18437-58-6 | Page 11 of 13 | Pyridine-derivatives

Manley, Peter J.’s team published research in Bioorganic & Medicinal Chemistry Letters in 13 | CAS: 18437-58-6

Bioorganic & Medicinal Chemistry Letters published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Safety of 4-Amino-2-picoline.

Manley, Peter J. published the artcile2,4-Disubstituted pyrimidines: A novel class of KDR kinase inhibitors, Safety of 4-Amino-2-picoline, the publication is Bioorganic & Medicinal Chemistry Letters (2003), 13(10), 1673-1677, database is CAplus and MEDLINE.

2,4-Disubstituted pyrimidines were synthesized as a novel class of KDR kinase inhibitors. Evaluation of the SAR of the screening lead compound I (R = H) (KDR IC₅₀=105 nM, Cell IC₅₀=8% inhibition at 500 nM) led to the potent 3,5-dimethylaniline derivative I (R = Me) (KDR IC₅₀=6 nM, cell IC₅₀=19 nM).

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

Rombouts, Frederik J. R.’s team published research in Journal of Medicinal Chemistry in 60 | CAS: 18437-58-6

Journal of Medicinal Chemistry published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Recommanded Product: 4-Amino-2-picoline.

Rombouts, Frederik J. R. published the artcileDiscovery of N-(Pyridin-4-yl)-1,5-naphthyridin-2-amines as Potential Tau Pathology PET Tracers for Alzheimer’s Disease, Recommanded Product: 4-Amino-2-picoline, the publication is Journal of Medicinal Chemistry (2017), 60(4), 1272-1291, database is CAplus and MEDLINE.

A mini-HTS on 4000 compounds selected using 2D fragment-based similarity and 3D pharmacophoric and shape similarity to known selective tau aggregate binders identified N-(6-methylpyridin-2-yl)quinolin-2-amine 10 as a novel potent binder to human AD aggregated tau with modest selectivity vs. aggregated β-amyloid (Aβ). Initial medicinal chem. efforts identified key elements for potency and selectivity, as well as suitable positions for radiofluorination, leading to a first generation of fluoroalkyl-substituted quinoline tau binding ligands with suboptimal physicochem. properties. Further optimization toward a more optimal pharmacokinetic profile led to the discovery of 1,5-naphthyridine 75, a potent and selective tau aggregate binder with potential as a tau PET tracer.

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

Down, Kenneth’s team published research in Journal of Medicinal Chemistry in 64 | CAS: 18437-58-6

Down, Kenneth published the artcileDiscovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode, Recommanded Product: 4-Amino-2-picoline, the publication is Journal of Medicinal Chemistry (2021), 64(18), 13780-13792, database is CAplus and MEDLINE.

Optimization of a previously reported lead series of PI3Kδ inhibitors with a novel binding mode led to the identification of a clin. candidate compound 31 (GSK251)(I). Removal of an embedded Ames-pos. heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound 9 (II). Further optimization to avoid glutathione trapping, to enhance potency and selectivity, and to optimize an oral pharmacokinetic profile led to the discovery of compound 31 (GSK251) that had a low predicted daily dose (45 mg, b.i.d) and a rat toxicity profile suitable for further development.

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

Bagley, Mark C.’s team published research in Synlett in 27 | CAS: 18437-58-6

Synlett published new progress about 18437-58-6. 18437-58-6 belongs to pyridine-derivatives, auxiliary class Pyridine,Amine, name is 4-Amino-2-picoline, and the molecular formula is C6H8N2, Recommanded Product: 4-Amino-2-picoline.

Bagley, Mark C. published the artcileRapid Protium-Deuterium Exchange of 4-Aminopyridines in Neutral D₂O under Microwave Irradiation, Recommanded Product: 4-Amino-2-picoline, the publication is Synlett (2016), 27(17), 2467-2472, database is CAplus.

4-Aminopyridines underwent rapid and highly selective H/D exchange at C-2 and C-6 in neutral D₂O upon microwave irradiation at only 190° for two hours in a sealed vessel. This method contrasted and complemented the acid-mediated H/D exchange, required no catalyst, and was appropriate for the synthesis of deuterium isotopologues of N- and C-substituted 4-aminopyridines and other nitrogen heterocycles.

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

Ghiazza, Clement’s team published research in Nature Chemistry in 2022 | CAS: 18437-58-6

4-Amino-2-picoline(cas: 18437-58-6) belongs to anime. In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (NH3), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines).Application In Synthesis of 4-Amino-2-picoline

Ghiazza, Clement; Faber, Teresa; Gomez-Palomino, Alejandro; Cornella, Josep published an article on January 31 ,2022. The article was titled 《Deaminative chlorination of aminoheterocycles》, and you may find the article in Nature Chemistry.Application In Synthesis of 4-Amino-2-picoline The information in the text is summarized as follows:

Herein we present a simple methodol. that enabled the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)-NH2 could be converted into C(sp2)-Cl bonds. The method was characterized by its wide functional group tolerance and substrate scope, allowing the modification of different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enabled practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents. After reading the article, we found that the author used 4-Amino-2-picoline(cas: 18437-58-6Application In Synthesis of 4-Amino-2-picoline)

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chen, Ying-Chu’s team published research in Bioconjugate Chemistry in 2020 | CAS: 18437-58-6

4-Amino-2-picoline(cas: 18437-58-6) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Recommanded Product: 4-Amino-2-picoline

Recommanded Product: 4-Amino-2-picolineOn March 18, 2020, Chen, Ying-Chu; Faver, John C.; Ku, Angela F.; Miklossy, Gabriella; Riehle, Kevin; Bohren, Kurt M.; Ucisik, Melek N.; Matzuk, Martin M.; Yu, Zhifeng; Simmons, Nicholas published an article in Bioconjugate Chemistry. The article was 《C-N Coupling of DNA-Conjugated (Hetero)aryl Bromides and Chlorides for DNA-Encoded Chemical Library Synthesis》. The article mentions the following:

DNA-encoded chem. library (DECL) screens are a rapid and economical tool to identify chem. starting points for drug discovery. As a robust transformation for drug discovery, palladium-catalyzed C-N coupling is a valuable synthetic method for the construction of DECL chem. matter; however, currently disclosed methods have only been demonstrated on DNA-attached (hetero)aromatic iodide and bromide electrophiles. We developed conditions utilizing an N-heterocyclic carbene-palladium catalyst that extends this reaction to the coupling of DNA-conjugated (hetero)aromatic chlorides with (hetero)aromatic and select aliphatic amine nucleophiles. In addition, we evaluated steric and electronic effects within this catalyst series, carried out a large substrate scope study on two representative (hetero)aryl bromides, and applied this newly developed method within the construction of a 63 million-membered DECL.4-Amino-2-picoline(cas: 18437-58-6Recommanded Product: 4-Amino-2-picoline) was used in this study.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Arnold, Eric P.’s team published research in ACS Combinatorial Science in 2020 | CAS: 18437-58-6

4-Amino-2-picoline(cas: 18437-58-6) 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.Reference of 4-Amino-2-picoline

Arnold, Eric P.; Mondal, Prolay K.; Schmitt, Daniel C. published an article on January 13 ,2020. The article was titled 《Oxidative Cyclization Approach to Benzimidazole Libraries》, and you may find the article in ACS Combinatorial Science.Reference of 4-Amino-2-picoline The information in the text is summarized as follows:

An efficient approach to the parallel synthesis of benzimidazoles from anilines is described. Library approaches to vary the N1 and C2 vectors of benzimidazoles are well established; however, C4-C7 variation has traditionally relied on 1,2-dianiline building blocks, providing limited chem. space coverage. We have developed an amidine formation/oxidative cyclization sequence that enables anilines as a diversity set for benzimidazole C4-C7 SAR generation in parallel format. The amidine annulation was achieved using PIDA or Cu-mediated oxidation to access both N-H and N-alkyl benzimidazoles. This library protocol has now been utilized for analog production in four medicinal chem. projects. Addnl., the synthesis of aza-benzimidazoles from aminopyridines was achieved via an analogous sequence. After reading the article, we found that the author used 4-Amino-2-picoline(cas: 18437-58-6Reference of 4-Amino-2-picoline)

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Down, Kenneth’s team published research in Journal of Medicinal Chemistry in 2021 | CAS: 18437-58-6

4-Amino-2-picoline(cas: 18437-58-6) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Recommanded Product: 4-Amino-2-picoline

Recommanded Product: 4-Amino-2-picolineOn September 23, 2021 ,《Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode》 was published in Journal of Medicinal Chemistry. The article was written by Down, Kenneth; Amour, Augustin; Anderson, Niall A.; Barton, Nick; Campos, Sebastien; Cannons, Edward P.; Clissold, Cole; Convery, Maire A.; Coward, John J.; Doyle, Kevin; Duempelfeld, Birgit; Edwards, Christopher D.; Goldsmith, Michael D.; Krause, Jana; Mallett, David N.; McGonagle, Grant A.; Patel, Vipulkumar K.; Rowedder, James; Rowland, Paul; Sharpe, Andrew; Sriskantharajah, Srividya; Thomas, Daniel A.; Thomson, Douglas W.; Uddin, Sorif; Hamblin, J. Nicole; Hessel, Edith M.. The article contains the following contents:

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Chunting’s team published research in Journal of Medicinal Chemistry in 2020 | CAS: 18437-58-6

4-Amino-2-picoline(cas: 18437-58-6) belongs to anime. Many important products require amines as part of their syntheses. Methylamine is utilized in the production of the analgesic meperidine (trade name Demerol) and the photographic developer Metol (trademark), and dimethylamine is used in the synthesis of the antihistamine diphenhydramine (trade name Benadryl), the solvent dimethylformamide (DMF), and the rocket propellant 1,1-dimethylhydrazine. The synthesis of the insect repellent N,N-diethyl-m-toluamide (DEET) incorporates diethylamine while that of the synthetic fibre Kevlar requires aromatic amines.Electric Literature of C6H8N2

Electric Literature of C6H8N2On June 11, 2020, Wang, Chunting; Pei, Yameng; Wang, Lin; Li, Shuo; Jiang, Chao; Tan, Xu; Dong, Yi; Xiang, Ye; Ma, Yao; Liu, Gang published an article in Journal of Medicinal Chemistry. The article was 《Discovery of (1H-Pyrazolo[3,4-c]pyridin-5-yl)sulfonamide Analogues as Hepatitis B Virus Capsid Assembly Modulators by Conformation Constraint》. The article mentions the following:

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) have been suggested to be effective anti-HBV agents in both preclin. and clin. studies. In addition to blocking HBV replication, CAMs could reduce the formation of covalently closed circular DNA (cccDNA), which accounts for the persistence of HBV infection. Here, we describe the discovery of (1H-indazole-5-yl)sulfonamides and (1H-pyrazolo[3,4-c]pyridin-5-yl)sulfonamides as new CAM chemotypes by constraining the conformation of the sulfamoylbenzamide derivatives Lead optimization resulted in compound 56 with an EC50 value of 0.034μM and good metabolic stability in mouse liver microsomes. To increase the solubility, the amino acid prodrug (65) and its citric acid salt (67) were prepared Compound 67 dose dependently inhibited HBV replication in a hydrodynamic injection-based mouse model of HBV infection, while 56 did not show in vivo anti-HBV activity, likely owing to its suboptimal solubility This class of compounds may serve as a starting point to develop novel anti-HBV drugs. In addition to this study using 4-Amino-2-picoline, there are many other studies that have used 4-Amino-2-picoline(cas: 18437-58-6Electric Literature of C6H8N2) was used in this study.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yuan, Xinrui’s team published research in Bioorganic & Medicinal Chemistry in 2019 | CAS: 18437-58-6

《Design, synthesis and biological evaluation of pyridone-aminal derivatives as MNK1/2 inhibitors》 was written by Yuan, Xinrui; Wu, Hanshu; Bu, Hong; Zheng, Peiyuan; Zhou, Jinpei; Zhang, Huibin. Synthetic Route of C6H8N2 And the article was included in Bioorganic & Medicinal Chemistry on April 1 ,2019. The article conveys some information:

Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone-aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematol. cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 μM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer. In the experiment, the researchers used many compounds, for example, 4-Amino-2-picoline(cas: 18437-58-6Synthetic Route of C6H8N2)

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem