400744-49-2

Usage

Uses

3''-Chlorobiphenyl-4-carbaldehyde

Upstream product

• 108-37-2 1-bromo-3-chlorobenzene 
• 87199-17-5 4-formylphenylboronic acid, 
• 93308-05-5 7-<3-Chlor-phenyl>-tropiliden 
• 63503-60-6 3-chlorophenylboronic acid 
• 1122-91-4 4-bromo-benzaldehyde 
• 104-88-1 4-chlorobenzaldehyde 

Downstream Products

• 1413776-83-6 C₂₅H₃₃ClN⁽¹⁺⁾*I^(1-) 
• 1413776-95-0 C₂₅H₃₁ClN⁽¹⁺⁾*I^(1-) 
• 1413776-89-2 1-(3'-chlorobiphenyl-4-yl)-N-(((1S,5R)-6,6-dimethylbicyclo[3.1.1]hept-2-en-3-yl)methyl)-N,N-dimethylmethanaminium iodide 
• 1419403-47-6 ethyl 6-(3-chlorophenyl)-1H-indole-2-carboxylate 
• 1419403-49-8 ethyl 6-(3-chlorophenyl)-3-(phenyldiazenyl)-1H-indole-2-carboxylate 
• 1419403-51-2 ethyl 3-amino-6-(3-chlorophenyl)-1H-indole-2-carboxylate 
• 1419403-55-6 ethyl 6-(3-chlorophenyl)-3-(ethoxycarbonylamino)-1H-indole-2-carboxylate 
• 1419403-58-9 7-(3-chlorophenyl)-3-methyl-1H-pyrimido[5,4-b]indole-2,4(3H,5H)-dione 
• 1462885-96-6 (R)-3-{N-(3'-chlorobiphenyl-4-ylmethyl)-N'-[3-(4-methoxybenzyloxy)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid isopropyl ester 
• 1382978-22-4 C₁₈H₁₉ClN₂O₂ 

Relevant academic research and scientific papers

Gold Catalysts Can Generate Nitrone Intermediates from a Nitrosoarene/Alkene Mixture, Enabling Two Distinct Catalytic Reactions: A Nitroso-Activated Cycloheptatriene/Benzylidene Rearrangement

Gold-catalyzed reactions of cycloheptatrienes with nitrosoarenes yield nitrone derivatives efficiently. This reaction sequence enables us to develop gold-catalyzed aerobic oxidations of cycloheptatrienes to afford benzaldehyde derivatives using CuCl and nitrosoarenes as co-catalysts (10-30 mol %). Our density functional theory calculations support a novel nitroso-activated rearrangement, tropylium → benzylidene. With the same nitrosoarenes, we developed their gold-catalyzed [2 + 2 + 1]-annulations between nitrosobenzene and two enol ethers to yield 5-alkoxyisoxazolidines using 1,4-cyclohexadienes as hydrogen donors.

Continuous slurry plug flow Fe/ppm Pd nanoparticle-catalyzed Suzuki-Miyaura couplings in water utilizing novel solid handling equipment

Herein are reported initial efforts to develop a generally accessible flow process, applying a heterogenous nanocatalyst to aqueous micelle-enabled Suzuki-Miyaura coupling reactions. Also disclosed is a new engineering solution (i.e., a self-draining back pressure regulator), which, when applied, enabled 1.5 hours of continuous operation leading to the production of 20 grams of a pharmaceutical intermediate.

The Discovery of Novel ACA Derivatives as Specific TRPM2 Inhibitors that Reduce Ischemic Injury Both in Vitro and in Vivo

The transient receptor potential melastatin 2 (TRPM2) channel is associated with ischemia/reperfusion injury, inflammation, cancer, and neurodegenerative diseases. However, the limit of specific inhibitors impedes the development of TRPM2-targeted therapeutic agents. To discover more potent and selective TRPM2 inhibitors, 59 N-(p-amylcinnamoyl) anthranilic acid (ACA) derivatives were synthesized and evaluated using calcium imaging and electrophysiology approaches. Systematic structure-activity relationship studies resulted in some potent compounds inhibiting the TRPM2 channel with sub-micromolar half-maximal inhibitory concentration values. Among them, the preferred compound A23 exhibited TRPM2 selectivity over TRPM8 and TRPV1 channels as well as phospholipase A2 and showed neuroprotective activity in vitro. Following pharmacokinetic studies, A23 was further evaluated in a transient middle cerebral artery occlusion model in vivo, which significantly reduced cerebral infarction. These data indicate that A23 might serve as a useful tool for TRPM2-related research as well as a lead compound for the development of therapeutic agents for ischemic injury.

