73291-09-5Relevant articles and documents
Natural-product-inspired design and synthesis of two series of compounds active against Trypanosoma cruzi: Insights into structure–activity relationship, toxicity, and mechanism of action
Grand, Lucie,Popowycz, Florence,Schenkel, Eloir Paulo,Steindel, Mario,da Rosa, Rafael,Campos Bernardes, Lílian Sibelle,Dambrós, Bibiana Paula,H?ehr de Moraes, Milene,Jacolot, Ma?wenn
, (2021/11/30)
Chemical scaffolds of natural products have historically been sources of inspiration for the development of novel molecules of biological relevance, including hit and lead compounds. To identify new compounds active against Trypanosoma cruzi, we designed and synthesized 46 synthetic derivatives based on the structure of two classes of natural products: tetrahydrofuran lignans (Series 1) and oxazole alkaloids (Series 2). Compounds were screened in vitro using a cellular model of T. cruzi infection. In the first series of compounds, 11 derivatives of hit compound 5 (EC50 = 1.1 μM) were found to be active; the most potent (7, 8, and 13) had EC50 values of 5.1–34.2 μM. In the second series, 17 analogs were found active at 50 μM; the most potent compounds (47, 49, 59, and 63) showed EC50 values of 24.2–49.1 μM. Active compounds were assessed for selectivity, hemocompatibility, synergistic potential, effects on mitochondrial membrane potential, and inhibitory effect on trypanothione reductase. All active compounds showed low toxicity against uninfected THP-1 cells and human erythrocytes. The potency of compounds 5 and 8 increased steadily in combination with benznidazole, indicating a synergistic effect. Furthermore, compounds 8, 47, 49, 59, and 63 inhibited parasitic mitochondria in a dose-dependent manner. Although increased reactive oxygen species levels might lead to mitochondrial effects, the results indicate that the mechanism of action of the compounds is not dependent on trypanothione reductase inhibition. In silico calculation of chemical descriptors and principal component analysis showed that the active compounds share common chemical features with other trypanocidal molecules and are predicted to have a good ADMET profile. Overall, the results suggest that the compounds are important candidates to be further studied for their potential against T. cruzi.
COMPOUND HAVING ALKENYL GROUP AT BOTH TERMINALS, LIQUID CRYSTAL COMPOSITION AND LIQUID CRYSTAL DISPLAY ELEMENT
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Paragraph 0154, (2017/05/16)
PROBLEM TO BE SOLVED: To provide a liquid crystalline compound satisfying at least one of demands for physical properties such as high stability to heat or light, a high clearing point (or a high maximum temperature), low minimum temperature of a liquid crystal phase, small viscosity, suitable optical anisotropy, large dielectric anisotropy, suitable elastic modulus and good compatibility with other liquid crystalline compounds, a liquid crystal composition comprising the above compound, and a liquid crystal display element containing the composition. SOLUTION: A compound represented by formula (1) is provided. In the formula, R1 and R2 each independently represent an alkenyl group having 2 to 10 carbon atoms, or the like; ring A1, ring A2 and ring A3 each independently represent 1,4-phenylene or 1-4-phenylene in which at least one hydrogen is replaced by fluorine or chlorine; Z1 and Z2 each independently represent an alkylene having 1 to 4 carbon atoms, or the like and at least one of Z1 and Z2 may be a single bond; and a represents 1 or 2. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPO&INPIT
METHOD OF CONVERTING ALCOHOL TO HALIDE
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Page/Page column 51; 166; 170, (2017/01/02)
The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.
