Arnold R. Romero Bohórquez

An efficient synthesis of new C-2 aryl substituted quinolines based on three component imino Diels-Alder reaction

New effective approach to the synthesis of a wide variety of C-2 nitro or aminophenyl substituted quinolines was reported using diverse intermediate 4-(2-oxopyrrolinidyl-1)-tetrahydroquinolines that were prepared by a three component imino Diels-Alder reaction was reported. The key aromatisation process occurs cleanly with the loss of the 2-oxopyrrolinidyl-1 fragment.

A Straightforward Synthetic Approach to Antitumoral Pyridinyl Substituted 7H-Indeno[2,1-c]Quinoline Derivatives Via Three-Component Imino Diels- Alder Reaction

Abstract: A simple and efficient synthetic method of obtaining pyridinyl substituted indeno[2,1- c ]quinolinederivatives has been developed. This method involves a three-component imino Diels-Alder cycloadditionbetween anilines, pyridinecarboxyaldehydes and indene as the key ring forming step and subsequent treatmentof obtained 5,6,6a,11b-tetrahydroindeno[2,1- c ]quinolines with powdered sulfur to give correspondingindeno[2,1- c ]quinolines. Some of them were treated with potassium permanganate in acetone to afford the 7 H -indeno[2,1- c ]quinolin-7-ones. Most compounds of the series were devoid of antifungal properties against apanel of standard dermatophytes, however, nearly all of them were active against breast (MCF-7), lung (H-460)and central nervous system (SF-268) human cancer cell lines. Keywords: Multi-component reaction, imino Diels-Alder reaction, indeno[2,1- c ]quinolines, antitumoral and antifungalactivities. INTRODUCTION NNH ONH 3 CHOCH 3 Tetrahydroquinoline derivatives are an important class ofnatural and synthetic compounds, which have shown a widerange of biological activities [1] including antimalarial [2],antitumoral [3], antioxidant [4] and anti-inflammatory [5].Moreover, their polycyclic analogs such as indenoquinolinederivatives are used as potential pharmaceuticals [6]. Thus,many synthetic procedures have been developed to preparethese polycyclic quinoline systems [7], where theindeno[2,1-

Selective activity of 2,4-diaryl-1,2,3,4-tetrahydroquinolines on Trypanosoma cruzi epimastigotes and amastigotes expressing β-galactosidase

The growth inhibitory effect on Trypanosoma cruzi epimastigotes and the unspecific cytotoxicity over NCTC-929 fibroblasts of two series of previously synthesized 2,4-diaryl-1,2,3,4-tetrahydroquinolines (THQ), have been studied in vitro and compared with those of benznidazole (BZ). Derivatives AR39, AR40, AR41, AR91 and DM15 achieved outstanding selectivity indexes (SI) on the extracellular form (SITHQ>SIBZ>9.44) and thus, were tested in a more specific in vitro assay against amastigotes, showing less effectiveness than the reference drug (SIBZ>320) but also accomplishing great selectivity on the intracellular stage (SITHQ>25). These promising results, supported by the in silico prediction of high bioavailability and less potential risk than benznidazole, reveal several tetrahydroquinolines as prototypes of potential antichagasic drugs.

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% (87.50%) and 89.01% (84.38%) of the chemicals in training (test) sets, respectively. They showed large Matthews correlation coefficients of 0.75 (0.71) and 0.78 (0.65) for the training (test) sets, correspondingly. Later, both models were applied to the virtual screening of 21 chemicals to find new lead antitrichomonal agents. Predictions agreed with experimental results to a great extent because a correct classification for both models of 95.24% (20 of 21) of the chemicals was obtained. Of the 21 compounds that were screened and synthesized, 2 molecules (chemicals G-1, UC-245) showed high to moderate cytocidal activity at the concentration of 10 μg/ml, another 2 compounds (G-0 and CRIS-148) showed high cytocidal activity only at the concentration of 100 μg/ml, and the remaining chemicals (from CRIS-105 to CRIS-153, except CRIS-148) were inactive at these assayed concentrations. Finally, the best candidate, G-1 (cytocidal activity of 100% at 10 μg/ml) was in vivo assayed in ovariectomized Wistar rats achieving promising results as a trichomonacidal drug-like compound. (Journal of Biomolecular Screening 2008:785-794).

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% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in‐house synthesized compounds to find new pro‐lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16/18) of the chemicals. Sixteen compounds show more than 70% of epimastigote inhibition at a concentration 100 μg/mL. In addition, three compounds (CRIS 112, CRIS 140 and CRIS 147) present more than 70% of epimastigote inhibition at a concentration of 10 μg/mL (79.95%, 73.97% and 78.13%, respectively) with low values of cytotoxicity (19.7%, 7.44% and 20.63%, correspondingly).Taking into account all these results, we could say that these three compounds could be optimized in forthcoming works. Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals.

X-ray powder diffraction data and characterization of Mirabegron

Mirabegron, (C 21 H 24 N 4 O 2 S), is a β 3 -adrenoceptor agonist approved in Japan, the USA, Canada and Europe, for the treatment of overactive bladder symptoms. There are no entries for this important active pharmaceutical ingredient in the Cambridge Structural Database or the Powder Diffraction File-4/Organics database. In this contribution, the powder diffraction pattern of Mirabegron, an unreported phase, are presented with a study by spectroscopy methods (Fourier-transform infrared spectroscopy [FT-IR] and RAMAN) and thermal analysis (thermogravimetric analysis [TGA]-differential scanning calorimetry [DSC]).

2-Ethyl-6-(2-pyrid-yl)-5,6,6a,11b-tetra-hydro-7H-indeno[2,1-c]quinoline.

The title compound, C23H22N2, was obtained using the three-component imino Diels–Alder reaction via a one-pot condensation between anilines, α-pyridinecarboxyaldehyde and indene using BF3·OEt2 as the catalyst. The molecular structure reveals the cis-form as the unique diastereoisomer. The crystal structure comprises one-dimensional zigzag ribbons connected via N—H⋯N hydrogen bonds. C—H⋯π interactions also occur.

Reacción de imino diels-Alder de tres componentes con precursores de origen natural. Generación de nuevas tetrahidroquinolinas 2, 4-diaril disustituidas

The efficient and diastereoselective synthesis of the new substituted 2,4-diaryl1,2,3,4,-tetrahydroquinoline (THQ) was realized via trans-anethole or cis/transisoeugenol, anilines and benzaldehydes condensation with acid catalysts. The BF3?OEt2 was the most efficient catalyst for this reaction. In addition, the essential oil of anise was employed for the direct synthesis of these compounds (THQ). Finally, the extract of the dry anise seeds was used after the extraction under supercritical fluid conditions (scCO2) and the THQ was obtained in good yield and solventless.