Category: 324579-90-0

Zheng, Shilong; Zhong, Qiu; Xi, Yulan; Mottamal, Madhusoodanan; Zhang, Qiang; Schroeder, Richard L.; Sridhar, Jayalakshmi; He, Ling; McFerrin, Harris; Wang, Guangdi published the artcile< Modification and Biological Evaluation of Thiazole Derivatives as Novel Inhibitors of Metastatic Cancer Cell Migration and Invasion>, Related Products of 324579-90-0, the main research area is thiazole derivative preparation antitumor cancer metastasis.

Fascin has recently emerged as a potential therapeutic target, as its expression in cancer cells is closely associated with tumor progression and metastasis. Following the initial discovery of a series of thiazole derivatives that demonstrated potent antimigration and antiinvasion activities via possible inhibition of fascin function, we report here the design and synthesis of 63 new thiazole derivatives by further structural modifications in search of more potent fascin inhibitors. The 5 series of analogs with longer alkyl chain substitutions on the thiazole nitrogen exhibited greater antimigration activities than those with other structural motifs. The most potent analog, 5p, inhibited 50% of cell migration at 24 nM. Moreover, the thiazole analogs showed strong antiangiogenesis activity, blocking new blood vessel formation in a chicken embryo membrane assay. Finally, a functional study was conducted to investigate the mechanism of action via interaction with the F-actin bundling protein fascin.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Related Products of 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Wang, Ning-Yu; Xu, Ying; Zuo, Wei-Qiong; Xiao, Kun-Jie; Liu, Li; Zeng, Xiu-Xiu; You, Xin-Yu; Zhang, Li-Dan; Gao, Chao; Liu, Zhi-Hao; Ye, Ting-Hong; Xia, Yong; Xiong, Ying; Song, Xue-Jiao; Lei, Qian; Peng, Cui-Ting; Tang, Hong; Yang, Sheng-Yong; Wei, Yu-Quan; Yu, Luo-Ting published the artcile< Discovery of Imidazo[2,1-b]thiazole HCV NS4B Inhibitors Exhibiting Synergistic Effect with Other Direct-Acting Antiviral Agents>, HPLC of Formula: 324579-90-0, the main research area is imidazothiazole HCV NS4B inhibitor drug synergism antiviral.

The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (I, EC50 = 16 nM) and 28g (II, EC50 = 31 nM). The resistance profile studies revealed that 26f and 28g targeted HCV NS4B, more precisely the second amphipathic α helix of NS4B (4BAH2). Cross-resistance between our 4BAH2 inhibitors and other direct-acting antiviral agents targeting NS3/4A, NS5A, and NS5B was not observed For the first time, the synergism of a series of combinations based on 4BAH2 inhibitors was evaluated. The results demonstrated that our 4BAH2 inhibitor 26f was synergistic with NS3/4A inhibitor simeprevir, NS5A inhibitor daclatasvir, and NS5B inhibitor sofosbuvir, and it could also reduce the dose of these drugs at almost all effect levels. Our study suggested that favorable effects could be achieved by combining 4BAH2 inhibitors such as 26f with these approved drugs and that new all-oral antiviral combinations based on 4BAH2 inhibitors were worth developing to supplement or even replace current treatment regimens for curing HCV infection.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, HPLC of Formula: 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Samet, A. V.; Firgang, S. I.; Semenov, V. V. published the artcile< Rearrangement of 2-amino-4-cyclopropylthiazolium bromide>, Synthetic Route of 324579-90-0, the main research area is pyrrolothiazolinium bromide preparation; aminocyclopropylthiazolium bromide rearrangement.

A procedure for preparation of aminodihydropyrrolothiazolinium bromide is reported. Rearrangement of 2-amino-4-cyclopropylthiazolium bromide (I) provided 3-amino-6,7-dihydro-5H-pyrrolo[1,2-c]thiazolinium bromide (II) in excellent yield.

Chemistry of Heterocyclic Compounds (New York, NY, United States) published new progress about Thermal rearrangement. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Synthetic Route of 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Patel, Snahel; Harris, Seth F.; Gibbons, Paul; Deshmukh, Gauri; Gustafson, Amy; Kellar, Terry; Lin, Han; Liu, Xingrong; Liu, Yanzhou; Liu, Yichin; Ma, Changyou; Scearce-Levie, Kimberly; Ghosh, Arundhati Sengupta; Shin, Young G.; Solanoy, Hilda; Wang, Jian; Wang, Bei; Yin, Jianping; Siu, Michael; Lewcock, Joseph W. published the artcile< Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12)>, Application In Synthesis of 324579-90-0, the main research area is preparation pyrazolylpyridinamine leucine zipper kinase inhibitor.

Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12) has therapeutic potential for treatment of a number of indications ranging from acute neuronal injury to chronic neurodegenerative disease. Thus, high demand exists for selective small mol. DLK inhibitors with favorable drug-like properties and good CNS penetration. Herein the authors describe a shape-based scaffold hopping approach to convert pyrimidine 1 to a pyrazole core with improved physicochem. properties. The authors also present the first crystal structures of DLK. By utilizing a combination of property and structure-based design, the authors identified inhibitor I, a potent, selective, and brain-penetrant inhibitor of DLK with activity in an in vivo nerve injury model.

Journal of Medicinal Chemistry published new progress about Blood-brain barrier. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Application In Synthesis of 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Felts, Andrew S.; Rodriguez, Alice L.; Morrison, Ryan D.; Blobaum, Anna L.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A. published the artcile< Discovery of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide negative allosteric modulators of metabotropic glutamate receptor subtype 5>, Name: 4-Cyclopropylthiazol-2-amine, the main research area is pyrimidinylmethylquinolinecarboxamide preparation neg allosteric modulator glutamate receptor mGluR5; Central nervous system (CNS); G protein-coupled receptor (GPCR); Metabotropic glutamate receptor subtype 5 (mGlu(5)); Negative allosteric modulator (NAM); Quinoline.

Based on previous work that established fused heterocycles as viable alternatives for the picolinamide core of the authors’ lead series of mGlu5 neg. allosteric modulators (NAMs), the authors designed a novel series of 6-(pyrimidin-5-ylmethyl)quinoline-8-carboxamide mGlu5 NAMs. These new quinoline derivatives also contained carbon linkers as replacements for the diaryl ether oxygen atom common to the authors’ previously published chemotypes. Compounds were evaluated in a cell-based functional mGlu5 assay, and an exemplar analog 27 (6-(difluoro(pyrimidin-5-yl)methyl)-N-(4-methylthiazol-2-yl)quinoline-8-carboxamide) was >60-fold selective vs. the other seven mGlu receptors. Selected compounds were also studied in metabolic stability assays in rat and human S9 hepatic fractions and exhibited a mixture of P 450- and non-P 450-mediated metabolism

Bioorganic & Medicinal Chemistry Letters published new progress about Allosterism. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Name: 4-Cyclopropylthiazol-2-amine.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Bogolubsky, Andrey V.; Moroz, Yurii S.; Savych, Olena; Pipko, Sergey; Konovets, Angelika; Platonov, Maxim O.; Vasylchenko, Oleksandr V.; Hurmach, Vasyl V.; Grygorenko, Oleksandr O. published the artcile< An Old Story in the Parallel Synthesis World: An Approach to Hydantoin Libraries>, SDS of cas: 324579-90-0, the main research area is hydantoin compound combinatorial synthesis Aurora kinase A inhibitor; 2,2,2-trifluoroethylcarbamates; amino esters; condensation; kinase inhibitors; nitrogen heterocycles.

An approach to the parallel synthesis of hydantoin libraries by reaction of in situ generated 2,2,2-trifluoroethylcarbamates and α-amino esters was developed. To demonstrate utility of the method, a library of 1158 hydantoins designed according to the lead-likeness criteria (MW 200-350, cLogP 1-3) was prepared The success rate of the method was analyzed as a function of physicochem. parameters of the products, and it was found that the method can be considered as a tool for lead-oriented synthesis. A hydantoin-bearing submicromolar primary hit acting as an Aurora kinase A inhibitor was discovered with a combination of rational design, parallel synthesis using the procedures developed, in silico and in vitro screenings.

ACS Combinatorial Science published new progress about Amidation. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, SDS of cas: 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Delpire, Eric; Days, Emily; Lewis, L. Michelle; Mi, Dehui; Kim, Kwangho; Lindsley, Craig W.; Weaver, C. David published the artcile< Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2>, Product Details of C6H8N2S, the main research area is potassium chlorine cotransporter KCC2 inhibitor preparation drug screening.

KCC2, a neuronal-specific K-Cl co-transporter, plays a major role in maintaining intracellular Cl- concentration in neurons below its electrochem. equilibrium potential, thus favoring robust GABA hyperpolarizing or inhibitory responses. The pharmacol. of the K-Cl co-transporter is dominated by loop diuretics such as furosemide and bumetanide, mols. used in clin. medicine because they inhibit the loop of Henle Na-K-2Cl co-transporter with much higher affinity. To identify mols. that affect KCC2 activity, the authors developed a fluorescence-based assay suitable for high-throughput screening (HTS) and used the assay to screen a library of 234,000 small mols. They identified a large number of mols. that either decrease or increase the activity of the co-transporter. Here, they report the characterization of a small number of inhibitors, some of which inhibit KCC2 activity in the submicromolar range without substantially affecting NKCC1 activity. Using medicinal chem., they synthesized a number of variants, tested their effect on KCC2 function, and provide an anal. of structure/activity relationships. They also used one of the compounds to demonstrate competitive inhibition in regard to external [K+] vs. non-competitive inhibition in respect to external [Cl-].

Proceedings of the National Academy of Sciences of the United States of America published new progress about Carrier-mediated biological transport. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Product Details of C6H8N2S.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Sami, Yuichi; Morita, Masataka; Kubota, Hirokazu; Hirabayashi, Ryoji; Seo, Ryushi; Nakagawa, Nobuaki published the artcile< Discovery of a novel orally active TRPV4 inhibitor: Part 1. Optimization from an HTS hit>, SDS of cas: 324579-90-0, the main research area is oral TRPV4 inhibitor preparation analgesic osteoarthritis.

Novel oral TRPV4 inhibitors were prepared and their potential for pain management in osteoarthritis discussed.

Bioorganic & Medicinal Chemistry published new progress about Analgesics. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, SDS of cas: 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Felts, Andrew S.; Rodriguez, Alice L.; Morrison, Ryan D.; Venable, Daryl F.; Manka, Jason T.; Bates, Brittney S.; Blobaum, Anna L.; Byers, Frank W.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Emmitte, Kyle A. published the artcile< Discovery of VU0409106: A negative allosteric modulator of mGlu5 with activity in a mouse model of anxiety>, HPLC of Formula: 324579-90-0, the main research area is anxiolytic mGlu5 modulator VU0409106 analog preparation anxiety; Allosteric modulator; Anxiety; CNS; Glutamate; mGlu(5).

Development of SAR in an aryl ether series of mGlu5 NAMs leading to the identification of tool compound VU0409106 is described in this Letter. VU0409106 is a potent and selective neg. allosteric modulator of mGlu5 that binds at the known allosteric binding site and demonstrates good CNS exposure following i.p. dosing in mice. VU0409106 also proved efficacious in a mouse marble burying model of anxiety, an assay known to be sensitive to mGlu5 antagonists as well as clin. efficacious anxiolytics.

Bioorganic & Medicinal Chemistry Letters published new progress about Anxiolytics. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, HPLC of Formula: 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Vilaboa, Nuria; Bore, Alba; Martin-Saavedra, Francisco; Bayford, Melanie; Winfield, Natalie; Firth-Clark, Stuart; Kirton, Stewart B.; Voellmy, Richard published the artcile< New inhibitor targeting human transcription factor HSF1: effects on the heat shock response and tumor cell survival>, Recommanded Product: 4-Cyclopropylthiazol-2-amine, the main research area is human transcription factor HSF1 inhibitor preparation heat shock antitumor.

Comparative modeling of the DNA-binding domain of human HSF1 facilitated the prediction of possible binding pockets for small mols. and definition of corresponding pharmacophores. In silico screening of a large library of lead-like compounds identified a set of compounds that satisfied the pharmacophoric criteria, a selection of which compounds was purchased to populate a biased sublibrary. A discriminating cell-based screening assay identified compound 001, which was subjected to systematic anal. of structure-activity relationships, resulting in the development of compound 115 (IHSF115). IHSF115 bound to an isolated HSF1 DNA binding domain fragment. The compound did not affect heat-induced oligomerization, nuclear localization and specific DNA binding but inhibited the transcriptional activity of human HSF1, interfering with the assembly of ATF1-containing transcription complexes. IHSF115 was employed to probe the human heat shock response at the transcriptome level. In contrast to earlier studies of differential regulation in HSF1-naive and -depleted cells, the authors’ results suggest that a large majority of heat-induced genes is pos. regulated by HSF1. That IHSF115 effectively countermanded repression in a significant fraction of heat-repressed genes suggests that repression of these genes is mediated by transcriptionally active HSF1. IHSF115 is cytotoxic for a variety of human cancer cell lines, multiple myeloma lines consistently exhibiting high sensitivity.

Nucleic Acids Research published new progress about Activating transcription factor 1 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Recommanded Product: 4-Cyclopropylthiazol-2-amine.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica