Category: 85740-98-3

Li, Jian-Yuan; Miklossy, Gabriella; Modukuri, Ram K.; Bohren, Kurt M.; Yu, Zhifeng; Palaniappan, Murugesan; Faver, John C.; Riehle, Kevin; Matzuk, Martin M.; Simmons, Nicholas published the artcile< Palladium-Catalyzed Hydroxycarbonylation of (Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis>, Safety of 4-Chloro-3-methoxybenzoic acid, the main research area is palladium catalyzed hydroxycarbonylation heteroaryl halide DNA encoded library synthesis.

A strategy for DNA-compatible, palladium-catalyzed hydroxycarbonylation of (hetero)aryl halides on DNA-chem. conjugates has been developed. This method generally provided the corresponding carboxylic acids in moderate to very good conversions for (hetero)aryl iodides and bromides, and in poor to moderate conversions for (hetero)aryl chlorides. These conditions were further validated by application within a DNA-encoded chem. library synthesis and subsequent discovery of enriched features from the library in selection experiments against two protein targets.

Bioconjugate Chemistry published new progress about Carbonylation. 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Safety of 4-Chloro-3-methoxybenzoic acid.

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

Brotschi, Christine; Bolli, Martin H.; Gatfield, John; Heidmann, Bibia; Jenck, Francois; Roch, Catherine; Sifferlen, Thierry; Treiber, Alexander; Williams, Jodi T.; Boss, Christoph published the artcile< From Oxadiazole to Triazole Analogues: Optimization toward a Dual Orexin Receptor Antagonist with Improved in vivo Efficacy in Dogs>, HPLC of Formula: 85740-98-3, the main research area is insomnia disorders orexin receptor antagonist metabolic stability orally brain; drug design; dual orexin receptor antagonists; insomnia; sleep disorders; structure-activity relationships.

The orexin system is responsible for regulating the sleep-wake cycle. Suvorexant, a dual orexin receptor antagonist (DORA) is approved by the FDA for the treatment of insomnia disorders. Herein, we report the optimization efforts toward a DORA, where our starting point was (5-methoxy-4-methyl-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-[5-(2-trifluoromethoxy-phenyl)-[1,2,4]oxadiazol-3-yl]-pyrrolidin-1-yl}methanone (6), a compound which emerged from our inhouse research program. Compound 6 was shown to be a potent, brain-penetrating DORA with in vivo efficacy similar to suvorexant in rats. However, shortcomings from low metabolic stability, high plasma protein binding (PPB), low brain free fraction (fu brain), and low aqueous solubility, were identified and hence, compound 6 was not an ideal candidate for further development. Our optimization efforts addressing the above-mentioned shortcomings resulted in the identification of (4-chloro-2-[1,2,3]triazol-2-yl-phenyl)-{(S)-2-methyl-2-[5-(2-trifluoromethoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-pyrrolidin-1-yl}l-methanone (42), a DORA with improved in vivo efficacy compared to 6.

ChemMedChem published new progress about Blood proteins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (plasma protein binding). 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, HPLC of Formula: 85740-98-3.

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

Duan, Y. T.; Parmar, T. H.; Sangani, C. B.; Shah, A. S.; Ameta, R. K. published the artcile< 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-Oxide Hexafluorophosphate (HATU)/Hydroxybenzotriazole (HOBT)-based One-Pot Cyclization of N-Substituted 2-Arylbenzimidazole Derivatives>, SDS of cas: 85740-98-3, the main research area is benzoic acid methyl phenylenediamine HATU HOBT cyclocondensation green chem; phenyl methylbenzimidazole preparation.

A simple one-pot synthesis of N-methyl-phenylbenzimidazoles was developed from substituted benzoic acids and N-methyl-o-phenylenediamine in the presence of 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate/hydroxybenzotriazole (HATU/HOBT) and N,N-diisopropylethylamine in DMF at 100° C, featuring good to excellent yields and easy workup. The protocol was scaled to gram quantities, and no chromatog. purification was required.

Russian Journal of Organic Chemistry published new progress about Benzimidazoles Role: SPN (Synthetic Preparation), PREP (Preparation). 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, SDS of cas: 85740-98-3.

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

Liu, Wentao; Huang, Wei; Lin, Qian; Tsai, Mei-Hsuan; Zhang, Rui; Fan, Lijun; Scott, Jack D.; Liu, Guansai; Wan, Jinqiao published the artcile< Development of DNA-compatible hydroxycarbonylation reactions using chloroform as a source of carbon monoxide>, Recommanded Product: 4-Chloro-3-methoxybenzoic acid, the main research area is DNA encoded hydroxycarbonylation aryl halide chloroform; Chloroform; DNA compatible reaction; DNA-encoded library; Hydroxycarbonylation; Palladium catalysis.

A robust palladium-catalyzed hydroxycarbonylation of aryl halides on DNA has been developed. Instead of Mo(CO)6 as a source of carbon monoxide as previously described in the literature, chloroform was used as a surrogate in this report for the purpose of avoiding to use a large excess of molybdenum reagent which is not totally soluble in aqueous reaction mixtures

Bioorganic & Medicinal Chemistry published new progress about Aromatic carboxylic acids Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Recommanded Product: 4-Chloro-3-methoxybenzoic acid.

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

Granchi, Carlotta; Lapillo, Margherita; Glasmacher, Sandra; Bononi, Giulia; Licari, Cristina; Poli, Giulio; El Boustani, Maguie; Caligiuri, Isabella; Rizzolio, Flavio; Gertsch, Jurg; Macchia, Marco; Minutolo, Filippo; Tuccinardi, Tiziano; Chicca, Andrea published the artcile< Optimization of a Benzoylpiperidine Class Identifies a Highly Potent and Selective Reversible Monoacylglycerol Lipase (MAGL) Inhibitor>, COA of Formula: C8H7ClO3, the main research area is benzoylpiperidine monoacylglycerol lipase inhibitor optimization antitumor.

Monoacylglycerol lipase (MAGL) is the enzyme degrading the endocannabinoid 2-arachidonoylglycerol, and it is involved in several physiol. and pathol. processes. The therapeutic potential of MAGL is linked to several diseases, including cancer. The development of MAGL inhibitors has been greatly limited by the side effects associated with the prolonged MAGL inactivation. Importantly, it could be preferable to use reversible MAGL inhibitors in vivo, but nowadays only few reversible compounds have been developed. In the present study, structural optimization of a previously developed class of MAGL inhibitors led to the identification of compound 23, which proved to be a very potent reversible MAGL inhibitor (IC50 = 80 nM), selective for MAGL over the other main components of the endocannabinoid system, endowed of a promising antiproliferative activity in a series of cancer cell lines and able to block MAGL both in cell-based as well as in vivo assays.

Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, COA of Formula: C8H7ClO3.

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

Haffner, Curt D.; Charnley, Adam K.; Aquino, Christopher J.; Casillas, Linda; Convery, Maire A.; Cox, Julie A.; Elban, Mark A.; Goodwin, Nicole C.; Gough, Peter J.; Haile, Pamela A.; Hughes, Terry V.; Knapp-Reed, Beth; Kreatsoulas, Constantine; Lakdawala, Ami S.; Li, Huijie; Lian, Yiqian; Lipshutz, David; Mehlmann, John F.; Ouellette, Michael; Romano, Joseph; Shewchuk, Lisa; Shu, Arthur; Votta, Bartholomew J.; Zhou, Huiqiang; Bertin, John; Marquis, Robert W. published the artcile< Discovery of Pyrazolocarboxamides as Potent and Selective Receptor Interacting Protein 2 (RIP2) Kinase Inhibitors>, Application In Synthesis of 85740-98-3, the main research area is pyrazolo carboxamide derivative preparation RIP2 kinase inhibitor cancer; receptor interacting protein kinase target cancer.

Herein we report the discovery of pyrazolocarboxamides as novel, potent, and kinase selective inhibitors of receptor interacting protein 2 kinase (RIP2). Fragment based screening and design principles led to the identification of the inhibitor series, and X-ray crystallog. was used to inform key structural changes. Through key substitutions about the N1 and C5 N positions on the pyrazole ring significant kinase selectivity and potency were achieved. Bridged bicyclic pyrazolocarboxamide 11 represents a selective and potent inhibitor of RIP2 and will allow for a more detailed investigation of RIP2 inhibition as a therapeutic target for autoinflammatory disorders.

ACS Medicinal Chemistry Letters published new progress about Anti-inflammatory agents. 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Application In Synthesis of 85740-98-3.

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

Ali, Eslam M. H.; El-Telbany, Rania Farag A.; Abdel-Maksoud, Mohammed S.; Ammar, Usama M.; Mersal, Karim I.; Zaraei, Seyed-Omar; El-Gamal, Mohammed I.; Choi, Se-In; Lee, Kyung-Tae; Kim, Hee-Kwon; Lee, Kwan Hyi; Oh, Chang-Hyun published the artcile< Design, synthesis, biological evaluation, and docking studies of novel (imidazol-5-yl)pyrimidine-based derivatives as dual BRAFV600E/p38α inhibitors>, Quality Control of 85740-98-3, the main research area is imidazolyl pyrimidine preparation BRAFV600E p38alpha inhibitor antitumor mol docking; BRAF(V600E); Imidazol-5-ylpyrimidine; MAPK14; Melanoma; Molecular docking; TNF-α.

In the present work, a new series of (imidazol-5-yl)pyrimidine I ( Ar = C6H5, 4-ClC6H4, 4-BrC6H4 etc.; X = F, Cl; R = OCH3, OH) was designed and synthesized as dual inhibitors of BRAFV600E and p38α kinases which are considered as key regulators in mitogen-activated protein kinase signalling pathway. The target compounds were evaluated for dual kinase inhibitory activity. The tested compounds exhibited nanomolar scale IC50 values against BRAFV600E and low to sub-micromolar IC50 range against p38α. Compound I (Ar = 4-OHC6H4; X = F; R = OH) was identified as the most potent dual BRAFV600E/p38α inhibitor with IC50 values of 2.49 and 85 nM, resp. Further deep investigation revealed that Compound I (Ar = 4-OHC6H5; X = F; R = OH) possesses inhibitory activity of TNF-α production in lipopolysaccharide-induced RAW 264.7 macrophages with IC50 value of 96.3 nM. Addnl., the target compounds efficiently frustrated the proliferation of LOX-IMVI melanoma cell line. Compound I (Ar = 4-OHC6H5; X = F; R = OH) showed a satisfactory antiproliferative activity with IC50 value of 13μM, while, compound I (Ar = 3-FC6H4; X = F; R = OCH3) exhibited the highest cytotoxicity potency with IC50 value of 0.9μM. Compound I (Ar = 3-FC6H4; X = F; R = OCH3) is 11.11-fold more selective toward LOX-IMVI melanoma cells than IOSE-80PC normal cells.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 85740-98-3 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H7ClO3, Quality Control of 85740-98-3.

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