Category: 1454848-00-0

Qiao, Jun published the artcileMagnetically Reusable Fe3O4@NC@Pt Catalyst for Selective Reduction of Nitroarenes, Related Products of pyridine-derivatives, the publication is Catalysts (2021), 11(10), 1219, database is CAplus.

A novel reusable Fe3O4@NC@Pt heterogeneous catalyst was synthesized by immobilizing platinum on nitrogen-doped carbon magnetic nanostructures. It was characterized by IR anal. (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The catalytic efficiency of Fe3O4@NC@Pt was investigated by reduction of nitro aromatic compounds The catalyst showed good catalytic activity, wide range of substrates, and good chem. selectivity, especially for the substrates of compounds containing halide and carbonyl groups. The magnetically catalyst can readily be reused up to ten cycles without loss of catalytic activity. Moreover, the key pharmaceutical intermediate Lorlatini can be facilely achieved through this strategy.

Catalysts published new progress about 1454848-00-0. 1454848-00-0 belongs to pyridine-derivatives, auxiliary class Aromatic Fluorinated Building Blocks, name is (R)-Methyl 2-(1-((2-amino-5-bromopyridin-3-yl)oxy)ethyl)-4-fluorobenzoate, and the molecular formula is C15H14BrFN2O3, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Elleraas, Jeff published the artcileConformational Studies and Atropisomerism Kinetics of the ALK Clinical Candidate Lorlatinib (PF-06463922) and Desmethyl Congeners, Recommanded Product: (R)-Methyl 2-(1-((2-amino-5-bromopyridin-3-yl)oxy)ethyl)-4-fluorobenzoate, the publication is Angewandte Chemie, International Edition (2016), 55(11), 3590-3595, database is CAplus and MEDLINE.

Lorlatinib (PF-06463922) is an ALK/ROS1 inhibitor and is in clin. trials for the treatment of ALK pos. or ROS1 pos. NSCLC (i.e. specific subsets of NSCLC). One of the laboratory objectives for this mol. indicated that it would be desirable to advance a mol. which was CNS penetrant in order to treat brain metastases. From this perspective, a macrocyclic template was attractive for a number of reasons. In particular, this template reduces the number of rotatable bonds, provides the potential to shield polar surface area and reinforces binding through a restricted conformation. All of these features led to better permeability for the mols. of interest and thus increased the chance for better blood brain barrier penetration. With a CNS penetrant mol., kinase selectivity is a key consideration particularly with regard to proteins such as TrkB, which are believed to influence cognitive function. Removal of the chiral benzylic Me substituent from lorlatinib was perceived as not only a means to simplify synthetic complexity, but also as a strategy to further truncate the mol. of interest. Examination of the NMR of the desmethyl analogs revealed that the compound existed as a mixture of atropisomers, which proved separable by chiral SFC. The individual atropisomers were evaluated through a series of in vitro assays, and shown to have a favorable selectivity profile when compared to lorlatinib. The challenge to develop such a mol. lies in the rate at which the atropisomers interchange dictated by the energy barrier required to do this. Here, we describe the synthesis of the desmethyl macrocycles, conformational studies on the atropisomers, and the kinetics of the interconversion. In addition, the corresponding conformational studies on lorlatinib are reported providing a hypothesis for why a single diastereomer is observed when the chiral benzylic Me group is introduced.

Angewandte Chemie, International Edition published new progress about 1454848-00-0. 1454848-00-0 belongs to pyridine-derivatives, auxiliary class Aromatic Fluorinated Building Blocks, name is (R)-Methyl 2-(1-((2-amino-5-bromopyridin-3-yl)oxy)ethyl)-4-fluorobenzoate, and the molecular formula is C15H14BrFN2O3, Recommanded Product: (R)-Methyl 2-(1-((2-amino-5-bromopyridin-3-yl)oxy)ethyl)-4-fluorobenzoate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Johnson, Ted W. published the artcileDiscovery of (10R)-7-Amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a Macrocyclic Inhibitor of Anaplastic Lymphoma Kinase (ALK) and c-ros Oncogene 1 (ROS1) with Preclinical Brain Exposure and Broad-Spectrum Potency against ALK-Resistant Mutations, Related Products of pyridine-derivatives, the publication is Journal of Medicinal Chemistry (2014), 57(11), 4720-4744, database is CAplus and MEDLINE.

Although crizotinib demonstrates robust efficacy in anaplastic lymphoma kinase (ALK)-pos. non-small-cell lung carcinoma patients, progression during treatment eventually develops. Resistant patient samples revealed a variety of point mutations in the kinase domain of ALK, including the L1196M gatekeeper mutation. In addition, some patients progress due to cancer metastasis in the brain. Using structure-based drug design, lipophilic efficiency, and phys.-property-based optimization, highly potent macrocyclic ALK inhibitors were prepared with good absorption, distribution, metabolism, and excretion (ADME), low propensity for p-glycoprotein 1-mediated efflux, and good passive permeability. These structurally unusual macrocyclic inhibitors were potent against wild-type ALK and clin. reported ALK kinase domain mutations. Significant synthetic challenges were overcome, utilizing novel transformations to enable the use of these macrocycles in drug discovery paradigms. This work led to the discovery of 8k (PF-06463922), combining broad-spectrum potency, central nervous system ADME, and a high degree of kinase selectivity.

Journal of Medicinal Chemistry published new progress about 1454848-00-0. 1454848-00-0 belongs to pyridine-derivatives, auxiliary class Aromatic Fluorinated Building Blocks, name is (R)-Methyl 2-(1-((2-amino-5-bromopyridin-3-yl)oxy)ethyl)-4-fluorobenzoate, and the molecular formula is C15H14BrFN2O3, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem