- Dehydrogenative and Redox-Neutral N-Heterocyclization of Aminoalcohols Catalyzed by Manganese Pincer Complexes
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A new manganese catalyzed heterocyclization of aminoalcohols has been accomplished. A wide range of heterocycles were synthesized, including 1,2,3,4-tetrahydroquinolines, dihydroquinolinones, and 2,3,4,5-tetrahydro-1H-benzo[b]azepines. The reaction is performed under mild reaction conditions using air and moisture stable manganese catalysts. The desired heterocycles were obtained in good to excellent yields.
- Brzozowska, Aleksandra,Rueping, Magnus,Sklyaruk, Jan,Zubar, Viktoriia
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supporting information
(2022/03/17)
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Provided herein are novel heterocyclic compounds, for example, compounds having Formula I, I-P, II, lI-P, or III. Also provided herein are pharmaceutical compositions comprising the compounds and methods of using the same, for example, in inhibiting aldehyde dehydrogenases and/or for treating various cancers, cancer metastasis, type 2 diabetes, pulmonary arterial hypertension (PAH) or neointimal hyperplasia (NIH).
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Paragraph 0276
(2021/07/31)
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- DIACYLGLYCEROL KINASE MODULATING COMPOUNDS
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The present disclosure provides diacylglycerol kinase modulating compounds, and pharmaceutical compositions thereof, for treating cancer, including solid tumors, and viral infections, such as HIV or hepatitis B virus infection. The compounds can be used alone or in combination with other agents.
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Paragraph 1465-1466
(2021/07/02)
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- Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists
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The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
- Xia, Yuehan,Yu, Mingcheng,Zhao, Yunpeng,Xia, Li,Huang, Yafei,Sun, Nannan,Song, Meiqi,Guo, Huimin,Zhang, Yunyi,Zhu, Di,Xie, Qiong,Wang, Yonghui
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supporting information
(2020/12/04)
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- TETRAHYDROQUINOLINO DERIVATIVES FOR THE TREATMENT OF METASTATIC AND CHEMORESISTANT CANCERS
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Disclosed herein are compounds of Structural Formula I. Compounds of Structural Formula I inhibit aldehyde dehydrogenase isoform Ia3 (ALDHIa3) and are useful for treating cancer, for example, metastatic or chemoresistant cancer, such as metastatic cancer resistant to chemotherapy. Also disclosed herein are compositions comprising compounds of Structural Formula I and uses of compounds of Structural Formula I for treating cancer, for example, metastatic or chemoresistant cancer.
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Paragraph 00173
(2020/02/23)
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- RETRACTED ARTICLE: Site-selective enzymatic C-H amidation for synthesis of diverse lactams
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A major challenge in carbon?hydrogen (C?H) bond functionalization is to have the catalyst control precisely where a reaction takes place. In this study, we report engineered cytochrome P450 enzymes that perform unprecedented enantioselective C?H amidation reactions and control the site selectivity to divergently construct b-, g-, and d-lactams, completely overruling the inherent reactivities of the C?H bonds. The enzymes, expressed in Escherichia coli cells, accomplish this abiological carbon?nitrogen bond formation via reactive iron-bound carbonyl nitrenes generated from nature-inspired acyl-protected hydroxamate precursors. This transformation is exceptionally efficient (up to 1,020,000 total turnovers) and selective (up to 25:1 regioselectivity and 97%, please refer to compound 2v enantiomeric excess), and can be performed easily on preparative scale.
- Cho, Inha,Jia, Zhi-Jun,Arnold, Frances H.
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p. 575 - 578
(2019/06/07)
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- Multibond Forming Tandem Reactions of Anilines via Stable Aryl Diazonium Salts: One-Pot Synthesis of 3,4-Dihydroquinolin-2-ones
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A fast and effective one-pot tandem process that generates Heck coupled products from readily available anilines via stable aryl diazonium tosylate salts was developed. The mild and simple procedure involves rapid formation of aryl diazonium salts using a polymer-supported nitrite reagent and p-tosic acid, followed by a base-free Heck-Matsuda coupling with acrylates and styrenes. Using 2-nitroanilines as substrates, the one-pot tandem process was extended for the direct synthesis of 3,4-dihydroquinolin-2-ones. In this case, following diazotization and Heck-Matsuda coupling to give methyl cinnamates, addition of hydrogen and reutilization of the palladium catalyst for reduction of the nitro group and hydrogenation of the alkene resulted in efficient formation of 3,4-dihydroquinolin-2-ones. The synthetic utility of this one-pot, four-stage process was demonstrated with the five-pot synthesis of a quinolinone-based sodium ion channel modulator.
- Faggyas, Réka J.,Grace, Megan,Williams, Lewis,Sutherland, Andrew
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p. 12595 - 12608
(2018/10/15)
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- Triazole derivative having HSP90 (Heat Shock Protein) inhibiting activity, as well as preparation method and application of triazole derivative
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The invention discloses a triazole derivative having an HSP90 (Heat Shock Protein) inhibiting activity, as well as a preparation method and an application of the triazole derivative. Specifically, the invention relates to the triazole derivative having a structure as shown in a formula (I), a stereisomer of the triazole derivative and a pharmaceutically acceptable salt, wherein the definition of each substituent group in the formula (I) and the definition in a description are the same. The compound with a novel structure has the HSP90 inhibiting activity, can be used to cure cancers, neurodegenerative disorders, inflammation diseases, autoimmune diseases, ischemic brain injuries and the like, and has a broad application prospect.
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Paragraph 0488; 0492; 0493; 0494; 0495
(2017/08/02)
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- NEW DIHYDROQUINOLINE PYRAZOLYL COMPOUNDS
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R15, R16, R17 and n are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 39
(2016/05/19)
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- 4,5,6,7-TETRAHYDRO-1 H-PYRAZOLO[4,3-C]PYRIDIN-3-AMINE COMPOUNDS AS CBP AND/OR EP300 INHIBITORS
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The present invention relates to compounds of formula (I) or formula (II): and to salts thereof, wherein R1-R4 of formula (I) and R1-R3 of formula (II) have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) of formula (II) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders.
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Page/Page column 273; 274
(2016/06/14)
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- NEW DIHYDROQUINOLINE PYRAZOLYL COMPOUNDS AS ALDOSTERONE SYNTHASE INHIBITORS
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R10, R11, R12, R13, R14, R15, R16, R17 and m are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 32
(2016/05/19)
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- Novel pyridyl substituted 4,5-dihydro-[1,2,4]triazolo[4,3-a ]quinolines as potent and selective aldosterone synthase inhibitors with improved in vitro metabolic stability
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CYP11B2 inhibition is a promising treatment for diseases caused by excessive aldosterone. To improve the metabolic stability in human liver miscrosomes of previously reported CYP11B2 inhibitors, modifications were performed via a combination of ligand-and
- Hu, Qingzhong,Yin, Lina,Ali, Amjad,Cooke, Andrew J.,Bennett, Jonathan,Ratcliffe, Paul,Lo, Michael Man-Chu,Metzger, Edward,Hoyt, Scott,Hartmann, Rolf W.
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supporting information
p. 2530 - 2537
(2015/03/30)
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- DIHYDROQUINOLINE-2-ONE DERIVATIVES FOR USE AS ALDOSTERONE SYNTHASE INHIBITORS
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R9, R10 and R11 are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 31
(2014/09/29)
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- Multicomponent multicatalyst reactions (MC)2R: One-pot synthesis of 3,4-dihydroquinolinones
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A Rh/Pd/Cu catalyst system led to an efficient synthesis of dihydroquinolinones in one-pot, two operations. The reaction features the first triple metal-catalyzed transformations in one reaction vessel, without any intermediate workup. The conjugate-addition/amidation/amidation reaction sequence is highly modular, divergent, and practical.
- Zhang, Lei,Sonaglia, Lorenzo,Stacey, Jason,Lautens, Mark
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supporting information
p. 2128 - 2131
(2013/06/05)
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- DIHYDROQUINOLINE-2-ONE DERIVATIVES
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, A1, A2 and A3 are as described herein, compositions including the compounds and methods of using the compounds. These compounds are useful for therapy or prophylaxis in a mammal, and in particular as aldosterone synthase (CYP11B2 or CYP11B1) inhibitors for the treatment or prophylaxis of chronic kidney disease, congestive heart failure, hypertension, primary aldosteronism and Cushing syndrome.
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Paragraph 0875; 0876
(2013/03/28)
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- NEW BICYCLIC DIHYDROQUINOLINE-2-ONE DERIVATIVES
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12/
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Paragraph 0394; 0395
(2013/04/10)
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- NEW DIHYDROQUINOLINE-2-ONE DERIVATIVES
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4? R5, R6, R7, A1, A2 and A3 are as described herein, compositions including the compounds and methods of using the compounds.
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Page/Page column 231
(2013/03/28)
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- NEW BICYCLIC DIHYDROQUINOLINE-2-ONE DERIVATIVES
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The invention provides novel compounds having the general formula (I) wherein R1, R2, R3, R4? R5, R6, R7, R8, R9, R10, R11, R12/
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Page/Page column 78; 79
(2013/04/10)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 86
(2012/07/27)
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- ALDOSTERONE SYNTHASE INHIBITORS
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This invention relates to tricyclic triazole analogues of the formula I or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthetase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthetase.
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Page/Page column 124
(2012/11/13)
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- TETRAHYDROQUINOLINE, INDOLINE, AND RELATED ANILINE DERIVATIVES OF HETEROCYCLE-FUSED BENZODIOXAN METHYLAMINES
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The present invention relates to a compound of the formula: or an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, useful as modulators of 5 -HTi A receptor activity and/or serotonin reuptake. These compounds are useful in treating nervous system disorders, such as anxiety-related disorders, cognition-related disorders, depression, schizophrenia, or sexual dysfunction and related illnesses.
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Page/Page column 59
(2008/06/13)
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- Heterocyclic aldose reductase inhibitors and methods of using them
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The invention relates to new compounds of the formula: STR1 Aldose reductase inhibitors. Treatment of certain complications of diabetes.
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