Tag: 100-200

Zhang, Chun-Hui; Spasov, Krasimir A.; Reilly, Raquel A.; Hollander, Klarissa; Stone, Elizabeth A.; Ippolito, Joseph A.; Liosi, Maria-Elena; Deshmukh, Maya G.; Tirado-Rives, Julian; Zhang, Shuo; Liang, Zhuobin; Miller, Scott J.; Isaacs, Farren; Lindenbach, Brett D.; Anderson, Karen S.; Jorgensen, William L. published their research in ACS Medicinal Chemistry Letters on August 12 ,2021. The article was titled 《Optimization of triarylpyridinone inhibitors of the main protease of SARS-CoV-2 to low-nanomolar antiviral potency》.Safety of 3,3,3-Trifluoropropan-1-ol The article contains the following contents:

Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018μM for inhibition of enzymic activity and EC50 values as low as 0.8μM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of Mpro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallog. confirmed the desired S4 placement. Here we report inhibitors with EC50 values as low as 0.080μM, while remdesivir yields values of 0.5-2μM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 (I) and 21 (II) are particularly promising as potential therapies for COVID-19, featuring IC50 values of 0.044-0.061μM, EC50 values of ca. 0.1μM, good aqueous solubility, and no cytotoxicity. The experimental process involved the reaction of 3,3,3-Trifluoropropan-1-ol(cas: 2240-88-2Safety of 3,3,3-Trifluoropropan-1-ol)

3,3,3-Trifluoropropan-1-ol(cas: 2240-88-2) is a important organic intermediate. It can be used in agrochemical, pharmaceutical and dyestuff field.Safety of 3,3,3-Trifluoropropan-1-ol

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Harrison, Lee A.; Atkinson, Stephen J.; Bassil, Anna; Chung, Chun-wa; Grandi, Paola; Gray, James R. J.; Levernier, Etienne; Lewis, Antonia; Lugo, David; Messenger, Cassie; Michon, Anne-Marie; Mitchell, Darren J.; Preston, Alex; Prinjha, Rab K.; Rioja, Inmaculada; Seal, Jonathan T.; Taylor, Simon; Wall, Ian D.; Watson, Robert J.; Woolven, James M.; Demont, Emmanuel H. published their research in Journal of Medicinal Chemistry on August 12 ,2021. The article was titled 《Identification of a Series of N-Methylpyridine-2-carboxamides as Potent and Selective Inhibitors of the Second Bromodomain (BD2) of the Bromo and Extra Terminal Domain (BET) Proteins》.Synthetic Route of C8H19NO2 The article contains the following contents:

Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicol. aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving >1000-fold selectivity for BD2 over BD1, while retaining favorable phys. chem. properties, compound 36 was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with >1 mg/mL solubility in FaSSIF media. 36 Represents a valuable new in vivo ready mol. for the exploration of the BD2 phenotype. In addition to this study using 4,4-Diethoxybutan-1-amine, there are many other studies that have used 4,4-Diethoxybutan-1-amine(cas: 6346-09-4Synthetic Route of C8H19NO2) was used in this study.

4,4-Diethoxybutan-1-amine(cas: 6346-09-4) belongs to anime. Aniline, ethanolamines, and several other amines are major industrial commodities used in making rubber, dyes, pharmaceuticals, and synthetic resins and fibres and for a host of other applications. Most of the numerous methods for the preparation of amines may be broadly divided into two groups: (1) chemical reduction (replacement of oxygen with hydrogen atoms in the molecule) of members of several other classes of organic nitrogen compounds and (2) reactions of ammonia or amines with organic compounds.Synthetic Route of C8H19NO2

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Name: 2-Amino-2-(4-isopropylphenyl)ethanolOn September 14, 2017 ,《Discovery and Optimization of 5-Amino-1,2,3-triazole-4-carboxamide Series against Trypanosoma cruzi》 was published in Journal of Medicinal Chemistry. The article was written by Brand, Stephen; Ko, Eun Jung; Viayna, Elisabet; Thompson, Stephen; Spinks, Daniel; Thomas, Michael; Sandberg, Lars; Francisco, Amanda F.; Jayawardhana, Shiromani; Smith, Victoria C.; Jansen, Chimed; De Rycker, Manu; Thomas, John; MacLean, Lorna; Osuna-Cabello, Maria; Riley, Jennifer; Scullion, Paul; Stojanovski, Laste; Simeons, Frederick R. C.; Epemolu, Ola; Shishikura, Yoko; Crouch, Sabrinia D.; Bakshi, Tania S.; Nixon, Christopher J.; Reid, Iain H.; Hill, Alan P.; Underwood, Tim Z.; Hindley, Sean J.; Robinson, Sharon A.; Kelly, John M.; Fiandor, Jose M.; Wyatt, Paul G.; Marco, Maria; Miles, Timothy J.; Read, Kevin D.; Gilbert, Ian H.. The article contains the following contents:

Chagas’ disease, caused by the protozoan parasite Trypanosoma cruzi, is the most common cause of cardiac-related deaths in endemic regions of Latin America. There is an urgent need for new safer treatments because current standard therapeutic options, benznidazole and nifurtimox, have significant side effects and are only effective in the acute phase of the infection with limited efficacy in the chronic phase. Phenotypic high content screening against the intracellular parasite in infected VERO cells was used to identify a novel hit series of 5-amino-1,2,3-triazole-4-carboxamides (ATC). Optimization of the ATC series gave improvements in potency, aqueous solubility, and metabolic stability, which combined to give significant improvements in oral exposure. Mitigation of a potential Ames and hERG liability ultimately led to two promising compounds, one of which demonstrated significant suppression of parasite burden in a mouse model of Chagas’ disease. After reading the article, we found that the author used 2-Amino-2-(4-isopropylphenyl)ethanol(cas: 910443-18-4Name: 2-Amino-2-(4-isopropylphenyl)ethanol)

2-Amino-2-(4-isopropylphenyl)ethanol(cas: 910443-18-4) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Name: 2-Amino-2-(4-isopropylphenyl)ethanol

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SDS of cas: 6346-09-4On June 5, 2020, Tripathi, Shashank; Ambule, Mayur D.; Srivastava, Ajay Kumar published an article in Journal of Organic Chemistry. The article was 《Construction of Highly Functionalized Piperazinones via Post-Ugi Cyclization and Diastereoselective Nucleophilic Addition》. The article mentions the following:

Aminals were prepared by Ugi multicomponent cyclocondensation reactions of 2-aminoacetaldehyde di-Me acetal, aldehydes or ketones such as 3-indolecarboxaldehyde, carboxylic acids such as benzoic acid, and isocyanides such as benzyl isocyanide. In the presence of BF3·Et2O in CH2Cl2, the aminals underwent (diastereoselective) substitution reactions with nucleophiles such as Me3SiR [R = H2C:CHCH2, NC, N3, OCPh(:CH2)], triethylsilane, or N-methylindole to yield piperazinones such as I (X = Y = O). Ugi reactions with aminoaldehyde acetals with longer carbon chains yielded only acyclic products. I (X = Y = H2) was prepared as a dragmacidin C analog, while two piperazinones were used to prepare praziquantel analogs. The results came from multiple reactions, including the reaction of 4,4-Diethoxybutan-1-amine(cas: 6346-09-4SDS of cas: 6346-09-4)

4,4-Diethoxybutan-1-amine(cas: 6346-09-4) belongs to anime.Typically the presence of an amine functional group is deduced by a combination of techniques, including mass spectrometry as well as NMR and IR spectroscopies. 1H NMR signals for amines disappear upon treatment of the sample with D2O. In their infrared spectrum primary amines exhibit two N-H bands, whereas secondary amines exhibit only one.SDS of cas: 6346-09-4

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Quality Control of 4,4-Diethoxybutan-1-amineOn November 30, 2019 ,《Synthesis of 1-(2-aminoethylsulfonyl)-2-phosphorylpyrrolidines via consecutive Arbuzov and aza-Michael reactions and their antitumor activity》 appeared in Mendeleev Communications. The author of the article were Bagautdinova, Roza Kh.; Vagapova, Lilia I.; Smolobochkin, Andrey V.; Gazizov, Almir S.; Burilov, Alexander R.; Pudovik, Michail A.; Voloshina, Alexandra D.. The article conveys some information:

1-(2-Aminoethylsulfonyl)-2-phosphorylpyrrolidines were synthesized via B trifluoride-catalyzed Arbuzov reaction of 2-ethoxy-1-(vinylsulfonyl)pyrrolidine with tri-Et phosphite followed by aza-Michael reaction of thus obtained 2-phosphoryl-1-(vinylsulfonyl)pyrrolidine with secondary amines. The cytotoxicity of the prepared 1-(2-aminoethylsulfonyl)-2-phosphorylpyrrolidines against M-Hela tumor cell line is comparable with that of tamoxifen, whereas the cytotoxicity against normal cell line is 2-fold lower. In the experiment, the researchers used many compounds, for example, 4,4-Diethoxybutan-1-amine(cas: 6346-09-4Quality Control of 4,4-Diethoxybutan-1-amine)

4,4-Diethoxybutan-1-amine(cas: 6346-09-4) belongs to anime. Amine, any member of a family of nitrogen-containing organic compounds that is derived, either in principle or in practice, from ammonia (NH3). Naturally occurring amines include the alkaloids, which are present in certain plants; the catecholamine neurotransmitters (i.e., dopamine, epinephrine, and norepinephrine); and a local chemical mediator, histamine, that occurs in most animal tissues.Quality Control of 4,4-Diethoxybutan-1-amine

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SDS of cas: 133082-13-0On November 30, 2008 ,《One-pot conversion of trimethylsilyl ethers into urethanes using chlorosulfonyl isocyanate: Application to the synthesis of a novel neuromodulator carisbamate》 appeared in Archives of Pharmacal Research. The author of the article were Dong, Guang Ri; Li, Qing Ri; Woo, Seol Hee; Kim, In Su; Jung, Young Hoon. The article conveys some information:

This paper reports a novel synthetic method for the preparation of various urethanes and the application to the synthesis of carisbamate. The reaction of primary (2a, 2e and 2f) or secondary (2g-2i) trimethylsilyl ethers with chlorosulfonyl isocyanate afforded the corresponding urethanes in good yields without affecting the olefin moiety. However, in the case of secondary benzylic trimethylsilyl ether 2j, the corresponding urethane 3j was obtained in low yield. From the difference in reactivity between the primary and secondary benzylic trimethylsilyl ethers, the one-pot synthesis of carisbamate 1 from bis-trimethylsilyl ether 2l was achieved. In the experimental materials used by the author, we found (1S)-1-(2-chlorophenyl)ethane-1,2-diol(cas: 133082-13-0SDS of cas: 133082-13-0)

(1S)-1-(2-chlorophenyl)ethane-1,2-diol(cas: 133082-13-0) belongs to hydroxy-containing compounds. Hydroxy-containing compounds engage in intermolecular hydrogen bonding increasing the electrostatic attraction between molecules and thus to higher boiling and melting points than found for compounds that lack this functional group. Organic compounds, which are often poorly soluble in water, become water-soluble when they contain two or more hydroxy groups, as illustrated by sugars and amino acid.SDS of cas: 133082-13-0

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《α-Lithiation-Electrophile Trapping of N-Thiopivaloylazetidin-3-ol: Stereoselective Synthesis of 2-Substituted 3-Hydroxyazetidines》 was written by Hodgson, David M.; Pearson, Christopher I.; Thompson, Amber L.. Name: Azetidin-3-ol hydrochlorideThis research focused onthiopivaloylazetidinol alpha lithiation electrophile trapping; hydroxyazetidine substituted derivative stereoselective preparation deuterium labeling. The article conveys some information:

α-Lithiation of N-thiopivaloylazetidin-3-ol and subsequent electrophile trapping provides access to a range of 2-substituted 3-hydroxyazetidines with generally good trans-diastereoselectivity, aside from deuteration, which gives the cis-diastereoisomer. Deuterium labeling studies indicate that the initial α-deprotonation occurs preferentially, but not exclusively, in a trans-selective manner. These studies also suggest that the stereochem. outcome of the electrophile trapping depends on the electrophile used but is independent of which α-proton (cis or trans to the hydroxyl group) is initially removed. The results came from multiple reactions, including the reaction of Azetidin-3-ol hydrochloride(cas: 18621-18-6Name: Azetidin-3-ol hydrochloride)

Azetidin-3-ol hydrochloride(cas:18621-18-6) is one of azetidine.Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products.Name: Azetidin-3-ol hydrochloride Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor.

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Alcohol – Wikipedia,
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《Dynamic Helicates Self-Assembly from Homo- and Heterotopic Dynamic Covalent Ligand Strands》 was written by Santoro, Antonio; Holub, Jan; Fik-Jaskolka, Marta A.; Vantomme, Ghislaine; Lehn, Jean-Marie. Category: alcohols-buliding-blocksThis research focused ontransition metal schiff base helicate complex preparation self assembly; crystal structure transition metal schiff base helicate; double-helical structures; dynamic covalent chemistry; metallo-supramolecular structures; programmed self-assembly. The article conveys some information:

The understanding and the application of reversible covalent reactions and coordination chem. together with the proper design of the mol. frameworks, allow to achieve not only well-defined output architectures but also different grades of complex behavior. In this work, the dynamic nature of the helical systems offers an addnl. level of complexity by combining self-sorting on two levels: (1) the build-up of the ligand strand constituents from their components through dynamic covalent chem.; (2) the assembly of the helicates from the ligands and the metal cations through dynamic metallo-supramol. chem. The information encoded in the ligands constituent mol. was read differently (and accurately at the same time) by metal cations that varied in the coordination algorithms. It enabled the selective formation of a specific type of helicates from a wide library of helicates formed by the possible combination of subcomponents. Ligands containing dynamic tridentate and/or bidentate binding motifs in the same strand were studied to explore the helicates self-assembly with appropriate metal cations. The experimental part of the paper was very detailed, including the reaction process of 2,6-Pyridinedimethanol(cas: 1195-59-1Category: alcohols-buliding-blocks)

2,6-Pyridinedimethanol(cas: 1195-59-1) belongs to pyridine. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Additionally, pyridine-based natural products continue to be discovered and studied for their properties and to understand their biosynthesis.Category: alcohols-buliding-blocks

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Safety of 2,6-PyridinedimethanolIn 2020 ,《Fast and Efficient Nickel(II)-catalyzed Transfer Hydrogenation of Quinolines with Ammonia Borane》 was published in Advanced Synthesis & Catalysis. The article was written by Vermaak, Vincent; Vosloo, Hermanus C. M.; Swarts, Andrew J.. The article contains the following contents:

The first Ni(II)-catalyzed transfer hydrogenation of quinolines using ammonia borane (AB) as hydrogen (H2) source was reported. An in situ generated Ni(II)-bis(pyrazolyl)pyridine pre-catalyst could hydrogenate quinoline and its derivatives in excellent yields of up to 90% at 25°C in 30 min. Spectroscopic studies revealed that a Ni(II)-hydride was responsible for the transfer hydrogenation of quinoline to 1,2,3,4-tetrahydroquinoline via a 1,4-dihydroquinoline intermediate. In the experiment, the researchers used many compounds, for example, 2,6-Pyridinedimethanol(cas: 1195-59-1Safety of 2,6-Pyridinedimethanol)

2,6-Pyridinedimethanol(cas: 1195-59-1) belongs to pyridine. Pyridines, quinolines, and isoquinolines have found a function in almost all aspects of organic chemistry. Pyridine has found use as a solvent, base, ligand, functional group, and molecular scaffold. As structural elements, these moieties are potent electron-deficient groups, metal-directing functionalities, fluorophores, and medicinally important pharmacophores. Safety of 2,6-Pyridinedimethanol

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《Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors》 was written by Lanman, Brian A.; Allen, Jennifer R.; Allen, John G.; Amegadzie, Albert K.; Ashton, Kate S.; Booker, Shon K.; Chen, Jian Jeffrey; Chen, Ning; Frohn, Michael J.; Goodman, Guy; Kopecky, David J.; Liu, Longbin; Lopez, Patricia; Low, Jonathan D.; Ma, Vu; Minatti, Ana E.; Nguyen, Thomas T.; Nishimura, Nobuko; Pickrell, Alexander J.; Reed, Anthony B.; Shin, Youngsook; Siegmund, Aaron C.; Tamayo, Nuria A.; Tegley, Christopher M.; Walton, Mary C.; Wang, Hui-Ling; Wurz, Ryan P.; Xue, May; Yang, Kevin C.; Achanta, Pragathi; Bartberger, Michael D.; Canon, Jude; Hollis, L. Steven; McCarter, John D.; Mohr, Christopher; Rex, Karen; Saiki, Anne Y.; San Miguel, Tisha; Volak, Laurie P.; Wang, Kevin H.; Whittington, Douglas A.; Zech, Stephan G.; Lipford, J. Russell; Cee, Victor J.. HPLC of Formula: 89466-08-0 And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:

KRASG12C has emerged as a promising target in the treatment of solid tumors. Covalent inhibitors targeting the mutant cysteine-12 residue have been shown to disrupt signaling by this long-“”undruggable”” target; however clin. viable inhibitors have yet to be identified. Here, we report efforts to exploit a cryptic pocket (H95/Y96/Q99) we identified in KRASG12C to identify inhibitors suitable for clin. development. Structure-based design efforts leading to the identification of a novel quinazolinone scaffold are described, along with optimization efforts that overcame a configurational stability issue arising from restricted rotation about an axially chiral biaryl bond. Biopharmaceutical optimization of the resulting leads culminated in the identification of AMG 510, a highly potent, selective, and well-tolerated KRASG12C inhibitor currently in phase I clin. trials (NCT03600883). The experimental part of the paper was very detailed, including the reaction process of 2-Hydroxyphenylboronic acid(cas: 89466-08-0HPLC of Formula: 89466-08-0)

2-Hydroxyphenylboronic acid(cas: 89466-08-0) belongs to acyl phenylboronic acid. Phenylboronic acid (PBA) has been used to extract β-blockers (a class of aminoalcohol-containing drugs) from aqueous solution, rat, and human plasma. HPLC of Formula: 89466-08-0

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