- PROCESS FOR PREPARATION OF AGOMELATINE AND CRYSTALLINE FORM I THEREOF
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An improved process for the preparation of agomelatine of formula (I) and a new process for the preparation of crystalline form I of agomelatine are provided.
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- Total synthesis of agomelatine via Friedel-Crafts acylation followed by Willgerodt-Kindler reaction
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Total synthesis of antidepressant drug, agomelatine is reported. Regio selective Friedel-Crafts acylation followed by Willgerodt-Kindler reactions is used as the key steps for the synthesis of agomelatine.
- Vujjini, Satish Kumar,Datla, V.R. Krishnam Raju,Badarla, Krishna Rao,Vetukuri, V.N.K.V. Prasada Raju,Bandichhor, Rakeshwar,Kagga, Mukkanti,Cherukupally, Praveen
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supporting information
p. 3885 - 3887
(2014/07/08)
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- AGOMELATINE AND PHARMACEUTICAL COMPOSITIONS THEREOF
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Agomelatine crystal, which is a drug for treating depression, and pharmaceutical compositions thereof are provided. The X-ray powder diffraction spectra of such agomelatine crystal, which is irradiated by Cu-Kα and showed by 20(degree), has characteristic diffraction peaks at 12.84, 13.84, 16.14, 18.56, 19.12, 20.86, 21.20, 23.84; its IR absorption pattern has characteristic absorption peaks at about 3234, 3060, 2940, 1638, 1511, 1436, 1249, 1215, 1184, 1032, 908, 828, 755, 588 cm-1; and its DSC endothermic transition temperature is 97.6°C. The use of the agomelatine crystal as an active ingredient in preparing a medicament for the treatment of depression is also provided.
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- SUBSTITUTED NAPHTHALENES
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Disclosed herein are substituted naphthalene-based melatonin (MT) receptor modulators and/or 5-HT receptor modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 35
(2008/12/08)
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- Microsomal activation of dibenzo[def,mno]chrysene (anthanthrene), a hexacyclic aromatic hydrocarbon without a bay-region, to mutagenic metabolites
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Metabolically formed dihydrodiol epoxides in the bay-region of polycyclic aromatic hydrocarbons are thought to be responsible for the genotoxic properties of these environmental pollutants. The hexacyclic aromatic hydrocarbon dibenzo[def,mno]chrysene (anthanthrene), although lacking this structural feature, was found to exhibit considerable bacterial mutagenicity in histidine-dependent strains TA97, TA98, TA100, and TA104 of S. typhimurium in the range of 18-40 his+-revertant colonies/nmol after metabolic activation with the hepatic postmitochondrial fraction of Sprague-Dawley rats treated with Aroclor 1254. This mutagenic effect amounted to 44-84% of the values determined with benzo[a]pyrene under the same conditions. The specific mutagenicity of anthanthrene in strain TA100 obtained with the cell fraction of untreated animals was 6 his+-revertant colonies/nmol and increased 2.7-fold after treatment with phenobarbital and 4.5-fold after treatment with 3-methylcholanthrene. To elucidate the metabolic pathways leading to genotoxic metabolites, the microsomal biotransformation of anthanthrene was investigated. A combination of chromatographic, spectroscopic, and biochemical methods allowed the identification of the trans-4,5-dihydrodiol, 4,5-oxide, 4,5-, 1,6-, 3,6-, and 6,12-quinones, and 1- and 3-phenols. Furthermore, two diphenols derived from the 3-phenol, possibly the 3,6 and 3,9 positional isomers, as well as two phenol dihydrodiols were isolated. Three pathways of microsomal biotransformation of anthanthrene could be distinguished: The K-region metabolites are formed via pathway I dominated by monooxygenases of the P450 1B subfamily. On pathway II the polynuclear quinones of anthanthrene are formed. Pathway III is preferentially catalyzed by monooxygenases of the P450 1A subfamily and leads to the mono- and diphenols of anthanthrene. The K-region oxide and the 3-phenol are the only metabolites of anthanthrene with strong intrinsic mutagenicity, qualifying them as ultimate mutagens or their precursors. From the intrinsic mutagenicity of these two metabolites and their metabolic formation, the maximal mutagenic effect was calculated. This demonstrates the dominating role of pathway III in the mutagenicity of anthanthrene under conditions where it exhibits the strongest bacterial mutagenicity. platt@ mail.uni-mainz.de.
- Platt, Karl L.,Degenhardt, Christian,Grupe, Stefanie,Frank, Heinz,Seidel, Albrecht
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p. 332 - 342
(2007/10/03)
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- O-arylmethyl-N-(thio)acylhydroxylamines
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The invention relates to a compound selected from those of formula (I): STR1 in which Ar, X, R 1 and R 2 are as defined in the description and a medicinal product containing the same in order to treat a disorder of the melatoninergic system.
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- Intramolecular Diels-Alder Reactions. 4. Additions to Naphthalene
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N-Methyl-N-2-propynyl-1-naphthalenecarboxamide, N-methyl-N-2-propynyl-1-naphthaleneacetamide, and N-methyl-N-3-butynyl-1-naphthalenecarboxamide undergo intramolecular Diels-Alder reactions at 190 deg C, 250 deg C, and 270 deg C to give lactams 1, 6, and 9, respectively.The cyclization temperatures are higher by 80-120 deg C as compared to those of the corresponding anthracene derivatives.Elaboration of lactam 6 gave the trans-4a-aryldecahydroisoquinoline derivative 7a which, as the (-) isomer, was shown to have the same absolute stereochemistry as morphine.
- Ciganek, Engelbert,Wuonola, Mark A.,Harlow, Richard L.
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p. 1251 - 1258
(2007/10/02)
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