Tag: 200-300

《Synthesis of Nα-protected amino acid/peptide Weinreb amides employing N,N’-carbonyldiimidazole as activating agent; studies on docking and antibacterial activities》 was written by Uma, K.; Lalithamba, H. S.; Raghavendra, M.; Chandramohan, Vivek; Anupama, C.. Application In Synthesis of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide And the article was included in ARKIVOC (Gainesville, FL, United States) in 2016. The article conveys some information:

An efficient method for the synthesis of Nα-protected amino/peptide Weinreb amides (N-methoxy-N-methylamides) employing N,N’-carbonyldiimidazole (CDI) has been achieved. Nα-protected amino/peptide acids were treated with N,N’-carbonyldiimidazole, followed by the addition of N,O-dimethylhydroxylamine hydrochloride salt to yield the desired compounds The synthesized compounds were mainly gums, a few were solids, after the simple workup, and were characterized by IR, 1H NMR, 13C NMR and HRMS. The Weinreb amides were subjected to in silico studies, to predict the preferred orientation and binding affinity between the mols. using scoring functions. The ligand N-Fmoc-L-Phe-N(OCH3)CH3 showed min. binding energy – 29.85 kcal/mol with Escherichia coli and the ligand N-Fmoc-L-Ala-N(OCH3)CH3 showed min. binding energy -24.79 kcal/mol with Pseudomonas aeruginosa, -25.01 kcal/mol with Staphylococcus aureus. Based on the min. binding energies, antibacterial activities have been conducted for a few of the synthesized compounds In the experiment, the researchers used many compounds, for example, (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Application In Synthesis of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide)

(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. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors.Application In Synthesis of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide 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

《LMP2 Inhibitors as a Potential Treatment for Alzheimer’s Disease》 was written by Bhattarai, Deepak; Lee, Min Jae; Baek, Ahruem; Yeo, In Jun; Miller, Zachary; Baek, Yu Mi; Lee, Sukyeong; Kim, Dong-Eun; Hong, Jin Tae; Kim, Kyung Bo. Recommanded Product: 87694-50-6 And the article was included in Journal of Medicinal Chemistry on April 9 ,2020. The article conveys some information:

The immunoproteasome (iP), an inducible proteasome variant harboring three immunosubunits, low mol. mass polypeptide-2 (LMP2), multicatalytic endopeptidase complex subunit-1, and low mol. mass polypeptide-7 (LMP7), is involved in multiple facets of inflammatory responses. We recently reported that YU102, a dual inhibitor of the iP subunit LMP2 and the constitutive proteasome catalytic subunit β1, ameliorates cognitive impairments in mouse models of Alzheimer’s disease (AD) independently of amyloid deposits. To investigate whether inhibition of LMP2 is sufficient to improve the cognitive functions of AD mice, here we prepared 37 YU102 analogs and identified a potent LMP2 inhibitor DB-310 (28) (IC50: 80.6 nM) with improved selectivity and permeability in cells overexpressing ABCB1 transporters. We show that DB-310 induces suppression of IL-1α production in microglia cells and improves cognitive functions in the Tg2576 transgenic mouse model of AD. This study supports that inhibition of LMP2 is a promising therapeutic strategy for treatment of AD. The experimental process involved the reaction of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Recommanded Product: 87694-50-6)

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides.Recommanded Product: 87694-50-6Amides are pervasive in nature and technology. Proteins and important plastics like Nylons, Aramid, Twaron, and Kevlar are polymers whose units are connected by amide groups (polyamides); these linkages are easily formed, confer structural rigidity, and resist hydrolysis.

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

Name: tert-Butyl N,N’-diisopropylcarbamimidateIn 2010 ,《A New Arylsulfate Sulfotransferase Involved in Liponucleoside Antibiotic Biosynthesis in Streptomycetes》 was published in Journal of Biological Chemistry. The article was written by Kaysser, Leonard; Eitel, Kornelia; Tanino, Tetsuya; Siebenberg, Stefanie; Matsuda, Akira; Ichikawa, Satoshi; Gust, Bertolt. The article contains the following contents:

Sulfotransferases are involved in a variety of physiol. processes and typically use 3′-phosphoadenosine 5′-phosphosulfate (PAPS) as the sulfate donor substrate. In contrast, microbial arylsulfate sulfotransferases (ASSTs) are PAPS-independent and utilize arylsulfates as sulfate donors. Yet, their genuine acceptor substrates are unknown. In this study we demonstrate that Cpz4 from Streptomyces sp. MK730-62F2 is an ASST-type sulfotransferase responsible for the formation of sulfated liponucleoside antibiotics. Gene deletion mutants showed that cpz4 is required for the production of sulfated caprazamycin derivatives Cloning, overproduction, and purification of Cpz4 resulted in a 58-kDa soluble protein. The enzyme catalyzed the transfer of a sulfate group from p-nitrophenol sulfate (Km 48.1 μM, kcat 0.14 s-1) and Me umbelliferone sulfate (Km 34.5 μM, kcat 0.15 s-1) onto phenol (Km 25.9 and 29.7 mM, resp.). The Cpz4 reaction proceeds by a ping pong bi-bi mechanism. Several structural analogs of intermediates of the caprazamycin biosynthetic pathway were synthesized and tested as substrates of Cpz4. Des-N-methyl-acyl-caprazol was converted with highest efficiency 100 times faster than phenol. The fatty acyl side chain and the uridyl moiety seem to be important for substrate recognition by Cpz4. Liponucleosides, partially purified from various mutant strains, were readily sulfated by Cpz4 using p-nitrophenol sulfate. No product formation could be observed with PAPS as the donor substrate. Sequence homol. of Cpz4 to the previously examined ASSTs is low. However, numerous orthologs are encoded in microbial genomes and represent interesting subjects for future investigations. In the experiment, the researchers used tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Name: tert-Butyl N,N’-diisopropylcarbamimidate)

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) belongs to anime. To avoid the problem of multiple alkylation, methods have been devised for “blocking” substitution so that only one alkyl group is introduced. The Gabriel synthesis is one such method; it utilizes phthalimide, C6H4(CO)2NH, whose one acidic hydrogen atom has been removed upon the addition of a base such as KOH to form a salt.Name: tert-Butyl N,N’-diisopropylcarbamimidate

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

In 2018,Chien, Huan-Chieh; Colas, Claire; Finke, Karissa; Springer, Seth; Stoner, Laura; Zur, Arik A.; Venteicher, Brooklynn; Campbell, Jerome; Hall, Colton; Flint, Andrew; Augustyn, Evan; Hernandez, Christopher; Heeren, Nathan; Hansen, Logan; Anthony, Abby; Bauer, Justine; Fotiadis, Dimitrios; Schlessinger, Avner; Giacomini, Kathleen M.; Thomas, Allen A. published 《Reevaluating the substrate specificity of the L-type amino acid transporter (LAT1)》.Journal of Medicinal Chemistry published the findings.Electric Literature of C11H24N2O The information in the text is summarized as follows:

The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogs of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogs were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Addnl., the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Electric Literature of C11H24N2O)

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Electric Literature of C11H24N2O

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

In 2015,Tsarkova, Aleksandra S.; Dubinnyi, Maxim A.; Baranov, Mikhail S.; Petushkov, Valentin N.; Rodionova, Natalja S.; Zagudaylova, Marina B.; Yampolsky, Ilia V. published 《Total synthesis of AsLn2 – a luciferin analogue from the Siberian bioluminescent earthworm Fridericia heliota》.Mendeleev Communications published the findings.Recommanded Product: 71432-55-8 The information in the text is summarized as follows:

Total synthesis of AsLn2 (I), a luciferin analog isolated from the Siberian bioluminescent earthworm F. heliota, was performed from (Z)-5-(2,3-dimethoxy-3-oxoprop-1-en-1-yl)-2-hydroxybenzoic acid in six steps. 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: 71432-55-8Recommanded Product: 71432-55-8) was used in this study.

