Category: 2382-10-7

Hong, Cynthia M.; Whittaker, Aaron M.; Schultz, Danielle M. published the artcile< Nucleophilic Fluorination of Heteroaryl Chlorides and Aryl Triflates Enabled by Cooperative Catalysis>, Synthetic Route of 2382-10-7, the main research area is heteroaryl chloride crown ether catalyst nucleophilic fluorination; heteroaromatic fluoride preparation; phenyl triflate crown ether catalyst nucleophilic fluorination; fluorobenzene preparation.

A new approach that leverages the cooperative action of 18-crown-6 ether and tetramethylammonium chloride to catalytically access the reactivity of tetramethylammonium fluoride and achieve halex fluorinations under mild conditions with operational ease was reported. The described methodol. readily converts both heteroaryl chlorides and aryl triflates to their corresponding (hetero)aryl fluorides in high yields and purities.

Journal of Organic Chemistry published new progress about Aryl chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Synthetic Route of 2382-10-7.

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

Oxoby, Mayalen; Moreau, Francois; Durant, Lionel; Denis, Alexis; Genevard, Jean-Marie; Vongsouthi, Vanida; Escaich, Sonia; Gerusz, Vincent published the artcile< Towards Gram-positive antivirulence drugs: New inhibitors of Streptococcus agalactiae Stk1>, Recommanded Product: 2,6-Dichloro-9-methyl-9H-purine, the main research area is preparation structure antibacterial antivirulence inhibitor Streptococcus agalactiae Stk1.

A structure-activity relationship study from a screening hit and structure-based design strategy has led to the identification of bisarylureas as potent inhibitors of Streptococcus agalactiae Stk1. As this target has been directly linked to bacterial virulence, these inhibitors can be considered as a promising step towards antivirulence drugs.

Bioorganic & Medicinal Chemistry Letters published new progress about Antibacterial agents. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Recommanded Product: 2,6-Dichloro-9-methyl-9H-purine.

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

Zhang, Yang-Ming; Gu, Min; Ma, Hui; Tang, Jie; Lu, Wei; Nan, Fa-Jun published the artcile< An efficient synthesis of 2-chloropyrimidines via Pd-catalyzed regioselective dechlorination of 2,4-dichloropyrimidines in the presence of NaHCO3>, Name: 2,6-Dichloro-9-methyl-9H-purine, the main research area is chloropyrimidine regioselective dechlorination palladium catalyst sodium hydrocarbonate; pyrimidine chloro preparation.

An efficient synthesis of 2-chloropyrimidines from readily accessible 2,4-dichloropyrimidines was achieved via Pd-catalyzed regioselective dechlorination in the presence NaHCO3.

Chinese Journal of Chemistry published new progress about Dechlorination (regioselective). 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Name: 2,6-Dichloro-9-methyl-9H-purine.

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

Roggen, Heidi; Bohlin, Lars; Burman, Robert; Charnock, Colin; Felth, Jenny; Gorbitz, Carl Henrik; Larsson, Rolf; Tamm, Toomas; Gundersen, Lise-Lotte; IUPAC Commission published the artcile< 2-substituted agelasine analogs: synthesis and biological activity, and structure and reactivity of synthetic intermediates>, Formula: C6H4Cl2N4, the main research area is purine agelasine analog synthesis tautomerization antimicrobial activity; anticancer cytotoxicity purine agelasine analog synthesis; protozoacide activity purine agelasine analog synthesis; fungicide activity purine agelasine analog synthesis; DFT B3LYP calculation tautomer structure purine agelasine analog synthesis; hydrogen bonding purine agelasine analog synthesis; antibacterial activity purine agelasine analog synthesis; antimycobacterial activity purine agelasine analog synthesis; crystal structure purine agelasine analog synthesis.

2-Substituted N-methoxy-9-methyl-9H-purin-6-amines, such as I [R2 = H, Me, NHMe, NMe2, OEt, OMe, CF3, Cl, NO2, R7 = CH2Ph; R2 = H, Me, NHMe, NMe2, OEt, OMe, CF3, Cl, NO2, OH, R7 = geranylgeranyl], were synthesized either from their corresponding 6-chloro-9-methyl-9H-purines or 2-chloro-N-methoxy-9-methyl-9H-purin-6-amine. Great diversity in the amino/imino tautomeric ratios was observed and calculated based on 1H NMR. The tautomers were identified by 1D and 2D 1H, 13C, and 15N NMR techniques, and showed significant variation both in 13C and 15N shift values. Comparison of the tautomeric ratios with Hammett F values revealed that as the field/inductive withdrawing abilities of the 2-substituent increased, the ratio of amino:imino tautomers was shifted toward the amino tautomer. Computational chem. exposed the significance of hydrogen bonding between solvent and the compound in question to reach accurate predictions for tautomeric ratios. B3LYP/def2-TZVP d. functional theory (DFT) calculations resulted in quant. more accurate predictions than when employing the less expensive BP86 functional. N-7-Alkylation of the 2-substituted N-methoxy-9-methyl-9H-purin-6-amines showed that when the field/inductive withdrawing ability of the 2-substituent reached a certain point the reactivity drastically dropped. This correlated with the at. charges on N-7 calculated using a natural bond orbital (NBO) anal. Biol. screening of the 2-substituted agelasine geranylgeralyl analogs indicated that the introduction of a Me group in the 2-position is advantageous for antimycobacterial and antiprotozoal activity, and that an amino function may improve activity against several cancer cell lines.

Pure and Applied Chemistry published new progress about Antibacterial agents. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Formula: C6H4Cl2N4.

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

Liang, Mary; Tarr, Tyler B.; Bravo-Altamirano, Karla; Valdomir, Guillermo; Rensch, Gabriel; Swanson, Lauren; DeStefino, Nicholas R.; Mazzarisi, Cara M.; Olszewski, Rachel A.; Wilson, Gabriela Mustata; Meriney, Stephen D.; Wipf, Peter published the artcile< Synthesis and Biological Evaluation of a Selective N- and P/Q-Type Calcium Channel Agonist>, Safety of 2,6-Dichloro-9-methyl-9H-purine, the main research area is diaminopurine preparation calcium channel agonist structure activity; roscovitine analog preparation calcium channel agonist; cyclin dependent kinase inhibitor roscovitine analog; LEMS; Lambert−Eaton myasthenic syndrome; N/P/Q-type calcium channels; cdk2; neurological autoimmune disorder; roscovitine; selective agonist.

The acute effect of the potent cyclin-dependent kinase (cdk) inhibitor (R)-roscovitine on Ca2+ channels inspired the development of structural analogs as a potential treatment for motor nerve terminal dysfunction. On the basis of a versatile chlorinated purine scaffold, we have synthesized ca. 20 derivatives, I [R1 = n-Pr, Me, CHMe2, R2 = CH2Ph, CH(Ph)2, 3-pyridinylmethyl, etc.], and characterized their N-type Ca2+ channel agonist action. I were prepared by reacting 2,6-dichloro-9H-purine with R1X/K2CO3/DMSO (X = halo), followed by reaction with R2NH2/NEt2/BuOH, which gave the 4-chloro-6-amino derivatives; the final step consisted of treating the latter compounds with (R)-2-amino-1-butanol at 170°C. Agents that showed strong agonist effects were also characterized in a kinase panel for their off-target effects. Among several novel compounds with diminished cdk activity, we identified a new lead structure with a 4-fold improved N-type Ca2+ channel agonist effect and a 22-fold decreased cdk2 activity as compared to (R)-roscovitine. This compound was selective for agonist activity on N- and P/Q-type over L-type calcium channels.

ACS Medicinal Chemistry Letters published new progress about Cyclin-dependent kinase inhibitors. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Safety of 2,6-Dichloro-9-methyl-9H-purine.

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

Lenselink, Eelke B.; Louvel, Julien; Forti, Anna F.; van Veldhoven, Jacobus P. D.; de Vries, Henk; Mulder-Krieger, Thea; McRobb, Fiona M.; Negri, Ana; Goose, Joseph; Abel, Robert; van Vlijmen, Herman W. T.; Wang, Lingle; Harder, Edward; Sherman, Woody; IJzerman, Adriaan P.; Beuming, Thijs published the artcile< Predicting Binding Affinities for GPCR Ligands Using Free-Energy Perturbation>, COA of Formula: C6H4Cl2N4, the main research area is free energy perturbation ligand preparation GPCR binding structure activity; drug discovery adenosine CXCR4 opioid receptor adrenoceptor ligand binding.

The rapid growth of structural information for G-protein-coupled receptors (GPCRs) has led to a greater understanding of their structure, function, selectivity, and ligand binding. Although novel ligands have been identified using methods such as virtual screening, computationally driven lead optimization has been possible only in isolated cases because of challenges associated with predicting binding free energies for related compounds Here, the authors provide a systematic characterization of the performance of free-energy perturbation (FEP) calculations to predict relative binding free energies of congeneric ligands binding to GPCR targets using a consistent protocol and no adjustable parameters. Using the FEP+ package, first the authors validated the protocol, which includes a full lipid bilayer and explicit solvent, by predicting the binding affinity for a total of 45 different ligands across four different GPCRs (adenosine A2AAR, β1 adrenergic, CXCR4 chemokine, and δ opioid receptors). Comparison with exptl. binding affinity measurements revealed a highly predictive ranking correlation (average spearman ρ = 0.55) and low root-mean-square error (0.80 kcal/mol). Next, the authors applied FEP+ in a prospective project, where the authors predicted the affinity of novel, potent adenosine A2A receptor (A2AR) antagonists. Four novel compounds were synthesized and tested in a radioligand displacement assay, yielding affinity values in the nanomolar range. The affinity of two out of the four novel ligands (plus three previously reported compounds) was correctly predicted (within 1 kcal/mol), including one compound with approx. a 10-fold increase in affinity compared to the starting compound Detailed analyses of the simulations underlying the predictions provided insights into the structural basis for the two cases where the affinity was overpredicted. Taken together, these results establish a protocol for systematically applying FEP+ to GPCRs and provide guidelines for identifying potent mols. in drug discovery lead optimization projects.

ACS Omega published new progress about Adenosine A2A receptors Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study). 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, COA of Formula: C6H4Cl2N4.

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

Yu, Yu; Ran, Dongzhi; Jiang, Junhao; Pan, Tao; Dan, Yanrong; Tang, Qiang; Li, Wei; Zhang, Lin; Gan, LinLing; Gan, Zongjie published the artcile< Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2>, Electric Literature of 2382-10-7, the main research area is purin derivative preparation anticancer HDAC CDK dual inhibitor; Antitumor; CDKs; Dual inhibitors; HDACs; Purin.

HDAC and CDK inhibitors have been demonstrated to be synergistically in suppressing cancer cell proliferation and inducing apoptosis. In this work, we incorporated the pharmacophore groups of HDACs and CDKs inhibitors into one mol. to design and synthesize a series of purin derivatives as HDAC/CDK dual inhibitors. The lead compound I, showing good HDAC1 and CDK2 inhibitory activity with IC50 values of 5.8 and 56 nM, resp., exhibited attractive potency against several cancer cell lines in vitro. This work may lead to the discovery of a novel scaffold and potential dual HDAC/CDK inhibitors.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Electric Literature of 2382-10-7.

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

Lee, Wendy; Ortwine, Daniel F.; Bergeron, Philippe; Lau, Kevin; Lin, Lichuan; Malek, Shiva; Nonomiya, Jim; Pei, Zhonghua; Robarge, Kirk D.; Schmidt, Stephen; Sideris, Steve; Lyssikatos, Joseph P. published the artcile< A hit to lead discovery of novel N-methylated imidazolo-, pyrrolo-, and pyrazolo-pyrimidines as potent and selective mTOR inhibitors>, Recommanded Product: 2,6-Dichloro-9-methyl-9H-purine, the main research area is imidazolo pyrrolo pyrazolo pyrimidine preparation mTOR inhibitor; Mammalian target of rapamycin; Oncology; PI3K/Akt/mTOR pathway; Structure based design; mTOR kinase inhibitors.

A series of N-7-methyl-imidazolopyrimidine inhibitors I [R1 = Me, Et; R2 = N-morpholinyl, N-homomorpholinyl, N-(S)-3-methylmorpholinyl, N-(R)-3-methylmorpholinyl] of the mTOR kinase have been designed and prepared, based on the hypothesis that the N-7-Me substituent on imidazolopyrimidine would impart selectivity for mTOR over the related PI3Kα and δ kinases. The corresponding N-Me substituted pyrrolo[3,2-d]pyrimidines and pyrazolo[4,3-d]pyrimidines also show potent mTOR inhibition with selectivity toward both PI3α and δ kinases. The most potent compound synthesized is pyrazolo[4,3-d]pyrimidine II [R1 = Me, R2 = (S)-3-ethylmorpholin-4-yl]. Compound II shows a Ki of 2 nM against mTOR inhibition, remarkable selectivity (>2900×) over PI3 kinases, and excellent potency in cell-based assays.

Bioorganic & Medicinal Chemistry Letters published new progress about Molecular docking. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, Recommanded Product: 2,6-Dichloro-9-methyl-9H-purine.

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

Wang, Zian; Yao, Jingwen; Zhan, Lisi; Gong, Shaolong; Ma, Dongge; Yang, Chuluo published the artcile< Purine-based thermally activated delayed fluorescence emitters for efficient organic light-emitting diodes>, SDS of cas: 2382-10-7, the main research area is purine derivative thermally activated delayed fluorescence organic LED; diode light emitting organic purine derivative thermal delayed fluorescence; electroluminescent device organic purine derivative thermally activated delayed fluorescence.

Two thermally-activated delayed fluorescence (TADF) emitters (1PXZP and 2PXZP) based on a novel biol. base acceptor of 9-methylpurine and commonly used donor of phenoxazine (PXZ) were synthesized and characterized. Both target compounds possess nearly orthogonal configurations to reduce singlet-triplet splitting energy (ΔEST) for remarkable TADF character. The 2 emitters show good luminescence quantum yields (PLQYs), and the organic LEDs employing 1PXZP and 2PXZP as emitters display good performance with maximum external quantum efficiencies of 10.6 and 13.8%, resp. The efficiencies of 1PXZP based device show nearly no roll-off at 100 cd m-2 luminance due to the short delayed lifetime (τd) of 3.2μs. This work manifests that the biol. base is a promising acceptor for designing TADF materials.

Dyes and Pigments published new progress about Cyclic voltammetry. 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, SDS of cas: 2382-10-7.

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

Liao, Ke; Wu, Fengjin; Chen, Jiean; Huang, Yong published the artcile< Catalytic cleavage and functionalization of bulky and inert Csp3-Csp3 bonds via a relayed proton-coupled electron transfer strategy>, COA of Formula: C6H4Cl2N4, the main research area is alc radicalophile acridinium tetrafluoroborate regioselective photochem bond cleavage functionalization.

The direct, photoredox cleavage of hindered Csp3-Csp3 bonds of alcs. under neutral conditions was described. A relayed proton-coupled electron transfer (PCET) strategy was employed that overcame the previous requirement of a Bronsted base. Heavily branched alcs. with a high oxidation potential (Eox1/2 > +2 V vs. SCE) were cleaved and functionalized with remarkable efficiency and versatility. A simple, non-substituted Ph group can promote a relayed PCET process to deliver primary, secondary, and tertiary alkyl radicals under neutral conditions.

Cell Reports Physical Science published new progress about Alcohols Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 2382-10-7 belongs to class chlorides-buliding-blocks, and the molecular formula is C6H4Cl2N4, COA of Formula: C6H4Cl2N4.

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