KDS2010, a Newly Developed Reversible MAO-B Inhibitor, as an Effective Therapeutic Candidate for Parkinson’s Disease

Monoamine oxidase-B (MAO-B) is a well-established therapeutic target for Parkinson’s disease (PD); however, previous clinical studies on currently available irreversible MAO-B inhibitors have yielded disappointing neuroprotective effects. Here, we tested the therapeutic potential of KDS2010, a recently synthesized potent, selective, and reversible MAO-B inhibitor in multiple animal models of PD. We designed and synthesized a series of α-aminoamide derivatives and found that derivative KDS2010 exhibited the highest potency, specificity, reversibility, and bioavailability (> 100%). In addition, KDS2010 demonstrated significant neuroprotective and anti-neuroinflammatory efficacy against nigrostriatal pathway destruction in the mouse MPTP model of parkinsonism. Treatment with KDS2010 also alleviated parkinsonian motor dysfunction in 6-hydroxydopamine-induced and A53T mutant α-synuclein overexpression rat models of PD. Moreover, KDS2010 showed virtually no toxicity or side effects in non-human primates. KDS2010 could be a next-generation therapeutic candidate for PD.

N,S-chelating triazole-thioether ligand for highly efficient palladium-catalyzed Suzuki reaction

1,2,3-Triazole-thioether compounds could serve as efficient ligands for Pd-catalyzed Suzuki reactions of various aryl iodides, bromides and chlorides. The reactions feature wide substrate scope and mild reaction conditions. Besides, shorter reaction time, lower catalyst loadings and quantitative yields with a turnover-frequency (TOF) value of up to 11,880 h?1 are other advantageous of this attractive protocol. The crystal structure analyses and computational studies revealed that the higher catalytic activity of the corresponding chelated palladium complex ascribed to the lower energy gap and the lower redox potential.

Poly(: O -aminothiophenol)-stabilized Pd nanoparticles as efficient heterogenous catalysts for Suzuki cross-coupling reactions

Poly(o-aminothiophenol) (PATP)-stabilized Pd nanoparticles with Pd nanoparticles embedded in a polymer matrix have been obtained through a facile one-step route by mixing o-aminothiophenol monomer and Pd(NO3)2 in an acidic aqueous solution without additional template or surfactant. The redox reaction between o-aminothiophenol and Pd(NO3)2 leads to the simultaneous formation of a PATP polymer and Pd nanoparticles. The PATP-stabilized Pd nanoparticles have been characterized by TEM, FTIR, XRD, ICP-MS and XPS. Catalytic results showed that PATP-stabilized Pd nanoparticles were highly stable and active catalysts for Suzuki cross-coupling reactions, where high yields could be achieved with arylboronic acid and aryl halides bearing a variety of substituents.

Novel phosphorus-coordinated palladium(II) complexes derived from 3,5-disubstituted-1H-1,2,4-diazaphospholes: Synthesis and catalytic application in Suzuki-Miyaura cross-coupling reactions

Four novel phosphorus-coordinated palladium(II) complexes(I-IV) were easily prepared by the reaction of 3,5-disubstituted-1H-1,2,4-diazaphospholes with Pd(CH3CN)2Cl2at room temperature and characterized. The catalytic activity of palladium(II) complexes was further evaluated in Suzuki-Miyaura reaction of aryl halides with arylboronic acids, giving the biphenyl derivatives in good yields.

CRYSTALLINE FORMS OF (R)-3-[N-(3'-CHLOROBIPHENYL-4-YLMETHYL)-N'-(3-HYDROXYISOXAZOLE-5-CARBONYL)HYDRAZINO]-2-HYDROXYPROPIONIC ACID ISOPROPYL ESTER

The invention provides crystalline forms of (R)-3-[N-(3′-chlorobiphenyl-4-ylmethyl)-N′—(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid isopropyl ester. This invention also provides pharmaceutical compositions comprising the crystalline compound, processes and intermediates for preparing the crystalline compound, and methods of using the crystalline compound to treat diseases.

Chemical subtleties in small-molecule modulation of peptide receptor function: The case of CXCR3 biaryl-type ligands

The G protein-coupled chemokine receptor CXCR3 plays a role in numerous inflammatory events. The endogenous ligands for the chemokine receptors are peptides, but in this study we disclose small-molecule ligands that are able to activate CXCR3. A class of biaryl-type compounds that is assembled by convenient synthetic routes is described as a new class of CXCR3 agonists. Intriguingly, structure-activity relationship and structure-function relationship studies reveal that subtle chemical modifications on the outer aryl ring (e.g., either the size or position of a halogen atom) result in a full spectrum of agonist efficacies on CXCR3. Quantum mechanics calculations and nuclear Overhauser effect spectroscopy NMR studies suggest that the biaryl dihedral angle and the electronic nature of ortho-substituents play an important role in determining agonist efficacies. Compounds 38 (VUF11222) and 39 (VUF11418) are the first reported nonpeptidomimetic agonists on CXCR3, rendering them highly useful chemical tools for detailed assessment of CXCR3 activation as well as for studying downstream CXCR3 signaling.

NEPRILYSIN INHIBITORS

In one aspect, the invention relates to compounds having the formula: where R1-R6, a, b, and X are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.