Day: February 9, 2023

Synthetic studies to help elucidate the metabolism of the preclinical candidate TBAJ-876-a less toxic and more potent analogue of bedaquiline was written by Choi, Peter J.;Conole, Daniel;Sutherland, Hamish S.;Blaser, Adrian;Tong, Amy S. T.;Cooper, Christopher B.;Upton, Anna M.;Palmer, Brian D.;Denny, William A.. And the article was included in Molecules in 2020.Related Products of 51834-97-0 This article mentions the following:

Bedaquiline is a novel drug approved in 2012 by the FDA for treatment of drug-resistant tuberculosis (TB). Although it shows high efficacy towards drug-resistant forms of TB, its use has been limited by the potential for significant side effects. In particular, bedaquiline is a very lipophilic compound with an associated long terminal half-life and shows potent inhibition of the cardiac potassium hERG channel, resulting in QTc interval prolongation in humans that may result in cardiac arrhythmia. To address these issues, we carried out a drug discovery program to develop an improved second generation analog of bedaquiline. From this medicinal chem. program, a candidate (TBAJ-876) has been selected to undergo further preclin. evaluation. During this evaluation, three major metabolites arising from TBAJ-876 were observed in several preclin. animal models. We report here our synthetic efforts to unequivocally structurally characterize these three metabolites through their independent directed synthesis. In the experiment, the researchers used many compounds, for example, 5-Hydroxy-2-methoxylpyridine (cas: 51834-97-0Related Products of 51834-97-0).

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. 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.Related Products of 51834-97-0

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Sulfide analogues of flupirtine and retigabine with nanomolar K_V7.2/K_V7.3 channel opening activity was written by Bock, Christian;Surur, Abdrrahman S.;Beirow, Kristin;Kindermann, Markus K.;Schulig, Lukas;Bodtke, Anja;Bednarski, Patrick J.;Link, Andreas. And the article was included in ChemMedChem in 2019.Name: 6-Chloro-5-methyl-3-nitropyridin-2-amine This article mentions the following:

The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, resp., leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electrophilic quinones. These elusive, highly reactive metabolites may induce liver injury in the case of flupirtine and blue tissue discoloration after prolonged intake of retigabine. We examined which structural features can be altered to avoid the detrimental oxidation of the aromatic ring and shift oxidation toward the formation of more benign metabolites. Structure-activity relationship studies were performed to evaluate the K_V7.2/3 channel opening activity of 45 derivatives Sulfide analogs were identified that are devoid of the risk of quinone formation, but possess potent K_V7.2/3 opening activity. For example, flupirtine analog 3-(3,5-difluorophenyl)-N-(6-(isobutylthio)-2-(pyrrolidin-1-yl)pyridin-3-yl)propanamide (48) has 100-fold enhanced activity (EC₅₀=1.4 nM), a vastly improved toxicity/activity ratio, and the same efficacy as retigabine in vitro. In the experiment, the researchers used many compounds, for example, 6-Chloro-5-methyl-3-nitropyridin-2-amine (cas: 202217-19-4Name: 6-Chloro-5-methyl-3-nitropyridin-2-amine).

6-Chloro-5-methyl-3-nitropyridin-2-amine (cas: 202217-19-4) 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, 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. Name: 6-Chloro-5-methyl-3-nitropyridin-2-amine

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthesis of new thiopyranopyridines was written by Dunn, A. D.. And the article was included in Journal fuer Praktische Chemie (Leipzig) in 1987.Formula: C8H9NO2 This article mentions the following:

Thiopyranopyridinecarboxylates I and II (X, Y = CH, N; R = OH, NH₂) are prepared from pyridine esters (e.g., III; R¹ = Me, R² = CO₂Me; R¹ = CO₂Me, R² = Me) and nitriles (e.g., III; R¹ = Me, R² = CN) by photochem. bromination, followed by substitution reaction of the resulting bromomethyl derivative with HSCH₂CO₂Me, and then base-induced intramol. cyclocondensation. In the experiment, the researchers used many compounds, for example, Methyl 3-methylpicolinate (cas: 59718-84-2Formula: C8H9NO2).

