2-Sep-2021 News Top Picks: new discover of 4-Methylthiazol-2-amine

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2-Cyanoacetamido-4-methylthiazole (1) was utilized as a versatile precursor for the construction of new thiazole clubbed thiazolidine, thiophene, pyridine, or chromene scaffold. The base-catalyzed addition of 1 to phenyl isothiocyanate followed by subsequent treatment of the produced thiocarbamoyl intermediate with ethyl chloroacetate or chloroacetonitrile furnished the corresponding thiazolyl-thiazolidine and thiazolyl-thiophene hybrids. The reactions of compound 1 with chemical reagents, namely, acetylacetone, malononitrile, and/or 2-(4-anisylidene)-malononitrile have been studied and furnished the corresponding thiazole-pyridine hydrides 8?10. Furthermore, treatment of the precursor 1 with salicylaldehyde, various aryl diazonium chlorides, and/or aromatic aldehydes afforded their corresponding thiazolyl-chromene hybrid 12, arylhydrazono-nitriles 13, and unsaturated nitriles 14, respectively. The cytotoxicity of the synthesized compounds was screened against the cell lines HepG2, HCT-116, and MCF-7. Compounds 8, 10, and 12 recorded the best results, which was illustrated by molecular docking. Molecular Operating Environment molecular docking calculations carried out here is to rationalize correlation between docking results and biological data of thymidylate synthase (Protein Data Bank code: IHVY) inhibition. Docking has been carried out in the same co-crystallographic inhibitor binding site to predict if the binding mode of active compounds is analogous to that of native inhibitor.

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Reference:
Thiazole | C3H9950NS – PubChem,
Thiazole | chemical compound | Britannica

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Compounds of the formula STR1 wherein R1 is hydrogen, halogen or alkyl of 1 to 3 carbon atoms; R2 is hydrogen or alkyl of 1 to 3 carbon atoms; and R3 is aromatic hydrocarbyl of 6 to 10 carbon atoms or an aromatic heterocycle of 2 to 9 carbon atoms and 1 to 2 nitrogen atoms and/or an oxygen or a sulfur atom, where each of said aromatic substituents may in turn be substituted with one or two alkyls of 1 to 6 carbon atoms, halogen, hydroxyl, trifluoromethyl, halophenyl or alkoxy of 1 to 3 carbon atoms; and non-toxic, pharmacologically acceptable salts thereof formed with inorganic or organic bases; the compounds as well as their salts are useful as analgesics, antipyretics, antithrombotic and antiphlogistics.

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Reference:
Thiazole | C3H9829NS – PubChem,
Thiazole | chemical compound | Britannica

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Chiral derivatives of several substituted halopyridyl and thiazolyl PETT compounds were synthesized as non-nucleoside inhibitors of the reverse transcriptase (RT) enzyme (NNRTI) of the human immunodeficiency virus (HIV-1). Molecular modeling studies indicated that because of the asymmetric geometry of the NNRTI binding pocket, the R stereoisomers would fit the NNRTI binding pocket of the HIV-1 RT much better than the corresponding S stereoisomers, as reflected by their 104-fold lower Ki values. The R stereoisomers of several PETT derivatives inhibited recombinant RT in vitro with lower IC50 values than their enantiomers. The active compounds were further evaluated for their ability to inhibit HIV-1 replication in human peripheral blood mononuclear cells (PBMC). All the R isomers once again showed potent anti-HIV activity and inhibited the replication of the HIV-1 strain HTLVIIIB in peripheral blood mononuclear cells (PBMC) at nanomolar concentrations whereas their enantiomers were substantially less potent. The lead compounds in the respective groups were further tested against the NNRTI-resistant HIV strains, A17 (Y181C mutant), and A17Var (Y181C+K103N mutant) and RT MDR (V106N). The results showed that the lead compounds were several logs more potent than the standard NNRTI nevirapine. Structure-activity relationship studies also revealed a preference for the pyridyl unit with halo substitutions primarily at 5-position demonstrating the importance of regiochemistry. Our data provides experimental evidence that the stereochemistry as well as regiochemistry of NNRTI can profoundly affect their anti-HIV activity.

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Reference:
Thiazole | C3H9840NS – PubChem,
Thiazole | chemical compound | Britannica

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Interaction of some thiazole and benzothiazole derivatives as donors with certain di- and trinitrobenzene derivatives as acceptors results in the formation of 1:1 molecular species.The infrared, NMR and ultraviolet analysis of the complexes with non-acidic acceptors reveals the presence of ?-?* ineraction from a HOMO of the thiazole nucleus or the phenyl moiety of the benzothiazoles to a LUMO of the benzene ring of the acceptors.The existence of this type of interaction is supported by HMO calculations on the donor molecules.On the other hand, the molecular complexes derived from acidic acceptors are stabilized, in addition to the ?-?* interaction, by proton transfer from the hydroxyl or carboxylic group of the acceptor to the amino group of the aminothiazole donors.The ionization potentials of donors, electron affinities of acceptors as well as the energy of the CT complexes were computed from their u.v. and visible spectra.

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Reference:
Thiazole | C3H9773NS – PubChem,
Thiazole | chemical compound | Britannica

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Novel 1-aryl-3-quinolinecarboxamides and 1-aryl-3-isoquinolinecarboxamides, processes for the preparation thereof, and methods for treating pain and inflammation utilizing compounds and compositions thereof are disclosed.

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Reference:
Thiazole | C3H9753NS – PubChem,
Thiazole | chemical compound | Britannica

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Inhibition of Itk potentially constitutes a novel, nonsteroidal treatment for asthma and other T-cell mediated diseases. In-house kinase cross-screening resulted in the identification of an aminopyrazole-based series of Itk inhibitors. Initial work on this series highlighted selectivity issues with several other kinases, particularly AurA and AurB. A template-hopping strategy was used to identify a series of aminobenzothiazole Itk inhibitors, which utilized an inherently more selective hinge binding motif. Crystallography and modeling were used to rationalize the observed selectivity. Initial exploration of the SAR around this series identified potent Itk inhibitors in both enzyme and cellular assays.

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Reference:
Thiazole | C3H9775NS – PubChem,
Thiazole | chemical compound | Britannica

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Peptide deformylase (PDF) is a prokaryotic metalloenzyme that is essential for bacterial growth and is a new target for the development of antibacterial agents. All previously reported PDF inhibitors with sufficient antibacterial activity share the structural feature of a 2-substituted alkanoyl at the P1? site. Using a combination of iterative parallel synthesis and traditional medicinal chemistry, we have identified a new class of PDF inhibitors with N-alkyl urea at the P1? site. Compounds with MICs of ?4 mug/ml against gram-positive and gram-negative pathogens, including Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae, have been identified. The concentrations needed to inhibit 50% of enzyme activity (IC50s) for Escherichia coli Ni-PDF were ?0.1 muM, demonstrating the specificity of the inhibitors. In addition, these compounds were very selective for PDF, with IC50s of consistently >200 muM for matrilysin and other mammalian metalloproteases. Structure-activity relationship analysis identified preferred substitutions resulting in improved potency and decreased cytotoxity. One of the compounds (VRC4307) was cocrystallized with PDF, and the enzyme-inhibitor structure was determined at a resolution of 1.7 A. This structural information indicated that the urea compounds adopt a binding position similar to that previously determined for succinate hydroxamates. Two compounds, VRC4232 and VRC4307, displayed in vivo efficacy in a mouse protection assay, with 50% protective doses of 30.8 and 17.9 mg/kg of body weight, respectively. These N-alkyl urea hydroxamic acids provide a starting point for identifying new PDF inhibitors that can serve as antimicrobial agents.

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Reference:
Thiazole | C3H9747NS – PubChem,
Thiazole | chemical compound | Britannica

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A series of substituted tricyclic 4,4-dimethyl-3,4-dihydrochromeno[3,4-d]imidazole derivatives have been synthesized and their mPGES-1 biological activity has been disclosed in detail. Structure-activity relationship (SAR) optimization provided inhibitors with excellent mPGES-1 potency and low to moderate PGE2 release A549 cell potency. Among the mPGES-1 inhibitors studied, 7, 9 and 11l provided excellent selectivity over COX-2 (>200-fold) and >70-fold selectivity for COX-1 except 11l, which exhibited dual mPGES-1/COX-1 activity. Furthermore, the above tested mPGES-1 inhibitors demonstrated good metabolic stability in liver microsomes, high plasma protein binding (PPB) and no significant inhibition observed in clinically relevant CYP isoforms. Besides, selected mPGES-1 tool compounds 9 and 11l provided good in vivo pharmacokinetic profile and oral bioavailability (%F = 33 and 85). Additionally, the representative mPGES-1 tool compounds 9 and 11l revealed moderate in vivo efficacy in the LPS-induced thermal hyperalgesia guinea pig pain model.

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Reference:
Thiazole | C3H9884NS – PubChem,
Thiazole | chemical compound | Britannica

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SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SWI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.

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Reference:
Thiazole | C3H9704NS – PubChem,
Thiazole | chemical compound | Britannica

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Substituted imidazo[2,1-b]thiazole compounds corresponding to formula I, a method for producing them, pharmaceutical compositions containing them, and the use thereof for regularing mGluR5 receptors, or for treating or inhibiting disorders or disease states at least partially mediated by mGluR5 receptor such as pain, anxiety attacks, drug or alcohol dependency, and others.

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Thiazole | C3H9707NS – PubChem,
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