Tag: 100-200

The author of 《Dual-reporter high-throughput screen for small-molecule in vivo inhibitors of plasminogen activator inhibitor type-1 yields a clinical lead candidate》 were Reinke, Ashley A.; Li, Shih-Hon; Warnock, Mark; Shaydakov, Maxim E.; Guntaka, Naga Sandhya; Su, Enming J.; Diaz, Jose A.; Emal, Cory D.; Lawrence, Daniel A.. And the article was published in Journal of Biological Chemistry in 2019. Safety of Ethyl oxalyl monochloride The author mentioned the following in the article:

Plasminogen activator inhibitor type-1 (PAI-1) is a serine protease inhibitor (serpin) implicated in numerous pathol. processes, including coronary heart disease, arterial and venous thrombosis, and chronic fibrotic diseases. These associations have made PAI-1 an attractive pharmaceutical target. However, the complexity of the serpin inhibitory mechanism, the inherent metastability of serpins, and the high-affinity association of PAI-1 with vitronectin in vivo have made it difficult to identify pharmacol. effective small-mol. inhibitors. Moreover, the majority of current small-mol. PAI-1 inhibitors are poor pharmaceutical candidates. To this end and to find leads that can be efficiently applied to in vivo settings, we developed a dual-reporter high-throughput screen (HTS) that reduced the rate of nonspecific and promiscuous hits and identified leads that inhibit human PAI-1 in the high-protein environments present in vivo. Using this system, we screened >152,000 pure compounds and 27,000 natural product extracts (NPEs), reducing the apparent hit rate by almost 10-fold compared with previous screening approaches. Furthermore, screening in a high-protein environment permitted the identification of compounds that retained activity in both ex vivo plasma and in vivo. Following lead identification, subsequent medicinal chem. and structure-activity relationship (SAR) studies identified a lead clin. candidate, MDI-2268, having excellent pharmacokinetics, potent activity against vitronectin-bound PAI-1 in vivo, and efficacy in a murine model of venous thrombosis. This rigorous HTS approach eliminates promiscuous candidate leads, significantly accelerates the process of identifying PAI-1 inhibitors that can be rapidly deployed in vivo, and has enabled identification of a potent lead compound The experimental process involved the reaction of Ethyl oxalyl monochloride(cas: 4755-77-5Safety of Ethyl oxalyl monochloride)

Ethyl oxalyl monochloride(cas: 4755-77-5) belongs to acyl chlorides. In the laboratory, acyl chlorides are generally prepared by treating carboxylic acids with thionyl chloride (SOCl2). The reaction is catalyzed by dimethylformamide and other additives.Safety of Ethyl oxalyl monochloride

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

The author of 《Direct C-H Carbamoylation of Nitrogen-Containing Heterocycles》 were Jouffroy, Matthieu; Kong, Jongrock. And the article was published in Chemistry – A European Journal in 2019. Category: esters-buliding-blocks The author mentioned the following in the article:

Using bench stable and com. available alkyl oxamate and oxamic acid derivatives in combination with photoredox catalysis, a direct carbamoylation of heterocycles yielding amide functionalized pharmacophores in a single step was reported. The reaction conditions reported are compatible with structurally complex heterocyclic substrates of pharmaceutical interest. Notably, derivatives containing functional groups incompatible with standard amidation reactions, such as carboxylic acids and unprotected amines, were found to be amenable to this reaction paradigm. In the experiment, the researchers used Ethyl oxalyl monochloride(cas: 4755-77-5Category: esters-buliding-blocks)

Ethyl oxalyl monochloride(cas: 4755-77-5) belongs to acyl chlorides. In the laboratory, acyl chlorides are generally prepared by treating carboxylic acids with thionyl chloride (SOCl2). The reaction is catalyzed by dimethylformamide and other additives.Category: esters-buliding-blocks

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

《A universal one-pot assay strategy based on bio-inorganic cascade catalysts for different analytes by changing pH-dependent activity of enzymes on enzyme mimics》 was written by Zhang, Haijiao; Han, Lei; Li, Feng. Formula: C5H11NO2This research focused onuniversal assay bioinorganic catalyst pH dependent analyte enzyme activity. The article conveys some information:

In general, peroxidase mimics show optimal activity at acidic pH, while many enzymes work at physiol. pH. To realize one-pot colorimetric detection based on enzyme-nanozyme-coupled system, the usual strategy is to change the pH-dependent activity of nanozymes, which is difficult for most of nanozymes. Unlike common strategies, we changed the pH-dependent activity of enzymes rather than nanozymes. First, we facilely synthesized Co3O4 magnetic peroxidase mimics with uniform size, good dispersibility and superparamagnetism by using protein as templates at mild condition. The as-prepared Co3O4 magnetic nanoparticles (MNPs) were covered with the layers of protein, facilitating the further functionalization with enzymes. Exhilaratingly, we discovered that the immobilization on Co3O4 MNPs could regulated pH-dependent activity of enzymes, such as glucose oxidase (GOx) and glucoamylase (GA). Based on the overlapped pH range between peroxidase-like activity of Co3O4 MNPs and catalytic activity of GOx, the hybrid cascade catalysts were employed for a one-pot glucose detection, exhibiting wide detection range and good selectivity. Furthermore, GA and GOx were co-mobilized on Co3O4 MNPs to realize the one-pot colorimetric starch detection, confirming the universality of the proposed strategy. As an addnl. bonus, hybrid cascade catalysts could be expediently separated from the reaction solution under the magnetic field in order to rapidly terminate the reaction and recycle enzymes. This work would open an avenue for the various one-pot enzyme-nanozyme-coupled assay. In the experiment, the researchers used many compounds, for example, tert-Butyl carbamate(cas: 4248-19-5Formula: C5H11NO2)

tert-Butyl carbamate(cas: 4248-19-5) belongs to anime. Amines have a free lone pair with which they can coordinate to metal centers. Amine–metal bonds are weaker because amines are incapable of backbonding, but they are still important for sensing applications.While stronger than hydrogen bonds, amine–metal bonds are still weaker than both covalent and ionic bonds.Formula: C5H11NO2

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

Category: esters-buliding-blocksIn 2018 ,《Discovery of 12-Thiazole Abietanes as Selective Inhibitors of the Human Metabolic Serine Hydrolase hABHD16A》 was published in ACS Medicinal Chemistry Letters. The article was written by Ahonen, Tiina J.; Savinainen, Juha R.; Yli-Kauhaluoma, Jari; Kalso, Eija; Laitinen, Jarmo T.; Moreira, Vania M.. The article contains the following contents:

Screening of an inhouse library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative I, with an IC50 value of 3.4±0.2 μM and promising selectivity. ABHD16A has been highlighted as a new target for inflammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. The study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute toward understanding the significance of hABHD16A inhibition in vivo. In the experiment, the researchers used many compounds, for example, Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1Category: esters-buliding-blocks)

Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1) 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.Category: esters-buliding-blocks

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

Recommanded Product: 609-14-3In 2021 ,《Sulfonium Salts Enable the Direct Sulfenylation of Activated C(sp3)-H Bonds》 was published in European Journal of Organic Chemistry. The article was written by Zhang, Liang; Nagaraju, Sakkani; Paplal, Banoth; Lin, Yunliang; Liu, Shuhua. The article contains the following contents:

Herein, the direct α-sulfenylation of a series of β-dicarbonyl, β-ketophosphonate, and β-ketonitrile compounds, mediated by sulfonium salts has been described. Traditionally, sulfonium salts which are synthesized by activation of dialkylsulfoxides serve as oxidizing agents or precursors of sulfur ylide. In this transformation, sulfonium salts as readily prepared and operationally simple sulfenylation reagents firstly achieved alkylsulfenylation of various activated C(sp3)-H bonds with the formation of tetra-substituted carbon center. Thus, e.g., sulfenylation of Me 2-oxocyclopentanecarboxylate with DMSO in presence of AcCl as activator and NaSbF6 in MeCN afforded I (79%). The experimental part of the paper was very detailed, including the reaction process of Ethyl 2-methyl-3-oxobutanoate(cas: 609-14-3Recommanded Product: 609-14-3)

Ethyl 2-methyl-3-oxobutanoate(cas: 609-14-3) belongs to ketone compounds. They are most widely used as solvents, especially in industries manufacturing explosives, lacquers, paints, and textiles. Ketones are also used in tanning, as preservatives, and in hydraulic fluids.Recommanded Product: 609-14-3

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

Recommanded Product: 4949-44-4In 2020 ,《Efficient Asymmetric Synthesis of Ethyl (S)-4-Chloro-3-hydroxybutyrate Using Alcohol Dehydrogenase SmADH31 with High Tolerance of Substrate and Product in a Monophasic Aqueous System》 was published in Organic Process Research & Development. The article was written by Yang, Zeyu; Ye, Wenjie; Xie, Youyu; Liu, Qinghai; Chen, Rong; Wang, Hualei; Wei, Dongzhi. The article contains the following contents:

Bioredns. catalyzed by alc. dehydrogenases (ADHs) play an important role in the synthesis of chiral alcs. However, the synthesis of Et (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production Herein, we evaluated a novel ADH, SmADH31, obtained from the Stenotrophomonas maltophilia genome, which can tolerate extremely high concentrations (6 M) of both substrate and product. The coexpression of SmADH31 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli meant that as much as 660 g L-1 (4.0 M) Et 4-chloroacetoacetate was completely converted into (S)-CHBE in a monophasic aqueous system with a >99.9% ee value and a high space-time yield (2664 g L-1 d-1). Mol. dynamics simulation shed light on the high activity and stereoselectivity of SmADH31. Moreover, five other optically pure chiral alcs. were synthesized at high concentrations (100-462 g L-1) as a result of the broad substrate spectrum of SmADH31. All these compounds act as important drug intermediates, demonstrating the industrial potential of SmADH31-mediated bioredns. In the experimental materials used by the author, we found Ethyl 3-oxopentanoate(cas: 4949-44-4Recommanded Product: 4949-44-4)

Ethyl 3-oxopentanoate(cas: 4949-44-4) belongs to ketone compounds. They are most widely used as solvents, especially in industries manufacturing explosives, lacquers, paints, and textiles. Ketones are also used in tanning, as preservatives, and in hydraulic fluids.Recommanded Product: 4949-44-4

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

Recommanded Product: Ethyl 2-amino-2-thioxoacetateIn 2017 ,《Utilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT2C Receptor Agonists》 was published in Journal of Medicinal Chemistry. The article was written by Carpenter, Joseph; Wang, Ying; Wu, Gang; Feng, Jianxin; Ye, Xiang-Yang; Morales, Christian L.; Broekema, Matthias; Rossi, Karen A.; Miller, Keith J.; Murphy, Brian J.; Wu, Ginger; Malmstrom, Sarah E.; Azzara, Anthony V.; Sher, Philip M.; Fevig, John M.; Alt, Andrew; Bertekap, Robert L.; Cullen, Mary Jane; Harper, Timothy M.; Foster, Kimberly; Luk, Emily; Xiang, Qian; Grubb, Mary F.; Robl, Jeffrey A.; Wacker, Dean A.. The article contains the following contents:

Agonism of the 5-HT2C receptor represents one of the most well-studied and clin. proven mechanisms for pharmacol. weight reduction Selectivity over the closely related 5-HT2A and 5-HT2B receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT2C receptor to identify atypical agonist structures. We addnl. report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT2C. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT2C with high selectivity over the related 5-HT2A and 5-HT2B receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT2C antagonist. The experimental part of the paper was very detailed, including the reaction process of Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1Recommanded Product: Ethyl 2-amino-2-thioxoacetate)

Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1) belongs to anime. The methylamines occur in small amounts in some plants. Many polyfunctional amines (i.e., those having other functional groups in the molecule) occur as alkaloids in plants—for example, mescaline, 2-(3,4,5-trimethoxyphenyl)ethylamine; the cyclic amines nicotine, atropine, morphine, and cocaine; and the quaternary salt choline, N-(2-hydroxyethyl)trimethylammonium chloride, which is present in nerve synapses and in plant and animal cells.Recommanded Product: Ethyl 2-amino-2-thioxoacetate

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

HPLC of Formula: 6149-41-3In 2013 ,《Assessment of the chemical composition and in vitro antimicrobial potential of extracts of the liverwort Scapania aspera》 was published in Natural Product Communications. The article was written by Bukvicki, Danka R.; Tyagi, Amit K.; Gottardi, Davide G.; Veljic, Milan M.; Jankovic, Snezana M.; Guerzoni, Maria E.; Marin, Petar D.. The article contains the following contents:

The chem. composition of Scapania aspera extracts was determined by solid phase micro extraction gas chromatog.-mass spectrometry (SPME GC-MS) and 96 constituents were identified. The dominant compounds in the methanol extract were β-barbatene (25.1%), o-cymene (14.0%), α-barbatene (5.7%), allo-aromadendrene (4.9%) and β-bourbonene, while in the ethanol extract, o-cymene (17.8%), β-barbatene (17.6%), α-thujene (6.7%), octen-1-ol acetate (4.9%) and β-bazzanene (2.4%) were the major components. In the Et acetate extract, β-barbatene (14.3%), undecane (11.8%), 2-methyldecane (11.2%), decane (10.9%) and o-cymene (3.6%) were major components. The antimicrobial activity of the different extracts was evaluated against pathogenic and food spoilage microorganisms using disk diffusion and micro-broth dilution methods. The minimal inhibitory concentration (MIC) of extracts of S. aspera varied from 0.4 to 1.5 mg/mL and 1 to 3 mg/mL for yeast and bacterial strains, resp. The zone of inhibition of the methanol extract for yeast strains was higher than that for bacterial strains. The results suggest that S. aspera extracts have potential as natural antimicrobial agents. In the experiment, the researchers used many compounds, for example, Methyl 3-hydroxypropanoate(cas: 6149-41-3HPLC of Formula: 6149-41-3)

Methyl 3-hydroxypropanoate(cas: 6149-41-3) belongs to esters with low molecular weight are commonly used as fragrances and found in essential oils and pheromones. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. HPLC of Formula: 6149-41-3

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

HPLC of Formula: 2495-35-4In 2019 ,《Enantioselective Synthesis of Biaryl Atropisomers by Pd-Catalyzed C-H Olefination using Chiral Spiro Phosphoric Acid Ligands》 appeared in Angewandte Chemie, International Edition. The author of the article were Luo, Jun; Zhang, Tao; Wang, Lei; Liao, Gang; Yao, Qi-Jun; Wu, Yong-Jie; Zhan, Bei-Bei; Lan, Yu; Lin, Xu-Feng; Shi, Bing-Feng. The article conveys some information:

The discovery of proper ligands to simultaneously modulate the reactivity and effectively control the stereoselectivity is a central topic in the field of enantioselective C-H activation. Herein, we reported the synthesis of axially chiral biaryls by Pd-catalyzed atroposelective C-H olefination. A novel chiral spiro phosphoric acid, STRIP, was identified as a superior ligand for this transformation. A broad range of axially chiral quinoline derivatives were synthesized in good yields with excellent enantioselectivities (up to 98 % ee). D. functional theory was used to gain a theor. understanding of the enantioselectivities in this reaction. The experimental part of the paper was very detailed, including the reaction process of Benzyl acrylate(cas: 2495-35-4HPLC of Formula: 2495-35-4)

Benzyl acrylate(cas: 2495-35-4) is a reagent that can be used in the preparation of 2-(Phosphonomethyl)pentanedioic Acid, a selective glutamate carboxypeptidase 2 (GCP-II) inhibitor. It can also be used in the preparation of high refractive index polyacrylates.HPLC of Formula: 2495-35-4

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

In 2022,Ji, Jin; Shao, Wu-Bin; Chu, Pan-Long; Xiang, Hong-Mei; Qi, Pu-Ying; Zhou, Xiang; Wang, Pei-Yi; Yang, Song published an article in Journal of Agricultural and Food Chemistry. The title of the article was 《1,3,4-Oxadiazole Derivatives as Plant Activators for Controlling Plant Viral Diseases: Preparation and Assessment of the Effect of Auxiliaries》.Recommanded Product: 403-33-8 The author mentioned the following in the article:

Plant viral diseases cause the loss of millions of dollars to agriculture around the world annually. Therefore, the development of highly efficient, ultra-low-dosage agrochems. is desirable for protecting the health of crops and ensuring food security. Herein, a series of 1,3,4-oxadiazole derivatives bearing an isopropanol amine moiety was prepared, and the inhibitory activity against tobacco mosaic virus (TMV) was assessed. Notably, compound A14 (I) exhibited excellent anti-TMV protective activity with an EC50 value of 137.7 mg L-1, which was superior to that of ribavirin (590.0 mg L-1) and ningnanmycin (248.2 mg L-1). Moreover, the anti-TMV activity of some compounds could be further enhanced (by up to 5-30%) through supplementation with 0.1% auxiliaries. Biochem. assays suggested that compound A14 could suppress the biosynthesis of TMV and induce the plant’s defense response. Given these merits, designed compounds had outstanding bioactivities and unusual action mechanisms and were promising candidates for controlling plant viral diseases. The experimental process involved the reaction of Methyl 4-fluorobenzoate(cas: 403-33-8Recommanded Product: 403-33-8)

Methyl 4-fluorobenzoate(cas: 403-33-8) can be used in the synthesis of trisubstituted imidazole derivatives containing a 4-fluorophenyl group, a pyrimidine ring, and a CN- or CONH2-substituted benzyl moiety.Recommanded Product: 403-33-8

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