel condensation pathway(equation presented). 2013
Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB2 receptor agonists for pain management
Nelson, Derek W.,Frost, Jennifer M.,Tietje, Karin R.,Florjancic, Alan S.,Ryther, Keith,Carroll, William A.,Dart, Michael J.,Daza, Anthony V.,Hooker, Bradley A.,Grayson, George K.,Fan, Yihong,Garrison, Tiffany R.,El-Kouhen, Odile F.,Yao, Betty,Pai, Madhavi,Chandran, Prasant,Zhu, Chang,Hsieh, Gin C.,Meyer, Michael D.
supporting information; experimental part, p. 2604 - 2608 (2012/05/05)
SAR studies on a series of thiophene amide derivatives provided CB 2 receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A repre
Synthesis and SAR of thiophene containing kinesin spindle protein (KSP) inhibitors
Pinkerton, Anthony B.,Lee, Tom T.,Hoffman, Timothy Z.,Wang, Yan,Kahraman, Mehmet,Cook, Travis G.,Severance, Daniel,Gahman, Timothy C.,Noble, Stewart A.,Shiau, Andrew K.,Davis, Robert L.
, p. 3562 - 3569 (2008/12/23)
We have identified and synthesized a series of thiophene containing inhibitors of kinesin spindle protein. SAR studies led to the synthesis of 33, which was co-crystallized with KSP and determined to bind to an allosteric pocket previously described for o
