Expeditious and environmentally benign synthesis of imidazo[4,5,1-]quinolines sequential Povarov reaction/reductive cyclization.

In this contribution, a novel, simple, diastereoselective and environmentally benign two-step diversity-oriented synthesis of imidazo[4,5,1-]quinolines is described for the first time. The synthesis of the target compounds involves a deep eutectic solvent-mediated one-pot Povarov reaction leading to the obtention of 8-nitrotetrahydroquinolines, followed by a microwave-assisted reductive cyclocondensation employing different aromatic and aliphatic aldehydes. The target compounds were obtained in up to 70% overall yield starting from commercially available -nitroanilines, natural phenylpropanoids (-anethole and -isoeugenol) and aromatic or aliphatic aldehydes.

Diastereoselective multicomponent synthesis of dihydroisoindolo[2,1-]quinolin-11-ones mediated by eutectic solvents.

In this contribution, a series of dihydroisoindolo[2,1-]quinolin-11-ones was synthesized by a one-pot multicomponent Povarov reaction starting from anilines, alkenes (-anethole, methyl eugenol and indene) and 2-formylbenzoic acid. Different eutectic solvents bearing Lewis or Brønsted acids were evaluated as reaction media and catalysts for the model reaction employing -toluidine and -anethole finding that the eutectic mixture ChCl/ZnCl (1/2) allowed the obtention of the target compound in 77% isolated yield. Under the optimized reaction conditions, 20 derivatives were obtained in good to moderated yields using - and -susbstituted anilines, while the corresponding -analogs followed a different pathway affording isoindolinones.

Tin(ii) chloride dihydrate/choline chloride deep eutectic solvent: redox properties in the fast synthesis of -arylacetamides and indolo(pyrrolo)[1,2-]quinoxalines.

In this contribution a physicochemical, IR and Raman characterization for the tin(ii) chloride dihydrate/choline chloride eutectic mixture is reported. The redox properties of this solvent were also studied by cyclic voltammetry finding that it can be successfully used as an electrochemical solvent for electrosynthesis and electroanalytical processes and does not require negative potentials as verified by the reduction of nitrobenzene. The potential use of this eutectic mixture as a redox solvent was further explored in obtaining aromatic amines and -arylacetamides starting from a wide variety of nitroaromatic compounds.

Tariquidar-Related Chalcones and Ketones as ABCG2 Modulators.

ABC transporters, including ABCG2, play a vital role in defending the human body against the vast range of xenobiotics. Even though this is beneficial for human health, these protein transporters have been implicated in the emerging resistance of cancer cells to a variety of structurally and functionally diverse anticancer drugs. In order to investigate their role in resistance, potent and selective ABCG2 modulators have been described in the literature.

Crystal structure of ethyl ()-2-cyano-3-(thio-phen-2-yl)acrylate: two conformers forming a discrete disorder.

In the title compound, CHNOS, all the non-H atoms, except for the ethyl fragment, lie nearly in the same plane. Despite the mol-ecular planarity, the ethyl fragment presents more than one conformation, giving rise to a discrete disorder, which was modelled with two different crystallographic sites for the eth-oxy O and eth-oxy α-C atoms, with occupancy values of 0.5.

Crystal structures of three -(3-acetyl-phen-yl)quinoline-2-carboxamides.

In the title compounds, -(5-acetyl-2-methyl-phen-yl)quinoline-2-carboxamide [CHNO, (I)], -(5-acetyl-2-bromo-phen-yl)quinoline-2-carboxamide [CHBrNO, (II)] and -(5-acetyl-2-ethynylphen-yl)quinoline-2-carboxamide [CHNO, (III)], the quinoline ring system is essentially planar and forms a dihedral angles of 3.68 (5) (I), 5.59 (7) (II) and 1.

Crystal structure of -(2-benzoyl-5-ethynylphen-yl)quinoline-2-carboxamide.

In the title compound, CHNO, the quinoline ring system is essentially planar, with a maximum deviation of 0.030 (1) Å, and forms a dihedral angle of 20.9 (1)° with benzoyl benzene ring.

ABCG2/BCRP: Specific and Nonspecific Modulators.

Multidrug resistance (MDR) in cancer cells is the development of resistance to a variety of structurally and functionally nonrelated anticancer drugs. This phenomenon has become a major obstacle to cancer chemotherapy seriously affecting the clinical outcome. MDR is associated with increased drug efflux from cells mediated by an energy-dependent mechanism involving the ATP-binding cassette (ABC) transporters, mainly P-glycoprotein (ABCB1), the MDR-associated protein-1 (ABCC1), and the breast cancer resistance protein (ABCG2).

Quinoline carboxamide-type ABCG2 modulators: indole and quinoline moieties as anilide replacements.

ABC, it's easy as 1 2 3! Bioisosteric replacement of the anilide core by an indole moiety considerably increased stability and gave potent and selective ABCG2 (BCRP) inhibitors. Some compounds are superior to the reference substances fumitremorgin C and Ko143 in terms of potency and efficacy and are the most potent ABCG2 modulators reported so far.

Benzanilide-Biphenyl Replacement: A Bioisosteric Approach to Quinoline Carboxamide-Type ABCG2 Modulators.

Recently reported compounds such as UR-COP78 (6) are among the most potent and selective ABCG2 modulators known so far but are prone to rapid enzymatic cleavage at the central benzanilide moiety. In search for more stable analogues, according to a bioisosteric approach, a series of N-(biphenyl-3-yl)quinoline carboxamides was prepared by solid phase and solution phase synthesis. The biphenyl moiety was constructed by Suzuki coupling.

Identification in silico and in vitro of novel trypanosomicidal drug-like compounds.

Atom-based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis-based quantitative structure-activity relationship models, using non-stochastic and stochastic indices, provide accuracies of 89.02% (85.

Photoinduced energy transfer in bichromophoric pyrene-PPV oligomer systems: the role of flexible donor-acceptor bridges.

In this contribution, we report on the electronic energy transfer dynamics of bichromophoric systems incorporating two pyrene chromophores tethered by variable-length flexible alkyloxy chains to p-phenylenevinylene oligomers. These were studied using UV-vis absorption and both steady state and time-resolved fluorescence spectroscopy. Time-resolved emission measurements showed an efficient photoinduced energy transfer process in all the multichromophoric systems, which occurs on the time scale of tens of picoseconds after excitation at 265 nm.

Solid phase synthesis of tariquidar-related modulators of ABC transporters preferring breast cancer resistance protein (ABCG2).

Aiming at structural optimization of potent and selective ABCG2 inhibitors, such as UR-ME22-1, from our laboratory, an efficient solid phase synthesis was developed to get convenient access to this class of compounds. 7-Carboxyisatoic anhydride was attached to Wang resin to give resin bound 2-aminoterephthalic acid. Acylation with quinoline-2- or -6-carbonyl chlorides, coupling with tetrahydroisoquinolinylethylphenylamine derivatives, cleavage of the carboxylic acids from solid support and treatment with trimethylsilydiazomethane gave the corresponding methyl esters.

New antitrichomonal drug-like chemicals selected by bond (edge)-based TOMOCOMD-CARDD descriptors.

Bond-based quadratic indices, new TOMOCOMD-CARDD molecular descriptors, and linear discriminant analysis (LDA) were used to discover novel lead trichomonacidals. The obtained LDA-based quantitative structure-activity relationships (QSAR) models, using nonstochastic and stochastic indices, were able to classify correctly 87.91% (87.

Synthesis and antiparasitic properties of new 4-N-benzylamino-4-hetarylbut-1-enes.

New derivatives of 4-N-benzylamino-4-hetarylbut-1-ene containing a pyridyl nucleus were synthesized from benzylamines and pyridine aldehydes. N-oxide derivatives were obtained from these homoallylamines. Study of the antiparasitic properties of obtained pyridine derivatives as well as of four related benzazepines previously described, was carried out using cytotoxicity assays against Trichomonas vaginalis and epimastigote form of Trypanosoma cruzi protozoa.