Month: November 2022

Lambert, Kyle M. published the artcileFacile Oxidation of Primary Amines to Nitriles Using an Oxoammonium Salt, Computed Properties of 219543-09-6, the publication is Organic Letters (2014), 16(24), 6484-6487, database is CAplus and MEDLINE.

The oxidation of primary amines using a stoichiometric quantity of 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) in CH₂Cl₂-pyridine solvent at room temperature or at gentle reflux affords nitriles in good yield under mild conditions. The mechanism of the oxidation, which has been investigated computationally, involves a hydride transfer from the amine to the oxygen atom of 1 as the rate-limiting step.

Organic Letters 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, Computed Properties of 219543-09-6.

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

Tanzer, Maria C. published the artcilePhosphoproteome profiling uncovers a key role for CDKs in TNF signaling, Computed Properties of 1702809-17-3, the publication is Nature Communications (2021), 12(1), 6053, database is CAplus and MEDLINE.

Abstract: Tumor necrosis factor (TNF) is one of the few cytokines successfully targeted by therapies against inflammatory diseases. However, blocking this well studied and pleiotropic ligand can cause dramatic side-effects. Here, we reason that a systems-level proteomic anal. of TNF signaling could dissect its diverse functions and offer a base for developing more targeted therapies. Therefore, we combine phosphoproteomics time course experiments with subcellular localization and kinase inhibitor anal. to identify functional modules of protein phosphorylation. The majority of regulated phosphorylation events can be assigned to an upstream kinase by inhibiting master kinases. Spatial proteomics reveals phosphorylation-dependent translocations of hundreds of proteins upon TNF stimulation. Phosphoproteome anal. of TNF-induced apoptosis and necroptosis uncovers a key role for transcriptional cyclin-dependent kinase activity to promote cytokine production and prevent excessive cell death downstream of the TNF signaling receptor. This resource of TNF-induced pathways and sites can be explored at http://tnfviewer.biochem.mpg.de/.

Nature Communications 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 C4H5NS2, Computed Properties of 1702809-17-3.

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

Dahlbom, Richard published the artcileN- Alkyl – 3 – piperidyl phenothiazine – 10 – carboxylates, Category: piperidines, the publication is Acta Chemica Scandinavica (1961), 2043-6, database is CAplus.

cf. Biel, et al., CA 48, 694a; Schmitt, et al., CA 52, 1172d. From phenothiazine-10-carbonyl chlorides were prepared the title compounds, potential spasmolytic agents. 2-Methylphenothiazine (42.4 g.) in 750 ml. PhMe with 330 ml. 10% by volume COCl₂-PhMe was refluxed 4 hrs. at 90°, 50 ml. EtOH added to the cold product, and the solvent evaporated in vacuo to give 54 g. 2-methylphenothiazine-10-carbonyl chloride, m. 122-2.5° (AcOEt). 2-Ethyl- (I) and 2-methoxyphenothiazine-10-carbonyl chloride (II) were similarly prepared I did not crystallize. II (88% yield) m. 94-5° (MeOH). In the modified method for the preparation of 2-chlorophenothiazine-10-carbonyl chloride (III) from 46.5 g. 2-chlorophenothiazine (IV), heating 6 hrs. at 140° was followed by addition of 130 ml. more COCl₂ solution and heating 8 hrs. at 140°. Filtration, after the addition of C₆H₆ to the crude III, removed IV as a residue. Evaporation of C₆H₆ gave 35.0 g. III, m. 100-1° (AcOEt). AlCl₃ (200 g.) was added to 131 g. phenothiazine-10-carbonyl chloride (V) stirred in 800 ml. CS₂, the mixture refluxed to dissolve V, and to the cold product added 54.9 g. AcCl in portions. Heating to 30° started a vigorous reaction and after 1 hr. the mixture was refluxed 3 hrs. The cold lower layer from the product was poured on 1 kg. ice and 25 ml. 10N HCl to precipitate 150 g. 2-acetyl derivative of V, m. 120-2° (AcOEt), giving with KOH in EtOH 2-acetylphenothiazine. The appropriate 2-substituted V (0.05 mole), 0.05 mole N-methyl- (VI) or N-ethyl3-hydroxypiperidine (VII), 0.075 mole NEt₃, and 50 ml. PhMe were refluxed (4 hrs. with VI, 8 hrs. with VII), the Et₃NHCl filtered off from the cold product, the PhMe solution washed (H₂O), and then extracted (N HCl). VIII.HCl separated, was dissolved in H₂O, and the solution combined with the aqueous acidic extract before being made alk. (Na₂CO₃) to precipitate VIII. VIII was converted into VIII.HCl by HCl in Et₂O or was quaternized (CA 49, 4659c). Thus, the following VIII and derivatives were prepared [R, R’, nature of derivative, recrystallizing solvent, % yield, and m.p. (the salts decomposed) given]: H, Me, free base, petr. ether, 72, 88-90°; H, Me, HCl, MeOH-Et₂O (IX), -, 230-2°; H, Me, MeBr, MeOH, 86, 273-4°; H, Et, HCl, EtOH-Et₂O (X), 55, 222-3°; H, Et. MeBr, X, 67, 232-3°; H, Et, EtI, X, 71, 220-1°; Me, Me, HCl, X, 92, 242-4°; Me, Et, HCl, X, 69, 223.-4°; Et, Me, HCl, MeOH, 80, 240-2°; Et, Et, HCl, X, 57, 202-3°; MeO, Me, HCl, IX, 80, 242-4°; MeO, Et, HCl, IX, 66, 230-1°; Cl, Me, HCl, IX, 77, 235-7°; Cl, Et, HCl, X, 64, 220-2°; Ac, Me, free base, EtOH, 80, 112-14°; Ac, Me, HCl, EtOH, -, 236-8°; Ac, Et, HCl, X, 49, 188-9°.

Acta Chemica Scandinavica published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Category: piperidines.

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

Miller, Shelli A. published the artcileCatalytic Oxidation of Alcohols Using a 2,2,6,6-Tetramethylpiperidine-N-hydroxyammonium Cation, Category: piperidines, the publication is European Journal of Organic Chemistry (2019), 2019(6), 1413-1417, database is CAplus.

The oxidation of alcs. to aldehydes, ketones, and carboxylic acids is reported using 2,2,6,6-tetramethylpiperidine-4-acetamido-hydroxyammonium tetrafluoroborate as a catalyst in conjunction with sodium hypochlorite pentahydrate as a terminal oxidant. The reaction is generally complete within 30-120 min using an acetonitrile/water mix as the solvent, and no additives are required. Product yields are good to excellent and of particular note is that the methodol. can be used to access aryl α-trifluoromethyl ketones.

European Journal of Organic Chemistry 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, Category: piperidines.

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

Kung, Pei-Pei published the artcileCharacterization of Specific N-α-Acetyltransferase 50 (Naa50) Inhibitors Identified Using a DNA Encoded Library, Related Products of piperidines, the publication is ACS Medicinal Chemistry Letters (2020), 11(6), 1175-1184, database is CAplus and MEDLINE.

Two novel compounds were identified as Naa50 binders/inhibitors using DNA-encoded technol. screening. Biophys. and biochem. data as well as cocrystal structures were obtained for both compounds (3a and 4a) to understand their mechanism of action. These data were also used to rationalize the binding affinity differences observed between the two compounds and a MLGP peptide-containing substrate. Cellular target engagement experiments further confirm the Naa50 binding of 4a and demonstrate its selectivity toward related enzymes (Naa10 and Naa60). Addnl. analogs of inhibitor 4a were also evaluated to study the binding mode observed in the cocrystal structures.

ACS Medicinal Chemistry Letters published new progress about 72002-30-3. 72002-30-3 belongs to piperidines, auxiliary class Piperidine,Chiral,Carboxylic acid,Amide, name is (R)-6-Oxopiperidine-2-carboxylic acid, and the molecular formula is C6H9NO3, Related Products of piperidines.

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

Galambos, Janos published the artcileDiscovery of 4-amino-3-arylsulfoquinolines, a novel non-acetylenic chemotype of metabotropic glutamate 5 (mGlu₅) receptor negative allosteric modulators, Product Details of C6H12N2O, the publication is European Journal of Medicinal Chemistry (2017), 240-254, database is CAplus and MEDLINE.

Neg. allosteric modulators of metabotropic glutamate receptor 5 (mGlu₅) showed efficacy in a number of animal models of different CNS diseases including anxiety and depression. Virtually all of the compounds which reached the clinic belong to the same chemotype having an acetylenic linker that connects (hetero)cyclic moieties. Searching for new chemotypes we identified a morpholino-sulfoquinoline derivative (1) by screening our corporate compound deck. The HTS hit showed reasonable affinity and selectivity towards mGlu₅ receptors, however, its inferior metabolic stability prevented its testing in vivo. In a chem. program we aimed to improve the affinity, physicochem. properties and metabolic stability exploring three regions of the hit. Systematic variation of different amines at position 4 (region I) led to the identification of 4-methyl-piperidinyl analogs. Substituents of the quinoline core (region II) and the phenylsulfonyl moiety (region III) were mapped by parallel synthesis. Evaluation of both morpholino- and 4-methyl-piperidinyl-sulfoquinoline libraries of about 270 derivatives revealed beneficial substituent combinations in regions II and III. Blood levels of optimized 4-methyl-piperidinyl-sulfoquinolines, however, were still insufficient for robust in vivo efficacy. Finally, introducing 4-hydoxymethyl-piperidinyl substituent to region I resulted in new sulfoquinolines with greatly improved solubility and reasonable affinity coupled with affordable metabolic stability. The most promising analogs (24 and 25) showed high blood levels and demonstrated significant efficacy in the exptl. model of anxiety.

European Journal of Medicinal Chemistry 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, Product Details of C6H12N2O.

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

Negatu, Dereje Abate published the artcilePiperidine-4-carboxamides target DNA gyrase in Mycobacterium abscessus, HPLC of Formula: 39546-32-2, the publication is Antimicrobial Agents and Chemotherapy (2021), 65(8), e00676, database is CAplus and MEDLINE.

New, more-effective drugs for the treatment of lung disease caused by nontuberculous mycobacteria (NTM) are needed. Among NTM opportunistic pathogens, Mycobacterium abscessus is the most difficult to cure and intrinsically multidrug resistant. In a whole-cell screen of a compound collection active against Mycobacterium tuberculosis, we previously identified the piperidine-4-carboxamide (P4C) MMV688844 (844) as a hit against M. abscessus. Here, we identified a more potent analog of 844 and showed that both the parent and improved analog retain activity against strains representing all three subspecies of the M. abscessus complex. Furthermore, P4Cs showed bactericidal and antibiofilm activity. Spontaneous resistance against the P4Cs emerged at a frequency of 10^-8/CFU and mapped to gyrA and gyrB encoding the subunits of DNA gyrase. Biochem. studies with recombinant M. abscessus DNA gyrase showed that P4Cs inhibit the wild-type enzyme but not the P4C-resistant mutant. P4C-resistant strains showed limited cross-resistance to the fluoroquinolone moxifloxacin, which is in clin. use for the treatment of macrolide-resistant M. abscessus disease, and no cross-resistance to the benzimidazole SPR719, a novel DNA gyrase inhibitor in clin. development for the treatment of mycobacterial diseases. Analyses of P4Cs in recA promoter-based DNA damage reporter strains showed induction of recA promoter activity in the wild type but not in the P4C-resistant mutant background. This indicates that P4Cs, similar to fluoroquinolones, cause DNA gyrase-mediated DNA damage. Together, our results show that P4Cs present a novel class of mycobacterial DNA gyrase inhibitors with attractive antimicrobial activities against the M. abscessus complex.

Antimicrobial Agents and Chemotherapy 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, HPLC of Formula: 39546-32-2.

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

Pesci, Elisabetta published the artcileNovel Hits in the Correction of ΔF508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Protein: Synthesis, Pharmacological, and ADME Evaluation of Tetrahydropyrido[4,3-d]pyrimidines for the Potential Treatment of Cystic Fibrosis, Computed Properties of 39546-32-2, the publication is Journal of Medicinal Chemistry (2015), 58(24), 9697-9711, database is CAplus and MEDLINE.

Cystic fibrosis (CF) is a lethal genetic disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) with a prevalence of the ΔF508 mutation. Whereas the detailed mechanisms underlying disease have yet to be fully elucidated, recent breakthroughs in clin. trials have demonstrated that CFTR dysfunction can be corrected by drug-like mols. On the basis of this success, a screening campaign was carried out, seeking new drug-like compounds able to rescue ΔF508-CFTR that led to the discovery of a novel series of correctors based on a tetrahydropyrido[4,3-d]pyrimidine core. These mols. proved to be soluble, cell-permeable, and active in a disease relevant functional-assay. The series was then further optimized with emphasis on biol. data from multiple cell systems while keeping physicochem. properties under strict control. Three mols. were found to have promising profiles, and among them I confirmed the low metabolic data observed with CYP3A4 also in the intrinsic clearance assay. The pharmacol. and ADME profile of this corrector series hold promise for the development of more efficacious compounds to be explored for therapeutic use in CF.

Journal of Medicinal Chemistry 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, Computed Properties of 39546-32-2.

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

Carlet, Federica published the artcileOxoammonium-Mediated Allylsilane-Ether Coupling Reaction, Recommanded Product: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, the publication is European Journal of Organic Chemistry (2021), 2021(15), 2162-2168, database is CAplus.

A new C(sp³)-H functionalization reaction consisting of the oxidative α-allylation of allyl- and benzyl- Me ethers has been developed. The C-C coupling could be carried out under mild conditions thanks to the use of cheap and green oxoammonium salts. The scope of the reaction was studied over 27 examples, considering the nature of the substituents on the two coupling partners.

European Journal of Organic Chemistry 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, Recommanded Product: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate.

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

Quevedo, Camilo E. published the artcileAminothiazolones as potent, selective and cell active inhibitors of the PIM kinase family, Formula: C7H16N2, the publication is Bioorganic & Medicinal Chemistry (2020), 28(22), 115724, database is CAplus and MEDLINE.

We have previously reported the discovery of a series of rhodanine-based inhibitors of the PIM family of serine/threonine kinases. Here we described the optimization of those compounds to improve their physicochem. and ADME properties as well as reducing their off-targets activities against other kinases. Through mol. modeling and systematic structure activity relationship (SAR) studies, advanced mols. with high inhibitory potency, reduced off-target activity and minimal efflux were identified as new pan-PIM inhibitors. One example of an early lead, I, was found to inhibit PIMs with nanomolar potency (15 nM for PIM1), inhibit proliferation of two PIM-expressing leukemic cancer cell lines, MV4-11 and K562, and to reduce intracellular phosphorylation of a PIM substrate in a concentration dependent manner.

Bioorganic & Medicinal Chemistry published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C7H16N2, Formula: C7H16N2.

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