- RORγ MODULATORS
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The invention provides an RORγ receptor agonist comprising a compound of formula (I), wherein the variables are as defined herein. These compounds are analogous to known RORγ receptor antagonists. The invention further provides a method of activating -the nuclear receptor RORγ, comprising -contacting the RORγ with an effective amount or concentration of a compound of the invention; and a method of treating cancer in a patient, comprising administering to the patient an effective dose of a compound of the invention.
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Page/Page column 81
(2018/04/13)
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- Method for preparing halogenated aniline from halogenated nitrobenzene through catalytic hydrogenation
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The invention discloses a method for preparing halogenated aniline from halogenated nitrobenzene through catalytic hydrogenation. The method comprises the following steps: in a reaction kettle, performing liquid phase catalytic hydrogenation reaction to halogenated nitrobenzene under the action of a sulfur-doped carbon material loaded noble metal catalyst, to obtain halogenated aniline shown in the formula (II), wherein the loading quantity of noble metal in the sulfur-doped carbon material loaded noble metal catalyst is 0.1-5wt%. In the method, the catalyst has good stability, the hydrogenation halogen removal side effect can be effectively inhibited under the condition of having no added halogen removal inhibitor, and the product selectivity is high.
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Paragraph 0051-0053
(2017/07/22)
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- N-Arylsulfonyl Indolines as Retinoic Acid Receptor-Related Orphan Receptor γ (RORγ) Agonists
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The nuclear retinoic acid receptor-related orphan receptor γ (RORγ; NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17 (TH17) cell proliferation. As such, synthetic small-molecule repressors (inverse agonists) targeting RORγ have been extensively studied for their potential as therapeutic agents for various autoimmune diseases. Alternatively, enhancing TH17 cell proliferation through activation (agonism) of RORγ may boost an immune response, thereby offering a potentially new approach in cancer immunotherapy. Herein we describe the development of N-arylsulfonyl indolines as RORγ agonists. Structure–activity studies reveal a critical linker region in these molecules as the major determinant for agonism. Hydrogen/deuterium exchange coupled to mass spectrometry (HDX-MS) analysis of RORγ–ligand complexes help rationalize the observed results.
- Doebelin, Christelle,Patouret, Rémi,Garcia-Ordonez, Ruben D.,Chang, Mi Ra,Dharmarajan, Venkatasubramanian,Kuruvilla, Dana S.,Novick, Scott J.,Lin, Li,Cameron, Michael D.,Griffin, Patrick R.,Kamenecka, Theodore M.
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p. 2607 - 2620
(2016/12/09)
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- Direct and practical synthesis of primary anilines through iron-catalyzed C-H bond amination
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The direct C-H amination of arenes is an important strategy to streamline the discovery and preparation of functional molecules. Herein, we report an operationally simple arene C-H amination reaction that, in contrast to most literature precedent, affords directly the synthetically versatile primary aniline products without relying on protecting group manipulations. Inexpensive Fe(II)-sulfate serves as a convenient catalyst for the transformation. The reaction tolerates a wide scope of arenes, including structurally complex drugs. Importantly, the arene substrates are used as limiting reagents in the transformation. This operationally simple transformation should considerably accelerate the discovery of medicines and functional molecules.
- Legnani, Luca,Cerai, Gabriele Prina,Morandi, Bill
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p. 8162 - 8165
(2018/05/22)
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- PARASITICIDAL COMPOSITIONS COMPRISING INDOLE DERIVATIVES, METHODS AND USES THEREOF
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The invention relates to oral, topical or injectable compositions for combating liver fluke parasites in mammals, comprising at least one indole derivative active agent. The invention also provides for an improved method for eradicating and controlling liver fluke parasite infections and infestations in a mammal comprising administering the compositions of the invention to the mammal in need thereof.
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Paragraph 0132
(2016/03/08)
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- Subtle "supramolecular buttressing effects" in Cucurbit[7]uril/guest assemblies
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Biphenyl derivatives bearing a dimethylsulfonium group at position 3 and three different substituents at position 4 (H, F and CH3) have been prepared as probes to test the validity of the "supramolecular buttressing" concept. We define the latter as the alteration, by a neighboring unit, of a substituent effect on intermolecular recognition. In this case, the 4-substituents exert some pressure on the 3-dimethylsulfonium groups and control the ratio of their syn and anti conformations. As free species, biphenyls bearing 4-H and 4-F substituents are present as approximately equimolar mixtures of syn and anti-conformers, while the biphenyl scaffold with a 4-CH3 group adopts the anti-conformation exclusively. The 3-dimethylsulfonium substituents then interact with one of the carbonylated portals of Cucurbit[7]uril (CB[7]), and their conformations affect the position of the guests inside the cavity of the macrocycle, thereby validating our "supramolecular buttressing" model. Surprisingly however, binding affinities towards CB[7] are barely affected by the nature of the 4-substituents and the conformations of the neighboring sulfonium groups, despite very different electronic densities presented to the CB[7] portal in their syn or anti conformations. Solvation was found to dramatically smoothen host-guest Columbic interactions, although the latter remain important in the recognition process. Replacing the positively charged 3-dimethylsulfonium unit with an isopropyl substituent decreases the affinity of the biphenyl guest by 1000-fold. The Royal Society of Chemistry 2013.
