- INDOLE AHR INHIBITORS AND USES THEREOF
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The present invention provides compounds useful as inhibitors of AHR, compositions thereof, and methods of using the same.
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- Synthesis and cycloxygenase inhibitory properties of new naphthalene-methylsulfonamido, naphthalene-methylsulfonyl and tetrahydronaphthalen-methylsulfonamido compounds
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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.
- Nencetti, Susanna,Ciccone, Lidia,Rossello, Armando,Nuti, Elisa,Milanese, Claudio,Orlandini, Elisabetta
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p. 406 - 412
(2015/07/27)
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- Asymmetric amination of tetralone and chromanone derivatives employing ω-transaminases
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Various (S)-selective and (R)-selective ω-transaminases were investigated for the amination of 1- and 2-tetralone and derivatives as well as of 3- and 4-chromanone. All ketones tested were aminated to give the corresponding enantiopure amines (ee > 99%) employing at least one of the enzymes investigated. In most of the cases the (S)- as well as the (R)-enantiomer was obtained in optically pure form. The amination of 3-chromanone was performed on a 100 mg scale leading to optically pure (R)-3-aminochromane (ee > 99%) with complete conversion and 78% isolated yield.
- Pressnitz, Desiree,Fuchs, Christine S.,Sattler, Johann H.,Knaus, Tanja,Macheroux, Peter,Mutti, Francesco G.,Kroutil, Wolfgang
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p. 555 - 559
(2013/06/05)
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- Investigation of one-enzyme systems in the ω-transaminase-catalyzed synthesis of chiral amines
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ω-Transaminase (TA) catalyzed asymmetric syntheses of amines were carried out in the one enzyme systems with wild-type enzymes (S)-TA from Pseudomonas aeruginosa, (S)-TA from Paracoccus denitrificans and (R)-TA from Aspergillus terreus. The scope of amine donors and aromatic carbonyl substrates was thoroughly explored. Among the range of potential amino donors, 2-propylamine, 2-butylamine and 1-phenylethylamine were found as promising candidates, which gave superior conversions in the amination reactions compared to other donors. Various prochiral aromatic ketones were accepted as substrates by the investigated enzymes. In most cases, good to excellent conversions (up to 98%) to the amine products with excellent e.e.-values (>99.9% for (S) or (R)) were obtained by the action of a single enzyme and an appropriate amino donor. (S)-TA from Paracoccus denitrificans was found to accept bulky ketones, e.g. 1-indanone, α- and β-tetralone or 2-acetonaphthone, in the asymmetric amination. In some cases the enantiomeric excesses in the amination reactions were dependent on the amino donor. More-over, the influence of the pH, temperature and cosolvents on the outcome of reactions was additionally investigated.
- Fesko, Kateryna,Steiner, Kerstin,Breinbauer, Rolf,Schwab, Helmut,Schuermann, Martin,Strohmeier, Gernot A.
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p. 103 - 110
(2013/10/22)
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- Artificial multi-enzyme networks for the asymmetric amination of sec-alcohols
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Various artificial network designs that involve biocatalysts were tested for the asymmetric amination of sec-alcohols to the corresponding α-chiral primary amines. The artificial systems tested involved three to five redox enzymes and were exemplary of a range of different sec-alcohol substrates. Alcohols were oxidised to the corresponding ketone by an alcohol dehydrogenase. The ketones were subsequently aminated by employing a ω-transaminase. Of special interest were redox-neutral designs in which the hydride abstracted in the oxidation step was reused in the amination step of the cascade. Under optimised conditions up to 91 % conversion of an alcohol to the amine was achieved. Trickle-down effect: The asymmetric amination of sec-alcohols to the corresponding α-chiral primary amines was performed with a biocatalytic cascade whereby the various steps were interconnected through the cofactors/cosubstrates. In a redox-neutral cascade and under optimised conditions, up to 91 % conversion of an alcohol to the amine was achieved. Copyright
- Tauber, Katharina,Fuchs, Michael,Sattler, Johann H.,Pitzer, Julia,Pressnitz, Desiree,Koszelewski, Dominik,Faber, Kurt,Pfeffer, Jan,Haas, Thomas,Kroutil, Wolfgang
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p. 4030 - 4035
(2013/04/10)
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- Synthesis and antifungal activities of novel 2-aminotetralin derivatives
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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.
- Yao, Bin,Ji, Haitao,Cao, Yongbin,Zhou, Youjun,Zhu, Jü,Lü, Jiaguo,Li, Yaowu,Chen, Jun,Zheng, Canhui,Jiang, Yuanying,Liang, Rongmei,Tang, Hui
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p. 5293 - 5300
(2008/03/18)
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- SUBSTITUTED TETRALINS AND INDANES AND THEIR USE
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This invention features tetralin and indane compounds, compositions containing them, and methods of using them as PPAR alpha modulators to treat or inhibit the progression of, for example, diabetes.
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- SUBSTITUTED TETRALINS AND INDANES
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The invention features tetralin and indane compounds, compositions containing them, and methods of using them as PPAR alpha modulators to treat or inhibit the progression of, for example, dyslipidemia.
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- DPP IV inhibitors
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The present invention relates to compounds of formula (I) wherein R1, R2, and X are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV, such as diabetes, particularly non-insulin dependent diabetes mellitus, and impaired glucose tolerance.
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- Substituted pyridines/pyrimidines, their preparation and their use as pesticides
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The present invention relates to novel substituted pyridines/pyrimidines of the formula I where A is CH or N; X is NH, O or S(O)qwhere q is 0, 1 or 2; Y1, Y2and Y3independently of one another are a group of the
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- A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes
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A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes has been demonstrated starting from phthalimidovinylglycinol (PVG). Functionalisation of PVG via Heck reaction, olefin hydrogenation and cyclisation provides the title products. (C) 2000 Elsevier Science Ltd.
- Harris, Michael C. J.,Jackson, Mark,Lennon, Ian C.,Ramsden, James A.,Samuel, Helen
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p. 3187 - 3191
(2007/10/03)
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- Bicyclic fibrinogen antagonists
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PCT No. PCT/US95/15937 Sec. 371 Date Jun. 13, 1997 Sec. 102(e) Date Jun. 13, 1997 PCT Filed Dec. 7, 1995 PCT Pub. No. WO96/18602 PCT Pub. Date Jun. 20, 1996This invention relates to compounds of the formula: which are effective for inhibiting platelet agg
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- Microbial Reduction of 1-Tetralone 2-Carboxyesters as a Source of New Asymmetric Synthons
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The reduction of unsubstituted or methoxy-substituted (+/-)-2-carboxyethyl-1-tetralones by selected microorganisms affords optically active 1-hydroxy-2-carboxyethyl tetralins which can be used as versatile asymmetric synthons, for example in the preparation of biologically active methoxy-substituted 2R-aminotetralins. 1R,2R-(cis)-hydroxyesters of high optical purity are obtained with yeast strains, while the use of filamentous fungi leads to the enantiomeric 1S,2S-(cis)-hydroxyesters.
- Buisson, Didier,Cecchi, Roberto,Laffitte, Jean-Alex,Guzzi, Umberto,Azerad, Robert
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p. 3091 - 3094
(2007/10/02)
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- Photoinduced nucleophilic addition of ammonia and alkylamines to methoxy-substituted styrene derivatives
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The photoamination of trans-1-arylpropenes (aryl = 2-methoxyphenyl), (1), 3-methoxyphenyl (2) 3,4-dimethoxyphenyl (3), and 4-methoxyphenyl (4) with NH3, i-PrNH2, and t-BuNH2 (RNH2), in the presence of p-dicyanobenzene (p-DCB) gave 2-alkylamino-1 arylpropanes (9) and/or 2-alkylamino-1-aryl-1-(4-cyanophenyl)propanes (10). The photoaminations of 1,2-dihydro-7-methoxynaphthalenes (6-8) with RNH2 in the presence of p-DCB gave mainly 2-alkylamino-1-(4-cyanophenyl)-6-methoxy-1,2,3,4-tetrahydronaphthalene s (13). The photoamination of trans-1-(3,5-dimethoxyphenyl)propene (5) with i-PrNH2 occurred at aromatic ring to give trans-1-(2-isopropylamino-3,5-dimethoxyphenyl)propene (11). The photoaminations of 1-4 and 6-8 with NH3 in the presence of m-dicyanobenzene gave the aminated products without incorporation of cyanophenyl group. Furthermore, the addition of 1,3,5-triphenylbenzene and m-terphenyl for these reactions improved the yields of the photoaminated products.
- Yamashita,Yamashita, Toshiaki,Yasuda,Yasuda, Masahide,Isami,Isami, Toshihiro,Tanabe,Tanabe, Kimiko,Shima,Shima, Kensuke
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p. 9275 - 9286
(2007/10/02)
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- 2-Amido-8-methoxytetralins: A Series of Nonindolic Melatonin-like Agents
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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.
- Copinga, Swier,Tepper, Pieter G.,Grol, Cor J.,Horn, Alan S.,Dubocovich, Margarita L.
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p. 2891 - 2898
(2007/10/02)
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- Synthesis of phenethylamine moiety by photoamination of styrene derivatives with ammonia
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The photoaminations of trans-1-arylpropenes and 7-methoxy-1,2-dihydronaphthalenes with ammonia in the presence of dicyanobenzene gave 1-aryl-2-propylamines and 2-amino-6-methoxy-1,2,3,4-tetrahydronaphthalenes, respectively. The yields of the aminated compounds were improved by the addition of 1,3,5-triphenylbenzene or m-terphenyl.
- Yamashita, Toshiaki,Yasuda, Masabide,Isami, Toshihiro,Nakano, Shozo,Tanabe, Kimiko,Shima, Kensuke
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p. 5131 - 5134
(2007/10/02)
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- Conformationally Restricted and Conformationally Defined Tyramine Analogues as Inhibitors of Phenylethanolamine N-Methyltransferase
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In a search for a selective inhibitor for the epinephrine synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28), phenolic 2-aminotetralins (12-15 as conformationally restricted analogues of tyramine) and phenolic benzobicyclo3.2.
- Ye, Qizhuang,Grunewald, Gary L.
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p. 478 - 486
(2007/10/02)
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- 1,2,3,4-Tetrahydronaphthalene derivatives
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New compounds of the formula: STR1 wherein R1 represents a hydrogen atom or an alkanoyl group containing from 1 to 4 carbon atoms, R2 and R3 each represent a hydrogen atom or a C1 -C4 alkyl group, and R4 represents a hydroxy or methoxy group in the 6-position or 7-position, have been found to be useful in therapy, and more particularly in the treatment of cardiovascular diseases and Parkinson's disease.
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- N-Aralkyl Substitution of 2-Amino-5,6- and -6,7-dihydroxy-1,2,3,4-tetrahydronaphthalenes. 2. Derivatives of a Hypotensive-Positive Inotropic Agent
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Seven derivatives of 2-amino>-6,7-dihydroxy-1,2,3,4-tetrahyronaphthalene, an inotropic agent which also causes a decrease in blood pressure, were synthesized and tested for inotropic potency, cardioselectivity, and
- Stout, David M.,Gorczynski, Richard J.
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p. 326 - 328
(2007/10/02)
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