Day: November 17, 2022

Zang, Yingda published the artcileClaulansine F-donepezil hybrids as anti-Alzheimer’s disease agents with cholinergic, free-radical scavenging, and neuroprotective activities, Product Details of C10H20N2O2, the main research area is Claulansine donepezil hybrid preparation docking anticholinesterase Alzheimer neuroprotective; AChE inhibitory activity; Alzheimer’s disease; Claulansine F–donepezil hybrids; free-radical scavenging activity; neuroprotective effects.

The multifactorial nature of Alzheimer’s disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. Twenty-six Claulansine F-donepezil hybrids I (X = nothing, CH2, CH2CH2; R1 = OMe, t-Bu; R2 = PhCH2, 2-FC6H4CH2, 4-ClC6H4CH2, etc.) were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC50) 1.63-4.62μM). Moreover, the compound I [X = CH2; R1 = t-Bu; R2 = 2-ClC6H4CH2; (II)] exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, the compound II could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, the compound II had stronger free-radical scavenging activity. Mol. docking studies revealed that II could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate the compound II as a leading structure worthy of further investigation.

Molecules published new progress about Alzheimer disease. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Product Details of C10H20N2O2.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Anderson, Fiona M. published the artcileSynthesis of new homochiral bispyrrolidines as potential DNA cross-linking antitumor agents, COA of Formula: C7H15Cl2N, the main research area is structure activity antitumor bispyrrolidine DNA crosslinking.

We are seeking to develop more effective bifunctional alkylating agents as antitumor agents. We previously synthesized conformationally restricted nitrogen mustards containing one piperidine ring, then bispiperidine derivatives were designed and prepared with varying lengths of carbon chain between the two rings and structure-activity relationships in these systems were studied. A bispiperidine with the shortest bridge of two carbon atoms was the most reactive bifunctional alkylating agent. In order to extend this work and investigate the effects of a change in the size of the heterocyclic systems, new bispyrrolidine salts 17-23 with chloromethyl groups at the 2-positions and a bridge between the two nitrogen atoms of 2-8 carbon atoms were synthesized from L-proline so that only the LL-enantiomers were produced. The free bases were designed to be bifunctional alkylating agents via aziridinium ion formation with different distances between the two alkylating sites. All of the bispyrrolidines were efficient cross-linkers of naked DNA apart from those with three-carbon (18) and four-carbon (19) bridges, in contrast to the results with the bispiperidines. A piperazine derivative 24 with two potential alkylating sites was also shown to be an efficient cross-linker, as was an alicyclic compound 25 with six carbon atoms between the two alkylating sites. Compounds 26 and 30 with an extra carbon atom between the nitrogen and the leaving group were not cross-linkers, as expected if aziridinium ion formation is crucial for crosslinking ability. The preformed aziridine 27 with a further alkylating site was an efficient cross-linker. Compounds 28-29 with only one potential alkylating center were not cross-linkers of DNA. None of the compounds, however, produced significant cytotoxicity in human tumor cells in vitro.

Anti-Cancer Drug Design published new progress about Alkylating agents. 27483-92-7 belongs to class piperidines, name is 2-(Chloromethyl)-1-methylpiperidine hydrochloride, and the molecular formula is C7H15Cl2N, COA of Formula: C7H15Cl2N.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Guo, Cuiping published the artcileMinimalist linkers suitable for irreversible inhibitors in simultaneous proteome profiling, live-cell imaging and drug screening, Computed Properties of 73874-95-0, the main research area is proteome profiling cell imaging drug screening linker fluorescent probe.

Activity-based protein profiling (ABPP) and bioimaging have been powerful approaches for in situ drug screening and target identification. However, these approaches are still hindered by the preparation of high-quality probes. To address this challenge, we developed a series of novel minimalist linkers for irreversible inhibitors by incorporation of various bioorthogonal handles into an α,β-unsaturated amide, a common moiety of many irreversible inhibitors. The linker-containing probes have been demonstrated to be suitable for simultaneous protein labeling, live cell imaging and drug screening.

Chemical Communications (Cambridge, United Kingdom) published new progress about Affinity labeling. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Computed Properties of 73874-95-0.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem