Tag: M.W=150-200

Campos, Ludmila E. published the artcileSearching new structural scaffolds for BRAF inhibitors. An integrative study using theoretical and experimental techniques, COA of Formula: C6H8N2O2S, the publication is Bioorganic Chemistry (2019), 103125, database is CAplus and MEDLINE.

The identification of the V600E activating mutation in the protein kinase BRAF in around 50% of melanoma patients has driven the development of highly potent small inhibitors (BRAFi) of the mutated protein. To date, Dabrafenib and Vemurafenib, two specific BRAFi, have been clin. approved for the treatment of metastatic melanoma. Unfortunately, after the initial response, tumors become resistant and patients develop a progressive and lethal disease, making imperative the development of new therapeutic options. The main objective of this work was to find new BRAF inhibitors with different structural scaffolds than those of the known inhibitors. Our study was carried out in different stages; in the first step we performed a virtual screening that allowed us to identify potential new inhibitors. In the second step, we synthesized and tested the inhibitory activity of the novel compounds founded. Finally, we conducted a mol. modeling study that allowed us to understand interactions at the mol. level that stabilize the formation of the different mol. complexes. Our theor. and exptl. study allowed the identification of four new structural scaffolds, which could be used as starting structures for the design and development of new inhibitors of BRAF. Our exptl. data indicate that the most active compounds reduced significantly ERK1/2 phosphorylation, a measure of BRAF inhibition, and cell viability. Thus, from our theor. and exptl. results, we propose new substituted hydroxynaphthalenecarboxamides, N-(hetero)aryl-piperazinylhydroxyalkylphenylcarbamates, substituted piperazinylethanols and substituted piperazinylpropandiols as initial structures for the development of new inhibitors for BRAF. Moreover, by performing QTAIM anal., we are able to describe in detail the mol. interactions that stabilize the different Ligand-Receptor complexes. Such anal. indicates which portion of the different mols. must be changed in order to obtain an increase in the binding affinity of these new ligands.

Bioorganic Chemistry published new progress about 64987-16-2. 64987-16-2 belongs to thiazole, auxiliary class Thiazole,Amine,Ester, name is Methyl 2-(2-aminothiazol-4-yl)acetate, and the molecular formula is C6H8N2O2S, COA of Formula: C6H8N2O2S.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Jarrige, Lucie published the artcileChiral phosphoric acid-catalyzed enantioselective construction of structurally diverse benzothiazolopyrimidines, Related Products of thiazole, the publication is Chemical Science (2019), 10(13), 3765-3769, database is CAplus and MEDLINE.

A highly efficient catalytic enantioselective [4+2] cycloaddition was developed between 2-benzothiazolimines and enecarbamates. A wide range of benzothiazolopyrimidines bearing three contiguous stereogenic centers was obtained in high to excellent yields and with excellent diastereo- and enantioselectivities (d.r. > 98 : 2 and up to >99% ee). Furthermore, this chiral phosphoric acid-catalyzed strategy was scalable and enabled access to a new class of optically pure Lewis base isothiourea derivatives

Chemical Science published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, Related Products of thiazole.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Liskovykh, Mikhail published the artcileA novel assay to screen siRNA libraries identifies protein kinases required for chromosome transmission, Quality Control of 95-24-9, the publication is Genome Research (2019), 29(10), 1719-1732, database is CAplus and MEDLINE.

One of the hallmarks of cancer is chromosome instability (CIN), which leads to aneuploidy, translocations, and other chromosome aberrations. However, in the vast majority of human tumors the mol. basis of CIN remains unknown, partly because not all genes controlling chromosome transmission have yet been identified. To address this question, we developed an exptl. high-throughput imaging (HTI) siRNA assay that allows the identification of novel CIN genes. Our method uses a human artificial chromosome (HAC) expressing the GFP transgene. When this assay was applied to screen an siRNA library of protein kinases, we identified PINK1, TRIO, IRAK1, PNCK, and TAOK1 as potential novel genes whose knockdown induces various mitotic abnormalities and results in chromosome loss. The HAC-based assay can be applied for screening different siRNA libraries (cell cycle regulation, DNA damage response, epigenetics, and transcription factors) to identify addnl. genes involved in CIN. Identification of the complete spectrum of CIN genes will reveal new insights into mechanisms of chromosome segregation and may expedite the development of novel therapeutic strategies to target the CIN phenotype in cancer cells.

Genome Research published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, Quality Control of 95-24-9.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Song, Xiaoxiao published the artcileHighly Stereoselective Palladium-Catalyzed [3+2] Cycloaddition of Vinyl Epoxides and N-Benzothiazolimines, Product Details of C7H5ClN2S, the publication is Asian Journal of Organic Chemistry (2019), 8(12), 2180-2183, database is CAplus.

An asym. [3+2] cycloaddition of racemic vinyl epoxides with N-benzothiazolimines was presented under Pd-catalysis. This transformation provided rapid access to highly functionalized oxazolidine scaffolds such as I [R = H, 4-Me, 5-Br, etc.; Ar = Ph, 1-naphthyl, 2-thienyl, etc.] in generally good yields along with high stereoselectivities (up to 99% ee, 8.5 : 1 d.r.) under mild conditions. The use of chiral BINAP ligand enabled this asym. transformation with a broad substrate tolerance.

Asian Journal of Organic Chemistry published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C16H12O, Product Details of C7H5ClN2S.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Zhang, Zhen published the artcileSynthesis and biological evaluation of novel indoleamide derivatives as antioxidative and antitumor agents, Formula: C7H5ClN2S, the publication is Journal of Heterocyclic Chemistry (2020), 57(3), 1165-1172, database is CAplus.

Novel indole amide derivatives I [R = pyrazin-2-amino, (2-methoxy-1-methyl-2-oxo-ethyl)amino, (2-oxoazepan-3-yl)amino, etc.] were successfully synthesized and characterized by ¹H NMR, ¹³C NMR, IR, MS, and elemental anal., and their mol. formulas were C₁₄H₁₀N₆O, C₁₃H₁₀N₄O, C₁₆H₁₃N₃O₂, C₁₉H₁₄N₂O₂, C₁₆H₁₁N₃OS, C₁₅H₁₃N₃O, C₁₂H₉N₅O, C₁₆H₁₀ClN₃OS, C₁₅H₁₇N₃O₂ and C₁₃H₁₄N₂O₃, resp. The primary biol. activities of these compounds I were evaluated in-vitro by the DPPH assay, H₂O₂ induced oxidative stress injury assay and cytotoxicity assay. The results indicated that compounds I [R = imidazo[4,5-d]pyridazin-4-amino, pyrazin-2-amino, 7-hydroxynaphthalen-1-amino, 5H-1,2,4-triazin-4-amino, (2-oxoazepan-3-yl)amino] exhibited DPPH·scavenging ability, while I [R = 2-carbamoylanilino, 7-hydroxynaphthalen-1-amino, 1,3-benzothiazol-2-amino, 6-chloro-1,3-benzothiazol-2-amino] showed potent growth-inhibitory activities against various human tumor cells, including MDA-MB-231, Hela, A549 and HT29. Interestingly, compound I [R = 7-hydroxynaphthalen-1-amino] showed potent scavenging effects on the DPPH radical and possessed protective effect on H₂O₂-induced oxidative stress injury in human neuroblastoma SH-SY5Y cells at low concentrations; however, I [R = 7-hydroxynaphthalen-1-amino] exhibited significant toxicity against four human tumor cells at a higher concentration in all treatments, and the range of IC₅₀ value was 7.91 to 13.35μM.

Journal of Heterocyclic Chemistry published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C19H17N2NaO4S, Formula: C7H5ClN2S.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Dogan, Kubra published the artcileNovel Fluorescent Azacyanine Compounds: Improved Synthesis and Optical Properties, Synthetic Route of 95-24-9, the publication is ACS Omega (2020), 5(36), 22874-22882, database is CAplus and MEDLINE.

Benzothiazoles are known to possess a number of biol. activities and therefore are considered to be an important scaffold in the design and synthesis of pharmacophores. In this study, an improved synthesis method for novel fluorescent benzothiazole-based cyclic azacyanine (CAC) dyes bearing different electron-donating/withdrawing groups on their scaffold is presented. The improved method enabled us to increase the synthesis yield for the previously reported CACs. More importantly, it allowed us to synthesize new CAC dyes that were not synthesizable with the previously reported method. The synthesized dyes were characterized by ¹H and ¹³C NMR spectroscopy, elemental anal., and mass spectrometry and their optical (absorption and fluorescence) properties were investigated. All of the synthesized CACs were found to be displaying strong absorption within the range of 387-407 nm. The spectral shifts observed in the absorption and fluorescence measurements suggested that the spectroscopic and optical properties of CACs can be directly modulated by the nature of the electron-donating/withdrawing substituents. The fluorescence quantum yields (QYs) of the unsubstituted (parent CAC) and substituted CACs were also measured and compared. The fluorescence QY of CACs with electron-donating substituents (methoxy or ethoxy) was found to be at least four times higher than that of the parent CAC with no substitutions.

ACS Omega published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, Synthetic Route of 95-24-9.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Petrou, Anthi published the artcileNovel thiazolidin-4-ones as potential non-nucleoside inhibitors of HIV-1 reverse transcriptase, Related Products of thiazole, the publication is Molecules (2019), 24(21), 3821, database is CAplus and MEDLINE.

Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and mol. docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower IC₅₀ values than nevirapine (0.3μM). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4μM. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC₅₀ values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC₅₀ 1 nM.

Molecules published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, Related Products of thiazole.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Al-Janabi, Ahmed S. M. published the artcileSynthesis, anti-bacterial evaluation, DFT study and molecular docking as a potential 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2 inhibitors of a novel Schiff bases, Quality Control of 95-24-9, the publication is Journal of Molecular Structure (2021), 129454, database is CAplus and MEDLINE.

New Schiff bases (L¹H) I (I), (L²H) II (II), (L³H) III (III) were synthesized by reaction of 2-benzoylpyridine with different amines (2-amino-6-chlorobenzothiazole, isonicotinohydrazide and N¹-(naphthalen-1-yl)ethane-1,2-diamine) and characterized by ¹H-NMR, ¹³C-NMR, IR mass spectroscopy and elemental anal. The compounds (I), (II) and (III) were assayed by the disk diffusion method for anti-bacterial against five pathogenic bacteria species (Staphylococcus aureus, Micrococcus luteus, Staphylococcus pyogenes, Bacillus subtilis, and E. coli). All prepared Schiff bases (I), (II) and (III) showed good activity compared to pos. control (streptomycin). Moreover the L³H showed the highest activity against S. aureus, and M. luteus than the other compounds and streptomycin. In addnl. mol. docking studies with 3-chymotrypsin-like protease (3CLpro), the essential enzyme for SARS-CoV-2 proliferation. The rest of compounds have shown promising results as 3CLpro inhibitors interacting with the active sites of the enzymes. Finally, DFT’s estimated electrostatic mol. potential results were used to illustrate the mol. docking findings. The DFT calculations showed that L³H has the highest dipole moment and electrophilicity index. Interestingly, L²H of the largest energy gap ΔE = 2.49 eV, there are several hydrophilic interactions that could facilitate the binding with the receptors. All of these parameters could be shared to significantly affect the protein sites of binding affinity with different extent.

Journal of Molecular Structure published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, Quality Control of 95-24-9.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Hill, Matthew D. published the artcileDevelopment of spiroguanidine-derived α7 neuronal nicotinic receptor partial agonists, Category: thiazole, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(3), 578-581, database is CAplus and MEDLINE.

We describe the synthesis of quinuclidine-containing spiroguanidines and their utility as α7 neuronal nicotinic acetylcholine receptor (nAChR) partial agonists. The convergent synthetic route developed for this study allowed for rapid SAR investigation and provided access to a structurally diverse set of analogs. A potent and selective α7 nAChR partial agonist, N-(6-methyl-1,3-benzoxazol-2-yl)-3′,5′-dihydro-4-azaspiro[bicyclo[2.2.2]octane-2,4′-imidazole]-2′-amine (BMS-910731, I), was identified. This compound induced immediate early genes c-fos and Arc in a preclin. rodent model of α7 nAChR-derived cellular activation and plasticity. Importantly, the ability to incorporate selectivity for the α7 nACh receptor over the 5-HT_3A receptor in this series suggested a significant difference in steric requirements between the two receptors.

Bioorganic & Medicinal Chemistry Letters published new progress about 31784-71-1. 31784-71-1 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorothiazolo[5,4-b]pyridin-2-amine, and the molecular formula is C6H4ClN3S, Category: thiazole.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Hoveyda, Hamid R. published the artcileDiscovery and Optimization of Novel Antagonists to the Human Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part I), HPLC of Formula: 1375066-73-1, the publication is Journal of Medicinal Chemistry (2015), 58(7), 3060-3082, database is CAplus and MEDLINE.

Neurokinin-3 receptor (NK₃R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. The authors therefore decided to explore NK₃R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma LH and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK₃R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described. A concomitant improvement in the antagonist bioactivity and ligand lipophilic efficiency (LLE) parameter were the principal guidelines in the lead optimization efforts. Examples of advanced lead analogs to demonstrate the amenability of this chemotype to achieving a suitable pharmacokinetic (PK) profile are provided as well as pharmacokinetic-pharmacodynamic (PKPD) correlations to analyze the trends observed for LH inhibition in castrated rats and monkeys that served as preliminary in vivo efficacy models.

Journal of Medicinal Chemistry published new progress about 1375066-73-1. 1375066-73-1 belongs to thiazole, auxiliary class Thiadiazole,Hydrazine,Amine,Hydrazide,Amide, name is 3-Methyl-1,2,4-thiadiazole-5-carbohydrazide, and the molecular formula is C4H6N4OS, HPLC of Formula: 1375066-73-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica