Author: Jessica.F

Netzeva, Tatiana I. published the artcileQSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data, Recommanded Product: 6-Chloro-2-fluoro-3-methylbenzaldehyde, the main research area is aldehyde lipophilicity electrophlicity structure aquatic toxicity.

The aim of the study was to develop quant. structure-activity relationships (QSARs) for a large group of 77 aromatic aldehydes tested for acute toxicity to the ciliate Tetrahymena pyriformis using mechanistically interpretable descriptors. The resulting QSARs revealed that the 1-octanol/water partition coefficient (log Kow), is the most important descriptor of aldehyde aquatic toxic potency. The model with log Kow was improved by adding electronic descriptor (the maximum acceptor superdelocalizability in a mol.-Amax) based on calculations with the semi-empirical AM1 model. The 2 descriptors reflect the 2 main processes responsible for demonstration of acute aquatic toxicity, namely penetration through cell membranes (log K ow) and interaction with the biomacromols. (Amax) into the cells. Results showed that generally the studied group of aldehydes could be modeled by this simple 2-descriptor approach. However, the group of 2- and/or 4-hydroxylated aldehydes demonstrates enhanced toxicity compared to the other aldehydes. Transformation to quinone-like structures is proposed as the explanation for this enhanced potency. The 2- and/or 4-hydroxylated aldehydes are modeled successfully by [log(1/IGC50) = 0.540(0.038) log Kow + 8.30(2.88)Amax – 3.11(0.92), n = 25, R2 = 0.916, R2CV = 0.896 , s = 0.141, F = 120], while the other aldehydes are modeled by the relationship [log(1/IGC50) = 0.583 (0.034)log Kow + 9.80(2.62)Amax – 4.04 (0.85), n = 52, R2 = 0.864, R2CV = 0.844, s = 0.203, F = 156], which is similar to the general benzene model.

Chemosphere published new progress about Aquatic toxicity. 286474-59-7 belongs to class chlorides-buliding-blocks, name is 6-Chloro-2-fluoro-3-methylbenzaldehyde, and the molecular formula is C8H6ClFO, Recommanded Product: 6-Chloro-2-fluoro-3-methylbenzaldehyde.

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

Lei, Beilei published the artcileAccurate prediction of aquatic toxicity of aromatic compounds based on genetic algorithm and least squares support vector machines, Application In Synthesis of 286474-59-7, the main research area is aquatic toxicity aromatic compound genetic algorithm statistics.

Quant. Structure – Toxicity Relationship (QSTR) plays an important role in ecotoxicol. for its fast and practical ability to assess the potential neg. effects of chems. The aim of this investigation was to develop accurate QSTR models for the aquatic toxicity of a large set of aromatic compounds through the combination of Least Squares Support Vector Machines (LS-SVMs) and a Genetic Algorithm (GA). Mol. descriptors calculated by DRAGON package and log P were used to describe the mol. structures. The most relevant descriptors used to build QSTR models were selected by a GA-Variable Subset Selection procedure. Multiple Linear Regression (MLR) and nonlinear LS-SVMs methods were employed to build QSTR models. The predictive ability of the derived models was validated using both the test set, selected from the whole data set by the Kennard – Stone Algorithm, and an external prediction set. The model applicability domain was checked by the leverage approach and the external prediction set was used to verify the predictive reliability of the models. The results indicated that the proposed QSTR models are robust and satisfactory, and can provide a feasible and promising tool for the rapid assessment of the toxicity of chems.

QSAR & Combinatorial Science published new progress about Aquatic toxicity. 286474-59-7 belongs to class chlorides-buliding-blocks, name is 6-Chloro-2-fluoro-3-methylbenzaldehyde, and the molecular formula is C8H6ClFO, Application In Synthesis of 286474-59-7.

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

Schultz, Terry W. published the artcileAssessing applicability domains of toxicological QSARs: definition, confidence in predicted values, and the role of mechanisms of action, Formula: C8H6ClFO, the main research area is modeling predictive toxicity QSAR Tetrahymena aromatic compound.

There are many issues relating to the use of Quant. Structure – Activity Relationships (QSARs) to make predictions for regulatory purposes. Among those issues, characterization of models and the development of suitable tools to determine applicability domains rank as the more important. With regard to aquatic toxicol., QSARs for acute effects (e.g., IGC50-1) often take the form of a hydrophobic [i.e., Logarithm of the 1-Octanol/Water Partition Coefficient (log P)]-electrophilic [e.g., Maximum Acceptor Superdelocalizability (Amax)]-dependent, regression-based model. In this study, the applicability domain of a model for the toxicity of aromatic compounds to Tetrahymena pyriformis [log (IGC50-1) = 0.545(0.015) log P + 16.2(0.62) Amax-5.91(0.20); n = 384, r2 (adj) = 0.859, r2(pred) = 0.856, s = 0.275, F = 1163, Pr > F = 0.0001] was assessed. The structural and physicochem. domains of the model were characterized using two test sets of toxicity data (one prescreened to be within the descriptor space and structural domain of the training set and the other to be outside the structural domain of the training set). For test set compounds inside the domain of the model, there was no relationship between absolute residue values for predictions and hydrophobicity; however, there was a linear relationship between absolute residue values and electrophilicity. It was concluded that predictivity in the region of the domain associated with higher electrophilicity, greater potency, and derivatives containing both halo- and nitro-groups is poorer than elsewhere in the domain, and therefore less confidence should be given to those values. Compounds in this region of the domain of the model are associated with the soft-, or pro-electrophilic mechanisms of toxic action. For the second test set, i.e., derivatives outside the structural domain, an examination of absolute residue values revealed that the observed toxicity is typically in excess of that predicted, especially for compounds in the structural space(s) of well-known electrophilic mechanisms of reactive toxicity. Caution is therefore urged in using statistical approaches to account for, and apply confidence to predictions from the applicability domain. An appreciation of the mechanism of toxicity appears to be critical to the determination of the most likely applicability domain.

QSAR & Combinatorial Science published new progress about Aquatic toxicity. 286474-59-7 belongs to class chlorides-buliding-blocks, name is 6-Chloro-2-fluoro-3-methylbenzaldehyde, and the molecular formula is C8H6ClFO, Formula: C8H6ClFO.

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

Cakir, Gizem published the artcileNovel 4-Thiazolidinones as Non-Nucleoside Inhibitors of Hepatitis C Virus NS5B RNA-Dependent RNA Polymerase, Related Products of chlorides-buliding-blocks, the main research area is thiazolidinone hepatitis C virus NS5B RNA dependent polymerase inhibitor; 4-Thiazolidinones; Antiviral agents; HCV NS5B polymerase; Hepatitis C; Molecular modeling.

In continuation of the authors efforts to develop new derivatives as hepatitis C virus (HCV) NS5B inhibitors, the authors synthesized novel 5-arylidene-4-thiazolidinones. The novel compounds 29-42, together with their synthetic precursors 22-28, were tested for HCV NS5B inhibitory activity; 12 of these compounds displayed IC50 values between 25.3 and 54.1 μM. Compound 33, an arylidene derivative, was the most active compound in this series with an IC50 value of 25.3 μM. Mol. docking studies were performed on the thumb pocket-II of NS5B to postulate the binding mode for these compounds

Archiv der Pharmazie (Weinheim, Germany) published new progress about Antiviral agents. 89978-31-4 belongs to class chlorides-buliding-blocks, name is 5-(2,6-Dichlorophenyl)-1,3,4-thiadiazol-2-amine, and the molecular formula is C8H5Cl2N3S, Related Products of chlorides-buliding-blocks.

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

Rolt, Adam published the artcileDiscovery and Optimization of a 4-Aminopiperidine Scaffold for Inhibition of Hepatitis C Virus Assembly, SDS of cas: 93118-03-7, the main research area is HCV 4AP life cycle viral replication antivirals SAR ADME.

The majority of FDA-approved HCV therapeutics target the viral replicative machinery. An automated high-throughput phenotypic screen identified several small mols. as potent inhibitors of hepatitis C virus replication. Here, we disclose the discovery and optimization of a 4-aminopiperidine (4AP) scaffold targeting the assembly stages of the HCV life cycle. The original screening hit (1) demonstrates efficacy in the HCVcc assay but does not show potency prior to or during viral replication. Colocalization and infectivity studies indicate that the 4AP chemotype inhibits the assembly and release of infectious HCV. Compound 1 acts synergistically with FDA-approved direct-acting antiviral compounds Telaprevir and Daclatasvir, as well as broad spectrum antivirals Ribavirin and cyclosporin A. Following an SAR campaign, several derivatives of the 4AP series, including 77b (I), have been identified with increased potency against HCV, reduced in vitro toxicity, as well as improved in vitro and in vivo ADME properties.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 93118-03-7 belongs to class chlorides-buliding-blocks, name is 2-Chloro-3-(trifluoromethyl)benzaldehyde, and the molecular formula is C8H4ClF3O, SDS of cas: 93118-03-7.

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

Hazeldine, Stuart T. published the artcileDesign, Synthesis, and Biological Evaluation of Analogues of the Antitumor Agent, 2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic Acid (XK469), Safety of 5-Chloroquinoxalin-2-ol, the main research area is chloroquinoxalinyloxyphenoxypropionic acid structure antitumor; quinoxalinyloxyphenoxypropionic acid antitumor preparation.

2-{4-[(7-Chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469) I is among the most highly and broadly active antitumor agents to have been evaluated and scheduled to enter clin. trials in 2001. The mechanism or mechanisms of action of I remain to be elaborated. Accordingly, an effort was initiated to establish a pharmacophore hypothesis to delineate the requirements of the active site, via a comprehensive program of synthesis of analogs of I and evaluation of the effects of structural modification(s) on solid tumor activity. The strategy formulated chose to dissect the two-dimensional parent structure into three regions: I, ring A of quinoxaline; II, the hydroquinone connector linkage; and III, the lactic acid moiety-to determine the resultant in vitro and in vivo effects of chem. alterations in each region. Neither the A-ring unsubstituted nor the B-ring 3-chloro-regioisomer of I showed antitumor activity. The modulating antitumor effect(s) of substituents of differing electronegativities, located at the several sites comprising the A-ring of region I, were next ascertained. Thus, a halogen substituent, located at the 7-position of a 2-{4-[(2-quinoxalinyl)oxy]phenoxy}propionic acid, generated the most highly and broadly active antitumor agents. A Me, methoxy, or an azido substituent at this site generated a much less active structure, whereas 5-, 6-, 8-chloro-, 6-, 7-nitro, and 7-amino derivatives all proved to be essentially inactive. When the connector linkage (region II) of I was changed from that of a hydroquinone to either a resorcinol or a catechol derivative, all antitumor activity was lost. Of the carboxylic acid derivatives of I (region III), i.e., CONH2, CONHMe, CONMe2, CONHOH, CONHNH2, CN, or CN4H (tetrazole), only the monomethyl- and N,N-dimethylamides proved to be active.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 55687-19-9 belongs to class chlorides-buliding-blocks, name is 5-Chloroquinoxalin-2-ol, and the molecular formula is C8H5ClN2O, Safety of 5-Chloroquinoxalin-2-ol.

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

Peng, Zhenghong published the artcileDegrasyn-like symmetrical compounds: Possible therapeutic agents for multiple myeloma, Synthetic Route of 286474-59-7, the main research area is degrasyn analog preparation antitumor multiple myeloma; Degrasyn; Inhibitors; Jak2/Stat3; Multiple myeloma; Small molecules; Synthesis.

A series of degrasyn-like sym. compounds, e.g. I [R = indol-3-yl, 4-(piperidin-1-yl)phenyl, 6-methoxypyridin-2-yl, etc.] have been designed, synthesized, and screened against B cell malignancy (multiple myeloma, mantle cell lymphoma) cell lines. The lead compounds T5165804 and CP2005 showed higher nanomolar potency against these tumor cells in comparison to degrasyn and inhibited Usp9x activity in vitro and in intact cells. These observations suggest that this new class of compounds holds promise as cancer therapeutic agents.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 286474-59-7 belongs to class chlorides-buliding-blocks, name is 6-Chloro-2-fluoro-3-methylbenzaldehyde, and the molecular formula is C8H6ClFO, Synthetic Route of 286474-59-7.

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

Dickens, Michael P. published the artcile5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2, Application In Synthesis of 93118-03-7, the main research area is deazaflavin derivative preparation p53 ubiquitination inhibitor SAR; Cancer; Deazaflavin; HDM2–p53; Ubiquitin E3 ligase; Ubiquitination inhibitors.

Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumor suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relation (SAR) anal. through systematic modification of the 5-deazaflavin template. This anal. shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e.g., I) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one addnl. halogen or Me substituent of the Ph group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 93118-03-7 belongs to class chlorides-buliding-blocks, name is 2-Chloro-3-(trifluoromethyl)benzaldehyde, and the molecular formula is C8H4ClF3O, Application In Synthesis of 93118-03-7.

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

Yan, Luping published the artcileStructure-Activity Relationships for the Marine Natural Product Sintokamides: Androgen Receptor N-Terminus Antagonists of Interest for Treatment of Metastatic Castration-Resistant Prostate Cancer, Application of Methyl 4,4,4-trichlorobutanoate, the main research area is marine sintokamide androgen receptor antagonist prostate cancer antitumor preparation.

Synthetic analogs of the marine natural product sintokamides have been prepared in order to investigate the structure-activity relationships for the androgen receptor N-terminal domain (AR NTD) antagonist activity of the sintokamide scaffold. An in vitro LNCaP cell-based transcriptional activity assay with an androgen-driven luciferase (Luc) reporter was used to monitor the potency of analogs. The data have shown that the chlorine atoms on the leucine side chains are essential for potent activity. Analogs missing the nonchlorinated Me groups of the leucine side chains (C-1 and C-17) are just as active and in some cases more active than the natural products. Analogs with the natural R configuration at C-10 and the unnatural R configuration at C-4 are most potent. Replacing the natural propionamide N-terminus cap with the more sterically hindered pivaloylamide N-terminus cap leads to enhanced potency. The tetramic acid fragment and the Me ether on the tetramic acid fragment are essential for activity. The SAR optimized analog 76 is more selective, easier to synthesize, more potent, and presumed to be more resistant to proteolysis than the natural sintokamides.

Journal of Natural Products published new progress about Antitumor agents. 19376-57-9 belongs to class chlorides-buliding-blocks, name is Methyl 4,4,4-trichlorobutanoate, and the molecular formula is C5H7Cl3O2, Application of Methyl 4,4,4-trichlorobutanoate.

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

Di Matteo, Mauro published the artcileSynthesis and biological characterization of 3-(imidazol-1-ylmethyl)piperidine sulfonamides as aromatase inhibitors, Category: chlorides-buliding-blocks, the main research area is imidazolylmethylpiperidine sulfonamide preparation aromatase inhibitor; Anticancer agents; Aromatase inhibitor; Imidazole; Sulfonamide; Synthesis.

The most frequently used treatment for hormone receptor pos. breast cancer in post-menopausal women are aromatase inhibitors. In order to develop new aromatase inhibitors, we designed and synthesized new imidazolylmethylpiperidine sulfonamides using the structure of the previously identified aromatase inhibitor SYN 20028567 as starting lead. By this approach, three new aromatase inhibitors with IC50 values that are similar to that of letrozole and SYN 20028567 were identified.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 7079-48-3 belongs to class chlorides-buliding-blocks, name is 4-Fluoro-2-methylbenzene-1-sulfonyl chloride, and the molecular formula is C7H6ClFO2S, Category: chlorides-buliding-blocks.

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