37566-39-5Relevant academic research and scientific papers
Synthesis of new 2,5-disubstituted-1,3,4-thiadiazole derivatives and their in vivo anticonvulsant activity
Harish,Mohana,Mallesha
, p. 97 - 105 (2014)
A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives were synthesized by the reaction of 3-(2-cyanopropan-2-yl)-N-(5-(piperazine-1-yl)-1, 3,4-thiadiazol-2-yl)benzamide with various sulfonyl chlorides and evaluated for their anticonvulsant activity in MES test. Rotorod method was employed to determine the neurotoxicity. The purity of the compounds is confirmed on the basis of their elemental analysis. The structures of all the new compounds are established on the basis of 1H NMR and mass spectral data. Out of fifteen compounds, three were found to be potent anticolvunstants. The same compounds showed no neurotoxicity at the maximum dose administered (100 mg/kg).
Synthesis, solid structure, and optical properties of new thiophene-based alternating π-conjugated copolymers containing 4-alkyl-1,2,4-triazole or 1,3,4-thiadiazole unit as the partner unit
Yasuda, Takuma,Imase, Tatsuya,Sasaki, Shintaro,Yamamoto, Takakazu
, p. 1500 - 1503 (2005)
The synthesis, characterization, and solid-state structure of new thiophene-based alternating π-conjugated polymers containing the 4-alkyl-1,2,4-triazole or 1,2,4-thiadiazole unit as per partner unit were reported. A new thiophene-based CT type alternating copolymers was synthesized to obtain further scope about the packing structure and chemical properties of such CT type alternating π-conjugated copolymers. It was observed that the difference between the syn and anti conformations was small. It was also observed that the calculated density (1.79 g cm-3) according to the packing model agreed with the observed density (1.73 g cm-3).
PPAR gamma targeted molecular docking and synthesis of some new amide and urea substituted 1, 3, 4-thiadiazole derivative as antidiabetic compound
Dewangan, Dhansay,Kashyap, Pranita,Mishra, Achal,Thakur, Alok Singh,Vaishnav, Yogesh,Verma, Santosh Kumar,Verma, Shekhar
, (2020)
The PPAR-γ agonist enhances the insulin sensitivity and avoids the disorganized hyperglycemic by promoting the insulin guided cellular uptake of blood glucose. Therefore, in the present work PPAR-γ has chosen as the target for the molecular docking study to design an effective agonist of the same. By this research work an effort has been made to prepare amide and urea series of 1, 3, 4-thiadiazole derivatives as 4-substituted-N-(5-(4-(1-piperidino)1-piperidinyl)-1,3,4-(2-thiadiazolyl)benzamide (4a-f) and 1-(4-substitutedphenyl)-3-(5-(4-(1-piperidino)1-piperidinyl)-1,3,4-(2-thiadiazolyl)urea (6a-f). Both the docking score as well as the pharmacological animal study data has been suggested that the electron donating group containing compound 4f and 6f are most potent molecules for the antidiabetic activity close to the standard drug pioglitazone. It was further observed that the unsubstituted aromatic ring containing derivatives have also considerable effect (4a and 6a) than the electron withdrawing containing derivatives. After the comparison of biological data for amide and urea series, it was concluded that the urea (6a-f) series is more effective than the amide series.
Quantitative structure–activity relationship of substituted imidazothiadiazoles for their binding against the ecdysone receptor of Sf-9 cells
Yokoi, Taiyo,Nakagawa, Yoshiaki,Miyagawa, Hisashi
, p. 5305 - 5309 (2017)
Imidazothiadiazoles (ITDs) are a class of potent nonsteroidal ecdysone agonists with larvicidal activity. Previously, we performed the Hansch–Fujita type of quantitative structure–activity relationship (QSAR) analysis for ITD analogs (Yokoi et al., Pestic. Biochem. Physiol. 2015, 120, 40–50). The activity was reasonably explained by hydrophobicity and electronegativity of substituents on the imidazothiadiazole ring system. However, the limited data points (n = 8) hampered the examination of other physicochemical parameters. In the present study, we expanded the library of ITD congeners and evaluated their receptor-binding affinity using intact Sf-9 cells. The QSAR analysis for the expanded set revealed the significance of the third physicochemical parameter, the negative steric effect for long substituents. We also evaluated the larvicidal activity of the synthesized compounds against Spodoptera litura; however, it was not correlated to the binding affinity. The results obtained here suggests that the pharmacokinetic properties must be improved to enhance the larvicidal activity of ITDs.
Discovery of potent and novel smoothened antagonists via structure-based virtual screening and biological assays
Lu, Wenfeng,Zhang, Dihua,Ma, Haikuo,Tian, Sheng,Zheng, Jiyue,Wang, Qin,Luo, Lusong,Zhang, Xiaohu
, p. 34 - 48 (2018)
The Hedgehog (Hh) signaling pathway plays a critical role in controlling patterning, growth and cell migration during embryonic development. Aberrant activation of Hh signaling has been linked to tumorigenesis in various cancers, such as basal cell carcinoma (BCC) and medulloblastoma. As a key member of the Hh pathway, the Smoothened (Smo) receptor, a member of the G protein-coupled receptor (GPCR) family, has emerged as an attractive therapeutic target for the treatment and prevention of human cancers. The recent determination of several crystal structures of Smo in complex with different antagonists offers the possibility to perform structure-based virtual screening for discovering potent Smo antagonists with distinct chemical scaffolds. In this study, based on the two Smo crystal complexes with the best capacity to distinguish the known Smo antagonists from decoys, the molecular docking-based virtual screening was conducted to identify promising Smo antagonists from ChemDiv library. A total of 21 structurally novel and diverse compounds were selected for experimental testing, and six of them exhibited significant inhibitory activity against the Hh pathway activation (IC50 50 lower than 1 μM. The important residues uncovered by binding free energy calculation (MM/GBSA) and binding free energy decomposition were highlighted and discussed. These findings suggest that the novel scaffold afforded by compound 20 can be used as a good starting point for further modification/optimization and the clarified interaction patterns may also guide us to find more potent Smo antagonists.
COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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Paragraph 0315-0317, (2021/04/23)
The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
1,3,4-thiadiazole heterocyclic compound having hedgehog pathway antagonist activity
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Paragraph 0042; 0044; 0045-0046, (2019/05/02)
The present invention discloses a 1,3,4-thiadiazole heterocyclic compound having hedgehog pathway antagonist activity, wherein the compound has a structure represented by a general formula I defined in the specification. According to the present invention, the 1,3,4-thiadiazole heterocyclic compound having hedgehog pathway antagonist activity can block tumor cell metastasis regeneration by antagonizing hedgehog pathway so as to achieve significant antitumor effect.
PHARMACEUTICAL COMPOSITIONS, METHODS FOR THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF CANCER
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Paragraph 0047-0048, (2018/07/29)
The present application is directed to pharmaceutical compositions comprising derivatives of 6-(4-substitutedphenyl)-2-(substituted piperidine)imidazo[2,1-b][1,3,4]thiadiazol-2-yl], to a method of treating cancer using these compositions and to processes for preparing these derivatives.
NOVEL GPR119 AGONIST COMPOUNDS
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Paragraph 0248-0250, (2017/10/26)
The present invention relates to novel compounds of formula (I), process for preparation of the same and composition comprising these compounds.
A novel Fer/FerT targeting compound selectively evokes metabolic stress and necrotic death in malignant cells
Elkis, Yoav,Cohen, Moshe,Yaffe, Etai,Satmary-Tusk, Shirly,Feldman, Tal,Hikri, Elad,Nyska, Abraham,Feiglin, Ariel,Ofran, Yanay,Shpungin, Sally,Nir, Uri
, (2017/10/25)
Disruption of the reprogrammed energy management system of malignant cells is a prioritized goal of targeted cancer therapy. Two regulators of this system are the Fer kinase, and its cancer cell specific variant, FerT, both residing in subcellular compartments including the mitochondrial electron transport chain. Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level. Notably, Fer was also found to associate with PARP-1 and E260 disrupted this association thereby leading to PARP-1 activation. The cooperative intervention with these metabolic pathways leads to energy crisis and necrotic death in malignant, but not in normal human cells, and to the suppression of tumors growth in vivo. Thus, E260 is a new anti-cancer agent which imposes metabolic stress and cellular death in cancer cells.