Methyl 3-methylpicolinate (cas: 59718-84-2) 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. Halopyridines are particularly attractive synthetic building blocks in a variety of cross-coupling methods, including the Suzuki-Miyaura cross-coupling reaction.Formula: C8H9NO2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Steric effects in S_N2 reactions. Determination of transition state structures for the quaternization of 2-alkylpyridines and -thiazoles by a combined experimental and molecular mechanics procedure was written by Berg, Ulf;Gallo, Roger. And the article was included in Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry in 1983.Quality Control of 2-Isopropylpyridine This article mentions the following:

S_N2 transition-state structures for the Menschutkin reactions between 2-alkylpyridines or -thiazoles and MeX (X = I, and SO₃F) are calculated by the Allinger 1973 force field method. Exptl. found differences in steric energies between the quaternary iminium ions and the activated complexes are used as measures for the elevation of the position of the transition state. Estimates of the C-N distance (r_C-N) in the transition state result in a 22±4% extension compared to the ground state value (1.48 Å), depending upon the transition state model used. The preferred model results in r_C-N = 1.812±0.013 Å. Consistent results were obtained with nucleophiles of different geometries (pyridines and thiazoles). A change of leaving group from iodide to fluorosulfonate leads to an extension of r_C-N by 0.04±0.02 Å. In the experiment, the researchers used many compounds, for example, 2-Isopropylpyridine (cas: 644-98-4Quality Control of 2-Isopropylpyridine).

2-Isopropylpyridine (cas: 644-98-4) 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. 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.Quality Control of 2-Isopropylpyridine

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Solvothermal synthesis of two new coordination polymers: in situ heterocycle conversion and N-alkylation, network topologies and luminescence properties was written by Fang, Zhenlan;Yang, Wenbin;He, Jiangang;Ding, Kaining;Wu, Xiaoyuan;Zhang, Qisheng;Yu, Rongmin;Lu, Canzhong. And the article was included in CrystEngComm in 2012.COA of Formula: C12H8N4O This article mentions the following:

Two new copper complexes [Cu^I₄(L2)I₅]_n (1, L2 = 3,5-bis(1-ethylpyridinium-4-yl)-1,2,4-triazol-4-ide) and [Cu^I₆(L3)₃Br₃]_n (2, L3 = 3,5-bis(4-pyridyl)-1,2,4-triazolate) were obtained from the solvothermal reactions of different copper halides with 2,5-bis(4-pyridyl)-1,3,4-oxadiazole (L1) in the presence of aqueous ammonia. The x-ray diffraction, IR spectrum and elemental analyses of 1 and 2 clearly show that the 1,3,4-oxadiazole ligand L1 has transformed into the triazolate ligands L2 and L3. Most fascinatingly, 1 represents the first example of an integrated reaction system involving heterocyclic conversion from oxadiazole to triazolate, N-alkylation, and further self-assembly of the in situ generated ligand L2 with metal cations to form a coordination polymer in one solvothermal spot. The possible formation mechanism of 1 is proposed, and in addition, the interesting topologies and luminescence properties of 2 were studied based on the results of the DFT calculations In the experiment, the researchers used many compounds, for example, 2,5-Di(pyridin-4-yl)-1,3,4-oxadiazole (cas: 15420-02-7COA of Formula: C12H8N4O).

2,5-Di(pyridin-4-yl)-1,3,4-oxadiazole (cas: 15420-02-7) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. COA of Formula: C12H8N4O

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

PMR Study of Structural Features of Ionic Liquids Based on 1-Alkyl-3-Methylpyridinium and Mechanism of their Interaction with Cellulose was written by Sashina, E. S.;Kashirskii, D. A.;Jankowski, S.. And the article was included in Fibre Chemistry in 2014.Recommanded Product: 1-Butyl-3-methylpyridinium Chloride This article mentions the following:

Ionic liquids (IL) based on 1-alkyl-3-methylpyridinium and cellulose solutions in them were studied exptl. using PMR. It was shown that the chem. shifts for H2 and H6 of the pyridine ring changed most upon changing the length of the alkyl substituent in the IL cation and in the cellulose solutions The exptl. results could be useful for explaining the interaction mechanism between natural polymers and IL. In the experiment, the researchers used many compounds, for example, 1-Butyl-3-methylpyridinium Chloride (cas: 125652-55-3Recommanded Product: 1-Butyl-3-methylpyridinium Chloride).

1-Butyl-3-methylpyridinium Chloride (cas: 125652-55-3) belongs to pyridine derivatives. The pyridine ring occurs in many important compounds, including agrochemicals, pharmaceuticals, and vitamins. 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.Recommanded Product: 1-Butyl-3-methylpyridinium Chloride

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Novel 18β-glycyrrhetinic acid analogues as potent and selective inhibitors of 11β-hydroxysteroid dehydrogenases was written by Su, Xiangdong;Lawrence, Harshani;Ganeshapillai, Dharshini;Cruttenden, Adrian;Purohit, Atul;Reed, Michael J.;Vicker, Nigel;Potter, Barry V. L.. And the article was included in Bioorganic & Medicinal Chemistry in 2004.Category: pyridine-derivatives This article mentions the following:

Extensive structural modifications to the 18β-glycyrrhetinic acid template are described and their effects on the SAR of the 11β-hydroxysteroid dehydrogenase isoenzymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors have been discovered and N-(2-hydroxyethyl)-3β-hydroxy-11-oxo-18β-olean-12-en-30-oic acid amide is highlighted as a very potent selective inhibitor of 11β-hydroxysteroid dehydrogenase 2 with an IC₅₀ = 4 pM. In the experiment, the researchers used many compounds, for example, 3-Amino-2,6-dimethoxypyridine (cas: 28020-37-3Category: pyridine-derivatives).

3-Amino-2,6-dimethoxypyridine (cas: 28020-37-3) belongs to pyridine derivatives. Pyridine has a dipole moment and a weaker resonant stabilization than benzene (resonance energy 117 kJ·mol−1 in pyridine vs. 150 kJ·mol−1 in benzene). 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. Category: pyridine-derivatives

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kinetic study on the conversion of pyridine- and quinolinecarboxylic acids to the corresponding trichloromethyl compounds was written by Takahashi, Kazuyuki;Takeda, Koichi;Mitsuhashi, Keiryo. And the article was included in Journal of Heterocyclic Chemistry in 1978.Formula: C7H6N2 This article mentions the following:

The apparent 2nd order rate constant of the conversion of substituted picolinic and quinaldinic acids to the corresponding trichloromethylpyridines and quinolines by treatment with PCl₅ in refluxing SOCl₂ was measured. The logarithms of the rate constants (log k) are linear with the basicities (pKa) of the unsaturated ring nitrogens in the substrates. The reaction constant ρ was estimated In the experiment, the researchers used many compounds, for example, 4-Methylpicolinonitrile (cas: 1620-76-4Formula: C7H6N2).

4-Methylpicolinonitrile (cas: 1620-76-4) 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.Formula: C7H6N2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Synthesis of 4-methoxy and 5-methoxy substituted 7-aza-isoindolin-1-ones was written by Zhou, Heng;Sun, Guanglong;Liu, Zenglu;Zhan, Xiaoping;Mao, Zhenmin. And the article was included in Heterocycles in 2013.Application of 59718-84-2 This article mentions the following:

A simple and convenient route for the synthesis of a series of 4-methoxy or 5-methoxy substituted 7-aza-isoindolin-1-ones is described. Methoxyl substituted pyridine derivatives were cyclized with different amines under alk. condition to give the desired products. In the experiment, the researchers used many compounds, for example, Methyl 3-methylpicolinate (cas: 59718-84-2Application of 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. Reduced pyridines, namely tetrahydropyridines, dihydropyridines and piperidines, are found in numerous natural and synthetic compounds. The synthesis and reactivity of these compounds have often been driven by the fact many of these compounds have interesting and unique pharmacological properties. Application of 59718-84-2

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Thermodynamic and infrared studies of tertiary amine oxide with bis(2,4-pentanedionato)oxovanadium(IV) was written by Popp, Carl J.;Nelson, John H.;Ragsdale, Ronald O.. And the article was included in Journal of the American Chemical Society in 1969.Synthetic Route of C7H9NO This article mentions the following:

The donor properties of a series of substituted pyridine N-oxide bases toward the reference acid bis(2,4-pentanedionato)oxovanadium(IV) [VO(acac)2] have been studied. Heats of reaction have been determined calorimetrically and, in the case of the 4-substituted pyridine N-oxide, correlate well with σPyNO. The change of the vanadium-vanadyl O stretching frequency (Δ v=o) and the vanadium-2,4-pentanedionate stretching frequency (Δ v-o) upon coordination were studied and were also found to correlate well with enthalpies of reaction. Substitution of alkyl groups in other than the 4 position of the pyridine N-oxide ring causes a decrease in the effective basicity toward the reference acid, VO(acac)2. The usefulness of VO-(acac)2 as a reference acid is discussed. The system is extended to the tertiary amine oxide p-bromo-N,N-dimethylaniline N-oxide and Me3NO. In the experiment, the researchers used many compounds, for example, 3,5-Dimethylpyridine 1-oxide (cas: 3718-65-8Synthetic Route of C7H9NO).

3,5-Dimethylpyridine 1-oxide (cas: 3718-65-8) 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. Pyridine groups exist in countless molecules, and their applications include catalysis, drug design, molecular recognition, and natural product synthesis.Synthetic Route of C7H9NO

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem