Author: Jessica.F

Grols, Jan Roland published the artcileMechanochemical co-crystallization: Insights and predictions, Application In Synthesis of 1453-82-3, the publication is Computers & Chemical Engineering (2021), 107416, database is CAplus.

Mechanochem. integrates mech. and chem. phenomena to spawn new modes of reactivity, faster reaction kinetics and the discovery of novel materials, in a solvent-free and environmental manner. This simple, yet efficient technique has become a well-established screening technique to discover pharmaceutical co-crystals – components that incorporate a secondary crystalline structure into the lattice of an active pharmaceutical ingredient (API) to improve its physicochem. properties. Today, predicting the reactivity of solid-state materials under mechanochem. conditions remains a major challenge. Here, we explore various machine learning algorithms and identified XGBoost ideal to accurately predict mechanochem. co-crystallization The model was trained using 1000 co-crystallization events and 2083 chem. descriptors, revealing fundamental insights about mechanochem. The model was implemented to screen secondary crystalline structures against a model API, yielding three new mechanochem.-formed co-crystals. This predictive model will accelerate the discovery of novel pharmaceuticals while its insights aid at developing a more sustainable chem. industry.

Computers & Chemical Engineering published new progress about 1453-82-3. 1453-82-3 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is Isonicotinamide, and the molecular formula is C6H6N2O, Application In Synthesis of 1453-82-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Ondachi, Pauline W. published the artcileSynthesis, Nicotinic Acetylcholine Receptor Binding, and in Vitro and in Vivo Pharmacological Properties of 2′-Fluoro-(substituted thiophenyl)deschloroepibatidine Analogues, Synthetic Route of 957345-71-0, the publication is ACS Chemical Neuroscience (2017), 8(1), 115-127, database is CAplus and MEDLINE.

The synthesis, nAChR in vitro and in vivo pharmacol. properties of 2′-fluoro-3′-(substituted thiophenyl)deschloroepibatidine analogs are presented herein. All had subnanomolar affinity at α4β2*-nAChRs. Contrary to lead structure epibatidine, a potent nAChR agonist, all were potent α4β2- and α3β4-AChR antagonists in an in vitro functional assay. In vivo, the compounds were also nAChR antagonists with various degrees of agonist activity. Many of the compounds had no agonist effects in the tail-flick, hot-plate, hypothermia, or spontaneous activity tests, whereas others did not have agonist activity in the tail-flick and hot-plate tests but like varenicline, were agonists in the hypothermia and spontaneous activity tests. Compound 4-(5-(7-azabicyclo[2.2.1]hept-2-yl)-2-fluoropyridin-3-yl)thiophene-2-carboxamide had agonist activity in all four in vivo tests. All the compounds were antagonists of nicotine-induced antinociception in the tail-flick test and most were antagonists of nicotine-induced antinociception in the hot-plate test. Compound 2-[5-(4-chlorothiophen-2-yl)-6-fluoropyridin-3-yl]-7-azabicyclo[2.2.1]heptane which had a Ki = 0.86 nM in the binding assay similar potency at α4β2/α3β4 with selectivity relative to α7 nAChRs, AD50 value of 0.001 μg/kg in the tail-flick test with no agonist activity in the in vitro or in vivo test had one of the more interesting profiles.

ACS Chemical Neuroscience published new progress about 957345-71-0. 957345-71-0 belongs to amides-buliding-blocks, auxiliary class Boronate Esters,Boronic acid and ester,Boronic acid and ester, name is 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxamide, and the molecular formula is C11H16BNO3S, Synthetic Route of 957345-71-0.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Sorbera, L. A. published the artcileIndiplon: Treatment of insomnia GABA-A agonist, Category: amides-buliding-blocks, the publication is Drugs of the Future (2003), 28(8), 739-746, database is CAplus.

Six different synthetic routes are investigated for the preparation of N-Methyl-N-[3-[3-[2-thienylcarbonyl]pyrazolo[1,5-a]pyrimidin-7-yl]phenyl]a cetamide (Indiplon) and its potential use as a drug for treatment of insomnia is evaluated. Indiplon is a GABA-A receptor partial agonist that promotes sleep by enhancing the inhibitory activity of GABA through specific binding to the BZ1 or α₁ subunit of the GABA-A receptor. Indiplon has been shown to be safe and well tolerated and is currently being developed in two formulations to treat all insomnia complaints, including sleep initiation, night awakenings and total sleep maintenance.

Drugs of the Future published new progress about 325715-13-7. 325715-13-7 belongs to amides-buliding-blocks, auxiliary class Amine,Benzene,Ketone,Amide, name is N-(3-Acetylphenyl)-N-methylacetamide, and the molecular formula is C12H10O4S, Category: amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Cacabelos, Ramon published the artcileSirtuins in Alzheimer’s disease: SIRT2-related genophenotypes and implications for pharmacoepigenetics, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is International Journal of Molecular Sciences (2019), 20(5), 1249, database is CAplus and MEDLINE.

Sirtuins (SIRT1-7) are NAD⁺ -dependent protein deacetylases/ADP ribosyltransferases with important roles in chromatin silencing, cell cycle regulation, cellular differentiation, cellular stress response, metabolism and aging. Sirtuins are components of the epigenetic machinery, which is disturbed in Alzheimer’s disease (AD), contributing to AD pathogenesis. There is an association between the SIRT2-C/T genotype (rs10410544) (50.92%) and AD susceptibility in the APOE ε4-neg. population (SIRT2-C/C, 34.72%; SIRT2-T/T 14.36%). The integration of SIRT2 and APOE variants in biogenic clusters yields 18 haplotypes. The 5 most frequent biogenic genotypes in AD are 33CT (27.81%), 33CC (21.36%), 34CT (15.29%), 34CC (9.76%) and 33TT (7.18%). There is an accumulation of APOE-3/4 and APOE-4/4 carriers in SIRT2-T/T > SIRT2-C/T > SIRT2-C/C carriers, and also of SIRT2-T/T and SIRT2-C/T carriers in patients who harbor the APOE-4/4 genotype. SIRT2 variants influence biochem., hematol., metabolic and cardiovascular phenotypes, and modestly affect the pharmacoepigenetic outcome in AD. SIRT2-C/T carriers are the best responders, SIRT2-T/T carriers show an intermediate pattern, and SIRT2-C/C carriers are the worst responders to a multifactorial treatment. In APOE-SIRT2 biogenic clusters, 33CC carriers respond better than 33TT and 34CT carriers, whereas 24CC and 44CC carriers behave as the worst responders. CYP2D6 extensive metabolizers (EM) are the best responders, poor metabolizers (PM) are the worst responders, and ultra-rapid metabolizers (UM) tend to be better responders that intermediate metabolizers (IM). In association with CYP2D6 genophenotypes, SIRT2-C/T-EMs are the best responders. Some Sirtuin modulators might be potential candidates for AD treatment.

International Journal of Molecular Sciences published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Name: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Ricci, F. published the artcileA High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem Cells, SDS of cas: 1011557-82-6, the publication is Combinatorial Chemistry & High Throughput Screening (2018), 21(1), 50-56, database is CAplus and MEDLINE.

Epithelial ovarian cancer has a poor prognosis, mostly due to its late diagnosis and the development of drug resistance after a first platinum-based regimen. The presence of a specific population of “cancer stem cells” could be responsible of the relapse of the tumor and the development of resistance to therapy. For this reason, it would be important to specifically target this subpopulation of tumor cells in order to increase the response to therapy. We screened a chem. compound library assembled during the COST CM1106 action to search for compound classes active in targeting ovarian stem cells. We here report the results of the high-throughput screening assay in two ovarian cancer stem cells and the differentiated cells derived from them. Interestingly, there were compounds active only on stem cells, only on differentiated cells, and compounds active on both cell populations. Even if these data need to be validated in ad hoc dose response cytotoxic experiments, the ongoing anal. of the compound structures will open up to mechanistic drug studies to select compounds able to improve the prognosis of ovarian cancer patients.

Combinatorial Chemistry & High Throughput Screening published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, SDS of cas: 1011557-82-6.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Couve-Bonnaire, Samuel published the artcileSynthesis of pyridylglyoxylic acid derivatives via a palladium-catalyzed double carbonylation of iodopyridines, Product Details of C10H14N2O, the publication is Tetrahedron Letters (1999), 40(19), 3717-3718, database is CAplus.

4-Iodopyridines react with CO and HNEt₂ or 2-BuOH/NEt₃ in the presence of a catalytic amount of PdCl₂(PPh₃)₂ to give the corresponding α-keto amides and esters in fair to high yields.

Tetrahedron Letters published new progress about 530-40-5. 530-40-5 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N,N-Diethylisonicotinamide, and the molecular formula is C10H14N2O, Product Details of C10H14N2O.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Couve-Bonnaire, Samuel published the artcileCatalytic synthesis and asymmetric reduction of pyridylglyoxylic amides and esters, Application In Synthesis of 530-40-5, the publication is Advanced Synthesis & Catalysis (2001), 343(3), 289-298, database is CAplus.

The preparation of 2-pyridyl- and 4-pyridylglyoxylic esters and amides in moderate to high yields via palladium-catalyzed double carbonylation of 2-iodo- and 4-iodopyridines is reported. The effect of temperature, CO pressure, solvent, nature and concentration of nucleophile, nature of catalyst precursor, and substituents on iodopyridines has been investigated. The reduction of 4-pyridylglyoxylate esters into the corresponding α-hydroxy esters via ruthenium-catalyzed asym. hydrogenation or using alpine-borane proceeded in high yields but poor enantioselectivity. The results for the carbonylation and the hydrogenation catalytic processes are discussed in terms of electronic effects induced by the pyridyl ring.

Advanced Synthesis & Catalysis published new progress about 530-40-5. 530-40-5 belongs to amides-buliding-blocks, auxiliary class Pyridine,Amine,Amide, name is N,N-Diethylisonicotinamide, and the molecular formula is C10H14N2O, Application In Synthesis of 530-40-5.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Desiante, Werner L. published the artcileWastewater microorganisms impact the micropollutant biotransformation potential of natural stream biofilms, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, the publication is Water Research (2022), 118413, database is CAplus and MEDLINE.

Biotransformation is the most important process removing manmade chems. from the environment, yet mechanisms governing this essential ecosystem function are underexplored. To understand these mechanisms, we conducted experiments in flow-through systems, by colonizing stream biofilms under different conditions of mixing river water with treated (and ultrafiltered) wastewater. We performed biotransformation experiments with those biofilms, using a set of 75 micropollutants, and could disentangle potential mechanisms determining the biotransformation potential of stream biofilms. We showed that the increased biotransformation potential downstream of wastewater treatment plants that we observed for specific micropollutants contained in household wastewaters (downstream effect) is caused by microorganisms released with the treated effluent, rather than by the instream exposure to those micropollutants. Complementary data from 16S rRNA amplicon-sequencing revealed 146 amplicon sequence variants (ASVs) that followed the observed biotransformation patterns. Our results align with findings for community tolerance, and provide clear exptl. evidence that microorganisms released with treated wastewater integrate into downstream biofilms and impact crucial ecosystem functions.

Water Research published new progress about 137862-53-4. 137862-53-4 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Angiotensin Receptor, name is (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid, and the molecular formula is C24H29N5O3, Application of (S)-2-(N-((2′-(1H-Tetrazol-5-yl)-[1,1′-biphenyl]-4-yl)methyl)pentanamido)-3-methylbutanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Rotili, Dante published the artcileSimplification of the tetracyclic SIRT1-selective inhibitor MC2141: Coumarin- and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile, Related Products of amides-buliding-blocks, the publication is Bioorganic & Medicinal Chemistry (2011), 19(12), 3659-3668, database is CAplus and MEDLINE.

In this report we describe the synthesis and biol. characterization of two series of sirtuins’ inhibitors (SIRTi), designed as simplification products of the previously reported SIRT1-selective inhibitor MC2141 (4). In the first series (5a-t) we report a number of 2-substituted-1,2-dihydrobenzo[f]chromen-3-ones with a marked selectivity for the inhibition of SIRT2 over SIRT1. Some of such derivatives showed also high pro-apoptotic (5i and 5l) and/or cytodifferentiating (5d, 5i, and 5o) properties in a human leukemia cell line (U937). The second group of SIRTi (6a-q) is characterized by some analogs of cambinol (3), a well known SIRTi active against the Burkitt lymphoma. Such compounds, differently from the unselective prototype, are endowed with a selective inhibition of SIRT1 over SIRT2, and, in some cases (6j, 6k, and 6q), are more efficient than 3 to induce apoptosis in U937 cells.

Bioorganic & Medicinal Chemistry published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C25H34N4O2S, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Morimoto, Mariko published the artcileChemoselective and Site-Selective Reductions Catalyzed by a Supramolecular Host and a Pyridine-Borane Cofactor, Product Details of C11H22N2O4, the publication is Journal of the American Chemical Society (2021), 143(4), 2108-2114, database is CAplus and MEDLINE.

Supramol. catalysts emulate the mechanism of enzymes to achieve large rate accelerations and precise selectivity under mild and aqueous conditions. While significant strides have been made in the supramol. host-promoted synthesis of small mols., applications of this reactivity to chemoselective and site-selective modification of complex biomols. remain virtually unexplored. We report here a supramol. system where coencapsulation of pyridine-borane with a variety of mols. including enones, ketones, aldehydes, oximes, hydrazones, and imines effects efficient reductions under basic aqueous conditions. Upon subjecting unprotected lysine to the host-mediated reductive amination conditions, we observed excellent ε-selectivity, indicating that differential guest binding within the same mol. is possible without sacrificing reactivity. Inspired by the post-translational modification of complex biomols. by enzymic systems, we then applied this supramol. reaction to the site-selective labeling of a single lysine residue in an 11-amino acid peptide chain and human insulin.

Journal of the American Chemical Society published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C11H22N2O4, Product Details of C11H22N2O4.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics