Author: Jessica.F

Electric Literature of C4H9NO2In 2020 ,《Preclinical optimization of gp120 entry-antagonists as anti-HIV-1 agents with improved cytotoxicity and ADME properties through rational design, synthesis, and antiviral evaluation》 appeared in Journal of Medicinal Chemistry. The author of the article were Curreli, Francesca; Ahmed, Shahad; Benedict Victor, Sofia M.; Iusupov, Ildar R.; Belov, Dmitry S.; Markov, Pavel O.; Kurkin, Alexander V.; Altieri, Andrea; Debnath, Asim K.. The article conveys some information:

To optimize the structure of previously reported HIV-1 gp120 antagonist NBD-14189 which showed antiviral activity against HIV-1HXB2 (IC50 = 89 nM) but had high cytotoxicity and poor aqueous solubility, a series of novel azaarenyl analogs I [R1 = H, HOCH2, HOCH2CHOH, etc.; R2 = H, HOCH2, HOCH2CHOH; R3, R4, R5 = R6 = H, Me; R7 = 5-chloro-2-pyridinyl, 6-trifluoromethyl-3-pyridazinyl, 5-chloro-2-pyrimidinyl, etc.] have been synthesized and evaluated. One of the new analogs, the compound (S)-I [R1 = H; R2 = HOCH2; R3 = R4 = R5 = H; R6 = Me; R7 = 5-trifluoromethyl-2-pyridinyl; NBD-14270] showed a marked improvement in cytotoxicity, with a 3-fold and 58-fold improvements in SI values compared with that of NBD-14189 and NBD-11021, resp. Furthermore, the in-vitro ADME data clearly showed improvements in aqueous solubility and other properties compared with those for NBD-14189. After reading the article, we found that the author used N-Methoxy-N-methylacetamide(cas: 78191-00-1Electric Literature of C4H9NO2)

N-Methoxy-N-methylacetamide(cas: 78191-00-1) belongs to anime. Hydrogen peroxide (H2O2) and peroxy acids generally add an oxygen atom to the nitrogen of amines. With primary amines, this step is normally followed by further oxidation, leading to nitroso compounds, RNO, or nitro compounds, RNO2. Secondary amines are converted to hydroxylamines, R2NOH, and tertiary amines to amine oxides, R3NO.Electric Literature of C4H9NO2

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

Synthetic Route of C11H9N3OOn June 3, 2020, Riascos-Rodriguez, Karina; Marks, Samuel; Evans, Paul G.; Hernandez-Rivera, Samuel P.; Ruiz-Caballero, Jose L.; Pinero, Dalice; Hernandez-Maldonado, Arturo J. published an article in Crystal Growth & Design. The article was 《Lithium Functionalization Promoted by Amide-Containing Ligands of a Cu(pzdc)(pia) Porous Coordination Polymer for CO2 Adsorption Enhancement》. The article mentions the following:

A pillared layer network containing amide functional groups (Cu(pzdc)(pia); pzdc = pyrazine-2,3-dicarboxylate; pia = N-(4-pyridyl)isonicotinamide) was used to test a postsynthesis metalation rationale to insert lithium and create a porous surface with enhanced CO2 adsorption capacity. Synchrotron powder X-ray diffraction (XRD) was used to determine variations after lithiation in long-range and textural properties. CO2 adsorption measurements at room temperature showed a concave up isotherm shape with an increasing adsorption at high pressures, surpassing by 1 order of magnitude the values previously reported for the unmodified material. There was significant hysteresis upon desorption, which suggests structural variations consequent to different or stronger adsorption sites. Results from elemental, thermal gravimetric, and crystal refinement analyses indicate that the lithium content is ca. 3 Li atoms per asym. unit. Raman scattering showed N-Li and Li-O stretching bands, a shift of pia amide- and pyridyl-related bands, and other significant skeletal vibrations associated with nitrogen and oxygen lone pair variations. In situ XRD and CO2 adsorption observations at up to 50 bar at ambient temperature were consistent with the anticipated structural dynamic variation. The lattice changes observed at pressures below 10 bar following lithiation may be directly related to an enhancement in the CO2 adsorption amount The experimental part of the paper was very detailed, including the reaction process of N-(Pyridin-4-yl)isonicotinamide(cas: 64479-78-3Synthetic Route of C11H9N3O)

N-(Pyridin-4-yl)isonicotinamide(cas: 64479-78-3) belongs to amides.Synthetic Route of C11H9N3O Amides include many other important biological compounds, as well as many drugs like paracetamol, penicillin and LSD. Low-molecular-weight amides, such as dimethylformamide, are common solvents.

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

SDS of cas: 70298-88-3On September 10, 2009 ,《Design, Synthesis, and Structure-Activity Relationships of Aminopyridine N-Oxides, a Novel Scaffold for the Potent and Selective Inhibition of p38 Mitogen Activated Protein Kinase》 was published in Journal of Medicinal Chemistry. The article was written by Lumeras, Wenceslao; Caturla, Francisco; Vidal, Laura; Esteve, Cristina; Balague, Cristina; Orellana, Adelina; Dominguez, Maria; Roca, Ramon; Huerta, Josep M.; Godessart, Nuria; Vidal, Bernat. The article contains the following contents:

A novel series of aminopyridine N-oxides, e.g. I, were designed, synthesized, and tested for their ability to inhibit p38α MAP kinase. Some of these compounds showed a significant reduction in the LPS-induced TNFα production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for a marked selectivity against other related kinases. Compound I was identified as a potent and selective p38α inhibitor with an appropriate balance between potency and pharmacokinetics. In vivo efficacy of I was demonstrated in reducing TNFα levels in an acute murine model of inflammation (ED50 = 1 mg/kg in LPS-induced TNFα production when dosed orally 1.5 h prior to LPS administration). The oral efficacy of I was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally (ED50 = 4.5 mg/kg). The experimental process involved the reaction of 2,2-Dimehtyl-N-pyridin-3-yl-propionamide(cas: 70298-88-3SDS of cas: 70298-88-3)

2,2-Dimehtyl-N-pyridin-3-yl-propionamide(cas: 70298-88-3) 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).SDS of cas: 70298-88-3

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

Related Products of 87694-50-6On March 4, 2020, Schwartz, Brett D.; Zhang, Meng Yao; Attard, Riley H.; Gardiner, Michael G.; Malins, Lara R. published an article in Chemistry – A European Journal. The article was 《Structurally Diverse Acyl Bicyclobutanes: Valuable Strained Electrophiles》. The article mentions the following:

This work reported two efficient pathways for the rapid preparation of over 20 structurally diverse bicyclo[1.1.0]butane (BCB) ketones, such as I [R = cuban-1-yl, BOCHNCH2, 4-MeOC6H4, etc.] encompassing simple alkyl and aryl derivatives, as well as unprecedented amino acid, dipeptide, bioisostere, and bifunctional linchpin reagents currently inaccessible using literature methods. Analogs were readily forged in two steps and in high yields from simple carboxylic acids or through unsym. ketone synthesis beginning with a convenient carbonyl dication equivalent The utility of this novel toolbox of strained electrophiles for selective modification of proteinogenic nucleophiles was highlighted. The results came from multiple reactions, including the reaction of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Related Products of 87694-50-6)

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides. Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N–C dipole.Related Products of 87694-50-6 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 primary and secondary amides, the presence of N–H dipoles allows amides to function as H-bond donors as well.

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

Fiakpui, Charles Y.; Knaus, Edward E. published an article in Canadian Journal of Chemistry. The title of the article was 《An improved synthesis of 1,3-dihydro-1-methyl-5-phenyl-2H-pyrido[3,4-e]-1,4-diazepin-2-one via ortho-directed lithiation of 3-[(tert-butylcarbonyl)- and 3-[(tert-butoxycarbonyl)amino)pyridine]》.Formula: C10H14N2O The author mentioned the following in the article:

The ortho-directed lithiation of the title compounds I (R = CMe3, OCMe3) with alkyllithiums and benzoylation with PhCONEt2 followed by acid hydrolysis gave 63-66% 3-amino-4-benzoylpyridine (II). Amidation of R1NHCH2CO2H (R1 = PhCH2O2C, Me3CO2C) with II afforded[[(aminomethyl)carbonyl]amino]benzoylpyridines III (same R1). Acid-catalyzed hydrolysis and cyclocondensation of III, followed by methylation gave pyridodiazepinone IV in 36% overall yield from I.2,2-Dimehtyl-N-pyridin-3-yl-propionamide(cas: 70298-88-3Formula: C10H14N2O) was used in this study.

2,2-Dimehtyl-N-pyridin-3-yl-propionamide(cas: 70298-88-3) 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.Formula: C10H14N2O

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

Pehere, Ashok D.; Nguyen, Steven; Garlick, Sarah K.; Wilson, Danny W.; Hudson, Irene; Sykes, Matthew J.; Morton, James D.; Abell, Andrew D. published an article on January 15 ,2019. The article was titled 《Tripeptide analogues of MG132 as protease inhibitors》, and you may find the article in Bioorganic & Medicinal Chemistry.Synthetic Route of C13H26N2O4 The information in the text is summarized as follows:

The 26S proteasome and calpain are linked to a number of important human diseases. Here, we report a series of analogs of the prototypical tripeptide aldehyde inhibitor MG132 that show a unique combination of high activity and selectivity for calpains over proteasome. Tripeptide aldehydes (1-3) with an aromatic P3 substituent show enhanced activity and selectivity against ovine calpain 2 relative to chymotrypsin-like activity of proteasome. Docking studies reveal the key contacts between inhibitors and calpain to confirm the importance of the S3 pocket with respect to selectivity between calpains 1 and 2 and the proteasome.(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Synthetic Route of C13H26N2O4) was used in this study.

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides. Amides include many other important biological compounds, as well as many drugs like paracetamol, penicillin and LSD. Low-molecular-weight amides, such as dimethylformamide, are common solvents.Synthetic Route of C13H26N2O4

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

The author of 《Mild Access to N-Formylation of Primary Amines using Ethers as C1 Synthons under Metal-Free Conditions》 were Mutra, Mohana Reddy; Dhandabani, Ganesh Kumar; Wang, Jeh-Jeng. And the article was published in Advanced Synthesis & Catalysis in 2018. Application of 4746-61-6 The author mentioned the following in the article:

A new synthetic protocol for the synthesis of N-formamide derivatives HC(O)NHR1 [R1 = C6H5, 3-ClC6H4, 3-NO2C6H4, etc.] was developed via N-formylation of primary amines using ethers as a C1 synthon under metal-free reaction conditions. The reaction was proceeded through C-H functionalization, C-O cleavage and C-N bond formation. Mechanistic studies disclosed that the reaction proceeds through a radical pathway. Synthesis of amino ethanones PhNHCH(R4)C(O)R2 [R2 = C6H5, 3-MeC6H4, 4-BrC6H4; R3 = tetrahydrofuran-2-yl, 1,4-dioxan-2-yl] were developed via α-alkylation of α-amino ketones with ethers. By replacing dioxane with Tetramethylethylenediamine (TMEDA) under standard conditions also gave the N-formamide derivatives HC(O)NHR1 in moderate yields. After reading the article, we found that the author used 2-Hydroxy-N-phenylacetamide(cas: 4746-61-6Application of 4746-61-6)

2-Hydroxy-N-phenylacetamide(cas: 4746-61-6) belongs to amides.Application of 4746-61-6 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.

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

Zaiter, Samantha S.; Huo, Yuantao; Tiew, Fong Y.; Gestwicki, Jason E.; McAlpine, Shelli R. published an article on January 24 ,2019. The article was titled 《Designing de Novo Small Molecules That Control Heat Shock Protein 70 (Hsp70) and Heat Shock Organizing Protein (HOP) within the Chaperone Protein-Folding Machinery》, and you may find the article in Journal of Medicinal Chemistry.COA of Formula: C11H22N2O4 The information in the text is summarized as follows:

Protein-protein interactions (PPIs) regulate all signaling pathways for cellular function. Developing mols. that modulate PPIs through the interface of their protein surfaces has been a significant challenge and there has been little success controlling PPIs through standard mol. library screening approaches. PPIs control the cell’s protein-folding machinery, and this machinery relies on a multi-protein complex formed with heat shock protein 70 (Hsp70). Described is the design, synthesis, and biol. evaluation of mols. aimed to regulate the interaction between two proteins that are critical to the protein-folding machinery: heat shock protein 70 (Hsp70) and cochaperone heat shock organizing protein (HOP). We report the first class of compounds that directly regulate these two protein-protein interactions and inhibit protein folding events. In the experiment, the researchers used many compounds, for example, H-Lys(Boc)-OH(cas: 2418-95-3COA of Formula: C11H22N2O4)

H-Lys(Boc)-OH(cas: 2418-95-3) belongs to amino acids. In addition to subunits of proteins, amino acids have many other functions as well, including osmoregulation (proline), neurotransmitters (gamma-aminobutyric acid), metabolic intermediates (ornithine and citrulline), and inhibitors (dehydroproline).COA of Formula: C11H22N2O4

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

In 2010,Koivisto, Jari J.; Kumpulainen, Esa T. T.; Koskinen, Ari M. P. published 《Conformational ensembles of flexible β-turn mimetics in DMSO-d6》.Organic & Biomolecular Chemistry published the findings.Synthetic Route of C11H24N2O The information in the text is summarized as follows:

β-Turns play an important role in peptide and protein chem., biophysics, and bioinformatics. The aim of this research was to study short linear peptides that have a high propensity to form β-turn structures in solution In particular, we examined conformational ensembles of β-turn forming peptides with a general sequence CBz-L-Ala-L-Xaa-Gly-L-Ala-OtBu. These tetrapeptides, APGA, A(4R)MePGA, and A(4S)MePGA, incorporate proline, (4R)-methylproline, and (4S)-methylproline, resp., at the Xaa position. To determine the influence of the 4-Me substituted prolines on the β-turn populations, the NAMFIS (NMR anal. of mol. flexibility in solution) deconvolution anal. for these three peptides were performed in DMSO-d6 solution The NBO (natural bond orbital) method was employed to gain further insight into the results obtained from the NAMFIS anal. The emphasis in the NBO anal. was to characterize remote intramol. interactions that could influence the backbone-backbone interactions contributing to β-turn stability. NAMFIS results indicate that the enantiospecific incorporation of the Me substituent at the Cγ (C4) position of the proline residue can be used to selectively control the pyrrolidine ring puckering propensities and, consequently, the preferred ϕ,ψ angles associated with the proline residue in β-turn forming peptides. The NAMFIS analyses show that the presence of (4S)-methylproline in A(4S)MePGA considerably increased the type II β-turn population with respect to APGA and A(4R)MePGA. The NBO calculations suggest that this observation can be rationalized based on an n → π* interaction between the N-terminus alanine carbonyl oxygen and the proline carbonyl group. Several other interactions between remote orbitals in these peptides provide a more detailed explanation for the observed population distributions. In addition to this study using tert-Butyl N,N’-diisopropylcarbamimidate, there are many other studies that have used tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Synthetic Route of C11H24N2O) was used in this study.

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) belongs to anime. Amines characteristically form salts with acids; a hydrogen ion, H+, adds to the nitrogen. With the strong mineral acids (e.g., H2SO4, HNO3, and HCl), the reaction is vigorous. Salt formation is instantly reversed by strong bases such as NaOH. Neutral electrophiles (compounds attracted to regions of negative charge) also react with amines; alkyl halides (R′X) and analogous alkylating agents are important examples of electrophilic reagents.Synthetic Route of C11H24N2O

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

In 2018,Mackman, Richard L.; Steadman, Victoria A.; Dean, David K.; Jansa, Petr; Poullennec, Karine G.; Appleby, Todd; Austin, Carol; Blakemore, Caroline A.; Cai, Ruby; Cannizzaro, Carina; Chin, Gregory; Chiva, Jean-Yves C.; Dunbar, Neil A.; Fliri, Hans; Highton, Adrian J.; Hui, Hon; Ji, Mingzhe; Jin, Haolun; Karki, Kapil; Keats, Andrew J.; Lazarides, Linos; Lee, Yu-Jen; Liclican, Albert; Mish, Michael; Murray, Bernard; Pettit, Simon B.; Pyun, Peter; Sangi, Michael; Santos, Rex; Sanvoisin, Jonathan; Schmitz, Uli; Schrier, Adam; Siegel, Dustin; Sperandio, David; Stepan, George; Tian, Yang; Watt, Gregory M.; Yang, Hai; Schultz, Brian E. published 《Discovery of a potent and orally bioavailable cyclophilin inhibitor derived from the sanglifehrin macrocycle》.Journal of Medicinal Chemistry published the findings.Name: N-Methoxy-N-methylacetamide The information in the text is summarized as follows:

Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead (I) derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor (II). The macrocycle ring size was reduced by one atom, and an internal hydrogen bond drove improved permeability and drug-like properties. II demonstrates potent Cyp inhibition (Kd = 5 nM), potent anti-HCV 2a activity (EC50 = 98 nM), and high oral bioavailability in rat (100%) and dog (55%). The synthetic accessibility and properties of II support its potential as an anti-HCV agent and for interrogating the role of Cyp inhibition in a variety of diseases. In the experimental materials used by the author, we found N-Methoxy-N-methylacetamide(cas: 78191-00-1Name: N-Methoxy-N-methylacetamide)

N-Methoxy-N-methylacetamide(cas: 78191-00-1) 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).Name: N-Methoxy-N-methylacetamide

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