19835-38-2Relevant articles and documents
Enantioresolution and chameleonic mimicry of 2-Butanol with an adamantylacetyl derivative of cholic acid
Miragaya, Javier,Jover, Aida,Fraga, Francisco,Meijide, Francisco,Tato, Jose Vazquez
, p. 1124 - 1129 (2010)
[3β,5β,7α,12α]-3[(Adamantyl-l-acetyl)-amino] -7-12-dihydroxycholan-24-oic acid (AdCH2CA) was synthesized by the reaction between 1-adamantyl acetyl chloride and the methyl ester of 3β-amino-cholic acid and hydrolysis of the ester. The acid was recrystallized from racemic 2-butanol (0.1% water). Crystals are orthorhombic (P212121) and form inclusion complexes with water and 2-butanol with a 1:1:1 stoichiometry. Only the S-enantiomer is included into the structure of the crystal, exhibiting a chameleonic mimicry with the steroid bilayers. The isolation of crystals allows the enantioresolution of the racemate with a high purity (≈99%) of S-2-butanol. The steroid molecules are disposed in an antiparallel orientation in the hydrophobic layer and a parallel orientation in the hydrophilic one.
Full characterization and some reactions of 1-(2-adamantyl)-3-(1-adamantyl) aziridin-2-one
Lengyel, Istvan,Taldone, Tony,Lyons, Theresa,Cesare, Victor
, p. 803 - 810 (2008)
(Chemical Equation Presented) We found that 1-(2-adamantyl)-3-tert- butylaziridin-2-one (5a) is unstable. It slowly decomposes at room temperature, although detectable by IR spectroscopy (1840 cm-1 band in CCl 4). On the other hand, a closely related analogue, 1-(2-adamantyl)-3-(1-adamantyl)aziridin-2-one (5b), is very stable, in concurrence with an earlier report [1]. We fully characterized aziridinone 5b, identified its thermal decomposition products (7 and 8) and reacted it with two aprotic ionic (tBuO- and HO-) and one protic non-ionic nucleophile (benzylamine). All three products (9b, 10, and 11) result from exclusive cleavage of the lactam (1-2) bond.
Synthesis and evaluation of bifunctional PTP4A3 phosphatase inhibitors activating the ER stress pathway
Rastelli, Ettore J.,Sannino, Sara,Hart, Duncan J.,Sharlow, Elizabeth R.,Lazo, John S.,Brodsky, Jeffrey L.,Wipf, Peter
, (2021)
We developed JMS-053, a potent inhibitor of the dual specificity phosphatase PTP4A3 that is potentially suitable for cancer therapy. Due to the emerging role of the unfolded protein response (UPR) in cancer pathology, we sought to identify derivatives that combine PTP4A3 inhibition with induction of endoplasmatic reticulum (ER) stress, with the goal to generate more potent anticancer agents. We have now generated bifunctional analogs that link the JMS-053 pharmacophore to an adamantyl moiety and act in concert with the phosphatase inhibitor to induce ER stress and cell death. The most potent compound in this series, 7a, demonstrated a ca. 5-fold increase in cytotoxicity in a breast cancer cell line and strong activation of UPR and ER stress response genes in spite of a ca. 13-fold decrease in PTP4A3 inhibition. These results demonstrate that the combination of phosphatase inhibition with UPR/ER-stress upregulation potentiates efficacy.
Highly Porous Hybrid Metal–Organic Nanoparticles Loaded with Gemcitabine Monophosphate: a Multimodal Approach to Improve Chemo- and Radiotherapy
Li, Xue,Porcel, Erika,Menendez-Miranda, Mario,Qiu, Jingwen,Yang, Xiaomin,Serre, Christian,Pastor, Alexandra,Desma?le, Didier,Lacombe, Sandrine,Gref, Ruxandra
, p. 274 - 283 (2020)
Nanomedicine recently emerged as a novel strategy to improve the performance of radiotherapy. Herein we report the first application of radioenhancers made of nanoscale metal-organic frameworks (nanoMOFs), loaded with gemcitabine monophosphate (Gem-MP), a radiosensitizing anticancer drug. Iron trimesate nanoMOFs possess a regular porous structure with oxocentered Fe trimers separated by around 5 ? (trimesate linkers). This porosity is favorable to diffuse the electrons emitted from nanoMOFs due to activation by γ radiation, leading to water radiolysis and generation of hydroxyl radicals which create nanoscale damages in cancer cells. Moreover, nanoMOFs act as “Trojan horses”, carrying their Gem-MP cargo inside cancer cells to interfere with DNA repair. By displaying different mechanisms of action, both nanoMOFs and incorporated Gem-MP contribute to improve radiation efficacy. The radiation enhancement factor of Gem-MP loaded nanoMOFs reaches 1.8, one of the highest values ever reported. These results pave the way toward the design of engineered nanoparticles in which each component plays a role in cancer treatment by radiotherapy.
3D-printed cartridge system for in-flow photo-oxygenation of 7-aminothienopyridinones
Rastelli, Ettore J.,Yue, Doris,Millard, Caroline,Wipf, Peter
supporting information, (2020/12/29)
A 3D-printed polypropylene (PP) continuous-photoflow cell based on a modular cartridge system was developed for the photo-oxygenation of 7-aminothieno[3,2-c]pyridin-4(5H)-ones, using ambient air as the sole co-reactant. This strategy takes advantage of the versatility of 3D-printing to construct cost-effective meso-scale reactors. In addition to scalability, a short residence time (tR 2 min) in 100-W blue LED light that minimizes the formation of dark, insoluble decomposition products is a tangible benefit of this technology.