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) 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: 71432-55-8

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

In 2013,Tanaka, Taisaku; Sugawara, Hajime; Maruoka, Hiroshi; Imajo, Seiichi; Muto, Tsuyoshi published 《Discovery of novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as human chymase inhibitors using structure-based drug design》.Bioorganic & Medicinal Chemistry published the findings.Recommanded Product: 71432-55-8 The information in the text is summarized as follows:

A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones were explored as human chymase inhibitors using structure-based drug design according to the x-ray cocrystal structure of chymase and SUN13834. The optimization focused on the prime site led to the attainment of compounds that showed potent inhibitory activity, and among them, 6-(5-Chloro-2-methoxybenzyl)-3,7-dioxo-N-{(1R)-1-[(1H-tetrazol-5-ylamino)carbonyl]propyl}-1,4-diazepan-1-carboxamide shows a novel interaction mode. In the experimental materials used by the author, we found tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8Recommanded Product: 71432-55-8)

tert-Butyl N,N’-diisopropylcarbamimidate(cas: 71432-55-8) 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: 71432-55-8

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

Whiting, Matthew; Tripp, Jonathan C.; Lin, Ying-Chuan; Lindstrom, William; Olson, Arthur J.; Elder, John H.; Sharpless, K. Barry; Fokin, Valery V. published their research in Journal of Medicinal Chemistry on December 28 ,2006. The article was titled 《Rapid Discovery and Structure-Activity Profiling of Novel Inhibitors of Human Immunodeficiency Virus Type 1 Protease Enabled by the Copper(I)-Catalyzed Synthesis of 1,2,3-Triazoles and Their Further Functionalization》.Electric Literature of C13H26N2O4 The article contains the following contents:

Building from the results of a computational screen of a range of triazole-containing compounds for binding efficiency to human immunodeficiency virus type 1 protease (HIV-1-Pr), a novel series of potent inhibitors has been developed. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), which provides ready access to 1,4-disubstituted-1,2,3-triazoles, was used to unite a focused library of azide-containing fragments with a diverse array of functionalized alkyne-containing building blocks. In combination with direct screening of the crude reaction products, this method led to the rapid identification of a lead structure and readily enabled optimization of both azide and alkyne fragments. Replacement of the triazole with a range of alternative linkers led to greatly reduced protease inhibition; however, further functionalization of the triazoles at the 5-position gave a series of compounds with increased activity, exhibiting Ki values as low as 8 nM. In the part of experimental materials, we found many familiar compounds, such as (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Electric Literature of C13H26N2O4)

(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.Electric Literature of C13H26N2O4 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

Skiles, Jerry W.; Miao, Clara; Sorcek, Ronald; Jacober, Stephen; Mui, Philip W.; Chow, Grace; Weldon, Steve M.; Possanza, Genus; Skoog, Mark published their research in Journal of Medicinal Chemistry on December 25 ,1992. The article was titled 《Inhibition of human leukocyte elastase by N-substituted peptides containing α,α-difluorostatone residues at P1》.Name: (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide The article contains the following contents:

A series of tripeptides which contain α,α-difluorostatone residues at P1-P1′ and span the S3-S1′ subsites have been shown to be potent inhibitors of human leukocyte elastase (HLE). The tripeptides described contain the nonproteinogenic achiral residue N-(2,3-dihydro-1H-inden-2-yl)glycine at the P2-position. This residue has previously been shown in the case of HLE to be a good bioisosteric replacement for L-proline. Of the peptides prepared, those which contain the α,α-difluoromethylene ketone derivative of L-valine (difluorostatone) are the preferred residue at the P1-primary specificity position. Substitution at P1 by the corresponding a,α-difluoromethylene ketones of L-leucine and L-phenylalanine gives inactive compounds Of the tripeptides described the most potent in vitro compound is peptide I (IC50 = 0.635 μM). It is presumed that the inhibitor I interacts with the S3-S1′ binding regions of HLE. Addnl. extended binding inhibitors were prepared which interact with the S3-S3′ binding subsites of HLE. In order to effect interaction with the S1′-S3′ substitutes of HLE, the leaving group side of cleaved peptides, spacers based upon Gly-Gly, and those linked via the Nε of L-lysine were utilized. One of the most potent extended compounds (P3-P3′) in vitro is peptide II (IC50 = 0.057 μM). The described in vitro active inhibitors were also evaluated in hamsters in an elastase-induced pulmonary hemorrhage (EPH) model. In this model, intratracheal administration of peptide III, 5 min prior to HLE challenge (10 μg, it.) effectively inhibited hemorrhage (94.6%) in a dose-dependent manner. The described α,α-difluoromethylene ketone inhibitors are assumed to act as transition-state analogs. The inhibition process presumably acts via hemiketal formation with the active site Ser195 of HLE, and is facilitated by the strongly electron withdrawing effect of the α,α-difluoromethylene functionality.(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Name: (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide) was used in this study.

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) belongs to amides.Name: (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide 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

de Bruin, Gerjan; Huber, Eva M.; Xin, Bo-Tao; van Rooden, Eva J.; Al-Ayed, Karol; Kim, Kyung-Bo; Kisselev, Alexei F.; Driessen, Christoph; van der Stelt, Mario; van der Marel, Gijsbert A.; Groll, Michael; Overkleeft, Herman S. published an article in Journal of Medicinal Chemistry. The title of the article was 《Structure-Based Design of β1i or β5i Specific Inhibitors of Human Immunoproteasomes》.Reference of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide The author mentioned the following in the article:

Mammalian genomes encode seven catalytic proteasome subunits, namely, β1c, β2c, β5c (assembled into constitutive 20S proteasome core particles), β1i, β2i, β5i (incorporated into immunoproteasomes), and the thymoproteasome-specific subunit β5t. Extensive research in the past decades has yielded numerous potent proteasome inhibitors including compounds currently used in the clinic to treat multiple myeloma and mantle cell lymphoma. Proteasome inhibitors that selectively target combinations of β1c/β1i, β2c/β2i, or β5c/β5i are available, yet ligands truly selective for a single proteasome activity are scarce. The authors report the development of cell-permeable β1i and β5i selective inhibitors that outperform existing leads in terms of selectivity and/or potency. These compounds are the result of a rational design strategy using known inhibitors as starting points and introducing structural features according to the x-ray structures of the murine constitutive and immunoproteasome 20S core particles. The experimental process involved the reaction of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Reference of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide)

(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. The presence of a C=O dipole and, to a lesser extent a N–C dipole, allows amides to act as H-bond acceptors.Reference of (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide 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

Name: (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamideOn June 15, 2000, Cristau, Michele; Devin, Chantal; Oiry, Catherine; Chaloin, Olivier; Amblard, Muriel; Bernad, Nicole; Heitz, Annie; Fehrentz, Jean-Alain; Martinez, Jean published an article in Journal of Medicinal Chemistry. The article was 《Synthesis and biological evaluation of bombesin constrained analogs》. The article mentions the following:

Analogs of bombesin which incorporate dipeptide or turn mimetics have been synthesized. One of them, peptide I containing a seven-membered lactam ring revealed a good affinity for GRP/BN receptors on rat pancreatic acini (Ki = 1.7 ± 0.4 nM) and on Swiss 3T3 cells (Ki = 1.0 ± 0.2 nM). On the basis of this observation, antagonists containing the same dipeptide mimic were obtained by modification of the C-terminal part of the bombesin analogs. The most potent constrained peptides II and III (pHPPA = p-hydroxy-3-phenylpropionyl) were able to antagonize 1 nM bombesin-stimulated amylase secretion from rat pancreatic acini with high potency (Ki = 21 ± 3 and 3.3 ± 1.0 nM, resp.) and 10-7 M bombesin-stimulated [3H]thymidine incorporation into Swiss 3T3 cells (Ki = 7.8 ± 2.0 and 0.5 ± 0.1 nM, resp.). In the experimental materials used by the author, we found (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6Name: (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide)

(S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide(cas: 87694-50-6) 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.Name: (S)-N-Methyl-N-methoxy-2-(tert-butoxycarbonylamino)-4-methylpentanamide

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