Tag: 100-200

Discovery of 3-Benzyl-1-(trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors was written by Ito, Masahiro;Tanaka, Toshio;Toita, Akinori;Uchiyama, Noriko;Kokubo, Hironori;Morishita, Nao;Klein, Michael G.;Zou, Hua;Murakami, Morio;Kondo, Mitsuyo;Sameshima, Tomoya;Araki, Shinsuke;Endo, Satoshi;Kawamoto, Tomohiro;Morin, Gregg B.;Aparicio, Samuel A.;Nakanishi, Atsushi;Maezaki, Hironobu;Imaeda, Yasuhiro. And the article was included in Journal of Medicinal Chemistry in 2018.Safety of 6-Fluoronicotinonitrile This article mentions the following:

Cyclin-dependent kinase 12 (CDK12) plays a key role in the coordination of transcription with elongation and mRNA processing. CDK12 mutations found in tumors and CDK12 inhibition sensitize cancer cells to DNA-damaging reagents and DNA-repair inhibitors. This suggests that CDK12 inhibitors are potential therapeutics for cancer that may cause synthetic lethality. Here, we report the discovery of 3-benzyl-1-(trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea derivatives as novel and selective CDK12 inhibitors. Structure-activity relationship studies of a HTS hit, structure-based drug design, and conformation-oriented design using the Cambridge Structural Database afforded the optimized compound 2, which exhibited not only potent CDK12 (and CDK13) inhibitory activity and excellent selectivity but also good physicochem. properties. Furthermore, 2 inhibited the phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II and induced growth inhibition in SK-BR-3 cells. Therefore, 2 represents an excellent chem. probe for functional studies of CDK12 and could be a promising lead compound for drug discovery. In the experiment, the researchers used many compounds, for example, 6-Fluoronicotinonitrile (cas: 3939-12-6Safety of 6-Fluoronicotinonitrile).

6-Fluoronicotinonitrile (cas: 3939-12-6) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Safety of 6-Fluoronicotinonitrile

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Development of an ionization method using hydrogenated plasma for mass analysis of surface adhesive compounds was written by Aida, Mari;Iwai, Takahiro;Okamoto, Yuki;Miyahara, Hidekazu;Seto, Yasuo;Okino, Akitoshi. And the article was included in Journal of Analytical Atomic Spectrometry in 2018.Synthetic Route of C8H11N This article mentions the following:

Currently, atm. plasmas are applied to the desorption and ionization of surface adhesive materials for rapid and highly sensitive anal. One widely used chem. ionization method applies protons generated from atm. water mols. to a desorbed sample; however, a detailed study of the ionization mechanism has not been addressed thus far. Therefore, this paper proposes an ionization method that adds a small, optimized amount of hydrogen to the helium plasma for generating protons in the sample ionization source. Using this technique, mass spectrometry was performed on the sample surface deposits of 2-isopropylpyridine and 4-isopropylaniline. The hydrogen flow rate was optimized to the addition ratio of 2%, and the lowest limit of detection achieved is 0.1 and 42 pmol for 2-isopropylpyridine and 4-isopropylaniline, resp. By optimizing the hydrogen addition flow rate, the optimum number of protons for sample ionization was attained, and it became possible to realize control of proton content in the sample, irresp. of humidity and surrounding environmental factors during mass spectrometry. In the experiment, the researchers used many compounds, for example, 2-Isopropylpyridine (cas: 644-98-4Synthetic Route of C8H11N).

2-Isopropylpyridine (cas: 644-98-4) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Synthetic Route of C8H11N

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Late-stage synthesis and application of photoreactive probes derived from direct benzoylation of heteroaromatic C-H bonds was written by Hesp, Kevin D.;Xiao, Jun;West, Graham M.. And the article was included in Organic & Biomolecular Chemistry in 2020.SDS of cas: 59718-84-2 This article mentions the following:

A C-H functionalization strategy for the expedient access to photoreactive chem. probes of commonly found heterocyclic fragments RC₆H₄C(O)R¹ [R = H, 4-(CHCCH₂O), 4-N₃, 3-(CHC), etc.; R¹ = pyrazin-2-yl, isoquinolin-1-yl, pyridazin-4-yl, etc.] or drug mols. of pharmaceutical relevance is described. A series of aryl glyoxylic acid reagents featuring pendant alkyne or azide clickable handles RC₆H₄C(O)C(O)OH have been developed for application in the radical-mediated appendage of benzoyl fragments onto simple heteroaromatic fragments RC₆H₄C(O)R¹, as well as more complex drug-like compounds This unprecedented strategy of chem. probe synthesis allows for direct access to photoreactive chem. probes without any requirement of fragment pre-functionalization or significant synthetic re-evaluation. In the experiment, the researchers used many compounds, for example, Methyl 3-methylpicolinate (cas: 59718-84-2SDS of cas: 59718-84-2).

Methyl 3-methylpicolinate (cas: 59718-84-2) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.SDS of cas: 59718-84-2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Pd-Catalyzed Synthesis of Aryl and Heteroaryl Triflones from Reactions of Sodium Triflinate with Aryl (Heteroaryl) Triflates was written by Smyth, Lynette A.;Phillips, Eric M.;Chan, Vincent S.;Napolitano, Jose G.;Henry, Rodger;Shekhar, Shashank. And the article was included in Journal of Organic Chemistry in 2016.Safety of 5-Hydroxy-2-methoxylpyridine This article mentions the following:

A novel method for Pd-catalyzed triflination of aryl and heteroaryl triflates using NaSO₂CF₃ as the nucleophile is described. The combination of Pd₂(dba)₃ and RockPhos formed the most effective catalyst. A broad range of functional groups and heteroaromatic compounds were tolerated under the neutral reaction conditions. The order of reactivity ArOTf ≥ ArCl ≥ ArBr is consistent with transmetalation being a slow step of the reaction. In the experiment, the researchers used many compounds, for example, 5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0Safety of 5-Hydroxy-2-methoxylpyridine).

5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Safety of 5-Hydroxy-2-methoxylpyridine

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthesis of 3-aminochromenes: the Zincke reaction revisited was written by Costa, Marta;Rodrigues, Ana I.;Proenca, Fernanda. And the article was included in Tetrahedron in 2014.COA of Formula: C7H7ClN2 This article mentions the following:

3-(Amino)coumarin derivatives and 2-(imino)-3-chromenamine derivatives were efficiently prepared by a Zincke-reaction-ring-opening reaction of the corresponding 2H-chromene-3-pyridinium chlorides using N-methylpiperazine. This methodol. unravels the marked potential of pyridinium salts as protective groups for primary amines. These scaffolds can be considered important building blocks for N-[7-[[3-O-(aminocarbonyl)-6-deoxy-5-C-methyl-4-O-methyl-α-L–lyxo-hexopyranosyl]oxy]-4-hydroxy-8-methyl-2-oxo-2H-1-benzopyran-3-yl]-4-hydroxy-3-(3-methyl-2-buten-1-yl)benzamide (novobiocin) analogs and similar heterocyclic compounds The synthesis of the target compounds was achieved by a cyclization (heterocyclization, Zincke reaction) of 2-hydroxybenzoic acid derivatives with 1-(cyanomethyl)pyridinium chloride. The title compounds thus formed included 1-(2-imino-2H-1-benzopyran-3-yl)pyridinium chloride derivatives (chromene-imine derivatives) and 1-(2-oxo-2H-1-benzopyran-3-yl)pyridinium chloride derivatives (coumarin derivatives). These compounds was intermediates for 3-amino-2H-1-benzopyran-2-one derivatives (amine-coumarin derivatives) and 2-(imino)-2H-1-benzopyran-3-amine derivatives In the experiment, the researchers used many compounds, for example, 1-(Cyanomethyl)pyridin-1-ium chloride (cas: 17281-59-3COA of Formula: C7H7ClN2).

1-(Cyanomethyl)pyridin-1-ium chloride (cas: 17281-59-3) belongs to pyridine derivatives. Pyridine has a conjugated system of six π electrons that are delocalized over the ring. The molecule is planar and, thus, follows the Hückel criteria for aromatic systems. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.COA of Formula: C7H7ClN2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Electron collision-induced rearrangement in α-substituted N-heterocycles was written by Neuner-Jehle, N.. And the article was included in Tetrahedron Letters in 1968.Quality Control of 2-Phenoxypyridine This article mentions the following:

Mass spectra were observed for nine α-substituted N-heterocyclic compounds (MXR) (where XR represents the α-substituent, R is a Me or Ph portion of the substituent). Fragment ions whose masses correspond to MR+ were observed with high relative yields (MXR and relative intensity of MR fragment % given): 2-dimethylaminopyridine, 87; 2-dimethylaminoquinoline, 84; 6-dimethylamino-5-azaazulene, 61; 6-dimethylaminopurine, 100; 2-acetylpyridine, 24; 2-benzoylpyridine, 87; 2-benzoylpyrrole, 8; 2-benzoylindole, 5. For the ether, 2-phenoxypyridine, the fragment ion C10H9N, 49% relative intensity, was observed. The X group (NMe or CO) was lost except from the ether where a C atom is also lost. A mol. rearrangement is induced by electron collision. The R group migrates to the heterocyclic N. In the experiment, the researchers used many compounds, for example, 2-Phenoxypyridine (cas: 4783-68-0Quality Control of 2-Phenoxypyridine).

2-Phenoxypyridine (cas: 4783-68-0) 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. The lone pair is in an sp2 orbital, projecting outward from the ring in the same plane as the σ bonds. Several pyridine derivatives play important roles in biological systems. While its biosynthesis is not fully understood, nicotinic acid (vitamin B3) occurs in some bacteria, fungi, and mammals.Quality Control of 2-Phenoxypyridine

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ruthenium(II)-Catalyzed Regioselective C-8 Hydroxylation of 1,2,3,4-Tetrahydroquinolines was written by Chen, Changjun;Pan, Yixiao;Zhao, Haoqiang;Xu, Xin;Luo, Zhenli;Cao, Lei;Xi, Siqi;Li, Huanrong;Xu, Lijin. And the article was included in Organic Letters in 2018.SDS of cas: 4783-68-0 This article mentions the following:

Ru(II)-catalyzed chelation-assisted highly regioselective C8-hydroxylation of 1,2,3,4-tetrahydroquinolines has been developed. Various 1,2,3,4-tetrahydroquinolines underwent smooth C8-H hydroxylation with cheap and safe K₂S₂O₈ as the oxidant and oxygen source to furnish the corresponding products in good to excellent yields with high tolerance of the functional groups. The choice of a readily installable and removable N-pyrimidyl directing group is the key to catalysis. Mechanistic studies suggest the involvement of a six-membered ruthenacycle intermediate in the catalytic cycle. The method can also be extended to the direct hydroxylation of other (hetero)arene C-H bonds. In the experiment, the researchers used many compounds, for example, 2-Phenoxypyridine (cas: 4783-68-0SDS of cas: 4783-68-0).

2-Phenoxypyridine (cas: 4783-68-0) belongs to pyridine derivatives. Pyridine is diamagnetic and has a diamagnetic susceptibility of −48.7 × 10−6 cm3·mol−1.The molecular electric dipole moment is 2.2 debyes. The standard enthalpy of formation is 100.2 kJ·mol−1 in the liquid phase and 140.4 kJ·mol−1 in the gas phase. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.SDS of cas: 4783-68-0

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

An efficient protocol for the carbon-sulfur cross-coupling of sulfenyl chlorides with arylboronic acids using a palladium catalyst was written by Gogoi, Prasanta;Kalita, Mukul;Barman, Pranjit. And the article was included in Synlett in 2014.Application In Synthesis of (2,6-Dichloropyridin-4-yl)boronic acid This article mentions the following:

An efficient protocol for carbon-sulfur bond formation is developed, which involves the cross-coupling of sulfenyl chlorides and arylboronic acids catalyzed by a novel palladium-Schiff base complex. Good to high product yields, short reaction times, and mild reaction conditions are important features of this new method. In the experiment, the researchers used many compounds, for example, (2,6-Dichloropyridin-4-yl)boronic acid (cas: 1072951-54-2Application In Synthesis of (2,6-Dichloropyridin-4-yl)boronic acid).

(2,6-Dichloropyridin-4-yl)boronic acid (cas: 1072951-54-2) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. Pyridine groups exist in countless molecules, and their applications include catalysis, drug design, molecular recognition, and natural product synthesis.Application In Synthesis of (2,6-Dichloropyridin-4-yl)boronic acid

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthesis and evaluation of carbon-linked analogs of dual orexin receptor antagonist filorexant was written by Kuduk, Scott D.;Skudlarek, Jason W.;Di Marco, Christina N.;Bruno, Joseph G.;Pausch, Mark A.;O’Brien, Julie A.;Cabalu, Tamara D.;Stevens, Joanne;Brunner, Joseph;Tannenbaum, Pamela L.;Gotter, Anthony L.;Winrow, Christopher J.;Renger, John J.;Coleman, Paul J.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2014.Formula: C6H6BrNO This article mentions the following:

Analogs of the dual orexin receptor antagonist filorexant were prepared Replacement of the ether linkage proved highly sensitive toward modification with an acetylene linkage providing compounds with the best in vitro and in vivo potency profiles. In the experiment, the researchers used many compounds, for example, (4-Bromopyridin-2-yl)methanol (cas: 131747-45-0Formula: C6H6BrNO).

(4-Bromopyridin-2-yl)methanol (cas: 131747-45-0) belongs to pyridine derivatives. Pyridine’s the lone pair does not contribute to the aromatic system but importantly influences the chemical properties of pyridine, as it easily supports bond formation via an electrophilic attack. One of the examples of pyridines is the well-known alkaloid lithoprimidine, which is an A3 adenosine receptor antagonist and N,N-dimethylaminopyridine (DMAP) analog, commonly used in organic synthesis.Formula: C6H6BrNO

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Cobalt-catalyzed directed ortho-methylation of arenes with methyl tosylate was written by Sun, Qiao;Yoshikai, Naohiko. And the article was included in Organic Chemistry Frontiers in 2018.Quality Control of 2-(m-Tolyl)pyridine This article mentions the following:

A cobalt-catalyzed directed ortho C-H methylation reaction of arenes has been achieved using readily available Me tosylate as a methylating agent. An in situ-generated cobalt-N-heterocyclic carbene catalyst in combination with neopentyl magnesium bromide promotes the methylation at room temperature The reaction is applicable to various substrates bearing nitrogen directing groups such as N-aryl imine, N-H imine, and 2-pyridyl groups. The present protocol also allows for facile introduction of a trideuteriomethyl group into arenes. In the experiment, the researchers used many compounds, for example, 2-(m-Tolyl)pyridine (cas: 4373-61-9Quality Control of 2-(m-Tolyl)pyridine).

2-(m-Tolyl)pyridine (cas: 4373-61-9) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Pyridine groups exist in countless molecules, and their applications include catalysis, drug design, molecular recognition, and natural product synthesis.Quality Control of 2-(m-Tolyl)pyridine

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem