Polyamines are believed to be potent vectors for the selective delivery of chemotherapeutic agents into cancer cells. In this paper, we report effect spermine conjugation on cytotoxic and transport properties acridine. Six derivatives, composed a chain attached at its N1 position an acridine via aliphatic chain, were synthesized. The linker, comprised 3−5 methylene units, was connected position-9 heterocycle through either amide (amidoacridines 8−10) or amine (aminoacridines 11−13) linkage....

The effects of several N-sulfonyl-polyamines, including N¹-dansyl-spermine (N¹-DnsSpm) and<i>N</i>¹-(<i>n</i>-octanesulfonyl)-spermine (N¹-OsSpm), were studied at recombinant<i>N</i>-methyl-d-aspartate (NMDA) receptors expressed in <i>Xenopus laevis</i> oocytes. N¹-DnsSpm and N¹-OsSpm inhibited NMDA ∼1000-fold more potent than spermine oocytes voltage-clamped −70 mV. Block by was strongly voltage dependent, being pronounced...

A rapid and efficient one-step halopyridone synthesis has been developed based on gold-catalyzed cyclization of β-amino-ynone intermediates halodeauration process.

The diastereoselective synthesis of 4-hydroxypiperidines bearing a tetrasubstituted carbon stereocenter at C4 by aza-Prins cyclization is presented. These motifs are relevant because they present in considerable number drugs.

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The polyamine transport system (PTS) whose activity is up-regulated in cancer cells an attractive target for drug design. Two heterocyclic (azepine and benzazepine) systems were conjugated to various moieties through amidine bound afford 18 compounds which evaluated their affinity the PTS ability use cell delivery. Structure−activity relationship studies lead optimization afforded two targeting compounds. azepine−spermidine conjugate 14 a very selective substrate of that may serve as vector...

The syntheses of several alkaloids and nitrogen-containing compounds including N-Boc-coniine (14b), pyrrolizidine (1), δ-coniceine (2), pyrrolo[1,2a]azepine (3) are described. New C–C bonds in the α position relative to nitrogen atom were formed by alkylation metalated α-aminonitriles 4 6a–c with alkyl iodides possessing requisite size functionality. In all reported cases, pyrrolidine ring was aqueous medium through a favorable 5-exo-tet process involving primary or secondary amino group...

Five sets of heterocyclic derivatives various sizes and complexities coupled by an amidine function to putrescine, spermidine, or spermine were prepared. They essentially tested determine the influence polyamine chain on their cellular transport. To comment affinity selective transport via system (PTS), Ki values for uptake determined in L1210 cells, cytotoxicity accumulation conjugates CHO transport-deficient mutant CHO-MG as well α-difluoromethylornithine- (DFMO-) treated cells. Unlike...

A palladium-catalyzed coupling reaction of aryl bromides with vinylic acetates in the presence tributyltin methoxide has been described. Unexpected formation ketones was obtained. Preliminary mechanistic studies indicated that proceeded by addition moiety coordination sphere palladium to a ketene.

Abstract Piperidine derivatives are highly abundant in natural products and pharmaceutically relevant compounds. Aza‐Prins cyclization has emerged as a step‐ atom‐economical stereoselective method for the preparation of such azacycles. The possibility coupling aza‐Prins process with formation second cycle one‐pot manner is even more powerful makes object this review. Cascade/domino/tandem bis ‐cyclizations involving an process, rapid construction complex small molecules, discussed detail.

The use of standard deviation as a measure line broadening in the Scherrer equation is justified on grounds that, for commonly used approximating curves which can be fitted to X-ray profiles, breadth at half intensity directly proportional curve. If crystallite size known priori, deviation–width scaling function calculated; also some insight gained into nature curve describing diffraction profile. A computer program Fortran IV has been written fits Gaussian forms profiles and computes...

Site-selective scission of ribonucleic acids (RNAs) has attracted considerable interest, since RNA is an intermediate in gene expression and the genetic material many pathogenic viruses.Polyamineimidazole conjugates for site-selective scission, without free imidazole, were synthesized tested on yeast phenylalanine transfer RNA.These molecules catalyze hydrolysis non-randomly.Within polyamine chain, location imidazole residue, numbers nitrogen atoms their relative distances have notable...

Chagas disease, caused by the parasitic protozoan Trypanosoma cruzi, affects approximately 6-7 million people worldwide. There are limited available therapies and they exhibit low efficacy, often high toxicity in chronic cases some drug resistance. In this study, our objective was to develop ester prodrugs that inhibit proline racemase (TcPRAC), a enzyme previously identified characterised as promising target because of its essential role parasite's life cycle virulence, test their activity...

Abstract α‐ and β‐Amino‐ynones have been largely used to prepare heterocyclic rings in the presence of various electrophiles such as protic acids or gold(I). Herein we disclose unprecedented formation pyrrolidine exocyclic vinylogous amides, place expected azepinones piperidinones, starting from γ‐amino‐ynones derived amino acids. The process involves a tandem 1,2‐addition protected nitrogen carbonyl group followed by Meyer–Schuster rearrangement, which efficiently afforded enantiopure...

Abstract Amino‐ynones can be seen as precursors of various heterocyclic rings. Although γ‐amino‐ynones have been used to prepare exocyclic vinylogous amides in the presence Brønsted acids, we describe here use zinc chloride a weak Lewis acid for their conversion into acetylenic cyclic imines. This reaction, which was attempted diverse range γ‐amino‐ynones, proved robust and efficient most cases easily extended δ‐amino‐ynones yield Depending on workup procedure, latter compounds could...

Solid-phase organic synthesis (SPOS) routes to target unsymmetrical polyamines and their acridinyl dansyl conjugates have been developed based upon borane–pyridine complex (BAP) mediated reductive alkylation, azide reduction with triphenylphosphine, the use of pent-4-enoyl (Pnt) as an orthogonal amine protecting group.

Abstract We describe a method that starts from protected ( S )‐aspartic acid and employs gold‐catalyzed cyclization to give enantiopure dihydropyridone 2‐carboxylates, which are then converted into 6‐substituted 4‐oxo‐ 4‐hydroxypipecolic derivatives. Thus, the lateral chain carboxylic of commercially available, forms Weinreb amide, is an ynone followed by furnish enaminones in high yields. The steric hindrance protecting group was revealed as efficient guide for selectivity reduction...

The concise synthesis of a small library fluorinated piperidines from readily available dihydropyridinone derivatives has been described. effect the fluorination on different positions then evaluated by chemoinformatic tools. In particular, compounds' pKa's have calculated, revealing that fluorine atoms notably lowered their basicity, which is correlated to affinity for hERG channels resulting in cardiac toxicity. "lead-likeness" and three-dimensionality also assess ability as useful...