635293-05-9Relevant academic research and scientific papers
Novel agonists of free fatty acid receptor 1 (GPR40) based on 3-(1,3,4-thiadiazol-2-yl)propanoic acid scaffold
Krasavin, Mikhail,Lukin, Alexey,Zhurilo, Nikolay,Kovalenko, Alexey,Zahanich, Ihor,Zozulya, Sergey
, p. 1404 - 1410 (2016)
1,3,4-Thiadiazole was explored as a more polar, heterocyclic replacement for the phenyl ring in the 3-arylpropionic acid pharmacophore present in the majority of GPR40 agonists. Out of 13 compounds synthesized using a flexible, three-step protocol (involving no chromatographic purification), four compounds were confirmed to activate the target in micromolar concentration range. While the potency of the series should be subject of further optimization, the remarkable aqueous solubility and microsomal stability observed for the lead compound (8g) apparently attests to this new scaffold’s high promise in the GPR40 agonist field.
Novel steroidal 1,3,4-thiadiazines: Synthesis and biological evaluation in androgen receptor-positive prostate cancer 22Rv1 cells
Komendantova, Anna S.,Scherbakov, Alexander M.,Komkov, Alexander V.,Chertkova, Viktoriya V.,Gudovanniy, Alexey O.,Chernoburova, Elena I.,Sorokin, Danila V.,Dzichenka, Yaraslau U.,Shirinian, Valerii Z.,Volkova, Yulia A.,Zavarzin, Igor V.
supporting information, (2019/08/12)
A flexible approach to previously unknown spirofused and linked 1,3,4-thiadiazine derivatives of steroids with selective control of heterocyclization patterns is disclosed. (N-Arylcarbamoyl)spiroandrostene-17,6′ [1,3,4]thiadiazines and (N-arylcarbamoyl)17-[1′,3′,4′]thiadiazine-substituted androstenes, novel types of heterosteroids, were prepared from 16β,17β-epoxypregnenolone and 21-bromopregna-5,16-dien-20-one in good to high yields by the treatment with oxamic acid thiohydrazides. The synthesized compounds were screened for antiproliferative activity against the human androgen receptor-positive prostate cancer cell line 22Rv1. Most of (N-arylcarbamoyl)17-[1′,3′,4′]thiadiazine-substituted androstenes exhibit better antiproliferative potency (IC50 = 2.1–6.6 μM) than the antiandrogen bicalutamide. Compounds 7d with IC50 = 3.0 μM and 7j with IC50 = 2.1 μM proved to be the most active in the series under study. Lead synthesized compound 7j downregulates AR expression and activity in 22Rv1 cells. NF-κB activity is also blocked in 7j-treated 22Rv1 cells. Apoptosis is considered as a possible mechanism of 7j-induced cell death.
A Straightforward Approach toward Multifunctionalized Pyridazines via Imination/Electrocyclization
Komkov, Alexander V.,Komendantova, Anna S.,Menchikov, Leonid G.,Chernoburova, Elena I.,Volkova, Yulia A.,Zavarzin, Igor V.
supporting information, p. 3734 - 3737 (2015/08/18)
A facile synthesis of functionalized 3-carbamide pyridazines starting from readily available chlorovinyl aldehydes and oxamic acid thiohydrazides via cascade imination/electrocyclization is reported. In the presence of p-toluenesulfuric acid, various ketones have been efficiently incorporated into the pyridazine derivatives through a two-step sequence involving a Vilsmeier-Haack reaction and imination. The synthetic value of this method has been demonstrated by efficient synthesis of steroidal pyridazines.
Synthesis of oxamic acids thiohydrazides and carbamoyl-1,3,4-thiadiazoles
Yarovenko,Shirokov,Krupinova,Zavarzin,Krayushkin
, p. 1133 - 1139 (2007/10/03)
A convenient preparation method was developed for oxamic acids thiohydrazides by reaction of α-chloroacetamides with a preliminary prepared solution of elemental sulfur and hydrazines. A series of carbamoyl-1,3,4-thiadiazole derivatives was obtained.