- Joseph, Roymon,Masson, Eric
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p. 3116 - 3127
(2013/06/05)
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- 6' SUBSTITUTED COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I): wherein R1—R4 A, B, D, E, and G are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
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Page/Page column 34
(2008/12/08)
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- PYRANOBENZOTHIOPHENE DERIVATIVES TO TREAT INFECTION WITH HEPATITIS C VIRUS
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The invention is directed to a compound of the formula: (I) wherein substitutions at R1, R2 , R3 - R12,and Y are set forth in the specification; pharmaceutical compositions comprising said compound, methods of treating or preventing a Hepatitis C viral infection in a mammal comprising contacting the mammal with an effective amount of said compound or pharmaceutical compositions including said compound and methods of inhibiting replication of a Hepatitis C virus comprising contacting the HCV virus with an effective amount of said compound or pharmaceutical compositions including said compound.
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Page/Page column 33
(2008/06/13)
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- Discovery of pyrano[3,4-b]indoles as potent and selective HCV NS5B polymerase inhibitors
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A novel series of HCV NS5B RNA-dependent RNA polymerase inhibitors containing a pyrano-[3,4-b]indole scaffold is described leading to the discovery of compound 16, a highly potent and selective inhibitor that is active in the replicon system.
- Gopalsamy, Ariamala,Lim, Kitae,Ciszewski, Gregory,Park, Kaapjoo,Ellingboe, John W.,Bloom, Jonathan,Insaf, Shabana,Upeslacis, Janis,Mansour, Tarek S.,Krishnamurthy, Girija,Damarla, Murthy,Pyatski, Yelena,Ho, Douglas,Howe, Anita Y. M.,Orlowski, Mark,Feld, Boris,O'Connell, John
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p. 6603 - 6608
(2007/10/03)
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- R-ENANTIOMERS OF PYRANOINDOLE DERIVATIVES AGAINST HEPATITIS C
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The invention is directed to a compound and a pharmaceutical composition of the formula: Wherein substitutions at R1, R2, R3 - R12, and Y are set forth in the specification.
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- Pharmaceutical compositions and methods for use
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Pharmaceutical compositions aryl substituted amine compounds, and in particular, 3-aminophenyl amine compounds are provided. Representative compounds are (4E)-N-methyl-5-(3-acetamido-4-methylphenyl)-4-penten-2-amine, (4E)-N-methyl-5-(3-amino-4-methylphenyl)-4-penten-2-amine, (4E)-N-methyl-5-(3-(dimethylamino)phenyl)-4-penten-2-amine, (4E)-N-methyl-5-(4-methyl-3-nitrophenyl)-4-penten-2-amine, (4E)-N-methyl-5-(3-fluorophenyl)-4-penten-2-amine, (4E)-N-methyl-5-(3,4-dichlorophenyl)-4-penten-2-amine and (4E)-N-methyl-5-(3,4-methylenedioxyphenyl)-4-penten-2-amine.
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- Syntheses of 4-methoxymethylbenzyl permethrinates containing fluorine and their insecticidal activity
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In order to investigate the relationship between the position of fluorine atom and insecticidal activity about 4-methoxymethylbenzyl permethrinates containing fluorine, 2 and 3-fluoro-4-methoxymethylbenzyl (±)-cis-permethrinate were synthesized. Their insecticidal activities were tested and the fluorine effect of title compounds was discussed.
- Zou, Xinzhuo,Qiu, Zongxing
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p. 173 - 179
(2007/10/03)
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- Indium metal as a reducing agent in organic synthesis
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The low first ionisation potential (5.8 eV) of indium coupled with its stability towards air and water, suggest that this metallic element should be a useful reducing agent for organic substrates. The use of indium metal for the reduction of C=N bonds in imines, the heterocyclic ring in benzo-fused nitrogen heterocycles, of oximes, nitro compounds and conjugated alkenes and the removal of 4-nitrobenzyl protecting groups is described. Thus the heterocyclic ring in quinolines, isoquinolines and quinoxalines is selectively reduced using indium metal in aqueous ethanolic ammonium chloride. Treatment of a range of aromatic nitro compounds under similar conditions results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected. Likewise indium in aqueous ethanolic ammonium chloride is an effective method for the deprotection of 4-nitrobenzyl ethers and esters. Indium is also an effective reducing agent under non-aqueous conditions and α-oximino carbonyl compounds can be selectively reduced to the corresponding N-protected amine with indium powder, acetic acid in THF in the presence of acetic anhydride or di-tert-butyl dicarbonate. Conjugated alkenes are also reduced by indium in THF-acetic acid.
- Pitts,Harrison,Moody
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p. 955 - 977
(2007/10/03)
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- Pyridine derivatives and pharmaceutical compositions containing them
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The invention relates to novel pyridyl derivatives, their use as medicaments, pharmaceutical formulations containing them and methods for their preparation.
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- Tellurium mediated reduction of aromatic nitro groups
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Treatment of a wide range of aromatic nitro compounds with tellurium powder in aqueous methanolic ammonium chloride results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected.
- Khan, Rabat H.
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p. 290 - 291
(2007/10/03)
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- Indium as a reducing agent: Reduction of aromatic nitro groups
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Treatment of a range of aromatic nitro compounds with indium powder in aqueous ethanolic ammonium chloride results in selective reduction of the nitro groups; ester, nitrile, amide and halide substituents are unaffected.
- Moody, Christopher J.,Pitts, Michael R.
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p. 1028 - 1028
(2007/10/03)
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