Month: October 2022

Stress, Cedric J.; Sauter, Basilius; Schneider, Lukas A.; Sharpe, Timothy; Gillingham, Dennis published the artcile< A DNA-Encoded Chemical Library Incorporating Elements of Natural Macrocycles>, Category: thiazole, the main research area is DNA encoded library macrocycle compound; DNA chemistry; DNA-encoded libraries; Lipinski rules; chemical libraries; macrocycles.

Here the authors show a seven-step chem. synthesis of a DNA-encoded macrocycle library (DEML) on DNA. Inspired by polyketide and mixed peptide-polyketide natural products, the library was designed to incorporate rich backbone diversity. Achieving this diversity, however, comes at the cost of the custom synthesis of bifunctional building block libraries. This study outlines the importance of careful retrosynthetic design in DNA-encoded libraries, while revealing areas where new DNA synthetic methods are needed.

Angewandte Chemie, International Editionpublished new progress about Combinatorial library (DNA-encoded). 96929-05-4 belongs to class thiazole, and the molecular formula is C12H18N2O4S, Category: thiazole.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Delpire, Eric; Days, Emily; Lewis, L. Michelle; Mi, Dehui; Kim, Kwangho; Lindsley, Craig W.; Weaver, C. David published the artcile< Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2>, Recommanded Product: 4-Cyclopropylthiazol-2-amine, the main research area is potassium chlorine cotransporter KCC2 inhibitor preparation drug screening.

KCC2, a neuronal-specific K-Cl co-transporter, plays a major role in maintaining intracellular Cl- concentration in neurons below its electrochem. equilibrium potential, thus favoring robust GABA hyperpolarizing or inhibitory responses. The pharmacol. of the K-Cl co-transporter is dominated by loop diuretics such as furosemide and bumetanide, mols. used in clin. medicine because they inhibit the loop of Henle Na-K-2Cl co-transporter with much higher affinity. To identify mols. that affect KCC2 activity, the authors developed a fluorescence-based assay suitable for high-throughput screening (HTS) and used the assay to screen a library of 234,000 small mols. They identified a large number of mols. that either decrease or increase the activity of the co-transporter. Here, they report the characterization of a small number of inhibitors, some of which inhibit KCC2 activity in the submicromolar range without substantially affecting NKCC1 activity. Using medicinal chem., they synthesized a number of variants, tested their effect on KCC2 function, and provide an anal. of structure/activity relationships. They also used one of the compounds to demonstrate competitive inhibition in regard to external [K+] vs. non-competitive inhibition in respect to external [Cl-].

Proceedings of the National Academy of Sciences of the United States of Americapublished new progress about Carrier-mediated biological transport. 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Recommanded Product: 4-Cyclopropylthiazol-2-amine.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Penalver, Lilian; Schmid, Philipp; Szamosvari, David; Schildknecht, Stefan; Globisch, Christoph; Sawade, Kevin; Peter, Christine; Boettcher, Thomas published the artcile< A ligand selection strategy identifies chemical probes targeting the proteases of SARS-CoV-2>, Synthetic Route of 324579-90-0, the main research area is ligand selection strategy probe targeting protease SARS CoV2; COVID19 SARS CoV2 protease 3CLpro PLpro labeling inhibitor; ABPP; chemical probes; enzyme inhibitors; labeling; proteases.

Activity-based probes are valuable tools for chem. biol. However, finding probes that specifically target the active site of an enzyme remains a challenging task. Herein, we present a ligand selection strategy that allows to rapidly tailor electrophilic probes to a target of choice and showcase its application for the two cysteine proteases of SARS-CoV-2 as proof of concept. The resulting probes were specific for the active site labeling of 3CLpro and PLpro with sufficient selectivity in a live cell model as well as in the background of a native human proteome. Exploiting the probes as tools for competitive profiling of a natural product library identified salvianolic acid derivatives as promising 3CLpro inhibitors. We anticipate that our ligand selection strategy will be useful to rapidly develop customized probes and discover inhibitors for a wide range of target proteins also beyond corona virus proteases.

Angewandte Chemie, International Editionpublished new progress about Alkynyl groups (in enzyme probe). 324579-90-0 belongs to class thiazole, and the molecular formula is C6H8N2S, Synthetic Route of 324579-90-0.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Hsieh, Sheng-Ying; Bode, Jeffrey W. published the artcile< Lewis Acid Induced Toggle from Ir(II) to Ir(IV) Pathways in Photocatalytic Reactions: Synthesis of Thiomorpholines and Thiazepanes from Aldehydes and SLAP Reagents>, Application In Synthesis of 1003-32-3, the main research area is Lewis acid iridium thiomorpholine thiazepane photoredox catalyst.

The authors report that the inclusion of Lewis acids in photocatalytic reactions of organosilanes allows access to a distinct reaction pathway featuring an Ir(III)*/Ir(IV) couple instead of the previously employed Ir(III)*/Ir(II) pathway, enabling the transformation of aromatic and aliphatic aldehydes to thiomorpholines and thiazepanes. The role of the Lewis acid in accepting an electron-either directly or via coordination to an imine-can be extended to other classes of photocatalysts and transformations, including oxidative cyclizations. The combination of light induced reactions and Lewis acids therefore promises access to new pathways and transformations that are not viable using the photocatalysts alone.

ACS Central Sciencepublished new progress about Aliphatic aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application In Synthesis of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Ling, Xing; Lu, Weiwei; Miao, Lin; Marcaurelle, Lisa A.; Wang, Xuan; Ding, Yun; Lu, Xiaojie published the artcile< Divergent On-DNA Transformations from DNA-Linked Piperidones>, Application In Synthesis of 1003-32-3, the main research area is DNA linked heterocycle preparation.

A group of highly efficient and divergent transformations for constructing multiple DNA-linked chemotypes based on piperidones e.g., I core is successfully developed. The first procedure for the synthesis of DNA-conjugated piperidines II (R = H, Bn, (4-cyanophenyl)methyl, (3,4,5-trifluorophenyl)methyl, etc.; R1 = 2,2-dimethoxyethyl, Bn, 3-cyclohexylpropanoyl, etc.) intermediate under basic conditions was reported. Subsequently, this substructure was subjected to addnl. reactions to generate several privileged scaffolds, including 4-aminopiperidines II, fused [1,2,4]triazolo[1,5-a]pyrimidines III (R2 = methanesulfonyl, (3-fluorophenyl)methyl, benzenesulfonamido), and a quinoline derivative e.g., IV. These transformations paved the way for constructing focused scaffold-based DNA-encoded libraries with druglike properties.

Journal of Organic Chemistrypublished new progress about Acids Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application In Synthesis of 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Din Reshi, Noor U.; Senthurpandi, Dineshchakravarthy; Samuelson, Ashoka G. published the artcile< Asymmetric transfer hydrogenation of ketones using Ru(0) nanoparticles modified by Chiral Thiones>, COA of Formula: C10H11NS2, the main research area is ketone asym transfer hydrogenation; oxazolidinethione thiozolidinethione ruthenium half sandwich complex catalyst preparation.

The catalytic asym. transfer hydrogenation (ATH) of acetophenone in isopropanol by Ru(0) nanoparticles (NPs) obtained by the in-situ reduction of Ru(II) half-sandwich complexes of chiral 2-oxazolidinethiones and 2-thiozolidinethiones was examined and compared with the catalytic activity of Ru(0) NPs formed in-situ by the reduction of [Ru(p-cymene)(Cl)2]2 in presence of optically active ligands such as (S)-4-isobutylthiazolidine-2-thione, (S)-4-isopropyl-2(-2-pyridinyl)-2-oxazoline, (8S, 9R)-(-)-cinchonidine, (S)-leucinol, (S)-phenylalaninol, and (S)-leucine. Three of the best catalytic systems were then examined for ATH of thirteen aromatic ketones with different electronic and steric properties. A maximum of 24% ee was obtained using NPs generated from the Ru (II) half-sandwich complex with (S)-4-isobutylthiazolidine-2-thione in the TH of acetophenone. The NPs were characterized by TEM and DLS measurements. Kinetic studies and poisoning experiments confirmed that the reaction is catalyzed by the chiral NPs formed in-situ. Complete characterization of the complexes, including the X-ray crystallog. characterization of two complexes, was also carried out.

Applied Organometallic Chemistrypublished new progress about Alcohols Role: SPN (Synthetic Preparation), PREP (Preparation). 171877-39-7 belongs to class thiazole, and the molecular formula is C10H11NS2, COA of Formula: C10H11NS2.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Tao, Zhi-Fu; Chen, Zehan; Bui, Mai-Ha; Kovar, Peter; Johnson, Eric; Bouska, Jennifer; Zhang, Haiying; Rosenberg, Saul; Sowin, Thomas; Lin, Nan-Horng published the artcile< Macrocyclic ureas as potent and selective Chk1 inhibitors: An improved synthesis, kinome profiling, structure-activity relationships, and preliminary pharmacokinetics>, HPLC of Formula: 1003-32-3, the main research area is macrocyclic urea preparation selective Chk1 inhibitor; structure macrocyclic urea selectivity Chk1 inhibitor pharmacokinetics; doxorubicin macrocyclic urea combination antitumor activity; kinase selectivity inhibition macrocyclic urea; amine protection key step preparation macrocyclic urea; trimethylsilylethoxycarbonyl group protection amine key step preparation macrocyclic urea.

Macrocyclic ureas such as I [R = H, H2N, MeNH, Me2N, (HOCH2CH2)2N, HOCH2CH2NH, 5-thiazolylmethylamino, 4-pyridinecarbonylamino, 2-chloro-4-pyridinecarbonylamino, (S)-MeCH(NH2)CONH, 2-(4-morpholinyl)ethoxycarbonylamino, 2-oxo-3-oxazolidinyl, HO, HOCH2CH2O, HO(CH2)3O, MeO(CH2)3, 2-(4-morpholinyl)ethoxy, 3-(4-morpholinyl)propoxy, 4-(1-piperidinyl)-1-piperidinecarbonyloxy, (HO)2P(:O); X = CH2CH2, CH:CH] are prepared as selective Chk1 kinase inhibitors and as agents for the sensitization of tumor cells to doxorubicin for potential use as anticancer agents. The structure-activity relationship for Chk1 inhibition of substituted 14-membered urea macrocycles is determined, leading to the identification of sixteen compounds which are effective inhibitors of Chk1. The active urea macrocycles significantly sensitize tumor cells to the DNA-damaging antitumor agent doxorubicin in a cell-based assay and efficiently abrogate the doxorubicin-induced G2/M and camptothecin-induced S checkpoints. The inhibition of a panel of 120 kinases by I (R = 5-thiazolemethylamino; X = CH2CH2; II) is determined; II inhibits Chk1 at 100-fold lower concentrations than any of the other kinases in the panel. Pharmacokinetic studies of I (R = H; X = CH2CH2, CH2CH2CH2) suggest that 14-membered macrocycles such as I (R = H; X = CH2CH2) may possess better pharmacokinetic properties than their 15-membered counterparts such as I (R = H; X = CH2CH2CH2). An improved method for the preparation of amine-containing urea macrocycles I [R = H2N; X = CH:CH, CH2CH2] is determined; protection of the free amino group of a bisallyl diaryl urea intermediate with the trimethylsilylethoxycarbonyl group allows ring-closing macrocyclocondensation in the presence of the Hoveyda-Grubbs catalyst without the formation of inseparable and highly colored byproducts.

Bioorganic & Medicinal Chemistry Letterspublished new progress about Antitumor agents. 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, HPLC of Formula: 1003-32-3.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Dong, Jiaxing; Huang, Yumin; Qin, Xurong; Cheng, Yangyang; Hao, Jing; Wan, Danyang; Li, Wei; Liu, Xingyan; You, Jingsong published the artcile< Palladium(II)-Catalyzed Oxidative C-H/C-H Cross-Coupling between Two Structurally Similar Azoles>, HPLC of Formula: 20582-55-2, the main research area is azole palladium copper cocatalyst oxidative cross coupling; double carbon hydrogen activation azole cross coupling.

A widely functional-group tolerant, selective and rapid oxidative cross-coupling between two structurally similar azoles has been carried out by using a palladium/copper co-catalytic twofold C-H activation method.

Chemistry – A European Journalpublished new progress about Azoles Role: PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 20582-55-2 belongs to class thiazole, and the molecular formula is C7H9NO2S, HPLC of Formula: 20582-55-2.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Isbrandt, Eric S.; Nasim, Amrah; Zhao, Karen; Newman, Stephen G. published the artcile< Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand>, Recommanded Product: Thiazole-5-carboxyaldehyde, the main research area is aryl iodide aldehyde nickel diazadiphosphacyclooctane catalyst reductive Heck arylation; primary alc aryliodide nickel diazadiphosphacyclooctane catalyst reductive Heck arylation; secondary alc preparation.

A catalytic method to access secondary alcs. by the coupling of aryl iodides was reported. Either aldehydes or alcs. can be used as reaction partners, making the transformation reductive or redox-neutral, resp. The reaction was mediated by a Ni catalyst and a 1,5-diaza-3,7-diphosphacyclooctane. This P2N2 ligand, which was previously been unrecognized in cross-coupling and related reactions, was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs. An interrupted carbonyl-Heck type mechanism was proposed to be operative, with a key 1,2-insertion step forging the new C-C bond and forming a nickel alkoxide that may be turned over by an alc. reductant. The same catalyst was also found to enable synthesis of ketone products from either aldehydes or alcs., demonstrating control over the oxidation state of both the starting materials and products.

Journal of the American Chemical Societypublished new progress about Aldehydes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Recommanded Product: Thiazole-5-carboxyaldehyde.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Yin, Liuyan; Wang, Lanzhi published the artcile< Chemo-/regio-selective synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines using Lewis acid, CeCl3·7H2O>, Application of C4H3NOS, the main research area is dihydrobenzodiazepine aryl acetyl preparation chemoselective regioselective; phenylenediamine aryl aldehyde butynone condensation Lewis acid catalyst.

A unique and efficient method has been developed for the one-pot synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines I (Ar = 2-thiazolyl, 2-thienyl, 4-ClC6H4, etc.) in good yields using o-phenylenediamine, aromatic aldehyde and 3-butyn-2-one in the presence of a catalytic amount of CeCl3·7H2O in ethanol at ambient temperature An exclusive chemo-/regio-selective formation of substituted isomers of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines II (Ar = 2-thiazolyl, 2-thienyl, 4-ClC6H4, etc.; R = CH3, F, Cl, Br) was achieved from the different reaction process, by exploiting the strategy based on the variation of electrophilicity of the two electrophilic centers of aromatic aldehyde, 3-butyn-2-one and nucleophilic profiles of substituted o-phenylenediamines. This process offers an easy and efficient synthesis of 2-aryl-3-acetyl-2,4-dihydro-1H-5H-1,5-benzodiazepines in high yields.

Tetrahedron Letterspublished new progress about Aryl aldehydes Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-32-3 belongs to class thiazole, and the molecular formula is C4H3NOS, Application of C4H3NOS.

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica