Month: February 2023

Validated preclinical mouse model for therapeutic testing against multidrug-resistant Pseudomonas aeruginosa strains was written by Warawa, Jonathan M.;Duan, Xiaoxian;Anderson, Charles D.;Sotsky, Julie B.;Cramer, Daniel E.;Pfeffer, Tia L.;Guo, Haixun;Adcock, Scott;Lepak, Alexander J.;Andes, David R.;Slone, Stacey A.;Stromberg, Arnold J.;Gabbard, Jon D.;Severson, William E.;Lawrenz, Matthew B.. And the article was included in Microbiology Spectrum in 2022.Recommanded Product: 78110-38-0 This article mentions the following:

The rise in infections caused by antibiotic-resistant bacteria is outpacing the development of new antibiotics. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are a group of clin. important bacteria that have developed resistance to multiple antibiotics and are commonly referred to as multidrug resistant (MDR). The medical and research communities have recognized that, without new antimicrobials, infections by MDR bacteria will soon become a leading cause of morbidity and death. Therefore, there is an ever-growing need to expedite the development of novel antimicrobials to combat these infections. Toward this end, we set out to refine an existing mouse model of pulmonary Pseudomonas aeruginosa infection to generate a robust preclin. tool that can be used to rapidly and accurately predict novel antimicrobial efficacy. This refinement was achieved by characterizing the virulence of a panel of genetically diverse MDR P. aeruginosa strains in this model, by both 50% LD (LD₅₀) anal. and natural history studies. Further, we defined two antibiotic regimens (aztreonam and amikacin) that can be used as comparators during the future evaluation of novel antimicrobials, and we confirmed that the model can effectively differentiate between successful and unsuccessful treatments, as predicted by in vitro inhibitory data. This validated model represents an important tool in our arsenal to develop new therapies to combat MDR P. aeruginosa strains, with the ability to provide rapid preclin. evaluation of novel antimicrobials and support data from clin. studies during the investigational drug development process. IMPORTANCE The prevalence of antibiotic resistance among bacterial pathogens is a growing problem that necessitates the development of new antibiotics. Preclin. animal models are important tools to facilitate and speed the development of novel antimicrobials. Successful outcomes in animal models not only justify progression of new drugs into human clin. trials but also can support FDA decisions if clin. trial sizes are small due to a small population of infections with specific drug-resistant strains. However, in both cases the preclin. animal model needs to be well characterized and provide robust and reproducible data. Toward this goal, we have refined an existing mouse model to better predict the efficacy of novel antibiotics. This improved model provides an important tool to better predict the clin. success of new antibiotics. In the experiment, the researchers used many compounds, for example, 2-((((Z)-1-(2-Aminothiazol-4-yl)-2-(((2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid (cas: 78110-38-0Recommanded Product: 78110-38-0).

2-((((Z)-1-(2-Aminothiazol-4-yl)-2-(((2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid (cas: 78110-38-0) belongs to thiazole derivatives. Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Recommanded Product: 78110-38-0

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

2-Substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamides as BACE1 inhibitors: Synthesis, biological evaluation and docking studies was written by Yan, Gang;Hao, Lina;Niu, Yan;Huang, Wenjie;Wang, Wei;Xu, Fengrong;Liang, Lei;Wang, Chao;Jin, Hongwei;Xu, Ping. And the article was included in European Journal of Medicinal Chemistry in 2017.SDS of cas: 105512-81-0 This article mentions the following:

In this work, a series of 2-substituted-thio-N-(4-substituted-thiazol/1H-imidazol-2-yl)acetamide derivatives, I (R¹ = Ph, 4-MeC₆H₄, 2-O₂NC₆H₄, etc.; R₂ = 2-MeOC₆H₄,3-MeOC₆H₄, 4-MeOC₆H₄, 3-EtOC₆H₄), II (R³ = Ph, 3,5-Cl₂-4-NH₂Ph; R⁴ = 3-MeOPh, 3-EtOPh), were developed as β-secretase (BACE-1) inhibitors. Supported by docking study, a small library of derivatives were designed, synthesized and biol. evaluated in vitro. In addition, the selected compounds were tested with affinity (K_D) towards BACE-1, blood brain barrier (BBB) permeability and cytotoxicity. The studies revealed that the most potent analog II (R³ = Ph; R⁴ = 3-EtOC₆H₄) (IC₅₀ = 4.6 μM) with high predicted BBB permeability and low cellular cytotoxicity, could serve as a good lead structure for further optimization. In the experiment, the researchers used many compounds, for example, 2-Amino-4-(3-bromophenyl)thiazole (cas: 105512-81-0SDS of cas: 105512-81-0).

2-Amino-4-(3-bromophenyl)thiazole (cas: 105512-81-0) belongs to thiazole derivatives. Thiazoles in peptides or their ability to bind proteins, DNA and RNA has led to many synthetic studies and new applications. Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides.SDS of cas: 105512-81-0

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

Detection and Prevention of Aggregation-based False Positives in STD-NMR-based Fragment Screening was written by Vom, Amelia;Headey, Stephen;Wang, Geqing;Capuano, Ben;Yuriev, Elizabeth;Scanlon, Martin J.;Simpson, Jamie S.. And the article was included in Australian Journal of Chemistry in 2013.Recommanded Product: 4-(2-Amino-4-thiazolyl)phenol This article mentions the following:

Aggregation of small organic compounds is a problem encountered in a variety of assay screening formats where it often results in detection of false positives. A saturation transfer difference-NMR-detected screen of a com. available fragment library, followed by biochem. assay, identified several inhibitors of the enzyme ketopantoate reductase. These inhibitors were subsequently revealed to be aggregation-based false positives. Modification of the fragment screen by addition of detergent in the saturation transfer difference-NMR experiments allowed an assay format to be developed that resulted in the identification of genuine hit mols. suitable for further development. In the experiment, the researchers used many compounds, for example, 4-(2-Amino-4-thiazolyl)phenol (cas: 57634-55-6Recommanded Product: 4-(2-Amino-4-thiazolyl)phenol).

4-(2-Amino-4-thiazolyl)phenol (cas: 57634-55-6) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides.Recommanded Product: 4-(2-Amino-4-thiazolyl)phenol

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

Unsymmetrical nickel (PCN) pincer complexes with a benzothiazole side-arm: Synthesis, characterization and electrochemical properties was written by Luconi, Lapo;Tuci, Giulia;Gafurov, Zufar N.;Mercuri, Giorgio;Kagilev, Alexey A.;Pettinari, Claudio;Morozov, Vladimir I.;Yakhvarov, Dmitry G.;Rossin, Andrea;Giambastiani, Giuliano. And the article was included in Inorganica Chimica Acta in 2021.Name: 2-Chlorobenzothiazole This article mentions the following:

The newly prepared unsym. PCN-pincer ligand with a benzothiazole side-arm 2-(3-((di-tert-butylphosphino)methyl)phenoxy)benzothiazole [BzTz(H)PCN] has been cyclometalated with anhydrous NiBr₂ to get the corresponding Ni^II square planar bromo complex [(BzTzPCN)NiBr] (1) after HBr elimination and C-H activation on the pincer central Ph ring. Starting from 1, reaction with AgF in toluene or with AgBF₄ in THF led to bromide abstraction and formation of the fluoro complex [(BzTzPCN)NiF] (2) and the ionic aqua species [(BzTzPCN)Ni(H₂O)][BF₄] (3), resp. All species have been characterized in solution (multinuclear ¹H, ¹³C{¹H}, ³¹P{¹H} and ¹¹B NMR spectroscopy) and in the solid state (single-crystal X-ray diffraction anal.). Finally, comparative electrochem. measurements (CV and in situ EPR-spectroelectrochem.) carried out on the halide complexes 1 and 2 revealed that the anodic oxidation process leads to the formation of stable Ni^III species bearing a coordinated bromide ligand in case of 1 and a fluoride-free complex in case of 2. In the experiment, the researchers used many compounds, for example, 2-Chlorobenzothiazole (cas: 615-20-3Name: 2-Chlorobenzothiazole).

2-Chlorobenzothiazole (cas: 615-20-3) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. The pyridine-type nitrogen in the thiazole ring deactivates the ring for electrophilic substitution reactions, which is further reduced in acid due to protonation of the thiazole ring.Name: 2-Chlorobenzothiazole

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

Novel synthesis of 2-thiazolines was written by Fernandez, Xavier;Fellous, Roland;Dunach, Elisabet. And the article was included in Tetrahedron Letters in 2000.Synthetic Route of C4H7NS This article mentions the following:

The synthesis of a series of 2-thiazolines was carried out under mild conditions from the corresponding thiazolidines, by a Ru-catalyzed/TBHP oxidation reaction conditions. The reaction was chemoselective towards the amine-imine oxidation and was also regioselective, affording the unsaturation at the 2-position of the heterocycle, even with thiazolidine substrates bearing ester groups at the 4-position. In the experiment, the researchers used many compounds, for example, 2-Methyl-4,5-dihydrothiazole (cas: 2346-00-1Synthetic Route of C4H7NS).

2-Methyl-4,5-dihydrothiazole (cas: 2346-00-1) belongs to thiazole derivatives. Thiazoles frequently appear in peptide studies. Thiazoles can also be used as protected formyl groups, which can be released in later stages of complex natural product synthesis. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 °C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.Synthetic Route of C4H7NS

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

Design, Synthesis, Biological Evaluation and Molecular Docking Studies of 1,4-Disubstituted 1,2,3-Triazoles: PEG-400:H₂O Mediated Click Reaction of Fluorescent Organic Probes under Ultrasonic Irradiation was written by Reddivari, Chenna Krishna Reddy;Devineni, Subba Rao;Nemallapudi, Bakthavatchala Reddy;Sravya, Gundala;Avula, Balakrishna;Shaik, Nayabrasool;Badavath, Vishnu Nayak;Zyryanov, Grigory V.;YellalaVenkata, Rami Reddy;Chamarthi, Naga Raju. And the article was included in Polycyclic Aromatic Compounds in 2022.Name: 2-Bromothiazole This article mentions the following:

A PEG-400:H₂O mediated highly versatile, efficacious and selective “Click reaction” of fluorescent organic Probes under ultrasonic irradiation were reported. A rapid and efficient approach for the synthesis of 1,4-Disubstituted 1,2,3-triazoles I [R = (4-fluorophenyl)methyl, 2,4-dioxo-pyrimidin-5-yl, etc.] under Copper (I)-Catalyzed Azide-Alkyne [3 + 2] Cycloaddition (CuAAC) conditions in good to excellent yields in less time were described. This synthetic protocol were proved to endorse easy work-up under benign reaction conditions. The green solvent system employed was efficaciously reused several times without any loss of its activity in an aqueous medium. All the title compounds were characterized by using elemental anal., ¹HNMR, ¹³CNMR, FTIR, and mass spectral data. The newly synthesized compounds were biol. evaluated for their antioxidant activity. The antioxidant activity resulted demonstrate that all compounds showed good to excellent antioxidant activity, particularly the compounds I [R = (4-bromophenyl)methyl, 5-bromo-2-pyridyl, pyrimidin-2-yl, 2,4-dioxo-pyrimidin-5-yl] exhibited promising radical scavenging activity. Further, photophys. properties of the compounds were accomplished using spectrofluorimeter. Compounds I [R = (3-chlorophenyl)methyl, (4-nitrophenyl)methyl, (4-cyanophenyl)methyl, thiazol-2-yl, 5-bromo-2-pyridyl, pyrimidin-2-yl, 2,4-dioxo-pyrimidin-5-yl] exhibited fluorescence in the visible region. Mol. docking studies suggested the antioxidant activity of synthesized compounds were due to the inhibition of neuronal nitric oxide synthase (HnNOS). In the experiment, the researchers used many compounds, for example, 2-Bromothiazole (cas: 3034-53-5Name: 2-Bromothiazole).

2-Bromothiazole (cas: 3034-53-5) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity. There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Name: 2-Bromothiazole

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

Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial was written by Roostaei Firozabad, Amirreza;Meybodi, Zohreh Akhoundi;Mousavinasab, Seyed Ruhollah;Sahebnasagh, Adeleh;Jelodar, Mohsen Gholinataj;Karimzadeh, Iman;Habtemariam, Solomon;Saghafi, Fatemeh. And the article was included in BMC Infectious Diseases in 2021.HPLC of Formula: 14769-73-4 This article mentions the following:

Abstract: Background: Levamisole has shown clin. benefits in the management of COVID-19 via its immunomodulatory effect. However, the exact role of Levamisole effect in clin. status of COVID-19 patients is unknown. We aimed to evaluate the efficacy of Levamisole on clin. status of patients with COVID-19 during their course of the disease. Methods: This prospective, double-blind, randomized controlled clin. trial was performed in adult patients with mild to moderate COVID-19 (room-air oxygen saturation > 94%) from late Apr. 2020 to mid-August 2020. Patients were randomly assigned to receive a 3-day course of Levamisole or placebo in combination with routine standard of care. Results: With 25 patients in each arm, 50 patients with COVID-19 were enrolled in the study. Most of the study participants were men (60%). On days 3 and 14, patients in Levamisole group had significantly better cough status distribution when compared to the placebo group (P-value = 0.034 and 0.005, resp.). Moreover, there was significant differences between the two groups in dyspnea at follow-up intervals of 7 (P-value = 0.015) and 14 (P-value = 0.010) days after receiving the interventions. However, no significant difference in fever status was observed on days 1, 3, 7, and 14 in both groups (P-value > 0.05). Conclusion: The results of the current study suggest that Levamisole may improve most of clin. status of patients with COVID-19. The patients receiving Levamisole had significantly better chance of clin. status including cough and dyspnea on day 14 when compared to the placebo. However, the effect-size of this finding has uncertain clin. importance. Trial registration: The trial was registered as IRCT20190810044500N7 (19/09/2020). In the experiment, the researchers used many compounds, for example, (S)-6-Phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (cas: 14769-73-4HPLC of Formula: 14769-73-4).

(S)-6-Phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (cas: 14769-73-4) belongs to thiazole derivatives. The higher aromaticity of thiazole is due to delocalization of a lone pair of sulfur electrons across the ring, which is evidenced by chemical shifts of ring hydrogen at δ 7.27 and 8.77 ppm (C2 and C4), indicating diamagnetic ring current. Various laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis is a reaction between haloketones and thioamides.HPLC of Formula: 14769-73-4

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

Discovery of highly potent, selective, orally bioavailable, metabotropic glutamate subtype 5 (mGlu5) receptor antagonists devoid of cytochrome P450 1A2 inhibitory activity was written by Smith, Nicholas D.;Poon, Steve F.;Huang, Dehua;Green, Mitchell;King, Christopher;Tehrani, Lida;Roppe, Jeffrey R.;Chung, Janice;Chapman, Deborah P.;Cramer, Merryl;Cosford, Nicholas D. P.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2004.Recommanded Product: 3364-80-5 This article mentions the following:

Structure-activity relationship studies focused on bio-isosteric replacements of 2-pyridyl resulted in mGlu5 receptor antagonists with reduced inhibition of cytochrome P 450 1A2. This led to highly potent, selective and orally bioavailable 2-imidazolyl tetrazoles such as I that are devoid of cytochrome P 450 inhibitory activity. In the experiment, the researchers used many compounds, for example, Thiazole-4-carbaldehyde (cas: 3364-80-5Recommanded Product: 3364-80-5).

Thiazole-4-carbaldehyde (cas: 3364-80-5) belongs to thiazole derivatives. Thiazole rings are planar and aromatic. Thiazoles are characterized by larger pi-electron delocalization than the corresponding oxazoles and have therefore greater aromaticity.Various laboratory methods exist for the organic synthesis of thiazoles. For example, 2,4-dimethylthiazole is synthesized from thioacetamide and chloroacetone.Recommanded Product: 3364-80-5

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

Synthesis and in vitro antileishmanial activity of 5-substituted-2′-deoxyuridine derivatives was written by Peyron, Corinne;Benhida, Rachid;Bories, Christian;Loiseau, Philippe M.. And the article was included in Bioorganic Chemistry in 2005.Category: thiazole This article mentions the following:

We report herein the synthesis and the in vitro antileishmanial evaluation of 5-substituted-2′-deoxyuridine nucleosides. The most active compound against Leishmania donovani promastigotes was Thia-dU (3a) with an IC₅₀ = 3 μM. This compound exhibited the same activity as zidovudine (3′-azido-2′-deoxythymidine) used as nucleoside reference compound Considering the cytotoxicity of synthetic compounds on peritoneal murine macrophages, the most toxic compound was MeThio-dU (3d) with a MTC at 10 μM. Only Methia-dU (3b) was active against intra-macrophagic amastigotes with an IC₅₀ = 6.5 μM. This latter can now be evaluated in vivo, for further investigations through structure-based drug design. In the experiment, the researchers used many compounds, for example, 2-(Tributylstannyl)thiazole (cas: 121359-48-6Category: thiazole).

2-(Tributylstannyl)thiazole (cas: 121359-48-6) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.Category: thiazole

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

Nickel-catalysed direct alkylation of thiophenes via double C(sp³)-H/C(sp²)-H bond cleavage: the importance of KH₂PO₄ was written by Wang, Xie;Xie, Peipei;Qiu, Renhua;Zhu, Longzhi;Liu, Ting;Li, You;Iwasaki, Takanori;Au, Chak-Tong;Xu, Xinhua;Xia, Yuanzhi;Yin, Shuang-Feng;Kambe, Nobuaki. And the article was included in Chemical Communications (Cambridge, United Kingdom) in 2017.Product Details of 3034-53-5 This article mentions the following:

The efficient Ni-catalyzed oxidative C(sp³)-H/C(sp²)-H cross-dehydrogenative coupling reaction was developed for synthesis of highly functionalized alkyl (aryl)-substituted thiophenes such as I [R¹ = Me, Et, Ph; R² = Me, Ph, Bn, 2-naphthyl; R¹ = R² = Me, Ph; R¹R² = (CH₂)₅, Ph, 2-H₃CC₆H₄; R³ = 2-thienyl, benzothien-2-yl, 4-Br-2-thienyl, etc.] from thiophenes and aliphatic (aromatic) amides that contain an 8-aminoquinoline as a removable directing group in the presence of a silver oxidant. The approach enabled the facile one-step synthesis of substituted thiophenes I with high functional group compatibility via double C(sp³)-H/C(sp²)-H bond cleavage without affecting C-Br and C-I bonds and formation of C(alkyl)-C(heteroaryl) bonds. DFT calculations verified the importance of KH₂PO₄ as an additive for promoting C-H bond cleavage and supported the involvement of a Ni(III) species for efficient C(sp²)-H cleavage and C-C coupling. In the experiment, the researchers used many compounds, for example, 2-Bromothiazole (cas: 3034-53-5Product Details of 3034-53-5).

2-Bromothiazole (cas: 3034-53-5) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.Product Details of 3034-53-5

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