Month: December 2022

Evaluation of pH change effects on the HSA folding and its drug binding characteristics, a computational biology investigation was written by Gomari, Mohammad Mahmoudi;Rostami, Neda;Faradonbeh, Davood Rabiei;Asemaneh, Hamid Reza;Esmailnia, Giti;Arab, Shahriar;Farsimadan, Marziye;Hosseini, Arshad;Dokholyan, Nikolay V.. And the article was included in Proteins: Structure, Function, and Bioinformatics in 2022.Computed Properties of C23H28ClN3O5S This article mentions the following:

The binding of therapeutics to human serum albumin (HSA), which is an abundant protein in plasma poses a major challenge in drug discovery. Although HSA has several binding pockets, the binding site I on D2 and binding site II on D3 are the main binding pockets of HSA. To date, a few experiments were conducted to examine the effects of the potential of hydrogen (pH) changes on HSA attributes. The effect of acidic (pH 7.1) and basic states (pH 7.7) on HSA structure and its drug binding potency were examined in comparison with the physiol. state (pH 7.4). For this purpose, mol. dynamics (MD), free energy landscape (FEL), principal component anal. (PCA), probability distribution function (PDF), tunnel-cavity study, secondary structure anal., docking study, and free energy study were employed to study the effect of pH changes on the structural characteristics of HSA at the at. level. The results obtained from this study revealed the significant effect of pH alterations on the secondary and tertiary structure of HSA. In addition, HSA stability and its drug binding ability can be severely affected following pH changes. Given that pH change frequently occurs in various diseases such as cancer, diabetes, and kidney failure, therefore, pharmaceutical companies should allocate specific consideration to this subject throughout their drug design experiments In the experiment, the researchers used many compounds, for example, 5-Chloro-N-(4-(N-(cyclohexylcarbamoyl)sulfamoyl)phenethyl)-2-methoxybenzamide (cas: 10238-21-8Computed Properties of C23H28ClN3O5S).

5-Chloro-N-(4-(N-(cyclohexylcarbamoyl)sulfamoyl)phenethyl)-2-methoxybenzamide (cas: 10238-21-8) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors. The presence of the amide group –C(=O)N– is generally easily established, at least in small molecules. It can be distinguished from nitro and cyano groups in IR spectra. Amides exhibit a moderately intense νCO band near 1650 cm−1. By 1H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography, the C(=O)N center together with the three immediately adjacent atoms characteristically define a plane.Computed Properties of C23H28ClN3O5S

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

A CO₂-Catalyzed Transamidation Reaction was written by Yang, Yang;Liu, Jian;Kamounah, Fadhil S.;Ciancaleoni, Gianluca;Lee, Ji-Woong. And the article was included in Journal of Organic Chemistry in 2021.Safety of 4-Bromo-N-methoxy-N-methylbenzamide This article mentions the following:

Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Herein, a report on the use of CO₂ as a traceless catalyst: in the presence of catalytic amounts of CO₂, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular, N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO₂-catalyzed transamidation vs. a N₂ atmosphere. Comparative Hammett studies and kinetic anal. were conducted to elucidate the catalytic activation mechanism of mol. CO₂, which was supported by DFT calculations The pos. effect of CO₂ in the transamidation reaction was attributed to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO₂. In the experiment, the researchers used many compounds, for example, 4-Bromo-N-methoxy-N-methylbenzamide (cas: 192436-83-2Safety of 4-Bromo-N-methoxy-N-methylbenzamide).

4-Bromo-N-methoxy-N-methylbenzamide (cas: 192436-83-2) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors. In simple aromatic amides, fragmentation occurs on both sides of the carbonyl group. If a hydrogen is available in N-substituted aromatic amides, it tends to migrate and form an aromatic amine and the loss of a ketene.Safety of 4-Bromo-N-methoxy-N-methylbenzamide

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

A Mild Heteroatom (O-, N-, and S-) Methylation Protocol Using Trimethyl Phosphate (TMP)-Ca(OH)₂ Combination was written by Tang, Yu;Yu, Biao. And the article was included in Synthesis in 2022.Application In Synthesis of N-(4-Hydroxyphenyl)-4-methylbenzenesulfonamide This article mentions the following:

A mild heteroatom methylation protocol using tri-Me phosphate (TMP)-Ca(OH)₂ combination was developed, which proceeded in DMF, or water, or under neat conditions, at 80°C or at room temperature A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, were suitable substrates for this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmentally friendly nature of this protocol made it an attractive alternative to the conventional base-promoted heteroatom methylation procedures. In the experiment, the researchers used many compounds, for example, N-(4-Hydroxyphenyl)-4-methylbenzenesulfonamide (cas: 1146-43-6Application In Synthesis of N-(4-Hydroxyphenyl)-4-methylbenzenesulfonamide).

N-(4-Hydroxyphenyl)-4-methylbenzenesulfonamide (cas: 1146-43-6) belongs to amides. Amides can be viewed as a derivative of a carboxylic acid RC(=O)OH with the hydroxyl group –OH replaced by an amine group −NR′R″; or, equivalently, an acyl (alkanoyl) group RC(=O)− joined to an amine group. Ionic, or saltlike, amides are strongly alkaline compounds ordinarily made by treating ammonia, an amine, or a covalent amide with a reactive metal such as sodium.Application In Synthesis of N-(4-Hydroxyphenyl)-4-methylbenzenesulfonamide

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Salol reaction was written by Van Allan, James A.. And the article was included in Journal of the American Chemical Society in 1947.Formula: C11H15NO2 This article mentions the following:

The salol procedure is very convenient for the preparation of amides of o-HOC₆H₄CO₂H, particularly from the H₂NC₆H₄OH. o-H₂NC₆H₄OH or o-diamines give a cyclic compound The following were prepared from o-HOC₆H₄CO₂Ph (name of amine used, formula of resulting derivative of o-HOC₆H₄CO₂H, m.p. (or b.p.), and yield are given): piperidine, C₁₂H₁₅O₂N, m. 142-3°, 69%; cyclohexylamine, C₁₃H₁₇O₂N, m. 85-6°, 79%; PhCH₂NH₂, C₁₄H₁₃O₂N, m. 135-6°, 77%; dodecylamine, C₁₉H₃₁O₂N, m. 71-2°, 75%; Et₂NH, C₁₁H₁₅O₂N, b₄ 146-8°, 68%; (CH₂NH₂)₂, C₁₆H₁₆O₄N₂, m. 183-4°, 69%; ClC₆H₄NH₂ (isomer not given), C₁₃H₁₁ONCl, m. 155°, 83%; H₂NC₆H₄Ph (isomer not given), C₁₉H₁₅O₂N, m. 110°, 85%; o-H₂NC₆H₄OH, C₁₃H₉O₂N, m. 125°, 22.4%; m-isomer, C₁₃H₁₁O₂N, m. 184° 58%; 5-aminoindazole, C₁₄H₁₁O₂N₃, m. 230°, 37%; 6-isomer, m. 234-5°, 31%; 5-aminobenzotriazole, C₁₃H₁₀O₃N₄, m. 245°, 42%; 1,2,3,4-tetrahydroquinoline, C₁₆H₁₅O₂N, m. 138-9°, 34%. Compounds from 1,2-HOC₁₀H₆CO₂Ph:Et₂NH, C₁₅H₁₇O₂N, b₁ 130-3°, 63%; o-C₆H₄(NH₂)₂, C₁₇H₁₂ON₂, m. above 265°, 78%; o-H₂NC₆H₄OH, C₁₇H₁₁O₂N, m. 188°, 89%. In the experiment, the researchers used many compounds, for example, N,N-Diethylsalicylamide (cas: 19311-91-2Formula: C11H15NO2).

N,N-Diethylsalicylamide (cas: 19311-91-2) belongs to amides. Compared to amines, amides are very weak bases and do not have clearly defined acid–base properties in water. On the other hand, amides are much stronger bases than esters, aldehydes, and ketones. The presence of the amide group –C(=O)N– is generally easily established, at least in small molecules. It can be distinguished from nitro and cyano groups in IR spectra. Amides exhibit a moderately intense νCO band near 1650 cm−1. By 1H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography, the C(=O)N center together with the three immediately adjacent atoms characteristically define a plane.Formula: C11H15NO2

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Formamides as Isocyanate Surrogates: A Mechanistically Driven Approach to the Development of Atom-Efficient, Selective Catalytic Syntheses of Ureas, Carbamates, and Heterocycles was written by Bruffaerts, Jeffrey;von Wolff, Niklas;Diskin-Posner, Yael;Ben-David, Yehoshoa;Milstein, David. And the article was included in Journal of the American Chemical Society in 2019.Reference of 2387-23-7 This article mentions the following:

Despite the hazardous nature of isocyanates, they remain key building blocks in bulk and fine chem. synthesis. By surrogating them with less potent and readily available formamide precursors, we herein demonstrate an alternative, mechanistic approach to selectively access a broad range of ureas, carbamates, and heterocycles via ruthenium-based pincer complex catalyzed acceptorless dehydrogenative coupling reactions. The design of these highly atom-efficient procedures was driven by the identification and characterization of the relevant organometallic complexes, uniquely exhibiting the trapping of an isocyanate intermediate. D. functional theory (DFT) calculations further contributed to shed light on the remarkably orchestrated chain of catalytic events, involving metal-ligand cooperation. In the experiment, the researchers used many compounds, for example, 1,3-Dicyclohexylurea (cas: 2387-23-7Reference of 2387-23-7).

1,3-Dicyclohexylurea (cas: 2387-23-7) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors. The presence of the amide group –C(=O)N– is generally easily established, at least in small molecules. It can be distinguished from nitro and cyano groups in IR spectra. Amides exhibit a moderately intense νCO band near 1650 cm−1. By 1H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography, the C(=O)N center together with the three immediately adjacent atoms characteristically define a plane.Reference of 2387-23-7

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Asymmetric synthesis of isobenzofuranone derivatives and their unique character as protein kinase Cα (PKCα) activators was written by Hirai, Go;Ogoshi, Yosuke;Ohkubo, Megumi;Tamura, Yuki;Watanabe, Toru;Shimizu, Tadashi;Sodeoka, Mikiko. And the article was included in Tetrahedron Letters in 2009.Application In Synthesis of N,N-Diethylsalicylamide This article mentions the following:

An efficient enantioselective synthesis of conformationally constrained diacylglycerol analogs, 7-substituted isobenzofuranones, originally developed by the authors as PKCα ligands, was achieved by asym. dihydroxylation and γ-lactone formation via ortho-lithiation and carboxylation. A series of derivatives having straight and/or branched side-chains were synthesized and evaluated, and low-nanomolar-concentration affinity ligands and highly potent PKCα activators were found among them. These potent ligands induced phenotypic change of K562 cells, which is characteristic of PKC activators. In the experiment, the researchers used many compounds, for example, N,N-Diethylsalicylamide (cas: 19311-91-2Application In Synthesis of N,N-Diethylsalicylamide).

