Author: tianli

Chen, Qi-Yin; Chaturvedi, Pravin R.; Luesch, Hendrik published the artcile< Process development and scale-up total synthesis of largazole, a potent class I histone deacetylase inhibitor>, COA of Formula: C12H18N2O4S, the main research area is macrocyclic depsipeptide natural product largazole total enantioselective synthesis; largazole anticancer agent histone deacetylase inhibitor drug design; hydrolysis fragment condensation Seebach procedure formylation methylation safety; Aldol condensation enzymic resolution peptide coupling macrocyclization cross metathesis.

Herein we describe the research and development of the process for the scale-up total synthesis of largazole, a potent class I selective histone deacetylase (HDAC) inhibitor, a potential anticancer agent and also useful for the treatment of other disorders where transcriptional reprogramming might be beneficial. The synthetic route and conditions for each fragment and final product were modified and optimized to make them suitable for larger-scale synthesis. With the process we developed, hundreds of grams of each fragment and decagrams of final product largazole were synthesized in good to excellent yields. The final target largazole was obtained in 21% overall yield over eight steps based on the longest sequence with over 95% HPLC purity.

Organic Process Research & Development published new progress about Aldol condensation. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, COA of Formula: C12H18N2O4S.

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

de Souza, Daniel Rangel; Silva, Jaqueline Rodrigues; Moreira, Ariele; Viviani, Vadim R. published the artcile< Biosensing firefly luciferin synthesis in bacteria reveals a cysteine-dependent quinone detoxification route in Coleoptera>, Application of C11H8N2O3S2, the main research area is .

Abstract: Luciferin biosynthetic origin and alternative biol. functions during the evolution of beetles remain unknown. We have set up a bioluminescent sensing method for luciferin synthesis from cysteine and benzoquinone using E. coli and Pichia pastoris expressing the bright Amydetes vivianii firefly and P. termitilluminans click beetle luciferases. In the presence of D-cysteine and benzoquinone, intense bioluminescence is quickly produced, indicating the expected formation of D-luciferin. Starting with L-cysteine and benzoquinone, the bioluminescence is weaker and delayed, indicating that bacteria produce L-luciferin, and then racemize it to D-luciferin in the presence of endogenous esterases, CoA and luciferase. In bacteria the p-benzoquinone toxicity (IC50 ∼ 25 μM) is considerably reduced in the presence of cysteine, maintaining cell viability at 3.6 mM p-benzoquinone concomitantly with the formation of luciferin. Transcriptional anal. showed the presence of gene products involved with the sclerotization/tanning in the photogenic tissues, suggesting a possible link between these pathways and bioluminescence. The lack of two enzymes involved with the last steps of these pathways, indicate the possible accumulation of toxic quinone intermediates in the lanterns. These results and the abundance of cysteine producing enzymes suggest that luciferin first appeared as a detoxification byproduct of cysteine reaction with accumulated toxic quinone intermediates during the evolution of sclerotization/tanning in Coleoptera.

Scientific Reports published new progress about 2591-17-5. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Application of C11H8N2O3S2.

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

Robertson, Mark J.; Hadzic, Gordana; Ambrus, Joseph; Pome, D. Yuri; Hyde, Emily; Whiting, Ainslie; Mariana, Anna; von Kleist, Lisa; Chau, Ngoc; Haucke, Volker; Robinson, Phillip J.; McCluskey, Adam published the artcile< The Rhodadyns, a New Class of Small Molecule Inhibitors of Dynamin GTPase Activity>, SDS of cas: 10574-69-3, the main research area is dynamin GTPase inhibitor rhodanine analog preparation SAR; Knoevengal condensation; dynamin inhibition; rhodanine.

Six focused rhodanine-based libraries, 60 compounds in total, were synthesized and evaluated as potential dynamin I GTPase inhibitors. Twenty-six were more potent than the lead compound with 13 returning IC50 values ≤10 μM, making the Rhodadyn series among the most active dynamin inhibitors reported. Two analogs were highly effective at blocking receptor-mediated endocytosis: C10 and D10 (I) with IC50(RME) = 7.0 ± 2.2 and 5.9 ± 1.0 μM, resp. These compounds are equipotent with the best reported in-cell dynamin inhibitors.

ACS Medicinal Chemistry Letters published new progress about Drug targets (endocytosis). 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, SDS of cas: 10574-69-3.

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

da Silva, Monize M.; de Camargo, Mariana S.; Castelli, Silvia; de Grandis, Rone A.; Castellano, Eduardo E.; Deflon, Victor M.; Cominetti, Marcia R.; Desideri, Alessandro; Batista, Alzir A. published the artcile< Ruthenium(II)-mercapto complexes with anticancer activity interact with topoisomerase IB>, Safety of 4,5-Dihydrothiazole-2-thiol, the main research area is rutheniumII mercapto anticancer activity topoisomerase IB lung liver cancer.

Herein we present four new ruthenium(II) complexes: [Ru(mtz)2(dppb)] (1), [Ru(mmi)2(dppb)] (2), [Ru(dmp)2(dppb)] (3), and [Ru(mpca)2(dppb)] (4), where mtz = 2-mercaptothiazoline; mmi = 2-mercapto-1-methyl-imidazole; dmp = 4,6-diamino-2-mercaptopyrimidine; mpca = 6-mercaptopyridine-3-carboxylic acid; dppb = 1,4-bis(diphenylphosphino)butane. In vitro cell culture experiments revealed cytotoxic activity for complexes 2, 3 and 4 against MCF-7 (breast, non-invasive), MDA-MB-231 (breast, invasive), A549 (lung), DU-145 (prostate) and HepG2 (liver) tumor cells, in some cases lower than the half maximal inhibitory concentration (IC50) for the reference drug (cisplatin). The DNA (DNA) interactions studied by viscosity measurements, gel electrophoresis and square-wave voltammetry indicated that the DNA binding affinity primarily occurs through non-covalent interactions. Only complex 2 was able to fully inhibit the DNA supercoiled relaxation mediated by human topoisomerase IB (Top IB). The anal. indicates that complex 2 inhibits the cleavage and the reconnection steps of the catalytic cycle, being both a poison and a catalytic inhibitor.

Journal of the Brazilian Chemical Society published new progress about Antitumor agents. 96-53-7 belongs to class thiazole, and the molecular formula is C3H5NS2, Safety of 4,5-Dihydrothiazole-2-thiol.

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

Fan, Di; Wang, Ting; Hu, Jinhui; Zhou, Lin; Zhou, Jiahong; Wei, Shaohua published the artcile< Plasmid DNA-Based Bioluminescence-Activated System for Photodynamic Therapy in Cancer Treatment>, Electric Literature of 2591-17-5, the main research area is cervical cancer plasmid DNA bioluminescence photodynamic therapy; hypericin; luciferase; photodynamic therapy; plasmid DNA; singlet oxygen.

The low depth of tissue penetration by therapeutic light sources severely restricts photodynamic therapy (PDT) in treating deep-seated tumors. Using a luciferase/D-luciferin bioluminescence system to artificially create internal light sources in cells instead of external light sources is an effective means of solving the above problems. However, high-efficiency bioluminescence requires a higher concentration of luciferase in the cell, which poses a considerable challenge to the existing system of enzyme loading, delivery, activity and retention of drugs, and dramatically increases the cost of treatment. We loaded the substrate D-luciferin, and the photosensitizer hypericin into a polyethyleneimine (PEI)-modified nano-calcium phosphate (CaP) to solve this problem. Subsequently, the plasmid DNA containing the luciferase gene was loaded onto it using the high-d. pos. charge characteristic of PEI from the nanodrug (denoted DHDC). After the DHDC enters the tumor cell, it collapses and releases the plasmid DNA, which uses the intracellular protein synthesis system to continuously and massively express luciferase. Using endogenous ATP, Mg2+, and O2 in cells, luciferase oxidizes D-luciferin and produces luminescence. The luminescence triggers hypericin excitation to generate ROS and kill cancer cells. This study provides a new strategy for the application of bioluminescence in PDT treatment.

ChemMedChem published new progress about Antitumor agents. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Electric Literature of 2591-17-5.

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

Yang, Ping; Luo, Jia-Bao; Wang, Zi-Zhou; Zhang, Li-Lei; Xie, Xiao-Bao; Shi, Qing-Shan; Zhang, Xin-Guo published the artcile< Synthesis and in vitro antibacterial activity of N-acylarylhydrazone-ciprofloxacin hybrids as novel fluoroquinolone derivatives>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is acylarylhydrazone ciprofloxacin hybrid diastereoselective preparation mol docking antibacterial.

Twelve novel fluoroquinolone derivatives I [R = 3,4-di-HOC6H3, 2,3-di-FC6H3, 2,5-di-FC6H3, etc.] were rationally designed and synthesized by introducing N-acylarylhydrazone to the C-7 position of ciprofloxacin. Antibacterial evaluation revealed that compound I [R = (E)-2,6-di-FC6H3CH=CH] was over 4-folds more potent than ciprofloxacin against S. aureus, with a MIC value ≤0.125μg/mL. Compound I [R = (E)-4-BrC6H4CH=CH] showed activity against methicillin-resistant S. aureus (MRSA) with a MIC value of 32μg/mL. Time-killing assays showed that compound I [R = (E)-4-BrC6H4CH=CH] eradicated S. aureus in 4 h and E. coli in 2 h. Compound I [R = (E)-4-BrC6H4CH=CH] had a high affinity toward DNA topoisomerase IV, with a least binding energy of -9.9 kcal/mol, which was better than ciprofloxacin (-8.0 kcal/mol). The binding modes of compound I [R = (E)-4-BrC6H4CH=CH] to DNA topoisomerase IV differed from that of ciprofloxacin. Mol. dynamics simulation results support that the interaction between the receptor 3rae and the compound I [R = (E)-4-BrC6H4CH=CH] was stable. Besides, cytotoxicity and hemolysis assays demonstrated that compound I [R = (E)-4-BrC6H4CH=CH] and I [R = (E)-2,6-di-FC6H3CH=CH] had negligible risks of toxic effects.

Journal of Molecular Structure published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Recommanded Product: Thiazole-5-carboxyaldehyde.

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

Barton, Anne; Breukelman, Stephen P.; Kaye, Perry T.; Meakins, G. Denis; Morgan, David J. published the artcile< The preparation of thiazole-4- and -5-carboxylates, and an infrared study of their rotational isomers>, Category: thiazole, the main research area is cyclocondensation thiourea bromomethyloxopentanoate; isobutyraldehyde chloroacetate cyclocondensation thiourea; aminoispropylthiazolecarboxylate methyl; butylthiazolecarboxylate ethyl; thiazolecarboxylate preparation rotational isomerism IR.

A general procedure is reported for the preparation of thiazole-4- and -5-carboxylates containing alkyl and halo substituents. Treatment of Me2CHCHO and Cl2CHCO2Me with NaOMe in Et2O at 0°, followed by addition of (H2N)2CS and 4 h reflux in MeOH gave the aminothiazole I. The thiazole II was prepared by treatment of EtO2CCHBrCOCMe3 with (H2N)2CS in refluxing EtOH for 1 h, followed by deamination with NaNO2-H3PO2. Both series of esters show IR carbonyl doublets caused by rotational isomerism; the more intense absorptions of the 4-carboxylates are at lower wave number, whereas those of the 5-carboxylates are the higher wave number component. In both series, the stronger bands arise from the thermochem. more stable forms. For the 4-carboxylates, these forms are the carbonyl O,S-syn-s-trans-rotamers.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) published new progress about Aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 72054-60-5 belongs to class thiazole, and the molecular formula is C7H10N2O2S, Category: thiazole.

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

Powers, Jay P.; Piper, Derek E.; Li, Yang; Mayorga, Veronica; Anzola, John; Chen, James M.; Jaen, Juan C.; Lee, Gary; Liu, Jinqian; Peterson, M. Greg; Tonn, George R.; Ye, Qiuping; Walker, Nigel P. C.; Wang, Zhulun published the artcile< SAR and Mode of Action of Novel Non-Nucleoside Inhibitors of Hepatitis C NS5b RNA Polymerase>, COA of Formula: C10H9NOS2, the main research area is nonnucleoside inhibitor thioxothiazolidine aryl derivative hepatitis C NS5b polymerase.

Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochem. potency have been identified which are selective for the inhibition of HCV NS5b over other polymerases. The structures of the complexes formed between several of these inhibitors and HCV NS5b were determined by x-ray crystallog., and the inhibitors were found to bind in an allosteric binding site sep. from the active site. Structure-activity relationships and structural studies have identified the mechanism of action for compounds in this series, several of which possess drug-like properties, as unique, reversible, covalent inhibitors of HCV NS5b.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, COA of Formula: C10H9NOS2.

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

He, Xiao-Yang; Zou, Peng; Qiu, Jiayin; Hou, Ling; Jiang, Shibo; Liu, Shuwen; Xie, Lan published the artcile< Design, synthesis and biological evaluation of 3-substituted 2,5-dimethyl-N-(3-(1H-tetrazol-5-yl)phenyl)pyrroles as novel potential HIV-1 gp41 inhibitors>, Product Details of C10H9NOS2, the main research area is gp41 inhibitor HIV 1 antiviral tetrazolylphenylpyrrole preparation; pyrrole tetrazolylphenyl preparation gp41 inhibitor HIV 1 antiviral.

Based on the structure of HIV-1 gp41 binding site for small-mol. inhibitors, optimization of a lead compound resulted in the discovery of a new series of 2,5-dimethyl-3-(5-(N-phenylrhodaninyl)methylene)-N-(3-(1H-tetrazol-5-yl)phenyl)pyrrole compounds with improved anti-HIV-1 activity. The two most active compounds exhibited significant potency against gp41 6-HB formation with IC50 values of 4.4 and 4.6 μM and against HIV-1 replication in the MT-2 cells with EC50 values of 3.2 and 2.2 μM, resp., thus providing a new starting point to develop highly potent small-mol. HIV fusion inhibitors targeting gp41.

Bioorganic & Medicinal Chemistry published new progress about AIDS (disease). 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Product Details of C10H9NOS2.

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

Ogretir, Cemil; Demirayak, Seref; Duran, Murat published the artcile< Spectroscopic Determination and Evaluation of Acidity Constants for Some Drug Precursor 2-Amino-4-(3- or 4-substituted phenyl) Thiazole Derivatives>, Product Details of C9H7N3O2S, the main research area is spectroscopic determination acidity constant drug precursor amino phenyl thiazole.

Acid dissociation constants, Ka, of eight drug precursor 2-amino-4-(3- or 4-substituted phenyl) thiazole derivatives were determined using a UV-vis spectroscopic technique. The obtained Ka values were evaluated by structure elucidation and a protonation mechanism. The obtained tautomerization equilibrium constants, KT, indicated the predominance of amino forms for all studied compounds

Journal of Chemical & Engineering Data published new progress about Bond angle, dihedral. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Product Details of C9H7N3O2S.

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