Day: October 19, 2022

Synthetic Route of C9H12N2O2On September 28, 2017 ,《Discovery of Clinical Candidate N-((1S)-1-(3-Fluoro-4-(trifluoromethoxy)phenyl)-2-methoxyethyl)-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide (TAK-915): A Highly Potent, Selective, and Brain-Penetrating Phosphodiesterase 2A Inhibitor for the Treatment of Cognitive Disorders》 was published in Journal of Medicinal Chemistry. The article was written by Mikami, Satoshi; Nakamura, Shinji; Ashizawa, Tomoko; Nomura, Izumi; Kawasaki, Masanori; Sasaki, Shigekazu; Oki, Hideyuki; Kokubo, Hironori; Hoffman, Isaac D.; Zou, Hua; Uchiyama, Noriko; Nakashima, Kosuke; Kamiguchi, Naomi; Imada, Haruka; Suzuki, Noriko; Iwashita, Hiroki; Taniguchi, Takahiko. The article contains the following contents:

Phosphodiesterase (PDE) 2A inhibitors have emerged as a novel mechanism with potential therapeutic option to ameliorate cognitive dysfunction in schizophrenia or Alzheimer’s disease through upregulation of cyclic nucleotides in the brain, and thereby achieve potentiation of cyclic nucleotide signaling pathways. This article details the expedited optimization of the authors’ recently disclosed pyrazolo[1,5-a]pyrimidine lead compound 4b, leading to the discovery of clin. candidate 36 (I) (TAK-915), which demonstrates an appropriate combination of potency, PDE selectivity, and favorable pharmacokinetic (PK) properties, including brain penetration. Successful identification of 36 was realized through application of structure-based drug design (SBDD) to further improve potency and PDE selectivity, coupled with prospective design focused on physicochem. properties to deliver brain penetration. Oral administration of 36 demonstrated significant elevation of 3′,5′-cGMP levels in mouse brains, and improved cognitive performance in a novel object recognition task in rats. Consequently, compound 36 was advanced into human clin. trials. The experimental part of the paper was very detailed, including the reaction process of Ethyl 2-(3-aminopyridin-2-yl)acetate(cas: 295327-27-4Synthetic Route of C9H12N2O2)

Ethyl 2-(3-aminopyridin-2-yl)acetate(cas: 295327-27-4) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).Synthetic Route of C9H12N2O2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Magee, Thomas V.; Brown, Matthew F.; Starr, Jeremy T.; Ackley, David C.; Abramite, Joseph A.; Aubrecht, Jiri; Butler, Andrew; Crandon, Jared L.; Dib-Hajj, Fadia; Flanagan, Mark E.; Granskog, Karl; Hardink, Joel R.; Huband, Michael D.; Irvine, Rebecca; Kuhn, Michael; Leach, Karen L.; Li, Bryan; Lin, Jian; Luke, David R.; MacVane, Shawn H.; Miller, Alita A.; McCurdy, Sandra; McKim, James M.; Nicolau, David P.; Nguyen, Thuy-Trinh; Noe, Mark C.; O’Donnell, John P.; Seibel, Scott B.; Shen, Yue; Stepan, Antonia F.; Tomaras, Andrew P.; Wilga, Paul C.; Zhang, Li; Xu, Jinfeng; Chen, Jinshan Michael published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery of Dap-3 Polymyxin Analogues for the Treatment of Multidrug-Resistant Gram-Negative Nosocomial Infections》.Quality Control of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate The author mentioned the following in the article:

The authors report novel polymyxin analogs with improved antibacterial in vitro potency against polymyxin resistant recent clin. isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogs. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3-carbonyl side chain as a fatty acyl replacement yielded analog 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages. The experimental part of the paper was very detailed, including the reaction process of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate(cas: 77837-09-3Quality Control of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate)

Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate(cas: 77837-09-3) belongs to pyridine derivatives. The ring atoms in the pyridine molecule are sp2-hybridized. The nitrogen is involved in the π-bonding aromatic system using its unhybridized p orbital. Quality Control of Methyl 6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylateThe lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Tahtaoui, Chouaib; Parrot, Isabelle; Klotz, Philippe; Guillier, Fabrice; Galzi, Jean-Luc; Hibert, Marcel; Ilien, Brigitte published their research in Journal of Medicinal Chemistry on August 12 ,2004. The article was titled 《Fluorescent Pirenzepine Derivatives as Potential Bitopic Ligands of the Human M1 Muscarinic Receptor》.Application of 1028-86-0 The article contains the following contents:

Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, the authors synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All mols. reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other mols. (15-24 atom long linkers) is not. The data favor the idea that these analogs might interact with both the acetylcholine and the brucine binding domains. The experimental part of the paper was very detailed, including the reaction process of N-(2-Chloropyridin-3-yl)-2-nitrobenzamide(cas: 1028-86-0Application of 1028-86-0)

N-(2-Chloropyridin-3-yl)-2-nitrobenzamide(cas: 1028-86-0) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.Application of 1028-86-0

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2008,Kimball, F. Scott; Romero, F. Anthony; Ezzili, Cyrine; Garfunkle, Joie; Rayl, Thomas J.; Hochstatter, Dustin G.; Hwang, Inkyu; Boger, Dale L. published 《Optimization of α-Ketooxazole Inhibitors of Fatty Acid Amide Hydrolase》.Journal of Medicinal Chemistry published the findings.Recommanded Product: 29682-15-3 The information in the text is summarized as follows:

A series of α-ketooxazoles, e.g., I, containing conformational constraints in the flexible C2 acyl side chain of II (OL-135) and representative oxazole C5 substituents were prepared and examined as inhibitors of fatty acid amide hydrolase (FAAH). Exceptionally potent and selective FAAH inhibitors emerged from the series (e.g., 6, Ki = 200 and 260 pM for rat and rhFAAH). With simple and small C5 oxazole substituents, each series bearing a biphenylethyl, phenoxyphenethyl, or (phenoxymethyl)phenethyl C2 side chain was found to follow a well-defined linear relationship between -log Ki and Hammett σp of a magnitude (ρ = 2.7-3.0) that indicates that the substituent electronic effect dominates, confirming its fundamental importance to the series and further establishing its predictive value. Just as significantly, the nature of the C5 oxazole substituent substantially impacts the selectivity of the inhibitors whereas the effect of the C2 acyl chain was more subtle but still significant even in the small series examined Combination of these independent features, which display generalized trends across a range of inhibitor series, simultaneously improves FAAH potency and selectivity and can provide exquisitely selective and potent FAAH inhibitors. In the experiment, the researchers used Methyl 5-bromopicolinate(cas: 29682-15-3Recommanded Product: 29682-15-3)

Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. Pyridine is a relatively complex molecule and exhibits a number of different bands in IR spectra. Among others, the bands characterizing the ν8a and ν19b modes have been found to be sensitive to the coordination or protonation of the molecule. Note that the band that is diagnostic for the PyH+ ion at about 1545 cm− 1 (ν19b mode) does not overlap with any of the other bands.Recommanded Product: 29682-15-3

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2010,Young, Brandon M.; Hyatt, Janice L.; Bouck, David C.; Chen, Taosheng; Hanumesh, Parimala; Price, Jeanine; Boyd, Vincent A.; Potter, Philip M.; Webb, Thomas R. published 《Structure-Activity Relationships of Substituted 1-Pyridyl-2-phenyl-1,2-ethanediones: Potent, Selective Carboxylesterase Inhibitors》.Journal of Medicinal Chemistry published the findings.Synthetic Route of C5H5BrN2 The information in the text is summarized as follows:

Inhibition of intestinal carboxylesterases may allow modification of the pharmacokinetics/pharmacodynamic profile of existing drugs by altering half-life or toxicity. Since previously identified diarylethane-1,2-dione inhibitors are decidedly hydrophobic, a modified dione scaffold was designed and elaborated into a >300 member library, which was subsequently screened to establish the SAR for esterase inhibition. This allowed the identification of single digit nanomolar hiCE inhibitors that showed improvement in selectivity and measured solubility In the experiment, the researchers used 6-Bromopyridin-3-amine(cas: 13534-97-9Synthetic Route of C5H5BrN2)

6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.Synthetic Route of C5H5BrN2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2011,Kasparian, Annie J.; Savarin, Cecile; Allgeier, Alan M.; Walker, Shawn D. published 《Selective catalytic hydrogenation of nitro groups in the presence of activated heteroaryl halides》.Journal of Organic Chemistry published the findings.Category: pyridine-derivatives The information in the text is summarized as follows:

Chemoselective reduction of nitro groups in the presence of activated heteroaryl halides was achieved via catalytic hydrogenation with a com. available sulfided platinum catalyst. The optimized conditions employ low temperature, pressure, and catalyst loading (<0.1 mol % Pt) to afford heteroaromatic amines with minimal hydrodehalogenation byproducts. In addition to this study using 6-Bromopyridin-3-amine, there are many other studies that have used 6-Bromopyridin-3-amine(cas: 13534-97-9Category: pyridine-derivatives) was used in this study.

6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime.Typically the presence of an amine functional group is deduced by a combination of techniques, including mass spectrometry as well as NMR and IR spectroscopies. 1H NMR signals for amines disappear upon treatment of the sample with D2O. In their infrared spectrum primary amines exhibit two N-H bands, whereas secondary amines exhibit only one.Category: pyridine-derivatives

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2011,Radeke, Heike S.; Purohit, Ajay; Harris, Thomas D.; Hanson, Kelley; Jones, Reinaldo; Hu, Carol; Yalamanchili, Padmaja; Hayes, Megan; Yu, Ming; Guaraldi, Mary; Kagan, Mikhail; Azure, Michael; Cdebaca, Michael; Robinson, Simon; Casebier, David published 《Synthesis and Cardiac Imaging of 18F-Ligands Selective for β1-Adrenoreceptors》.ACS Medicinal Chemistry Letters published the findings.Recommanded Product: 6-Bromopyridin-3-amine The information in the text is summarized as follows:

A series of potent and selective β1-adrenoreceptor ligands were identified (IC50 range, 0.04-0.25 nM; β1/β2 selectivity range, 65-450-fold), labeled with the PET radioisotope fluorine-18 and evaluated in normal Sprague-Dawley rats. Tissue distribution studies demonstrated uptake of each radiotracers from the blood pool into the myocardium (0.48-0.62% ID/g), lung (0.63-0.97% ID/g), and liver (1.03-1.14% ID/g). Dynamic μPET imaging confirmed the in vivo dissection studies. The experimental process involved the reaction of 6-Bromopyridin-3-amine(cas: 13534-97-9Recommanded Product: 6-Bromopyridin-3-amine)

6-Bromopyridin-3-amine(cas: 13534-97-9) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Recommanded Product: 6-Bromopyridin-3-amine

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2017,Lu, Te-Jui; Lin, Po-Han; Lee, Kun-Mu; Liu, Ching-Yuan published 《End-Capping Groups for Small-Molecule Organic Semiconducting Materials: Synthetic Investigation and Photovoltaic Applications through Direct C-H (Hetero)arylation》.European Journal of Organic Chemistry published the findings.Product Details of 53939-30-3 The information in the text is summarized as follows:

A Pd-catalyzed C-H (hetero)arylation methodol. has been optimized for the efficient synthesis of various useful end-capping groups that are widely applied in small-mol. optoelectronic materials. We report herein the synthesis of a broad scope of target mols. ranging from donor-type through acceptor-type to hybrid-type end-capping groups. To demonstrate their application in dye-sensitized solar cells, we have designed two new D-A-π-A’-type organic sensitizers (CYL-3 and CYL-4), which were synthesized in a step-economic manner by sequential C-H arylations using the facilely obtained end-capping groups. The devices based on CYL-3 and CYL-4 give Voc values of 0.67-0.71 V, Jsc values of 10.07-11.63 mA cm-2, and FF values of 70.6-72.9 %, which correspond to overall power conversion efficiencies of 4.76-6.02 %. This work is expected to become a practical synthetic alternative allowing materials scientists to access small-mol. organic materials in fewer synthetic transformations.5-Bromo-2-chloropyridine(cas: 53939-30-3Product Details of 53939-30-3) was used in this study.

5-Bromo-2-chloropyridine(cas: 53939-30-3) belongs to pyridine. Pyridines are often used as catalysts or reagents; particular notice has been paid recently to how pyridine coordinates to metal centers enabling a wide range of valuable reactions. Product Details of 53939-30-3

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2018,Richardson, Jeffery; Mutton, Simon P. published 《Improved Substrate Scope in the Potassium Hexacyanoferrate(II)-Based Cyanation for the Synthesis of Benzonitriles and Their Heterocyclic Analogues》.Journal of Organic Chemistry published the findings.Category: pyridine-derivatives The information in the text is summarized as follows:

The use of Pd(DPEPhos)Cl2 (P26) as a catalyst for the formation of benzonitriles and their heterocyclic analogs provides excellent complementarity to existing catalysts, allowing highly electron-deficient heterocyclic aryl halides to be efficiently converted to the corresponding nitriles using K4[Fe(CN)6] as cyanide source. This catalyst significantly enhances the scope of this reaction to include a number of substrates that are highly relevant for pharmaceutical and agrochem. applications. Importantly, not only does this cyanation method employ a nontoxic cyanide source, simple semiquant. testing suggests that, unlike many other methods, no free cyanide is present in the reaction mixture or during a variety of potential workups, thus improving the safety aspects of this method from initial setup through to product isolation. Finally, developing and testing a series of convenient cyanation kits has allowed facile application and broader adoption of this method in our laboratories In the part of experimental materials, we found many familiar compounds, such as Methyl 5-bromopicolinate(cas: 29682-15-3Category: pyridine-derivatives)

Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. In industry and in the lab, pyridine is used as a reaction solvent, particularly when its basicity is useful, and as a starting material for synthesizing some herbicides, fungicides, and antiseptics.Category: pyridine-derivatives

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In 2019,Letters in Organic Chemistry included an article by Gavhane, Dinesh S.; Sarkate, Aniket P.; Karnik, Kshipra S.; Jagtap, Shritesh D.; Ansari, Sajed H.; Izankar, Ashwini V.; Narula, Ishudeep K.; Jambhorkar, Vaishnavi S.; Rajhans, Aishwarya P.. Computed Properties of C5H6BNO2. The article was titled 《Nano Copper Catalyzed Microwave Assisted Coupling of Benzene Boronic Acids with Thiophenols》. The information in the text is summarized as follows:

A proficient, microwave mediated methodol. using CuFe2O4 nanoparticle as the catalyst for S-arylation of substituted benzene boronic acids with thiophenol was developed. In this method, the substituted thioethers were easily obtained through a C-S bond formation using microwave irradiation technique as well as conventional heating in the presence of CuFe2O4 nanoparticles with modest to excellent yields with the less reaction time. The ligand free microwave technique helped in the preparation of substituted thioethers in measurable amount within 10 mins. The same results were obtained with conventional heating in 12h. The reported method was economically efficient and an alternative to the initial existing method for the preparation of substituted thioethers. In the part of experimental materials, we found many familiar compounds, such as 2-Pyridinylboronic acid(cas: 197958-29-5Computed Properties of C5H6BNO2)

2-Pyridinylboronic acid(cas: 197958-29-5) belongs to pyridine. In industry and in the lab, pyridine is used as a reaction solvent, particularly when its basicity is useful, and as a starting material for synthesizing some herbicides, fungicides, and antiseptics.Computed Properties of C5H6BNO2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem