Day: November 30, 2022

Zhang, Tinghu published the artcileCovalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors, COA of Formula: C30H32ClN7O2, the publication is Nature Chemical Biology (2016), 12(10), 876-884, database is CAplus and MEDLINE.

Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12-cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small mols. capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.

Nature Chemical Biology published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C15H20BNO2, COA of Formula: C30H32ClN7O2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Proietti, Giampiero published the artcileAccessing Perfluoroaryl Sulfonimidamides and Sulfoximines via Photogenerated Perfluoroaryl Nitrenes: Synthesis and Application as a Chiral Auxiliary, HPLC of Formula: 4972-31-0, the publication is Journal of Organic Chemistry (2021), 86(23), 17119-17128, database is CAplus and MEDLINE.

A light-promoted generation of perfluorinated aromatic nitrenes, from perfluorinated azides, that subsequently were allowed to react with sulfinamides and sulfoxides, generating achiral and chiral sulfonimidamides (SIAs) and sulfoximines (SOIs). One of enantiopure SIAs was evaluated as a novel chiral auxiliary in Grignard additions to imines yielding product in up to 96:4 diastereomeric ratio.

Journal of Organic Chemistry published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, HPLC of Formula: 4972-31-0.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Takajo, Tokuko published the artcileBasic investigations of singlet oxygen detection systems with ESR for the measurement of singlet oxygen quenching activities, Synthetic Route of 826-36-8, the publication is Chemical & Pharmaceutical Bulletin (2020), 68(2), 150-154, database is CAplus and MEDLINE.

Singlet oxygen (¹O₂) is highly oxidative and exerts strong cytotoxic effects. We tried to establish the best combination of a singlet oxygen generation system and a detection method with ESR, for measurement of the quenching activities of various substances. The photosensitizing reaction of rose bengal or thermal decomposition of 4-methyl-1,4-etheno-2,3-benzodioxin-1(4H)-propanoic acid (endoperoxide, EP) was used for the generation of ¹O₂, and a sterically hindered secondary amine, 2,2,6,6-tetramethyl-4-piperidone (TEMPD) or 2,2,6,6-tetramethyl-4-piperidinol (TEMP-OH), was used as the ¹O₂ detection probe. These secondary amines were oxidized by ¹O₂ to form stable nitroxide radicals, which were detectable by ESR. TEMPD was found to be readily oxidized by air, causing large background signals in comparison with TEMP-OH. The ESR signal obtained by the irradiation of rose bengal with visible light in the presence of TEMP-OH consisted of two kinds of nitroxide radical overlapping. In contrast, only a single nitroxide signal was observed when TEMP-OH was reacted with ¹O₂ generated from EP. Therefore, the best combination should be EP as the ¹O₂ generator and TEMP-OH as the detection probe. When using this combination, we found that the concentrations of some organic solvents such as DMSO and acetonitrile should be kept constant for reliable quantification, because the concentrations of organic solvents affect the ESR signal intensity.

Chemical & Pharmaceutical Bulletin published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C8H15NO, Synthetic Route of 826-36-8.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Boehme, Horst published the artcileAminal splittings with sulfonic, sulfinic, and sulfenic acid halides, Recommanded Product: 1-(Phenylsulfinyl)piperidine, the publication is Chemiker-Zeitung (1978), 102(2), 64-5, database is CAplus.

RSO_nCl (R = Ph, Me, CCl₃; n = 0-2) reacted with (R¹R²N)₂CH₂ (NR¹R² = NMe₂, piperidino, 4-methylpiperazino, NMeCH₂Ph) to give 53-94% R¹R²N⁺:CH₂Cl^– and RSO_nNR¹R².

Chemiker-Zeitung published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Recommanded Product: 1-(Phenylsulfinyl)piperidine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Savych, Olena published the artcileOne-Pot Parallel Synthesis of 5-(Dialkylamino)tetrazoles, COA of Formula: C6H12N2O, the publication is ACS Combinatorial Science (2019), 21(9), 635-642, database is CAplus and MEDLINE.

Two protocols for the combinatorial synthesis of 5-(dialkylamino)tetrazoles were developed. The best success rate (67%) was shown by the method that used primary and secondary amines, 2,2,2-trifluoroethylthiocarbamate, and sodium azide as the starting reagents. The key steps included the formation of unsym. thiourea, subsequent alkylation with 1,3-propane sultone and cyclization with azide anion. A 559-member aminotetrazole library was synthesized by this approach; the overall readily accessible (REAL) chem. space covered by the method exceeded 7 million feasible compounds

ACS Combinatorial Science published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, COA of Formula: C6H12N2O.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Biswas, Souvagya published the artcileEnantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer-Type Transformation using Phase-Transfer Catalysis, COA of Formula: C11H21BF4N2O2, the publication is Angewandte Chemie, International Edition (2018), 57(2), 589-593, database is CAplus and MEDLINE.

Reported is the first enantioselective oxidative Pummerer-type transformation using phase-transfer catalysis to deliver enantioenriched sulfur-bearing heterocycles. This reaction includes the direct oxidation of sulfides to a thionium intermediate, followed by an asym. intramol. nucleophilic addition to form chiral cyclic N,S-acetals with moderate to high enantioselectivities. Deuterium-labeling experiments were performed to identify the stereodiscrimination step of this process. Further anal. of the reaction transition states, by multidimensional correlations and DFT calculations, highlight the existence of a set of weak noncovalent interactions between the catalyst and substrate that govern the enantioselectivity of the reaction.

Angewandte Chemie, International Edition published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, COA of Formula: C11H21BF4N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Sardar, Mohammed Y. R. published the artcileSynthesis of Lewis^X-O-Core-1 threonine: A building block for O-linked Lewis^X glycopeptides, Name: 1-(Phenylsulfinyl)piperidine, the publication is Carbohydrate Research (2017), 47-53, database is CAplus and MEDLINE.

Lewis^X (Le^X) is a branched trisaccharide Galβ1â†?(Fucα1â†?)GlcNAc that is expressed on many cell surface glycoproteins and plays critical roles in innate and adaptive immune responses. However, efficient synthesis of glycopeptides bearing Le^X remains a major limitation for structure-function studies of the Le^X determinant. Here we report a total synthesis of a Le^X pentasaccharide 1 (I) using a regioselective 1-benzenesulfinylpiperidine/triflic anhydride promoted [3 + 2] glycosylation. The presence of an Fmoc-threonine amino acid facilitates incorporation of the pentasaccharide in solid phase peptide synthesis, providing a route to diverse O-linked Le^X glycopeptides. The described approach is broadly applicable to the synthesis of a variety of complex glycopeptides containing O-linked Le^X or sialyl Lewis^X (sLe^X).

Carbohydrate Research published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Name: 1-(Phenylsulfinyl)piperidine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Slabicki, Mikolaj published the artcileThe CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K, Category: piperidines, the publication is Nature (London, United Kingdom) (2020), 585(7824), 293-297, database is CAplus and MEDLINE.

Abstract: Mol. glue compounds induce protein-protein interactions that, in the context of a ubiquitin ligase, lead to protein degradation¹. Unlike traditional enzyme inhibitors, these mol. glue degraders act substoichiometrically to catalyze the rapid depletion of previously inaccessible targets². They are clin. effective and highly sought-after, but have thus far only been discovered serendipitously. Here, through systematically mining databases for correlations between the cytotoxicity of 4,518 clin. and preclin. small mols. and the expression levels of E3 ligase components across hundreds of human cancer cell lines^3-5, we identify CR8-a cyclin-dependent kinase (CDK) inhibitor⁶-as a compound that acts as a mol. glue degrader. The CDK-bound form of CR8 has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation Our studies demonstrate that chem. alteration of surface-exposed moieties can confer gain-of-function glue properties to an inhibitor, and we propose this as a broader strategy through which target-binding mols. could be converted into mol. glues.

Nature (London, United Kingdom) published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C15H12O6, Category: piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Eslahi, Negin published the artcileCorrelation Study Between Biochemical and Molecular Pathways of Trichoderma harzianum Recombinant Strains on Plant Growth and Health, HPLC of Formula: 826-36-8, the publication is Journal of Plant Growth Regulation (2022), 41(4), 1561-1577, database is CAplus.

The genus of Trichoderma are mostly found in soil. Trichoderma species are known as probiotic with biocontrol and biofertilizer activity. They are producers of secondary metabolites like volatile organic compounds (VOCs) with antifungal, antibacterial, and growth promoter properties. Trichoderma VOCs can induce resistance to plant pathogens leading to improved plant growth and health. In this study, we compared the performance of Trichoderma harzianum recombinant strains (T13 and T15), containing chimeric chit42 with Chitin Binding Domain (ChBD) and wild-type (Tw) strain on plant growth promotion. To achieve this goal, the ability of strains in plant growth-promoting (production of IAA and siderophore) and fungal gene expression involved in biocontrol and biofertilizer activity, as well as, VOCs from T. harzianum strains (wild-type and recombinants) by headspace gas chromatog.-mass spectrometry (GC-SPME) have been investigated. In addition, bean seeds were exposed to the T. harzianum strains in a shared atm. In addition to growth indexes (root fresh and dry weight, root length, and lateral root number), expression of root growth-related genes was measured by qTR-PCR. The results showed that recombinant strains had increased ability to produce IAA and siderophore. In addition, T. harzianum genes expression anal. demonstrated an upregulation in biocontrol and biofertilizer-associated genes in T13 and T15 strains. VOCs profile of strains revealed a total of 11, 57, and 29 metabolites from the Tw, T15, and T13, resp. Most of the VOCs produced from T13 and T15 had growth enhancement and biocontrol activity, resp., on the plant. The diversity of VOCs from T. harzianum recombinant strains (T13 and T15) involved in growth-promoting and biocontrol activity, was higher than the Tw strain. These compounds might work synergistically to promote growth, and enhance biocontrol and antifungal activity, and thus, recombinant strains with higher diversity of VOCs might be more effective than Tw. Plant phenotypic characterization and root genes expression showed that the recombinant strains, T13 particularly, were effective in growth-promoting compared to the Tw strain. In this study, we observed a pos. correlation among the production of secondary metabolite and mol. pathways of recombinant strains on plant growth activity. This finding can create a link between basic and applied studies in agriculture.

Journal of Plant Growth Regulation published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C9H17NO, HPLC of Formula: 826-36-8.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Aiba, Motohiro published the artcileEffect of bulky 2,6-bis(spirocyclohexyl)-substituted piperidine rings in bis(hindered amino)trisulfide on thermal healability of polymethacrylate networks, Related Products of piperidines, the publication is Materials Advances (2021), 2(23), 7709-7714, database is CAplus.

This paper describes the synthesis of highly sterically hindered piperidinyl trisulfide with four spirocyclohexyl moieties, bis(2,6-bis[spirocyclohexyl]piperidine-1-yl)trisulfide (BIBSCPS-S3), from com. available starting materials in short steps and its application as a dynamic covalent bond for thermally healable polymer networks. Conformational study on the BIBSCPS-S3 moiety in the solid state is performed by single-crystal X-ray diffraction. In bulk, a stress-relaxation experiment reveals that the increase in steric hindrance can not only decrease the activation energy for thermal exchange reactions but also suppress chain-transfer reactions during radical polymerization to some extent. Therefore, the dynamic crosslinking point containing BIBSCPS-S3 moiety can be efficiently incorporated into polymer networks with Et, Bu, or n-hexyl methacrylate monomers, which is in good accordance with the relatively low chain-transfer constants of the BIBSCPS-S3 moiety determined by the Mayo equation. As a result, BIBSCPS-S3-cross-linked poly(n-hexyl methacrylate) exhibits nearly quant. damage healability only by simple hot pressing at 90°C under mild pressure for 24 h.

Materials Advances published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C9H17NO, Related Products of piperidines.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem