Day: November 21, 2022

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

Gorski, Bartosz published the artcileCopper-catalysed amination of alkyl iodides enabled by halogen-atom transfer, Synthetic Route of 170364-89-3, the publication is Nature Catalysis (2021), 4(7), 623-630, database is CAplus.

Here, an alternative amination strategy was demonstrated for the synthesis of alkyl amines, e.g., I where alkyl iodides are used as radical precursors instead of electrophiles. Use of α-aminoalkyl radicals enabled the efficient conversion of the iodides into the corresponding alkyl radical by halogen-atom transfer, while copper catalysis assembled the sp³ C-N bonds at room temperature The process provided SN²-like programmability, and application in late-stage functionalization of several densely functionalized pharmaceuticals demonstrated its utility in the preparation of valuable N-alkylated drug analogs.

Nature Catalysis published new progress about 170364-89-3. 170364-89-3 belongs to piperidines, auxiliary class Indole,Piperidine,Amide, name is tert-Butyl 4-(1H-indol-1-yl)piperidine-1-carboxylate, and the molecular formula is C18H24N2O2, Synthetic Route of 170364-89-3.

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

Bobbitt, James M. published the artcileOxoammonium Salt Oxidations of Alcohols in the Presence of Pyridine Bases, Application of 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, the publication is Journal of Organic Chemistry (2014), 79(3), 1055-1067, database is CAplus and MEDLINE.

Oxidations of alcs. containing a β-oxygen atom with the oxoammonium salt 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate in the presence of pyridine yielded dimeric esters, while in the presence of 2,6-lutidine the oxidations yielded aldehydes. The changes in oxidation reactivity with the steric hindrance of the pyridine catalyst are explained by formation of betaines between unhindered pyridines and aldehydes which undergo oxidation to acylpyridinium ions followed by substitution reactions with the starting alcs. to yield esters; hindered pyridines do not form betaines with aldehydes and so do not react further. Six alcs. containing β-oxygen substituents were oxidized chemoselectively to aldehydes in the presence of 2,6-lutidine. The relative reactivities of a set of alcs. toward oxoammonium ion-mediated oxidation was determined An overall mechanism for oxoammonium cation oxidations is suggested based on the premise that nucleophilic additions to the oxoammonium ions occur by addition to the oxygen atom of the pos. charged nitrogen-oxygen double bond; possible mechanisms for oxidations of β-alkoxy alcs. to aldehydes and esters are given. Transition state structures and free energies of transition states and products were calculated for two of three potential mechanisms.

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, Application of 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate.

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

Shannon, Simon K. published the artcile4-(9-Fluorenylmethyloxycarbonyl)phenylhydrazine (FmPH): A New Chromophoric Reagent for Quantitative Monitoring of Solid-Phase Aldehydes, Formula: C19H21N, the publication is Journal of Organic Chemistry (2004), 69(14), 4586-4594, database is CAplus and MEDLINE.

A direct method for quantifying solid-phase aldehydes was developed, using a new reagent, 4-(9-fluorenylmethyloxycarbonyl)phenylhydrazine (FmPH). The FmPH reagent was synthesized in three steps (24% overall yield) from com. available p-hydrazinobenzoic acid. Resin-bound aldehydes reacted quant. with FmPH, in the presence of trimethylorthoformate (TMOF) as a dehydrating agent, to form a highly conjugated, immobilized FmPH-hydrazone. Next, mild treatment of the hydrazone with an excess of piperidine-DMF (1:1) released the piperidine-dibenzofulvene adduct chromophore (ε_301nm = 7800 M^-1 cm^-1) from the support. FmPH quantitation of aldehydes proved to be a straightforward, sensitive, and reproducible technique for monitoring resin-bound aldehydes [albeit insufficiently reactive to allow reliable quantification of ketones]. The FmPH aldehyde assay is applicable to a range of solid supports, as demonstrated specifically for poly(ethylene glycol)-polystyrene (PEG-PS), aminomethylpolystyrene (AMP), and cross-linked ethoxylate acrylate resin (CLEAR).

Journal of Organic Chemistry published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C9H13NO2, Formula: C19H21N.

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

Billin, Andrew N. published the artcileDiscovery of Novel Small Molecules that Activate Satellite Cell Proliferation and Enhance Repair of Damaged Muscle, Name: (1-Methylpiperidin-3-yl)methanamine, the publication is ACS Chemical Biology (2016), 11(2), 518-529, database is CAplus and MEDLINE.

Skeletal muscle progenitor stem cells (referred to as satellite cells) represent the primary pool of stem cells in adult skeletal muscle responsible for the generation of new skeletal muscle in response to injury. Satellite cells derived from aged muscle display a significant reduction in regenerative capacity to form functional muscle. This decrease in functional recovery has been attributed to a decrease in proliferative capacity of satellite cells. Hence, agents that enhance the proliferative abilities of satellite cells may hold promise as therapies for a variety of pathol. settings, including repair of injured muscle and age- or disease-associated muscle wasting. Through phenotypic screening of isolated murine satellite cells, we identified a series of 2,4-diaminopyrimidines (e.g., 2) that increased satellite cell proliferation. Importantly, compound 2 was effective in accelerating repair of damaged skeletal muscle in an in vivo mouse model of skeletal muscle injury. While these compounds were originally prepared as c-Jun N-terminal kinase 1 (JNK-1) inhibitors, structure-activity analyses indicated JNK-1 inhibition does not correlate with satellite cell activity. Screening against a broad panel of kinases did not result in identification of an obvious mol. target, so we conducted cell-based proteomics experiments in an attempt to identify the mol. target(s) responsible for the potentiation of the satellite cell proliferation. These data provide the foundation for future efforts to design improved small mols. as potential therapeutics for muscle repair and regeneration.

ACS Chemical Biology 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, Name: (1-Methylpiperidin-3-yl)methanamine.

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

Hu, Ziwei published the artcileIdentification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine-Quinolone Carboxamides, Formula: C7H16N2, the publication is ACS Medicinal Chemistry Letters (2019), 10(1), 132-136, database is CAplus and MEDLINE.

Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-N-(pyridin-3-ylmethyl)-2,3-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification of analogs that induce chemokines and cytokines in a TLR2-dependent manner. These results represent new leads for the development of vaccine adjuvants.

ACS Medicinal Chemistry Letters 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

Crich, David published the artcileImproved synthesis of 1-benzenesulfinyl piperidine and analogs for the activation of thioglycosides in conjunction with trifluoromethanesulfonic anhydride, Related Products of piperidines, the publication is Journal of Carbohydrate Chemistry (2005), 24(4-6), 415-424, database is CAplus and MEDLINE.

An improved protocol for the large-scale production of 1-benzenesulfinyl piperidine and other sulfinamides is described. It is demonstrated that 1-benzenesulfinyl pyrrolidine and N,N-di-Et benzenesulfinamide function analogously to 1-benzenesulfinyl piperidine in the trifluoromethanesulfonic anhydride-mediated activation of thioglycosides, and that their less crystalline nature enables them to be used at -78°C as opposed to the -60°C required to keep 1-benzenesulfinyl piperidine in solution N,N-Dicyclohexyl benzenesulfinamide does not activate thioglycosides in combination with trifluoromethanesulfonic anhydride, which is attributed to its greater steric bulk.

Journal of Carbohydrate 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, Related Products of piperidines.

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