Tag: 100-200

Formula: C8H14O4In 2022 ,《Design, synthesis, and evaluation of potent RIPK1 inhibitors with in vivo anti-inflammatory activity》 was published in European Journal of Medicinal Chemistry. The article was written by Li, Zhanhui; Hao, Yongjin; Yang, Chengkui; Yang, Qing; Wu, Shuwei; Ma, Haikuo; Tian, Sheng; Lu, Haohao; Wang, Jingrui; Yang, Tao; He, Sudan; Zhang, Xiaohu. The article contains the following contents:

RIPK1 plays a key role in the necroptosis pathway that regulates inflammatory signaling and cell death in various diseases, including inflammatory and neurodegenerative diseases. Herein, we report a series of potent RIPK1 inhibitors, represented by compound 70. Compound 70 efficiently blocks necroptosis induced by TNFα in both human and mouse cells (EC50 = 17-30 nM). Biophys. assay demonstrates that compound 70 potently binds to RIPK1 (Kd = 9.2 nM), but not RIPK3 (Kd > 10,000 nM). Importantly, compound 70 exhibits greatly improved metabolic stability in human and rat liver microsomes compared to compound 6 (PK68), a RIPK1 inhibitor reported in our previous work. In addition, compound 70 displays high permeability in Caco-2 cells and excellent in vitro safety profiles in hERG and CYP assays. Moreover, pre-treatment of 70 significantly ameliorates hypothermia and lethal shock in SIRS mice model. Lastly, compound 70 possesses favorable pharmacokinetic parameters with moderate clearance and good oral bioavailability in SD rat. Taken together, our work supports 70 as a potent RIPK1 inhibitor and highlights its potential as a prototypical lead for further development in necroptosis-associated inflammatory disorders. The experimental part of the paper was very detailed, including the reaction process of Diethyl 2-methylmalonate(cas: 609-08-5Formula: C8H14O4)

Diethyl 2-methylmalonate(cas: 609-08-5) belongs to aliphatic hydrocarbons. Aliphatic hydrocarbons belong to the most abundant fraction in crude oil. Aliphatics molecules are linear or branched open-chain structures such as n-alkanes, isoalkanes, cycloalkanes (naphthenes), terpenes and steranes.Formula: C8H14O4

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

Safety of Methyl 4-fluoro-3-nitrobenzoateIn 2017 ,《Structural insight into allosteric modulation of protease-activated receptor 2》 appeared in Nature (London, United Kingdom). The author of the article were Cheng, Robert K. Y.; Fiez-Vandal, Cedric; Schlenker, Oliver; Edman, Karl; Aggeler, Birte; Brown, Dean G.; Brown, Giles A.; Cooke, Robert M.; Dumelin, Christoph E.; Dore, Andrew S.; Geschwindner, Stefan; Grebner, Christoph; Hermansson, Nils-Olov; Jazayeri, Ali; Johansson, Patrik; Leong, Louis; Prihandoko, Rudi; Rappas, Mathieu; Soutter, Holly; Snijder, Arjan; Sundstrom, Linda; Tehan, Benjamin; Thornton, Peter; Troast, Dawn; Wiggin, Giselle; Zhukov, Andrei; Marshall, Fiona H.; Dekker, Niek. The article conveys some information:

Protease-activated receptors (PARs) are a family of G-protein-coupled receptors (GPCRs) that are irreversibly activated by proteolytic cleavage of the N-terminus, which unmasks a tethered peptide ligand that binds and activates the transmembrane receptor domain, eliciting a cellular cascade in response to inflammatory signals and other stimuli. PARs are implicated in a wide range of diseases, such as cancer and inflammation. PARs have been the subject of major pharmaceutical research efforts, but the discovery of small-mol. antagonists that effectively bind them has proved challenging. The only marketed drug targeting a PAR is vorapaxar, a selective antagonist of PAR1 used to prevent thrombosis. The structure of PAR1 in complex with vorapaxar has been reported previously. Despite sequence homol. across the PAR isoforms, discovery of PAR2 antagonists has been less successful, although GB88 has been described as a weak antagonist. Here, we report crystal structures of PAR2 in complex with two distinct antagonists and a blocking antibody. The antagonist AZ8838 binds in a fully occluded pocket near the extracellular surface. Functional and binding studies reveal that AZ8838 exhibits slow binding kinetics, which is an attractive feature for a PAR2 antagonist competing against a tethered ligand. Antagonist AZ3451 binds to a remote allosteric site outside the helical bundle. We propose that antagonist binding prevents structural rearrangements required for receptor activation and signalling. We also show that a blocking antibody antigen-binding fragment binds to the extracellular surface of PAR2, preventing access of the tethered ligand to the peptide-binding site. These structures provide a basis for the development of selective PAR2 antagonists for a range of therapeutic uses. After reading the article, we found that the author used Methyl 4-fluoro-3-nitrobenzoate(cas: 329-59-9Safety of Methyl 4-fluoro-3-nitrobenzoate)

Methyl 4-fluoro-3-nitrobenzoate(cas: 329-59-9) belongs to methyl benzoate. Methyl benzoate reacts at both the ring and the ester, depending on the substrate. Electrophiles attack the ring, illustrated by acid-catalysed nitration with nitric acid to give methyl 3-nitrobenzoate.Safety of Methyl 4-fluoro-3-nitrobenzoate

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

In 2022,Marrazzo, John-Paul R.; Chao, Allen; Li, Yajun; Fleming, Fraser F. published an article in Journal of Organic Chemistry. The title of the article was 《Copper-Catalyzed Conjugate Additions to Isocyanoalkenes》.Recommanded Product: Diethyl 2-methylmalonate The author mentioned the following in the article:

A copper iodide-Pyox complex catalyzed the first conjugate addition of diverse sulfur, nitrogen, and carbon nucleophiles to isocyanoalkenes to gave isocyano(aryl)ethyl(sulfane/alkyl/imidazole/isoindoline-1,3-dione) I [Ar = 2-MeOC6H4, 4-PhC6H4, R = allylsulfanyl, imidazol-1-yl, cyano(diphenyl)methyl, etc.]. The anionic addition generates metalated isocyanoalkanes capable of SNi displacements, provided a rapid route to a series of functionalized, cyclic isocyanoalkanes II [R1 = 2-MeC6H4, 2-MeOC6H4, 4-PhC6H4, etc.; R2 = H, n-Pr, R3 = Me, Et, t-Bu] and III. The Cu(I)I-Pyox complex efficiently catalyzes a first-in-class conjugate addition affording a range of complex, functionalized isocyanoalkanes I, II and III that were otherwise challenging to synthesize while laying a foundation for catalytic reactions that maintain the isocyanide group. In the experimental materials used by the author, we found Diethyl 2-methylmalonate(cas: 609-08-5Recommanded Product: Diethyl 2-methylmalonate)

Diethyl 2-methylmalonate(cas: 609-08-5) belongs to aliphatic hydrocarbons. Aliphatic hydrocarbons belong to the most abundant fraction in crude oil. Aliphatics molecules are linear or branched open-chain structures such as n-alkanes, isoalkanes, cycloalkanes (naphthenes), terpenes and steranes.Recommanded Product: Diethyl 2-methylmalonate

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

Kim, Heebum; Kim, Sung-Gon published an article in 2022. The article was titled 《Intramolecular oxa-Mannich reaction of 1,3-dihydro-2-benzofuran-1-ol for efficient synthesis of 1-aminophthalan derivatives》, and you may find the article in Journal of the Korean Chemical Society.Product Details of 4248-19-5 The information in the text is summarized as follows:

An efficient method for the synthesis of 1-aminophthalans I (R = Ts, Boc, Cbz, POPh2) has been developed. The intramol. oxa-Mannich reaction of 1,3-dihydro-2-benzofuran-1-ols II with amines RNH2 in the presence of Cs2CO3 as a base, without using any catalyst, provided the desired 1-aminophthalans in moderate to good yields. The experimental part of the paper was very detailed, including the reaction process of tert-Butyl carbamate(cas: 4248-19-5Product Details of 4248-19-5)

tert-Butyl carbamate(cas: 4248-19-5) 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.Product Details of 4248-19-5

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

Asahara, Haruyasu; Bonkohara, Atsushi; Takagi, Masaya; Iwai, Kento; Ito, Akitaka; Yoshioka, Kotaro; Tani, Shinki; Umezu, Kazuto; Nishiwaki, Nagatoshi published an article in 2022. The article was titled 《Development of a synthetic equivalent of α,α-dicationic acetic acid leading to unnatural amino acid derivatives via tetrafunctionalized methanes》, and you may find the article in Organic & Biomolecular Chemistry.Name: tert-Butyl carbamate The information in the text is summarized as follows:

Di-Et mesoxalate (DEMO) exhibits high electrophilicity and accepts the nucleophilic addition of a less nucleophilic acid amide to afford N,O-hemiacetal. However, our research showed that elimination of the amide moiety proceeded more easily than dehydration upon treatment with a base. This problem was overcome by reacting DEMO with an acid amide in the presence of acetic anhydride to efficiently obtain N,O-acetal. Acetic acid was eliminated leading to the formation of N-acylimine in situ upon treatment with the base. N-Acylimine is also electrophilic, accepting the second nucleophilic addition by pyrrole or indole to form α,α-disubstituted malonates. Subsequent hydrolysis followed by decarboxylation resulted in (α-indolyl-α-acylamino)acetic acid formation; homologs of tryptophan. Through this process, DEMO serves as a synthetic equivalent of α,α-dicationic acetic acid to facilitate nucleophilic introduction of the two substituents. After reading the article, we found that the author used tert-Butyl carbamate(cas: 4248-19-5Name: tert-Butyl carbamate)

tert-Butyl carbamate(cas: 4248-19-5) 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.Name: tert-Butyl carbamate

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

Chen, Ming; Wu, Zheng-Jian; Song, Jinshuai; Xu, Hai-Chao published an article in 2022. The article was titled 《Electrocatalytic Allylic C-H Alkylation Enabled by a Dual-Function Cobalt Catalyst》, and you may find the article in Angewandte Chemie, International Edition.Application In Synthesis of Ethyl 2-methyl-3-oxobutanoate The information in the text is summarized as follows:

An electrocatalytic allylic C-H alkylation reaction with carbon nucleophiles RCH(R1)(C(O)R2) (R = H, F, Me, Bn, etc. ; R1 = H, CN, Me, Et; R2 = Me, OEt, pyrrolidin-1-yl, etc.) employing an easily available cobalt-salen complex as the mol. catalyst was reported. These C(3)-H/C(sp3)-H cross-coupling reactions proceed through H2 evolution and require no external chem. oxidants. Importantly, the mild conditions and unique electrocatalytic radical process ensure excellent functional group tolerance and substrate compatibility with both linear and branched terminal alkenes e.g., (hex-5-en-1-yloxy)benzene. The synthetic utility of the electrochem. method is highlighted by its scalability (up to 200 mmol scale) under low loading of electrolyte (down to 0.05 equiv) and its successful application in the late-stage functionalization of complex structures. In the part of experimental materials, we found many familiar compounds, such as Ethyl 2-methyl-3-oxobutanoate(cas: 609-14-3Application In Synthesis of Ethyl 2-methyl-3-oxobutanoate)

Ethyl 2-methyl-3-oxobutanoate(cas: 609-14-3) belongs to ketone compounds. Ketones are highly reactive, although less so than aldehydes, to which they are closely related. Much of their chemical activity results from the nature of the carbonyl group. Ketones readily undergo a wide variety of chemical reactions.Application In Synthesis of Ethyl 2-methyl-3-oxobutanoate

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

Mirjalili, Bi Bi Fatemeh; Soltani, Roya; Bamoniri, Abdolhamid published an article in 2021. The article was titled 《Nano-kaolin/Ti(IV)/Fe3O4: a natural based magnetic nanocatalyst for the synthesis of coumarins》, and you may find the article in Journal of Nanostructures.Application In Synthesis of Ethyl 3-oxopentanoate The information in the text is summarized as follows:

Nano-kaolin/Ti(IV)/Fe3O4 as an efficient natural based magnetic nanocatalyst was synthesized and characterized using com. nano-kaoline. Structural properties of this catalyst were investigated by using various techniques such as fourier transform IR (FT-IR) spectroscopy, X-ray diffraction (XRD), field emission SEM (FESEM), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), thermal gravimetric anal. (TGA) and energy-dispersive X-ray spectroscopy (EDX). Coumarines have shown various biol. activities such as analgesic, antimicrobial, antimalarial, antioxidant, anti-inflammatory, anticancer, antituberculosis and anti-HIV properties. Nano-kaolin/Ti(IV)/Fe3O4 was used for the synthesis of coumarines via Pechmann condensation between phenols and β-ketoester under solvent-free conditions at 120°C. In this procedure, we have used phloroglucinol, resorcinol, 1-naphthol, pyrogalol and chatechol as nucleophile and Et acetoacetate, Et 2-chloro-acetoacetate, Et propionylacetate, Et 3-oxo-hexanoate, 2-ethoxycarbonyl cyclopentanone and Et benzoylacetate as electrophile. The structure of coumarine products was identified by FTIR and NMR spectroscopies. This method offers has several advantages such as easy workup, short reaction times, high product yields and reusability of catalyst. After reading the article, we found that the author used Ethyl 3-oxopentanoate(cas: 4949-44-4Application In Synthesis of Ethyl 3-oxopentanoate)

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.Application In Synthesis of Ethyl 3-oxopentanoate

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

Johannes, Jeffrey W.; Balazs, Amber; Barratt, Derek; Bista, Michal; Chuba, Matthew D.; Cosulich, Sabina; Critchlow, Susan E.; Degorce, Sebastien L.; Di Fruscia, Paolo; Edmondson, Scott D.; Embrey, Kevin; Fawell, Stephen; Ghosh, Avipsa; Gill, Sonja J.; Gunnarsson, Anders; Hande, Sudhir M.; Heightman, Tom D.; Hemsley, Paul; Illuzzi, Giuditta; Lane, Jordan; Larner, Carrie; Leo, Elisabetta; Liu, Lina; Madin, Andrew; Martin, Scott; McWilliams, Lisa; O′Connor, Mark J.; Orme, Jonathan P.; Pachl, Fiona; Packer, Martin J.; Pei, Xiaohui; Pike, Andrew; Schimpl, Marianne; She, Hongyao; Staniszewska, Anna D.; Talbot, Verity; Underwood, Elizabeth; Varnes, Jeffrey G.; Xue, Lin; Yao, Tieguang; Zhang, Ke; Zhang, Andrew X.; Zheng, Xiaolan published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs》.HPLC of Formula: 329-59-9 The article contains the following contents:

Poly-ADP-ribose-polymerase (PARP) inhibitors have achieved regulatory approval in oncol. for homologous recombination repair deficient tumors including BRCA mutation. However, some have failed in combination with first-line chemotherapies, usually due to overlapping hematol. toxicities. Currently approved PARP inhibitors lack selectivity for PARP1 over PARP2 and some other 16 PARP family members, and we hypothesized that this could contribute to toxicity. Recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for driving efficacy in a BRCA mutant background. Herein, we describe the structure- and property-based design of AZD5305, I, a potent and selective PARP1 inhibitor and PARP1-DNA trapper with excellent in vivo efficacy in a BRCA mutant HBCx-17 PDX model. Compound 25 is highly selective for PARP1 over other PARP family members, with good secondary pharmacol. and physicochem. properties and excellent pharmacokinetics in preclin. species, with reduced effects on human bone marrow progenitor cells in vitro. The experimental part of the paper was very detailed, including the reaction process of Methyl 4-fluoro-3-nitrobenzoate(cas: 329-59-9HPLC of Formula: 329-59-9)

Methyl 4-fluoro-3-nitrobenzoate(cas: 329-59-9) belongs to methyl benzoate. Methyl benzoate reacts at both the ring and the ester, depending on the substrate. Electrophiles attack the ring, illustrated by acid-catalysed nitration with nitric acid to give methyl 3-nitrobenzoate.HPLC of Formula: 329-59-9Methyl 4-fluoro-3-nitrobenzoate is used to prepare dimethyl 3-nitro-3′,4-oxydibenzoate by reacting with 3-hydroxy-benzoic acid methyl ester.

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

Liu, Chong; Yuan, Jing; Zhang, Zhenfeng; Gridnev, Ilya D.; Zhang, Wanbin published their research in Angewandte Chemie, International Edition in 2021. The article was titled 《Asymmetric Hydroacylation Involving Alkene Isomerization for the Construction of C3-Chirogenic Center》.Application In Synthesis of Methyl 4-fluorobenzoate The article contains the following contents:

A new transformation pattern for enantioselective intramol. hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals such as I (or their Z isomers) were converted to C3- or C3,C5-chirogenic cyclopentanones such as II with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theor. calculated and the origin of the stereoselection is rationally explained. In the part of experimental materials, we found many familiar compounds, such as Methyl 4-fluorobenzoate(cas: 403-33-8Application In Synthesis of Methyl 4-fluorobenzoate)

Methyl 4-fluorobenzoate(cas: 403-33-8) is an organic fluorinated building block used for the synthesis of various pharmaceutical compounds. It can be used for the preparation of Blonanserin.Application In Synthesis of Methyl 4-fluorobenzoate

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

The author of 《Ketamine esters and amides as short-acting anesthetics: structure-activity relationships for the side-chain》 were Dimitrov, Ivaylo V.; Harvey, Martyn G.; Voss, Logan J.; Sleigh, James W.; Bickerdike, Michael J.; Denny, William A.. And the article was published in Bioorganic & Medicinal Chemistry in 2019. Name: Diethyl 2-methylmalonate The author mentioned the following in the article:

N-Aliphatic ester analogs of the non-opioid ketamine (1) retain effective anesthetic/analgesic properties while minimizing ketamine’s psychomimetic side-effects. We show that the anesthetic/analgesic properties of these ester analogs depend critically on the length (from 2 to 4 carbons), polarity and steric cross-section of the aliphatic linker chain. More stable amide and ethylsulfone analogs generally showed weaker anesthetic/analgesic activity. There was no correlation between the anesthetic/analgesic properties of the compounds and their binding affinities for the N-methyl-D-aspartate (NMDA) receptor.Diethyl 2-methylmalonate(cas: 609-08-5Name: Diethyl 2-methylmalonate) was used in this study.

Diethyl 2-methylmalonate(cas: 609-08-5) belongs to aliphatic hydrocarbons. Aliphatic hydrocarbons belong to the most abundant fraction in crude oil. Aliphatics molecules are linear or branched open-chain structures such as n-alkanes, isoalkanes, cycloalkanes (naphthenes), terpenes and steranes.Name: Diethyl 2-methylmalonate

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