20876-29-3Relevant academic research and scientific papers
TRIAZOLOBENZAZEPINES AS VASOPRESSIN V1A RECEPTOR ANTAGONISTS
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, (2019/07/19)
The present invention relates to 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepine derivatives of general formula (I) and/or salts thereof and/or geometric isomers thereof and/or stereoisomers thereof and/or enantiomers thereof and/or racemates thereof and/or diastereomers thereof and/or biologically active metabolites thereof and/or prodrugs thereof and/or solvates thereof and/or hydrates thereof and/or polymorphs thereof which are centrally and/or peripherally acting V1a receptor modulators, particularly V1a receptor antagonists. Additional subject of the present invention is the process for the preparation of the compounds and the intermediates of the preparation process as well. The invention also relates to the pharmaceutical compositions containing the compounds or together with one or more other active substances, as well as to the use in the treatment and/or prophylaxis of a disease or condition associated with V1a receptor function.
Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua
Tanabe, Genzoh,Sugano, Youta,Shirato, Miki,Sonoda, Naoki,Tsutsui, Nozomi,Morikawa, Toshio,Ninomiya, Kiyofumi,Yoshikawa, Masayuki,Muraoka, Osamu
, p. 1536 - 1542 (2015/08/03)
The first total synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an α,α-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported 13C NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 μM) of 6 was 40 times stronger than that of arbutin (174 μM), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor within this class of compounds. (Chemical Equation Presented).
Novel synthesis of benzofuran- and indol-2-yl-methanamine derivatives
Schlosser, Joachim,Johannes, Eugen,Zindler, Melanie,Lemmerhirt, Jan,Sommer, Benjamin,Schütt, Martin,Peifer, Christian
, p. 89 - 94 (2015/02/02)
We report on a novel synthesis towards benzofuran-2-yl-methanamine and indol-2-yl-methanamine derivatives by using ortho-methoxy and ortho-nitro substituted phenylacetic acids as starting material, respectively. For each compound series, a key intermediate bearing the oxazole-4-carboxylic acid methylester moiety was produced. Refluxing the ortho-methoxy series in HBr/HAc produced the desired benzofuran-2-yl-methanamines. Accordingly, for the synthesis of indoles the nitro-group was first reduced and refluxing these intermediates in HCl gave the corresponding indol-2-yl-methanamines. The method worked well with electron donating substituents. Limitations regarding electron withdrawing substituents are discussed. This straightforward synthetic procedure can be a useful approach to generate a variety of substituted benzofuran-2-yl-methanamine and indol-2-yl-methanamine compounds by starting from readily available phenylacetic acid derivatives.
Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors
Mologni, Luca,Rostagno, Roberta,Brussolo, Stefania,Knowles, Phillip P.,Kjaer, Svend,Murray-Rust, Judith,Rosso, Enrico,Zambon, Alfonso,Scapozza, Leonardo,McDonald, Neil Q.,Lucchini, Vittorio,Gambacorti-Passerini, Carlo
experimental part, p. 1482 - 1496 (2010/04/29)
The synthesis, structure-activity relationships (SAR) and structural data of a series of indolin-2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped refine SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers.
Azomethine ylide cycloaddition/reductive heterocyclization approach to oxindole alkaloids: Asymmetric synthesis of (-)-horsfiline
Cravotto,Giovenzana,Pilati,Sisti,Palmisano
, p. 8447 - 8453 (2007/10/03)
The intermolecular [3 + 2] with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed π-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)- 2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.
Synthesis of 6h-pyrido[4,3-b]carbazoles
Modi, Sandeep P.,McComb, Todd,Zayed, Abdel-Hadi,Oglesby, R. Christopher,Archer, Sydney
, p. 5555 - 5562 (2007/10/02)
A few 6H-pyrido[4,3-b]carbazoles were prepared for cytotoxicity testing in cultures of human lung cancer cells. Methyl 6-methoxyindoleacetate 13, prepared by reduction of methyl 4-(2-nitro-5-methoxyphenyl)-3-oxobutyrate 11, was condensed with 3-acetylpyri
