4003-89-8Relevant academic research and scientific papers
Synthesis and cycloxygenase inhibitory properties of new naphthalene-methylsulfonamido, naphthalene-methylsulfonyl and tetrahydronaphthalen-methylsulfonamido compounds
Nencetti, Susanna,Ciccone, Lidia,Rossello, Armando,Nuti, Elisa,Milanese, Claudio,Orlandini, Elisabetta
, p. 406 - 412 (2015/07/27)
We synthesized a series of new naphthalene derivatives: naproxen- and 6-methoxy naphthalene acetic acid-like 1-5. In these compounds the carboxylic function, typical of the classical NSAIDs, was replaced by a methylsulfonamido (1, 2 and 6a-c) or methylsulfonyl (3-5) group present in some selective COX-2 inhibitors. We also synthesized compounds 7 and 8 in which the naphthalene portion was substituted by tetrahydronaphthalene ring. Some of the new compounds were assayed for their enzymatic inhibitory activity towards cycloxygenase enzymes. Compounds 4 and 6b, at a concentration of 10 μM exhibit percentage inhibition values of 65%, 50% and 29%, 87% towards COX-2 and COX-1, respectively. The substitution of carboxylic group with a mehylsulfonamido or a methylsulfonyl groups does not allow to direct the selectivity versus to cycloxygenase enzymes.
SUBSTITUTED HYDROXAMIC ACIDS AND USES THEREOF
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Page/Page column 60, (2012/02/01)
This invention provides compounds of formula (I): wherein R1, R1b, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.
Design and optimization of potent and orally bioavailable tetrahydronaphthalene raf inhibitors
Gould, Alexandra E.,Adams, Ruth,Adhikari, Sharmila,Aertgeerts, Kathleen,Afroze, Roushan,Blackburn, Christopher,Calderwood, Emily F.,Chau, Ryan,Chouitar, Jouhara,Duffey, Matthew O.,England, Dylan B.,Farrer, Cheryl,Forsyth, Nancy,Garcia, Khristofer,Gaulin, Jeffery,Greenspan, Paul D.,Guo, Ribo,Harrison, Sean J.,Huang, Shih-Chung,Iartchouk, Natalia,Janowik, Dave,Kim, Mi-Sook,Kulkarni, Bheemashankar,Langston, Steven P.,Liu, Jane X.,Ma, Li-Ting,Menon, Saurabh,Mizutani, Hirotake,Paske, Erin,Renou, Christelle C.,Rezaei, Mansoureh,Rowland, R. Scott,Sintchak, Michael D.,Smith, Michael D.,Stroud, Stephen G.,Tregay, Ming,Tian, Yuan,Veiby, Ole P.,Vos, Tricia J.,Vyskocil, Stepan,Williams, Juliet,Xu, Tianlin,Yang, Johnny J.,Yano, Jason,Zeng, Hongbo,Zhang, Dong Mei,Zhang, Qin,Galvin, Katherine M.
supporting information; experimental part, p. 1836 - 1846 (2011/05/30)
Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.
Asymmetric catalytic aziridination of dihydronaphthalenes for the preparation of substituted 2-aminotetralins
Aaseng, Jon Erik,Melnes, Silje,Reian, Gard,Gautun, Odd R.
experimental part, p. 9790 - 9797 (2011/02/22)
An enantioselective synthesis of substituted 2-aminotetralins from dihydronaphthalenes in four steps is described. The key step is the Jacobsen's (diimine)copper-catalyzed asymmetric aziridination of dihydronaphthalenes to the respective aziridines in 33-82% yields and 60-87% enantiomeric excess. The enantioselectivity and the yield were dependent on the properties of the nitrene precursor. pTsNIPh appeared in general to give better results than pNsNIPh. Aziridines were ring-opened in the benzylic position by catalytic hydrogenolysis in quantitative yields, and deprotected in two steps to the respective 2-aminotetralins in 66-85% yields. The synthesis of (S)-2-aminotetralin (>98% ee) and (S)-2-amino-7-methoxytetralin (56% ee) were accomplished in 30 and 52% overall yields, respectively.
Novel aminotransferase, gene encoding the same, and method of using them
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, (2010/12/29)
The invention relates to a novel aminotransferase, DNA encoding the enzyme, a recombinant vector into which the DNA has been introduced, and a transformant into which the vector has been introduced. Further, the invention also relates to a method for producing an optically active amino compound utilizing the enzyme or transformant. The aminotransferase of the invention has an ability of efficiently converting a ketone compound, particularly a cyclic ketone compound to an optically active amino compound. According to the invention, a method for efficiently producing an optically active amino compound, particularly an optically active cyclic amino compound is provided.
Synthesis and antifungal activities of novel 2-aminotetralin derivatives
Yao, Bin,Ji, Haitao,Cao, Yongbin,Zhou, Youjun,Zhu, Jü,Lü, Jiaguo,Li, Yaowu,Chen, Jun,Zheng, Canhui,Jiang, Yuanying,Liang, Rongmei,Tang, Hui
, p. 5293 - 5300 (2008/03/18)
Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14α-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.
Process for the preparation of substituted tetralin and substituted indane derivatives
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Page/Page column 34, (2008/06/13)
The present invention relates to novel processes for the preparation of substituted tetralin. and substituted indane derivatives. The present invention is further directed to novel processes for the preparation of intermediates in the preparation of the substituted tetralin and substituted indane derivatives.
PROCESS FOR PREPARATION OF 2-AMINOTETRALIN DERIVATIVES AND INTERMEDIATES THEREOF
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, (2008/06/13)
The present invention is to efficiently and simply prepare an optically active 7-substituted-2-aminotetralin with industrial advantage. In the process, a 7-substituted-2-tetralone or its bisulfite adduct is reduced with a microorganism to an optically active 7-substituted-2-tetralol. Then, a sulfonyl group is introduced to the hydroxy group to form an optically active 7-substituted-2-sulfonyloxytetralin. Then, with inversion of the configuration, a nitrogen substituent is introduced using a nitrogen nucleophile to form an optically active 2,7-substituted tetralin. Furthermore, if necessary, the nitrogen substituent is converted into a non-substituted amino group. Thus, an optically active 7-substituted-2-aminotetralin or its salt is prepared.
Affinity for dopamine D2, D3, and D4 receptors of 2-aminotetralins. Relevance of D2 agonist binding for determination of receptor subtype selectivity.
van Vliet,Tepper,Dijkstra,Damsma,Wikstroem,Pugsley,Akunne,Heffner,Glase,Wise
, p. 4233 - 4237 (2007/10/03)
A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but were never tested in vitro with single receptor subtypes, and these were examined again. None of the tested 2-aminotetralins showed high affinity for the dopamine D4 receptor. However, a number of the 2-aminotetralins showed high affinity for both the D2 and the D3 DA receptors, as exemplified by compounds 11-15 and 21-26, while some had a reasonable selectivity for the DA D3 receptors. The affinities of the 2-aminotetralins for the D21, receptor depended on the type of radioligand (agonist or antagonist) used. The agonist affinity data, obtained by using the agonist ligand [3H]N-0437, are thought to be more relevant for calculating DA receptor subtype selectivity.
2-Amido-8-methoxytetralins: A Series of Nonindolic Melatonin-like Agents
Copinga, Swier,Tepper, Pieter G.,Grol, Cor J.,Horn, Alan S.,Dubocovich, Margarita L.
, p. 2891 - 2898 (2007/10/02)
A series of unsubstituted and methoxy-substituted 2-amidotetralins (4a-q) was prepared and evaluated for their ability to complete for 2-iodomelatonin binding to chicken retinal membranes and for their potency to inhibit the calcium-dependent release of dopamine from rabbit retina.The lead compound, 2-acetamido-8-methoxytetralin (4j), showed a moderate affinity (Ki = 46 nM) and potency (IC50 = 1.4 nM) at the melatonin receptor.The structural requirements necessary for optimal agonistic activity at the melatonin receptor are as follows.First, the amido group, which should have a small, nonbranched alkyl group, is essential for affinity, and second, the methoxy substituent at the 8-position of the 2-amidotetralin ring is essential for optimal agonistic activity at the melatonin receptor.We concluded that this series of unsubstituted and methoxy-substituted 2-amidotetralins constitutes a class of nonindolic melatonin-like agents that can be used as pharmacological tools to further characterize melatonin receptors and to elucidate the mode of action of melatonin.
