23418-85-1Relevant articles and documents
Expedient construction of the [7-5-5] all-carbon tricyclic core of the daphniphyllum alkaloids daphnilongeranin B and daphniyunnine D
Darses, Benjamin,Michaelides, Iacovos N.,Sladojevich, Filippo,Ward, John W.,Rzepa, Paula R.,Dixon, Darren J.
, p. 1684 - 1687 (2012)
A synthetic strategy for the construction of the [7-5-5] all-carbon tricyclic core of numerous calyciphylline A-type Daphniphyllum alkaloids has been developed using a key intramolecular Pauson-Khand reaction. A subsequent base-mediated double-bond migration and a regio-and stereoselective radical late stage allylic oxygenation provide access to the substitution patterns of daphnilongeranin B and daphniyunnine D.
Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: Comparison between mono- and bisquaternary ammonium salts
Calas, Michèle,Ancelin, Marie L.,Cordina, Gérard,Portefaix, Philippe,Piquet, Gilles,Vidal-Sailhan, Valérie,Vial, Henri
, p. 505 - 516 (2000)
On the basis of a previous structure - activity relationship study, we identified some essential parameters, e.g. electronegativity and lipophilicity, required for polar head analogues to inhibit Plasmodium falciparum phospholipid metabolism, leading to parasite death. To improve the in vitro antimalarial activity, 36 cationic choline analogues consisting of mono-, bis-, and triquaternary ammonium salts with distinct substituents of increasing lipophilicity were synthesized. For monoquaternary ammonium salts, an increase in the lipophilicity around nitrogen was beneficial for antimalarial activity: IC50 decreased by I order of magnitude from trimethyl to tripropyl substituents. Irrespective of the polar head substitution (methyl, ethyl, hydroxyethyl, pyrrolidinium), increasing the alkyl chain length from 6 to 12 methylene groups always led to increased activity. The highest activity was obtained for the N,N,N-tripropyl-N-dodecyl substitution of nitrogen (IC50 33 nM). Beyond 12 methylene groups, the antimalarial activities of the compounds decreased slightly. The structural requirements for bisquaternary ammonium salts in antimalarial activity were very similar to those of monoquaternary ammonium salts, i.e. polar head steric hindrance and lipophilicity around nitrogen (methyl, hydroxyethyl, ethyl, pyrrolidinium, etc.). In contrast, with bisquaternary ammonium salts, increasing the lipophilicity of the alkyl chain between the two nitrogen atoms (from 5 to 21 methylene groups) constantly and dramatically increased the activity. Most of these duplicated molecules had activity around 1 nM, and the most lipophilic compound synthesized exhibited an IC50 as low as 3 pM (21 methylene groups). Globally, this oriented synthesis produced 28 compounds out of 36 with an IC50 lower than 1 μM, and 9 of them had an IC50 in the nanomolar range, with I compound in the picomolar range. This indicates that developing a pharmacological model for antimalarial compounds through choline analognes is a promising strategy.
A bifunctional amino acid to study protein-protein interactions
Li, Xiang David,Li, Xin,Yang, Tangpo
, p. 42076 - 42083 (2020)
Protein-protein interactions (PPIs) play crucial roles in regulating essentially all cellular processes. Photo-cross-linking represents a powerful method to study PPIs. To fulfil the requirements for the exploration of different PPIs, there is a continuous demand on the development of novel photo-reactive amino acids with diverse structural properties and functionalities. Reported herein is the development of a bifunctional amino acid termed dzANA, which contains a diazirine, for photo-cross-linking, and a terminal alkyne group, for bioorthogonal tagging. Using known PPIs between histone posttranslational modifications (PTMs) and their binding partners as models, we demonstrate that the dzANA-harbouring peptide-based photoaffinity probes could efficiently and selectively capture the weak and transient PPIs mediated by histone modifications. Our study indicates the potential of dzANA to identify and characterize unknown PPIs. This journal is
Synthesis of 5-tethered carborane-containing pyrimidine nucleosides as potential agents for DNA incorporation
Rong,Soloway
, p. 2021 - 2034 (1994)
Several 5-substituted-2'-deoxyuridines have been prepared in which the carborane moiety is attached at the terminus of a flexible hydrocarbon chain containing an ester linkage. These boron moieties as the B-10 enriched compounds have potentially for use in the treatment of cancer by means of boron neutron capture therapy. A convenient synthetic route, in high yield, has been developed for the preparation of these 5-tethered carborane- containing pyrimidine nucleosides.
Diversity oriented synthesis of pyran based polyfunctional stereogenic macrocyles and their conformational studies
Ajay, Arya,Sharma, Shrikant,Gupt, Munna Prasad,Bajpai, Vikas,Hamidullah,Kumar, Brijesh,Kaushik, Mahabir Prasad,Konwar, Rituraj,Ampapathi, Ravi Sankar,Tripathi, Rama Pati
, p. 4306 - 4309 (2012)
A new approach to synthesize a homologous series of 14-, 15-, and 16-membered drug-like, macrocyclic glycoconjugates involving TBAHS promoted azide-propenone intramolecular cycloaddition in designed C-glycopyranosyl butenones from a simple sugar D-glucose and D-mannose is reported.
Bifunctional Fluoroalcohol Catalysts Enabled Sustainable Synthesis of Poly(amino acid)s?
He, Wenjing,Tao, Youhua
supporting information, p. 2119 - 2124 (2021/06/16)
A series of novel bifunctional single-molecule hydrogen-bonding organocatalysts based on fluorinated tertiary alcohol were synthesized to mediate the metal-free polymerization of α-amino acid N-carboxyanhydride (NCA) monomer. Through the screening of catalysts, the polymerization catalyzed by the preferred bifunctional fluoroalcohol catalyst proceeded in a fast and controlled manner, affording high molecular weight polypeptide up to 35.2 × 104 Da with relatively narrow molecular weight distribution (? 1.20). A phenomenon of self-accelerating effect of polymerization induced by α-helical structure of polypeptides was observed, and a possible polymerization pathway has been discussed.
Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry
Huang, Boxuan,Li, Weijia,Mu, Yu,Shao, Liang,Su, Yangqing,Sun, Mengsi,Xu, Huan,Yang, Fan,Yu, Fei,Zhang, Jihong,Zhang, Yuan
, p. 1759 - 1765 (2021/11/18)
Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide-alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC50 in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with oseltamivir. In addition, these compounds also displayed strong biological activity against A/Hong Kong/4801/2014 and B/Sichuan/531/2018 (BV). The results of hemagglutination inhibition assays and surface plasmon resonance binding assays suggest that these OA trimers may interrupt the interaction between the HA protein of influenza virus and the host cell sialic acid receptor, thus blocking viral entry. These findings highlight the utility of multivalent OA conjugates to enhance the ligand-target interactions in anti-influenza virus drug design and are also helpful for studying antiviral drugs derived from natural products.
3,6-DISUBSTITUTED-2-PYRIDINALDOXIME SCAFFOLDS
-
Paragraph 0095; 0175-0177, (2020/08/27)
The present invention relates to a compound of formula (I), or one of its pharmaceutically acceptable salts: wherein R1, R2 and -X-Y- have specific definitions. It also relates to the use of such a compound as reactivator of acetylcholinesterase for treating organophosphorous nerve agents poisoning; and to a process for preparing it.
Catalytic Asymmetric Synthesis of α-Arylpyrrolidines and Benzo-fused Nitrogen Heterocycles
Dai, Xi-Jie,Engl, Oliver D.,León, Thierry,Buchwald, Stephen L.
supporting information, p. 3407 - 3411 (2019/02/24)
Herein, we report a practical two-step synthetic route to α-arylpyrrolidines through Suzuki–Miyaura cross-coupling and enantioselective copper-catalyzed intramolecular hydroamination reactions. The excellent stereoselectivity and broad scope for the transformation of substrates with pharmaceutically relevant heteroarenes render this method a practical and versatile approach for pyrrolidine synthesis. Additionally, this intramolecular hydroamination strategy facilitates the asymmetric synthesis of tetrahydroisoquinolines and medium-ring dibenzo-fused nitrogen heterocycles.
[18F]FPyZIDE: A versatile prosthetic reagent for the fluorine-18 radiolabeling of biologics via copper-catalyzed or strain-promoted alkyne-azide cycloadditions
Roche, Mélanie,Specklin, Simon,Richard, Mylène,Hinnen, Fran?oise,Génermont, Kevin,Kuhnast, Bertrand
, p. 95 - 108 (2019/01/08)
Methods for the radiolabeling of biologics with fluorine-18 have been of interest for several decades. A common approach consists in the preparation of a prosthetic reagent, a small molecule bearing a fluorine-18 that is conjugated with the macromolecule to an appropriate function. Click chemistry, and more particularly cycloadditions, is an interesting approach to radiolabel molecules thanks to mild reaction conditions, high yields, low by-products formation, and strong orthogonality. Moreover, the chemical functions involved in the cycloaddition reaction are stable in the drastic radiofluorination conditions, thus allowing a simple radiosynthetic route to prepare the prosthetic reagent. We report herein the radiosynthesis of 18F-FPyZIDE, a pyridine-based azide-bearing prosthetic reagent. We exemplified its conjugation via copper-catalyzed cycloaddition (CuAAC) and strain-promoted cycloaddition (SPAAC) with several terminal alkyne or strained alkyne model compounds.