N,N-Diethylsalicylamide (cas: 19311-91-2) belongs to amides. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. The presence of the amide group –C(=O)N– is generally easily established, at least in small molecules. It can be distinguished from nitro and cyano groups in IR spectra. Amides exhibit a moderately intense νCO band near 1650 cm−1. By 1H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography, the C(=O)N center together with the three immediately adjacent atoms characteristically define a plane.Application In Synthesis of N,N-Diethylsalicylamide

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

BeCl₂ as a new highly selective reagent for dealkylation of aryl-methyl ethers was written by Sharghi, Hashem;Tamaddon, Fatemeh. And the article was included in Tetrahedron in 1996.Name: N,N-Diethylsalicylamide This article mentions the following:

An efficient and simple method is introduced for the selective removal of a Me group from poly aryl-Me ethers with BeCl₂ in some important derivatives of benzophenones, xanthones, anthraquinones, aryl esters, benzamides, and nitroanisoles. In the experiment, the researchers used many compounds, for example, N,N-Diethylsalicylamide (cas: 19311-91-2Name: N,N-Diethylsalicylamide).

N,N-Diethylsalicylamide (cas: 19311-91-2) belongs to amides. Compared to amines, amides are very weak bases and do not have clearly defined acid–base properties in water. On the other hand, amides are much stronger bases than esters, aldehydes, and ketones. Amides can be recrystallised from large quantities of water, ethanol, ethanol/ether, aqueous ethanol, chloroform/toluene, chloroform or acetic acid. The likely impurities are the parent acids or the alkyl esters from which they have been made. The former can be removed by thorough washing with aqueous ammonia followed by recrystallisation, whereas elimination of the latter is by trituration or recrystallisation from an organic solvent.Name: N,N-Diethylsalicylamide

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Prolonged distribution of tranilast in the eyes after topical application onto eyelid skin was written by See, Gerard Lee;Arce, Florencio Jr.;Itakura, Shoko;Todo, Hiroaki;Sugibayashi, Kenji. And the article was included in Chemical & Pharmaceutical Bulletin in 2020.COA of Formula: C18H17NO5 This article mentions the following:

Tranilast, a lipophilic drug with various ophthalmic applications, was used as a model drug to establish the possibility of delivering lipophilic drugs through the eyelid skin. Pharmacokinetics and tissue distribution studies were conducted employing three application methods (topical application onto eyelid skin, eye drops, and i.v. injection in rats) to broaden the significance of delivering drugs through the eyelids. A two-compartment open model anal. was used for i.v. route while a non-compartmental evaluation was used for topical applications to estimate the pharmacokinetic parameters. Eyelid skin application, eye drops, and i.v. administration had mean residence times (MRTs) of 8.07, 1.79, and 3.25 h in the eyeball and 10.8, 1.29, and 2.97 h in the conjunctiva, correspondingly. In the eyeball, topical application of tranilast onto the eyelids corresponded to a 4.5- and 2.5-fold higher MRT compared with eye drops and i.v. administration, resp. An 8.4- or 3.6-fold higher MRT was observed in the conjunctiva after topical application compared with eye drops or i.v. administration, resp. This indicated a gradual penetration of tranilast into the eyeball and conjunctiva, subsequently a slow elimination from these target tissues. In the experiment, the researchers used many compounds, for example, 2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8COA of Formula: C18H17NO5).

2-(3-(3,4-Dimethoxyphenyl)acrylamido)benzoic acid (cas: 53902-12-8) belongs to amides. The solubilities of amides and esters are roughly comparable. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide, exhibit low solubility in water. In simple aromatic amides, fragmentation occurs on both sides of the carbonyl group. If a hydrogen is available in N-substituted aromatic amides, it tends to migrate and form an aromatic amine and the loss of a ketene.COA of Formula: C18H17NO5

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Deacylation-aided C-H alkylative annulation through C-C cleavage of unstrained ketones was written by Zhou, Xukai;Xu, Yan;Dong, Guangbin. And the article was included in Nature Catalysis in 2021.Synthetic Route of C9H10BrNO2 This article mentions the following:

Arene- and heteroarene-fused rings are pervasive in biol. active mols. Direct annulation between a C-H bond on the aromatic core and a tethered alkyl moiety provides a straightforward approach to access these scaffolds; however, such a strategy is often hampered by the need of special reactive groups and/or less compatible cyclization conditions. It would be synthetically appealing if a common native functional group can be used as a handle to enable a general C-H annulation with diverse aromatic rings. A deacylative annulation strategy for preparing a large variety of aromatic-fused rings from linear simple ketone precursors was demonstrated. The reaction starts with homolytic cleavage of the ketone α C-C bond via a pre-aromatic intermediate, followed by a radical-mediated dehydrogenative cyclization. Using widely available ketones as the robust radical precursors, this deconstructive approach allows streamlined assembly of complex polycyclic structures with broad functional group tolerance. In the experiment, the researchers used many compounds, for example, 4-Bromo-N-methoxy-N-methylbenzamide (cas: 192436-83-2Synthetic Route of C9H10BrNO2).

4-Bromo-N-methoxy-N-methylbenzamide (cas: 192436-83-2) belongs to amides. Amides can be viewed as a derivative of a carboxylic acid RC(=O)OH with the hydroxyl group –OH replaced by an amine group −NR′R″; or, equivalently, an acyl (alkanoyl) group RC(=O)− joined to an amine group. Amides can be freed from solvent or water by drying below their melting points. These purifications can also be used for sulfonamides and acid hydrazides.Synthetic Route of C9H10BrNO2

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Glibenclamide-malonic acid cocrystal with an enhanced solubility and bioavailability was written by Srivastava, Dipti;Fatima, Zeeshan;Kaur, Chanchal Deep;Mishra, Anjali;Nashik, Sanap Sachin;Rizvi, Dilshad A.;Prasad, Rammani. And the article was included in Drug Development and Industrial Pharmacy.COA of Formula: C23H28ClN3O5S This article mentions the following:

The objective of the work is to enhance the solubility, dissolution, and pharmacokinetic properties of glibenclamide (GLB) via cocrystn. technique. Glibenclamide is an oral hypoglycemic agent used for treating non-insulin-dependent (type II) diabetes mellitus. It exhibits poor aqueous solubility and oral bioavailability, thereby compromising its therapeutic effect. Therefore, utilizing cocrystal approach for enhancing the solubility will modulate the physicochem. properties of GLB without altering its mol. structure. Cocrystal was prepared by solution crystallization method using coformer malonic acid. The cocrystal was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform IR (FT-IR) studies. The prepared cocrystal was subjected to solubility, in vitro dissolution, and pharmacokinetic studies. The DSC endotherms, PXRD patterns, and the FT-IR spectra of the cocrystal established the formation of a cocrystal. The formation of eutectic mixture was refuted upon comparing the DSC endotherm and PXRD pattern of the cocrystal with that of the phys. mixture GLB showed a twofold enhancement in solubility and a significant improvement in the rate of dissolution (p < 0.05, independent t-test) after cocrystn. The pharmacokinetic parameters on male Sprague Drawly rats showed 1.45 enhancement in AUC_0-24 and 1.36-fold enhancement in the C_max of GLB as compared to the pure drug. These findings demonstrate that cocrystn. technique was able to tailor the solubility and dissolution profile of GLB leading to an enhanced pharmacokinetic property. In the experiment, the researchers used many compounds, for example, 5-Chloro-N-(4-(N-(cyclohexylcarbamoyl)sulfamoyl)phenethyl)-2-methoxybenzamide (cas: 10238-21-8COA of Formula: C23H28ClN3O5S).

5-Chloro-N-(4-(N-(cyclohexylcarbamoyl)sulfamoyl)phenethyl)-2-methoxybenzamide (cas: 10238-21-8) belongs to amides. In primary and secondary amides, the presence of N–H dipoles allows amides to function as H-bond donors as well. Thus amides can participate in hydrogen bonding with water and other protic solvents; the oxygen atom can accept hydrogen bonds from water and the N–H hydrogen atoms can donate H-bonds. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons. These hydrogen bonds are also have an important role in the secondary structure of proteins.COA of Formula: C23H28ClN3O5S

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics