Category: 128-09-6

Willis, Nicky J.; Bayle, Elliott D.; Papageorgiou, George; Steadman, David; Atkinson, Benjamin N.; Mahy, William; Fish, Paul V. published the artcile< An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent>, Name: 1-Chloropyrrolidine-2,5-dione, the main research area is Notum LP922056 chloro benziodoxol one pharmacokinetics; 1-chloro-1,2-benziodoxol-3-one; LP-922056; Notum inhibitor; brain penetration; electrophilic chlorination.

We are investigating the role of Notum in modulating Wnt signalling in the central nervous system and wished to establish if 1 would serve as a peripherally restricted control. Key modifications include: (1) the introduction of the C7-cyclopropyl group was most effectively achieved with a Suzuki-Miyaura cross-coupling reaction with MIDA-boronate 11 (5 → 6), and (2) C6 chlorination was performed with 1-chloro-1,2-benziodoxol-3-one (12) (6 → 7) as a mild and selective electrophilic chlorination agent. Pharmacokinetic studies in mouse showed CNS penetration of 1 is very low with a brain/plasma concentration ratio of just 0.01. A small library of amides 17 were prepared from acid 1 to explore if 1 could be modified to deliver a CNS penetrant tool by capping off the acid as an amide. Although significant Notum inhibition activity could be achieved, none of these amides demonstrated the required combination of metabolic stability along with cell permeability without evidence of P-gp mediated efflux. Mouse pharmacokinetic studies demonstrate that 1 is unsuitable for use in models of disease where brain penetration is an essential requirement of the compound but would be an ideal peripherally restricted control. These data will contribute to the understanding of drug levels of 1 to overlay with appropriate in vivo efficacy endpoints, i.e., the PK-PD relationship.

Beilstein Journal of Organic Chemistry published new progress about Central nervous system. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Name: 1-Chloropyrrolidine-2,5-dione.

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

Rogers, David A.; Hopkins, Megan D.; Rajagopal, Nitya; Varshney, Dhruv; Howard, Haley A.; LeBlanc, Gabriel; Lamar, Angus A. published the artcile< U.S. Food and Drug Administration-Certified Food Dyes as Organocatalysts in the Visible Light-Promoted Chlorination of Aromatics and Heteroaromatics>, Product Details of C4H4ClNO2, the main research area is aryl chloride regioselective preparation; arene chlorosuccinimide visible light promoted chlorination food dye organocatalyst.

Seven FDA-certified food dyes were investigated as organocatalysts. As a result, Fast Green FCF and Brilliant Blue FCF were discovered as catalysts for the chlorination of a wide range of arenes and heteroarenes in moderate to excellent yields and high regioselectivity. Mechanistic investigations of the sep. systems indicated that different modes of activation are in operation, with Fast Green FCF being a light-promoted photoredox catalyst that was facilitating a one-electron oxidation of N-chlorosuccinimide (NCS) and Brilliant Blue FCF serving as a chlorine-transfer catalyst in its sulfonphthalein form with 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) as stoichiometric chlorine source. Dearomatization of naphthol and indole substrates was observed in some examples using the Brilliant Blue/DCDMH system.

ACS Omega published new progress about Aromatic hydrocarbons Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Product Details of C4H4ClNO2.

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

Thiabaud, Gregory; He, Guangan; Sen, Sajal; Shelton, Kathryn A.; Baze, Wallace B.; Segura, Luke; Alaniz, Julie; Macias, Ruben Munoz; Lyness, Greg; Watts, Alan B.; Kim, Hyun Min; Lee, Hyunseung; Cho, Mi Young; Hong, Kwan Soo; Finch, Rick; Siddik, Zahid H.; Arambula, Jonathan F.; Sessler, Jonathan L. published the artcile< Oxaliplatin Pt(IV) prodrugs conjugated to gadolinium-texaphyrin as potential antitumor agents>, Computed Properties of 128-09-6, the main research area is preparation oxaliplatin prodrug conjugate gadolinium texaphyrin antitumor drug resistance; cancer; drug development; drug resistance; platinum prodrug; texaphyrins.

Described here is the development of gadolinium(III) texaphyrin-platinum(IV) conjugates capable of overcoming platinum resistance by 1) localizing to solid tumors, 2) promoting enhanced cancer cell uptake, and 3) reactivating p53 in platinum-resistant models. Side by side comparative studies of these Pt(IV) conjugates to clin. approved platinum(II) agents and previously reported platinum(II)-texaphyrin conjugates demonstrate that the present Pt(IV) conjugates are more stable against hydrolysis and nucleophilic attack. Moreover, they display high potent antiproliferative activity in vitro against human and mouse cell cancer lines. Relative to the current platinum clin. standard of care (SOC), a lead Gd(III) texaphyrin-Pt(IV) prodrug conjugate emerging from this development effort was found to be more efficacious in s.c. mouse models involving both cell-derived xenografts and platinum-resistant patient-derived xenografts. Comparative pathol. studies in mice treated with equimolar doses of the lead Gd texaphyrin-Pt(IV) conjugate or the US Food and Drug Administration (FDA)-approved agent oxaliplatin revealed that the conjugate was better tolerated. Specifically, the lead could be dosed at more than three times (i.e., 70 mg/kg per dose) the tolerable dose of oxaliplatin (i.e., 4 to 6 mg/kg per dose depending on the animal model) with little to no observable adverse effects. A combination of tumor localization, redox cycling, and reversible protein binding is invoked to explain the relatively increased tolerability and enhanced anticancer activity seen in vivo. On the basis of the present studies, we conclude that metallotexaphyrin-Pt conjugates may have substantial clin. potential as antitumor agents.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Antitumor agent resistance (to platinum). 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Computed Properties of 128-09-6.

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

Gupta, Shiv Shankar; Manisha; Kumar, Rakesh; Dhiman, Ankit Kumar; Sharma, Upendra published the artcile< Predictable site-selective functionalization: Promoter group assisted para-halogenation of N-substituted (hetero)aromatics under metal-free condition>, Safety of 1-Chloropyrrolidine-2,5-dione, the main research area is halo heteroaromatic compound preparation regioselective; heteroaromatic compound halosuccinimide halogenation.

Regioselective para-C-H halogenation of N-pyrimidyl (hetero)aromatics (such as 5-bromo-1-(pyrimidin-2-yl)indoline, N-(4-bromophenyl)pyrimidin-2-amine, 6-bromo-1-(pyrimidin-2-yl)-1,2,3,4-tetrahydroquinoline, etc.) through SEAr (electrophilic aromatic substitution) type reaction is disclosed. SEAr type reaction has been utilized for the C5-bromination of indolines (para-selective) (such as 1-(pyrimidin-2-yl)indoline, 6-fluoro-1-pyrimidin-2-yl-2,3-dihydro-1H-indole, 1-pyrimidin-2-yl-2,3-dihydro-1H-indole-2-carboxylic acid Et ester, etc.) with N-bromosuccinimide under metal and additive-free conditions in good to excellent yields. The developed methodol. is also applicable for iodination and challenging chlorination. The pyrimidyl group is identified as a reactivity tuner that also controls the regioselectivity. The present method is also applicable for selective halogenation of aniline, pyridine, indole, oxindole, pyrazole, tetrahydroquinoline, isoquinoline, and carbazole. DFT studies such as Fukui nucleophilicity and natural charge maps also support the observed p-selectivity. Post-functionalization of the title compound into the corresponding arylated, olefinated and dihalogenated products (5-phenyl-1-(pyrimidin-2-yl)indoline, 5-bromo-7-chloro-1-(pyrimidin-2-yl)indoline, (E)-1-(pyrimidin-2-yl)-5-styrylindoline) is achieved in a one-pot, two step fashion. Late-stage C-H bromination was also executed on drug/natural mols. (harmine, etoricoxib, clonidine, and chlorzoxazone) to demonstrate the applicability of the developed protocol.

Organic & Biomolecular Chemistry published new progress about Bromination, regioselective. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Safety of 1-Chloropyrrolidine-2,5-dione.

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

Mai, Thi Ly; Tran, Vinh Hung published the artcile< DFT study of electronic structure properties of SrAFe4As4 (A = Rb and Cs) superconductors>, Reference of 128-09-6, the main research area is strontium rubidium cesium iron arsenide DFT electronic structure property.

Using the full-potential linearised APW method and the PBE generalized gradient approximation, the electronic structure properties of SrAFe4As4 (A = Rb and Cs) superconductors were determined and compared with those of their parents SrFe2As4 (Fmmm), SrFe2As2 (I4/mmm), RbFe2As2 and CsFe2As2. It is found that associated with the Van Hove singularities, densities of states of SrAFe4As4 around Fermi energy level, mostly caused by Fe-3d orbitals, are relatively high but not enough to account for enhancement of Tc in these materials. We suggest rather a relationship between Tc values and interband scattering strength, which depends on the number of electronic bands crossing EF and forming hole-like pockets around the G point and electron-like pockets at the corners of Brillouin zone. It is established that Fermi surfaces of SrAFe4As4 are described by 2D and manifest the behavior of ±s-wave gap in Cs- and nodal gap in Rb-based. Electron Localization Function demonstrates the presence of both valence and metallic bondings. However, there is a stronger covalent bonding in AF2As2 than in SrAFe4As4, suggesting that the weakness of covalency accompanies higher Tc values.

Computational Materials Science published new progress about Brillouin zone. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Reference of 128-09-6.

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

Cabelof, Alyssa C.; Erny, Alec M.; Carta, Veronica; Pink, Maren; Caulton, Kenneth G. published the artcile< Anion metathesis and chlorination of late transition metal pincer complexes: Comparing Co, Rh and Zn>, Synthetic Route of 128-09-6, the main research area is crystal structure transition metal pincer complex preparation; phosphino pyrazole pyridine tridentate pincer transition metal complex.

The ability of (PNNH)CoCl2 (where PNNH is a phosphino and pyrazole substituted pyridine pincer) to serve as a precursor to coordinate the weak anion nitrate is investigated, giving a product with two coordinated nitrates, which demonstrate remarkable variability of nitrate binding in an overall six coordinate divalent cobalt complex. A synthetic variant with only one chloride per Co(II) is characterized, and retains coordination number 5. Comparison is made to rhodium, initially in oxidation state +1, including a carbonyl reporter ligand. The tridentate pincer displaces chloride and PPh3 from Rh(PPh3)2(CO)Cl to form the salt [(PNNH)Rh(CO)]Cl. That compound reacts with N-chloro succinimide with oxidation to trivalent rhodium, loss of carbon monoxide, but also with inadvertent chlorine substitution of pyrazole ring CH bond. As a comparison standard for PNNH ligand with a redox inert metal, (PNNH)ZnCl2 is characterized; bond lengths within the ligand allow the conclusion that the iron and cobalt analogs show no major back donation into the pincer ligand.

Inorganica Chimica Acta published new progress about Crystal structure. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Synthetic Route of 128-09-6.

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

Gasonoo, Makafui; Thom, Zachary W.; Laulhe, Sebastien published the artcile< Regioselective α-Amination of Ethers Using Stable N-Chloroimides and Lithium tert-Butoxide>, Recommanded Product: 1-Chloropyrrolidine-2,5-dione, the main research area is chloroimide ether amination lithium butoxide; hemiaminal ether regioselective preparation; lithium butoxide amination mediator.

Herein it is described a metal-free regioselective α-amination of ethers mediated by N-chloroimides in ethereal solvents in the presence of lithium tert-butoxide. This reactivity of N-chloroimides leads to the synthesis of hemiaminal ethers in good to excellent yields at room temperature This C-H functionalization is achieved without the use of a light, heat source, or external radical initiators. Initial mechanistic work indicates that the reaction proceeds through a radical pathway.

Journal of Organic Chemistry published new progress about Amination. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Recommanded Product: 1-Chloropyrrolidine-2,5-dione.

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

Arena, Chiara; Gado, Francesca; Di Cesare Mannelli, Lorenzo; Cervetto, Chiara; Carpi, Sara; Reynoso-Moreno, Ines; Polini, Beatrice; Vallini, Erika; Chicca, Stefano; Lucarini, Elena; Bertini, Simone; D′Andrea, Felicia; Digiacomo, Maria; Poli, Giulio; Tuccinardi, Tiziano; Macchia, Marco; Gertsch, Jurg; Marcoli, Manuela; Nieri, Paola; Ghelardini, Carla; Chicca, Andrea; Manera, Clementina published the artcile< The endocannabinoid system dual-target ligand N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide improves disease severity in a mouse model of multiple sclerosis>, Safety of 1-Chloropyrrolidine-2,5-dione, the main research area is endocannabinoid modulator preparation multiple sclerosis cannabinoid receptor analgesic; 1,2-Dihydropyridine-2-oxo-3-carboxamides; EAE mouse Model multiple sclerosis; Endocannabinoid system; Glutamate release; Microglial cell; Neuropathic pain.

Multiple sclerosis is a chronic inflammatory demyelinating disorder of the central nervous system that eventually leads to progressive neurodegeneration and disability. Recent findings highlighted the emerging role of each target of the endocannabinoid system in controlling the symptoms and disease progression of multiple sclerosis. Therefore, multi-target modulators of the endocannabinoid system could provide a more effective pharmacol. strategy as compared to the single target modulation. In this work, N-cycloheptyl-1,2-dihydro-5-bromo-1-(4-fluorobenzyl)-6-methyl-2-oxo-pyridine-3-carboxamide (B2) was identified as the most promising compound with dual agonism at cannabinoid receptors type-1 and cannabinoid receptors type-2 and good drug-like properties. In in vitro assays, B2 reduced glutamate release from rat synaptosomes through interaction with cannabinoid receptors type-1 and modulated the production of the pro- and anti-inflammatory cytokines (interleukins IL-1β and IL-6 and interleukin IL-10 resp.) via cannabinoid receptors type-2 activation. Furthermore, B2 demonstrated antinociceptive effects in an animal model of neuropathic pain and efficacy in an exptl. autoimmune encephalomyelitis model of multiple sclerosis.

European Journal of Medicinal Chemistry published new progress about Analgesics. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Safety of 1-Chloropyrrolidine-2,5-dione.

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

Grabarczyk, Malgorzata; Maczka, Wanda; Winska, Katarzyna; Zarowska, Barbara; Maciejewska, Gabriela; Gebarowska, Elzbieta; Jerzy Pietr, Stanislaw published the artcile< Antimicrobial chloro-hydroxylactones derived from the biotransformation of bicyclic halolactones by cultures of Pleurotus ostreatus>, HPLC of Formula: 128-09-6, the main research area is Pleurotus chlorohydroxylactone antimicrobial agent pathogenic microorganism; Biotransformations; Halolactones; Hydroxylation.

The aim of this research was to test the ability of cultures of edible fungi to biotransform three bicyclic halolactones. The substrates (2-chloro-, 2-bromo- and 2-iodo-4,4,6,7-tetramethyl-9-oxabicyclo[4.3.0]nonan-8-one) received by means of synthesis were transformed by oyster mushroom Pleurotus ostreatus and edible mushrooms of the genus Armillaria mellea, Marasmius scorodonius and Laetiporus sulfureus. The substrates were converted to hydroxyl derivatives only by the cultures of oyster mushroom. Out of seven strains of Pleurotus ostreatus – three were capable of hydroxylation of all substrates with the most effective conversion of chlorolactone. Bromo- and iodolactone were transformed to a small extent. Four new chloro-hydroxylactones were obtained as biotransformation products. The structures of substrates and products were established on the basis of spectroscopic data. Studies of antimicrobial activity performed on reference strains of pathogenic microorganisms showed that halolactones caused complete inhibition of growth of A. alternata and F. linii strains. On the other hand, chloro-hydroxylactones were able to completely inhibit the growth of A. alternata and F. linii strains and also C. albicans strain.

Bioorganic Chemistry published new progress about Antimicrobial agents. 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, HPLC of Formula: 128-09-6.

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

Trost, Barry M.; Tracy, Jacob S. published the artcile< Vanadium-Catalyzed Synthesis of Geometrically Defined Acyclic Tri- and Tetrasubstituted Olefins from Propargyl Alcohols>, Quality Control of 128-09-6, the main research area is bromo chloro iodo trisubstituted tetrasubstituted enone diastereoselective preparation; vanadium catalyst stereoselective bromination chlorination iodination propargyl alc; stereoselective bromination chlorination iodination propargyl alc aqueous hexafluoroisopropanol.

Aryl tri- and tetrasubstituted α-halo-α,β-unsaturated ketones and tetrasubstituted β-halo-α,β-unsaturated ketones were prepared diastereoselectively from propargyl alcs. and halonium ion sources using either the vanadium catalyst [(4-ClC6H4)3SiO]3V(:O) (for α-halo unsaturated ketones) or using halonium ion sources with aqueous hexafluoroisopropanol as the solvent via 1,2-aryl shifts (for β-halo unsaturated ketones). In some cases, isomerization of (E)-α-chloro-α,β-unsaturated ketones in the presence of DMAP in DMF yielded the corresponding (Z)-α-chloro-α,β-unsaturated ketones in > 20:1 diastereoselectivities. These methods allow the preparation of stereodefined tri- and tetrasubstituted olefins; the methods were used to prepare various compounds including the sesquiterpene (±)-myodesmone.

ACS Catalysis published new progress about Alcohols, propargyl Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 128-09-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C4H4ClNO2, Quality Control of 128-09-6.

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