Month: October 2022

Raju, D. Suryanarayana; Sasidhar, R. L. C.; Vidyadhara, S. published the artcile< Synthesis and characterization of some novel 5-chloro benzimidazole-2-one derivatives with specific docking studies against PPAR-γ>, HPLC of Formula: 611-19-8, the main research area is piperidinyl benzimidazolone preparation mol docking; peroxisome proliferator activated receptor gamma; benzyl halide acyl chloride alkylation acylation.

A series of 5-chloro-1-(piperidin-4-yl)-1H-benzo[d]imidazole-2(3H)-one derivatives I (Ar = Ph, 4-ClC6H4, 4-BrC6H4, etc.) and II have been synthesized. The compounds were docked against peroxisome proliferator activated receptor-γ (PPAR-γ) by using MCULE software. It was found that the synthesized mols. were active against PPAR-γ by their comparative docking scores with that of standard marketed drugs i.e. Rosiglitazone and Pioglitazone. In particular compounds II (Ar = 2-MeC6H4) and I (Ar = 2-MeC6H4, 4-MeC6H4) showed more binding capacity. The synthesized mols. were identified to have good binding capacity with PPAR- γ according to their docking data.

International Journal of Life Science and Pharma Research published new progress about Aralkyl chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 611-19-8 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2, HPLC of Formula: 611-19-8.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Jacobs, Jon; Grum-Tokars, Valerie; Zhou, Ya; Turlington, Mark; Saldanha, S. Adrian; Chase, Peter; Eggler, Aimee; Dawson, Eric S.; Baez-Santos, Yahira M.; Tomar, Sakshi; Mielech, Anna M.; Baker, Susan C.; Lindsley, Craig W.; Hodder, Peter; Mesecar, Andrew; Stauffer, Shaun R. published the artcile< Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease>, Electric Literature of 672948-03-7, the main research area is butylarylamidopyridinyl acetamide preparation; inhibitor severe acute respiratory syndrome coronavirus 3CL protease; SARS CoV inhibitor antiviral preparation.

A high-throughput screen of the NIH mol. libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (I), [(R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844]. Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, I is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S1′, S1, and S2 enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with I was instrumental in guiding subsequent rounds of chem. optimization. I provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 672948-03-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H3NO3, Electric Literature of 672948-03-7.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kong, Haiyan; Meng, Xianshe; Hou, Rui; Yang, Xiaoxiao; Han, Jihong; Xie, Zhouling; Duan, Yajun; Liao, Chenzhong published the artcile< Novel 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as potent selective human monoamine oxidase B inhibitors: Design, SAR development, and biological evaluation>, Formula: C8H8BrCl, the main research area is propynylamino dihydro indene thiol preparation hMAO B inhibitor; antiParkinson agent structure activity relationship; Fragment-based drug design; HMAO-B; Isoform selectivity; Structure activity relationship.

Successes have been achieved in developing human monoamine oxidase B (hMAO-B) inhibitors as anti-Parkinson’s disease (PD) drugs. However, low efficiency and unwanted side effects of the marketed hMAO-B inhibitors hamper their medical applications, therefore, novel potent selective hMAO-B inhibitors are still of great interest. Herein we report 1-(prop-2-yn-1-ylamino)-2,3-dihydro-1H-indene-4-thiol derivatives as hMAO-B inhibitors, which were designed by employing a fragment-based drug design strategy to link rasagiline to hydrophobic fragments. Among the synthesized 31 compounds, I and II demonstrated very encouraging hMAO-B inhibitory activities and selectivity over hMAO-A, better than rasagiline and safinamide. In vitro studies indicated that K8 and K24 are nontoxic to nervous tissue cells and they have considerable effects against ROS formation and potential neuroprotective activity. Further mice behavioral tests demonstrated these two compounds have good therapeutic effects on MPTP-induced PD model mice. All these experiment results suggest that compounds K8 and K24 can be promising candidates for further research for treatment of PD.

Bioorganic & Medicinal Chemistry Letters published new progress about Antiparkinsonian agents. 16799-05-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BrCl, Formula: C8H8BrCl.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Riley, Kevin E.; Murray, Jane S.; Fanfrlik, Jindrich; Rezac, Jan; Sola, Ricardo J.; Concha, Monica C.; Ramos, Felix M.; Politzer, Peter published the artcile< Halogen bond tunability II: the varying roles of electrostatic and dispersion contributions to attraction in halogen bonds>, Reference of 1435-43-4, the main research area is halogen bond tunability electrostatic dispersion contribution attraction.

In a previous study we investigated the effects of aromatic fluorine substitution on the strengths of the halogen bonds in halobenzene…acetone complexes (halo = chloro, bromo, and iodo). In this work, we have examined the origins of these halogen bonds (excluding the iodo systems), more specifically, the relative contributions of electrostatic and dispersion forces in these interactions and how these contributions change when halogen σ-holes are modified. These studies have been carried out using d. functional symmetry adapted perturbation theory (DFT-SAPT) and through analyses of intermol. correlation energies and mol. electrostatic potentials. It is found that electrostatic and dispersion contributions to attraction in halogen bonds vary from complex to complex, but are generally quite similar in magnitude. Not surprisingly, increasing the size and pos. nature of a halogen’s σ-hole dramatically enhances the strength of the electrostatic component of the halogen bonding interaction. Not so obviously, halogens with larger, more pos. σ-holes tend to exhibit weaker dispersion interactions, which is attributable to the lower local polarizabilities of the larger σ-holes.

Journal of Molecular Modeling published new progress about Correlation energy. 1435-43-4 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H3ClF2, Reference of 1435-43-4.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Macdonald, Jonathan D.; Chacon Simon, Selena; Han, Changho; Wang, Feng; Shaw, J. Grace; Howes, Jennifer E.; Sai, Jiqing; Yuh, Joannes P.; Camper, Demarco; Alicie, Bethany M.; Alvarado, Joseph; Nikhar, Sameer; Payne, William; Aho, Erin R.; Bauer, Joshua A.; Zhao, Bin; Phan, Jason; Thomas, Lance R.; Rossanese, Olivia W.; Tansey, William P.; Waterson, Alex G.; Stauffer, Shaun R.; Fesik, Stephen W. published the artcile< Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5-MYC Protein-Protein Interaction>, Recommanded Product: 5-Chloro-2-methoxybenzenesulfonyl chloride, the main research area is neoplasm WDR5 MYC protein interaction crystal structure.

The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy toward the inhibition of MYC via the disruption of the protein-protein interaction between MYC and its chromatin cofactor WD Repeat-Containing Protein 5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small-mol. inhibitors of this interaction with potent in vitro binding affinity and report structurally related neg. controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors and anticipate that the mols. disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.

Journal of Medicinal Chemistry published new progress about Crystal structure. 22952-32-5 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H6Cl2O3S, Recommanded Product: 5-Chloro-2-methoxybenzenesulfonyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Zurlinden, Todd J.; Saili, Katerine S.; Rush, Nathaniel; Kothiya, Parth; Judson, Richard S.; Houck, Keith A.; Hunter, E. Sidney; Baker, Nancy C.; Palmer, Jessica A.; Thomas, Russell S.; Knudsen, Thomas B. published the artcile< Profiling the ToxCast library with a pluripotent human (H9) stem cell line-based biomarker assay for developmental toxicity>, Reference of 6055-19-2, the main research area is toxcast library pluripotent human stem cell line development toxicity; developmental toxicity; embryonic stem cells; predictive toxicology.

The Stemina devTOX quickPredict platform is a human pluripotent stem cell-based assay that predicts the developmental toxicity potential based on changes in cellular metabolism following chem. exposure. Using this assay, we screened 1065 ToxCast phase I and II chems. in single-concentration or concentration-response for the targeted biomarker (ratio of ornithine to cystine secreted or consumed from the media). The dataset from the Stemina (STM) assay is annotated in the ToxCast portfolio as STM. Major findings from the anal. of ToxCast_STM dataset include (1) 19% of 1065 chems. yielded a prediction of developmental toxicity, (2) assay performance reached 79%-82% accuracy with high specificity (> 84%) but modest sensitivity (< 67%) when compared with in vivo animal models of human prenatal developmental toxicity, (3) sensitivity improved as more stringent weights of evidence requirements were applied to the animal studies, and (4) statistical anal. of the most potent chem. hits on specific biochem. targets in ToxCast revealed pos. and neg. associations with the STM response, providing insights into the mechanistic underpinnings of the targeted endpoint and its biol. domain. The results of this study will be useful to improving our ability to predict in vivo developmental toxicants based on in vitro data and in silico models. Toxicological Sciences published new progress about Analysis (toxicol.). 6055-19-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C7H17Cl2N2O3P, Reference of 6055-19-2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Marc, Julia; Sylvestre, Julia; Bemont, Bernard published the artcile< Preparation of cyclopropane acids from γ-lactones>, COA of Formula: C10H9ClO2, the main research area is .

Cyclization of γ-chlorinated esters, readily obtained from the corresponding lactones, gave good yields of esters of cyclopropanecarboxylic acid by treatment with bases under anhydrous conditions. Thus, with tert-AmONa or PhCMe2ONa in C6H6, Cl(CH2)3CO2Et was cyclized to Et cyclopropanecarboxylate; the free acid was characterized as its S-benzylthiuronium salt, m. 161°. Similarly, the anilide of 2-methylcyclopropanecarboxylic acid, m. 109°, resulted from the Et ester of the latter, produced from MeCHCl(CH2)2CO2Et. From BzCH2CH2CO2H was obtained γ-phenyl-γ-butyrolactone, converted by SOCl2 in C6H6 to PhCHClCH2CH2CO2Et, which, boiled with Me3-COK several hrs. and the solution washed with KMnO4 to remove olefinic compounds and distilled yielded Et 2-phenylcyclopropanecarboxylate, b0.2 105-6°, m. 38° (petr. ether); hydrolysis of the ester produced the free trans acid, m. 90° (anilide, m. 145°). Analogous procedures yielded 2-(p-chlorophenyl)cyclopropanecarboxylic acid, m. 112°; p-BrC6H4 analog, m. 122°; p-MeOC6H4 analog, m. 112° (Et ester, m. 79°). The latter compounds were prepared by condensation of succinic anhydride with the aromatic derivatives, reduction to the lactones, and conversion of the latter to the cyclopropanecarboxylic acids.

Compt. rend. published new progress about Lactones. 90940-40-2 belongs to class chlorides-buliding-blocks, and the molecular formula is C10H9ClO2, COA of Formula: C10H9ClO2.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Buchieri, Maria V.; Cimino, Mena; Rebollo-Ramirez, Sonia; Beauvineau, Claire; Cascioferro, Alessandro; Favre-Rochex, Sandrine; Helynck, Olivier; Naud-Martin, Delphine; Larrouy-Maumus, Gerald; Munier-Lehmann, Helene; Gicquel, Brigitte published the artcile< Nitazoxanide Analogs Require Nitroreduction for Antimicrobial Activity in Mycobacterium smegmatis>, Safety of 2-(Trifluoromethoxy)benzoyl chloride, the main research area is nitazoxanide analog nitroredn antimicrobial Mycobacterium.

In this study, we aimed to decipher the natural resistance mechanisms of mycobacteria against novel compounds isolated by whole-cell-based high-throughput screening (HTS). We identified active compounds using Mycobacterium Aurum. Further analyses were performed to determine the resistance mechanism of M. smegmatis against one hit, 3-bromo-N-(5-nitrothiazol-2-yl)-4-propoxybenzamide (3), which turned out to be an analog of the drug nitazoxanide (1). We found that the repression of the gene nfnB coding for the nitroreductase NfnB was responsible for the natural resistance of M. smegmatis against 3. The overexpression of nfnB resulted in sensitivity of M. smegmatis to 3. This compound must be metabolized into hydroxylamine intermediate for exhibiting antibacterial activity. Thus, we describe, for the first time, the activity of a mycobacterial nitroreductase against 1 analogs, highlighting the differences in the metabolism of nitro compounds among mycobacterial species and emphasizing the potential of nitro drugs as antibacterials in various bacterial species.

Journal of Medicinal Chemistry published new progress about Antibiotic resistance. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Safety of 2-(Trifluoromethoxy)benzoyl chloride.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Wan, Dong; Chen, Yong; Su, Jing; Liu, Lu; Zuo, Yuegang published the artcile< Ultraviolet absorption redshift induced direct photodegradation of halogenated parabens under simulated sunlight>, Category: chlorides-buliding-blocks, the main research area is simulation photodegradation halogenated paraben water sunlight UV Vis spectroscopy; Direct photodegradation; Estrogenic toxicity; Halogenated parabens; Mechanism; QSAR.

As disinfection byproducts of parabens, halogenated parabens are frequently detected in aquatic environments and exhibit higher persistence and toxicity than parabens themselves. An interesting phenomenon was found that UV absorption red shift (∼ 45nm) occurs after halogenation of parabens at circumneutral pH, leading to overlap with the spectrum of terrestrial sunlight. This work presents the first evidence on the direct photodegradation of seven chlorinated and brominated parabens under simulated sunlight. These halogenated parabens underwent rapid direct photodegradation, distinguished from the negligible degradation of the parent compounds The photodegradation rate depended on their forms and substituents. The deprotonation of halogenated parabens facilitated the direct photodegradation Brominated parabens exhibited higher degradation efficiency than chlorinated parabens, and mono-halogenated parabens had higher degradation than di-halogenated parabens. The pseudo-first-order rate constants (kobs) for brominated parabens (0.075-0.120 min-1) were approx. 7-fold higher than those of chlorinated parabens (0.011-0.017 min-1). A quant. structure-activity relationship (QSAR) model suggested that the photodegradation was linearly correlated with the C-X bond energies, electronic and steric effects of halogen substituents. The photodegradation products were identified using QTOF-MS analyses and a degradation pathway was proposed. The yeast two-hybrid estrogenicity assay revealed that the estrogenic activities of the photoproducts were negligible. These findings are important for the removal of halogenated parabens and predictions of their fate and potential impacts in surface waters.

Water Research published new progress about Bond energy. 3964-57-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics