Selective Elaboration of Aminodiols towards Small Ring α‐ and β‐Amino Acid Derivatives that Incorporate an Aziridine, Azetidine, or Epoxide Scaffold

Semina, Elena; Žukauskaitė, Asta; Šačkus, Algirdas; Kimpe, Norbert De; Mangelinckx, Sven

doi:10.1002/ejoc.201600036

Cited by 7 publications

(2 citation statements)

References 72 publications

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“…Various transformation reactions of compound 8 were performed to obtain amino acid 18, N-alkylated 19-22, and N-acylated 23-28 azetidine derivatives. Saponification of compound 8 by standard hydrolysis conditions [50] followed by the N-deprotection with 4 N HCl in dioxane [49] provided amino acid hydrochloride salt 18 (Scheme 2). Subsequently, N-derivatisation reactions were investigated.…”

Section: Synthesismentioning

confidence: 99%

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Šachlevičiūtė,

Gonzalez,

Kvasnicová

et al. 2023

Archiv der Pharmazie

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A library of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives was prepared from N‐Boc‐3‐azetidinone employing the Horner‐Wadsworth‐Emmons reaction, rhodium(I)‐catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N‐unprotected hydrochlorides, N‐alkylated and N‐acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol‐induced) and aspects of Alzheimer's disease (glutamate‐induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol‐ and glutamate‐induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase‐3/7 activity.

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Section: Synthesismentioning

confidence: 99%

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Šachlevičiūtė,

Gonzalez,

Kvasnicová

et al. 2023

Archiv der Pharmazie

Self Cite

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“…The obtained alcohols 3-7 were further converted into azides 9-12, respectively. Many methods have been developed for such a transformation, including Mitsunobu-type displacements [60,61], two-step procedures that involve a halogenated [62] or mesylated intermediate [63], the one-pot halogenation-azidation of alcohols [64], reactions with phosphitine intermediates [65], N-methyl-2-pyrolidone hydrosulphate, and trimethylsilylazide (TMSN 3 ) [51]. The latter method was chosen for the synthesis, and the reactions were performed in DCM with a catalytic amount of boron trifluoride diethyl etherate (BF 3 •Et 2 O).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Antiproliferative Activity of 2,4,6,7-Tetrasubstituted-2H-pyrazolo[4,3-c]pyridines

et al. 2021

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A library of 2,4,6,7-tetrasubstituted-2H-pyrazolo[4,3-c]pyridines was prepared from easily accessible 1-phenyl-3-(2-phenylethynyl)-1H-pyrazole-4-carbaldehyde via an iodine-mediated electrophilic cyclization of intermediate 4-(azidomethyl)-1-phenyl-3-(phenylethynyl)-1H-pyrazoles to 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridines followed by Suzuki cross-couplings with various boronic acids and alkylation reactions. The compounds were evaluated for their antiproliferative activity against K562, MV4-11, and MCF-7 cancer cell lines. The most potent compounds displayed low micromolar GI50 values. 4-(2,6-Diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol proved to be the most active, induced poly(ADP-ribose) polymerase 1 (PARP-1) cleavage, activated the initiator enzyme of apoptotic cascade caspase 9, induced a fragmentation of microtubule-associated protein 1-light chain 3 (LC3), and reduced the expression levels of proliferating cell nuclear antigen (PCNA). The obtained results suggest a complex action of 4-(2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-yl)phenol that combines antiproliferative effects with the induction of cell death. Moreover, investigations of the fluorescence properties of the final compounds revealed 7-(4-methoxyphenyl)-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine as the most potent pH indicator that enables both fluorescence intensity-based and ratiometric pH sensing.

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ChemInform Abstract: Selective Elaboration of Aminodiols Towards Small Ring α‐ and β‐Amino Acid Derivatives that Incorporate an Aziridine, Azetidine, or Epoxide Scaffold.

et al. 2016

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Selective Elaboration of Aminodiols towards Small Ring α‐ and β‐Amino Acid Derivatives that Incorporate an Aziridine, Azetidine, or Epoxide Scaffold

Cited by 7 publications

References 72 publications

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Synthesis and neuroprotective activity of 3‐aryl‐3‐azetidinyl acetic acid methyl ester derivatives

Synthesis and Antiproliferative Activity of 2,4,6,7-Tetrasubstituted-2H-pyrazolo[4,3-c]pyridines

ChemInform Abstract: Selective Elaboration of Aminodiols Towards Small Ring α‐ and β‐Amino Acid Derivatives that Incorporate an Aziridine, Azetidine, or Epoxide Scaffold.

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