Author: tianli

Aihara, Kazuhiro; Kano, Yuko; Shiokawa, Sohjiro; Sasaki, Toshiro; Setsu, Fumihito; Sambongi, Yumiko; Ishii, Miyuki; Tohyama, Kazuyo; Ida, Takashi; Tamura, Atsushi; Atsumi, Kunio; Iwamatsu, Katsuyoshi published the artcile< CP0569, A New Broad-Spectrum Injectable Carbapenem. Part 1: Synthesis and Structure-Activity Relationships>, Safety of Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate, the main research area is methylcarbapenem antimicrobial activity.

A series of 1β-methylcarbapenems bearing an (imidazo[5,1-b]thiazolium-6-yl)methyl moiety, a 5,5-fused heterobicycle, at the C-2 position was synthesized and evaluated for in vitro antibacterial activities. CP0569 (1r) and its analogs showed potent antibacterial activities against Gram-pos. bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and Gram-neg. bacteria, including Pseudomonas aeruginosa. Moreover, CP0569 (1r) exhibited stronger antibacterial activity against MRSA and higher resistance to renal dehydropeptidase-1 (DHP-1) than any currently marketed carbapenems, i.e., imipenem (IPM), panipenem (PAPM), and meropenem (MEPM).

Bioorganic & Medicinal Chemistry published new progress about Antimicrobial agents. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Safety of Ethyl 2-(((tert-butoxycarbonyl)amino)methyl)thiazole-4-carboxylate.

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

Jiang, Cheng; Yuan, Zhi; Wang, Ju-Fei; Fu, Jie; Jiang, Guang-Jun; Zheng, Liang-Rong published the artcile< Design of novel thiazole bearing pyrazole derivatives and their dual activities as ACE inhibitors and calcium channel blockers in cardiovascular disease>, Electric Literature of 57493-24-0, the main research area is cardiovascular disease thiazole pyrazole derivative ACE inhibitor calcium channel.

In an attempt to develop drugs for cardio-vascular disease, present manuscript deal with the development of dual acting agents targeting angiotensin converting enzyme (ACE) and calcium channel to treat hypertension. These mols. were developed via efficient multi-step synthetic route in excellent yield. In ACE inhibitors assay, these compounds showed considerable percentage of inhibition (32-94 %) with IC50 = 1.2 and 1.5 μM for most promising compound 6e and 6o, resp. In mol. docking study with ACE, compound 6e revealed similar fashion of mol. interaction with catalytic residues His353, Ala 354, Tyr 523, Tyr 520, and Glu 152, comparable with standard lisinopril. Addnl., in rat aortic strip model, these mols. significantly induce vasorelaxation via inhibiting Ca2+ channel in dose dependent manner.

Latin American Journal of Pharmacy published new progress about Angiotensin-converting enzyme inhibitors. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Electric Literature of 57493-24-0.

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

Doughty, Michael B.; Risinger, G. E.; Jungk, Steven J. published the artcile< Chemistry of the tricyclic form of thiamin with aldehydes in basic ethanol>, COA of Formula: C7H9NO2S, the main research area is thiamin aldehyde reaction; hydroxybenzylthiamin; pyrimidinylmethylfurothiazole; furothiazole pyrimidinylmethyl.

Upon the addition of PhCHO to basic thiamin solution gives an intermediate accumulates which gives rise to 2-(1-hydroxyphenylmethyl)thiamin-HCl upon acidification of the reaction mixture and high yields of both 3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-2-benzoyl-3a-methylperhydrofuro[2,3-d]thiazole and benzoin when the reaction mixture is stirred for 5 h. Given that thiamin is unstable under these conditions such that it is converted completely to its tricyclic species, the 2-(1-hydroxyalkyl)thiamin salts, which have an increased base lability due to the addition of a C-2/N-3 torsional interaction to the base-labile thiazolium ring, would also not be expected to accumulate in appreciable concentrations under identical conditions. Based on product isolation and the synthesis of 2-benzoyl-3,4-dimethyl-5-ethoxycarbonyl-[2H]-thiazoline in the reaction of 3,4-dimethyl-5-ethyoxycarbonylthiazolium iodide with PhCHO in basic MeOH, the intermediate which accumulates during the reaction of the tricyclic form of thiam with PhCHO is a 2-benzoylthiazoline in equilibrium with a low concentration of its enol isomer. Reasons for the increased catalytic power of thiamin under these conditions, as well as the relevance of this chem. to the active site chem. of thiamin pyrophosphate, are discussed.

Bioorganic Chemistry published new progress about 20582-55-2. 20582-55-2 belongs to class thiazole, and the molecular formula is C7H9NO2S, COA of Formula: C7H9NO2S.

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

Guggilapu, Sravanthi Devi; Guntuku, Lalita; Reddy, T. Srinivasa; Nagarsenkar, Atulya; Sigalapalli, Dilep Kumar; Naidu, V. G. M.; Bhargava, Suresh K.; Bathini, Nagendra Babu published the artcile< Synthesis of thiazole linked indolyl-3-glyoxylamide derivatives as tubulin polymerization inhibitors>, Safety of Ethyl 2-amino-5-methylthiazole-4-carboxylate, the main research area is thiazole indole glyoxylamide preparation tubulin polymerization inhibitor anticancer; Anticancer; Apoptosis; Indolyl-3-glyoxylamide; Thiazole; Tubulin polymerization inhibitor.

A series of thiazole linked indolyl-3-glyoxylamide derivatives were synthesized and evaluated for their in vitro cytotoxic activity against DU145 (prostate), PC-3 (prostate), A549 (lung) and HCT-15 (colon) cancer cell lines by employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized compounds, compound 13d (I) displayed cytotoxicity of IC50 = 93 nM towards DU145 cancer cell line. The most active compound 13d was also tested on RWPE-1 cells and was found to be safe compared to the DU145 cells. The target compounds were also evaluated for their inhibition activity of tubulin polymerization Further, the treatment of compound 13d on DU145 cells led to the inhibition of cell migration ability. The detailed studies such as acridine orange/ethidium Bromide (AO/EB), DAPI, annexin V-FITC/propidium iodide staining assay suggested that the compound 13d induced apoptosis in DU145 cells. The influence of the cytotoxic compound 13d on the cell cycle distribution was assessed on the DU145 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, the treatment with compound 13d caused collapse of mitochondrial membrane potential and elevated intracellular ROS levels in DU145 cells. The results from mol. modeling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Thus, this new mol. scaffold could be a new lead for the development of anticancer agents that target tubulin.

European Journal of Medicinal Chemistry published new progress about Amides, oxo Role: PAC (Pharmacological Activity), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), PREP (Preparation), USES (Uses). 72054-60-5 belongs to class thiazole, and the molecular formula is C7H10N2O2S, Safety of Ethyl 2-amino-5-methylthiazole-4-carboxylate.

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

Tissaoui, Khalil; Raouafi, Noureddine; Boujlel, Khaled published the artcile< Electrogenerated base-promoted synthesis of N-benzylic rhodanine and carbamodithioate derivatives>, Formula: C10H9NOS2, the main research area is rhodanine carbamodithioate benzylic electrosynthesis.

Electrogenerated magnesium-associated cyanomethyl anions/bases obtained from the electrochem. reduction of acetonitrile and the oxidation of a sacrificial magnesium rod were successfully used to promote the addition of carbon disulfide to primary benzylic amines. Alkylation with Et 3-bromopropionate or with Et 2-bromoacetate yields the corresponding carbamodithioates R1NHC(S)SCH2CH2CO2Et (R1 = PhCH2, 2-ClC6H4CH2, 2-pyridylmethyl, etc.) or cyclic rhodanines I (R2 = PhCH2, 2-ClC6H4CH2, 3-furylmethyl, etc.), resp. The effect of the amount of electrogenerated base on the yield of reaction was also evaluated.

Journal of Sulfur Chemistry published new progress about Aralkyl amines Role: RCT (Reactant), RACT (Reactant or Reagent). 10574-69-3 belongs to class thiazole, and the molecular formula is C10H9NOS2, Formula: C10H9NOS2.

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

Liu, Pei-Han; Urban, Pawel L. published the artcile< Spontaneous luminescence color change in the firefly luciferase assay system>, Application of C11H7KN2O3S2, the main research area is luminescence color firefly luciferase; ATP assay; Color switching; Luciferase; Luminescence.

The temporal effects of luciferase reaction luminescence have only been discussed in the context of light intensity (flash vs. glow). However, alterations in the color of the light emitted over the luciferase reaction have not been reported. Here, the authors show a temporal change in the light color emitted during the reaction catalyzed by unmodified firefly luciferase when concentrations of one of the substrates, ATP, are gradually increased. The temporal color change from green to red occurs within the first few minutes of the luciferase reaction when an ATP-containing solution is either added or synthesized in situ with the aid of an autocatalytic reaction occurring simultaneously. This color change is not accompanied by pH changes. An anal. of the red and green channels demonstrates dissimilar kinetics, suggesting the coexistence of two or more temporally shifted luminescence pathways. The implications of these findings might improve dual-color biosensing/imaging protocols and influence the engineering of biophotonic systems.

Analytical Biochemistry published new progress about Color. 115144-35-9 belongs to class thiazole, and the molecular formula is C11H7KN2O3S2, Application of C11H7KN2O3S2.

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

Schneider, Tanya L.; Walsh, Christopher T.; O’Connor, Sarah E. published the artcile< Utilization of Alternate Substrates by the First Three Modules of the Epothilone Synthetase Assembly Line>, Product Details of C12H18N2O4S, the main research area is substrate specificity epothilone synthetase Sorangium serine polyketide oxazole analog.

The epothilones, a family of macrolactone natural products produced by the myxobacterial species Sorangium cellulosum, are of current clin. interest as antitumor agents. Inspection of the structure of the epothilones suggests a hybrid polyketide/nonribosomal peptide biosynthetic origin, and the recent sequencing of the epothilone biosynthetic gene cluster has validated this proposal. Here we have examined unnatural substrates with the first two enzymes of the biosynthetic pathway, EpoA and EpoB, to investigate the enzymic construction of alternate heterocyclic structures and the subsequent elongation of these products by the third enzyme of the pathway, EpoC. The epothilone biosynthetic machinery can utilize serine to install an oxazole in place of a thiazole in the epothilone structure and will tolerate functionalized donor groups from the EpoA-ACP domain to produce epothilone fragments modified at the C21 position. These studies with the early enzymes of the epothilone biosynthesis cluster suggest that combinatorial biosynthesis may be a viable means for producing a variety of epothilone analogs that incorporate diversity into the heterocycle starter unit.

Journal of the American Chemical Society published new progress about Sorangium cellulosum. 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Product Details of C12H18N2O4S.

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

Hitchin, James R.; Blagg, Julian; Burke, Rosemary; Burns, Samantha; Cockerill, Mark J.; Fairweather, Emma E.; Hutton, Colin; Jordan, Allan M.; McAndrew, Craig; Mirza, Amin; Mould, Daniel; Thomson, Graeme J.; Waddell, Ian; Ogilvie, Donald J. published the artcile< Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments>, Quality Control of 57493-24-0, the main research area is LSD1 inhibitor SAR anticancer acute myeloid leukemia MAOA protein.

Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochem. fragment based screen of 2466 compounds The potency of the initial fragment hit was increased 32-fold through synthesis, with one series of compounds showing clear structure-activity relationships and inhibitory activities in the range of 7 to 187 μM in a biochem. assay. This series also showed selectivity against the related FAD-dependent enzyme mono-amine oxidase A (MAO-A). Although a wide range of irreversible inhibitors of LSD1 have been reported with activities in the low nanomolar range, this work represents one of the first reported examples of a reversible small mol. inhibitor of LSD1 with clear SAR and selectivity against MAO-A, and could provide a platform for the development of more potent reversible inhibitors. Herein, we also report the use of a recently developed cell-based assay for profiling LSD1 inhibitors, and present results on our own compounds as well as a selection of recently described reversible LSD1 inhibitors.

MedChemComm published new progress about Acute myeloid leukemia. 57493-24-0 belongs to class thiazole, and the molecular formula is C9H7N3O2S, Quality Control of 57493-24-0.

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

Chen, Tzu-Yin; Chen, Mei-Ru; Liu, Shan-Wen; Lin, Jin-Yan; Yang, Ya-Ting; Huang, Hsin-Ying; Chen, Jen-Kun; Yang, Chung-Shi; Lin, Kurt Ming-Chao published the artcile< Assessment of polyethylene glycol-coated gold nanoparticle toxicity and inflammation in vivo using NF-κB reporter mice>, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is polyethylene glycol coated gold nanoparticle toxicity inflammation reporter mice; NF-κB; PEG surface modification; gold nanoparticle; liver inflammation; reporter imaging; steatosis.

Polyethylene glycol (PEG) coating of gold nanoparticles (AuNPs) improves AuNP distribution via blood circulation. The use of PEG-coated AuNPs was shown to result in acute injuries to the liver, kidney, and spleen, but long-term toxicity has not been well studied. In this study, we investigated reporter induction for up to 90 days in NF-κB transgenic reporter mice following i.v. injection of PEG-coated AuNPs. The results of different doses (1 and 4μg AuNPs per g of body weight), particle sizes (13 nm and 30 nm), and PEG surfaces (methoxyl- or carboxymethyl-PEG 5 kDa) were compared. The data showed up to 7-fold NF-κB reporter induction in mouse liver from 3 h to 7 d post PEG-AuNP injection compared to saline-injected control mice, and gradual reduction to a level similar to control by 90 days. Agglomerates of PEG-AuNPs were detected in liver Kupffer cells, but neither gross pathol. abnormality in liver sections nor increased activity of liver enzymes were found at 90 days. Injection of PEG-AuNPs led to an increase in collagen in liver sections and elevated total serum cholesterol, although still within the normal range, suggesting that inflammation resulted in mild fibrosis and affected hepatic function. Administrating PEG-AuNPs inevitably results in nanoparticles entrapped in the liver; thus, further investigation is required to fully assess the long-term impacts by PEG-AuNPs on liver health.

International Journal of Molecular Sciences published new progress about Hepatotoxicity. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

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

Ingram, Nicola; McVeigh, Laura E.; Abou-Saleh, Radwa H.; Maynard, Juliana; Peyman, Sally A.; McLaughlan, James R.; Fairclough, Michael; Marston, Gemma; Valleley, Elizabeth M. A.; Jimenez-Macias, Jorge L.; Charalambous, Antonia; Townley, William; Haddrick, Malcolm; Wierzbicki, Antonia; Wright, Alexander; Volpato, Milene; Simpson, Peter B.; Treanor, Darren E.; Thomson, Neil H.; Loadman, Paul M.; Bushby, Richard J.; Johnson, Benjamin R. G.; Jones, Pamela F.; Evans, J. Anthony; Freear, Steven; Markham, Alexander F.; Evans, Stephen D.; Coletta, P. Louise published the artcile< Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues>, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid, the main research area is VEGFR2 SN38 liposome drug delivery circulation bioavailability colorectal cancer; Microbubble; VEGFR2; colorectal cancer; nanoformulation; ultrasound.

Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clin. translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs. Methods: Using a microfluidic microbubble production platform, we generated thMBs comprising VEGFR2-targeted microbubbles with attached liposomal payloads for localised ultrasound-triggered delivery of irinotecan and SN38 in mouse models of colorectal cancer. I.v. injection into tumor-bearing mice was used to examine targeting efficiency and tumor pharmacodynamics. High-frequency ultrasound and bioluminescent imaging were used to visualise microbubbles in real-time. Tandem mass spectrometry (LC-MS/MS) was used to quantitate intratumoral drug delivery and tissue biodistribution. Finally, 89Zr PET radiotracing was used to compare biodistribution and tumor accumulation of ultrasound-triggered SN38 thMBs with VEGFR2-targeted SN38 liposomes alone. Results: ThMBs specifically bound VEGFR2 in vitro and significantly improved tumor responses to low dose irinotecan and SN38 in human colorectal cancer xenografts. An ultrasound trigger was essential to achieve the selective effects of thMBs as without it, thMBs failed to extend intratumoral drug delivery or demonstrate enhanced tumor responses. Sensitive LC-MS/MS quantification of drugs and their metabolites demonstrated that thMBs extended drug exposure in tumors but limited exposure in healthy tissues, not exposed to ultrasound, by persistent encapsulation of drug prior to elimination. 89Zr PET radiotracing showed that the percentage injected dose in tumors achieved with thMBs was twice that of VEGFR2-targeted SN38 liposomes alone. Conclusions: thMBs provide a generic platform for the targeted, ultrasound-triggered delivery of cytotoxic drugs by enhancing tumor responses to low dose drug delivery via combined effects on circulation, tumor drug accumulation and exposure and altered metabolism in normal tissues.

Theranostics published new progress about Bioavailability. 2591-17-5 belongs to class thiazole, and the molecular formula is C11H8N2O3S2, Recommanded Product: (S)-2-(6-Hydroxybenzo[d]thiazol-2-yl)-4,5-dihydrothiazole-4-carboxylic acid.

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