- AZASPIROCYCLES AS MONOACYLGLYCEROL LIPASE MODULATORS
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Azaspirocycle compounds of Formula (I), and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, autism spectrum disorders, Asperger syndrome, bipolar disorder), cancers and eye conditions: wherein X, R1, R2a, R2b, R3, m, n, o, and p are defined herein.
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Page/Page column 71
(2021/10/02)
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- Stereoselective Diboration of Spirocyclobutenes: A Platform for the Synthesis of Spirocycles with Orthogonal Exit Vectors
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The diastereo- and enantioselective diboration of spirocyclobutenes provides a platform for the rapid preparation of a wide variety of chiral spirocyclic building blocks. The chemoselective functionalization of the carbon-boron bond in the products, including a stereospecific sp3-sp2 Suzuki–Miyaura cross-coupling reaction, provides a powerful tool to control the directionality and the nature of the exit vectors in the spirocyclic framework.
- Nóvoa, Luis,Trulli, Laura,Parra, Alejandro,Tortosa, Mariola
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supporting information
p. 11763 - 11768
(2021/04/26)
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- 6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS
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The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.
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Paragraph 0321-0322
(2021/11/13)
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- TARGETING COMPOUNDS
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The disclosure provides, at least in part, liver, intestine and/or kidney-targeting compounds and their use in treating liver, intestine and/or kidney disorders, such as non-alcoholic steatohepatitis, alcoholic steatohepatitis, hepatocellular carcinoma, liver cirrhosis, and hepatitis B; and/or chronic kidney disease, glomerular disease such as IGA nephropathy, lupus nephritis, or polycystic kidney disease. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
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Paragraph 0271
(2019/07/19)
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- OXADIAZOLES AS AGONISTS OF THE MUSCARINIC M1 AND/OR M4 RECEPTOR
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This invention relates to compounds that are agonists of the muscarinic M1 and/or M4 receptor and which are useful in the treatment of diseases mediated by the muscarinic M1 and M4 receptors. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds. Compounds provided are of formula (I) where X1; X2; X3; X4; R1 R2 and R4 are as defined herein.
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Page/Page column 56
(2020/01/11)
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- FXR RECEPTOR MODULATOR, PREPARATION METHOD THEREFOR, AND USES THEREOF
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The present disclosure disclosed a modulator of FXR receptor and preparation and use thereof, which relates to the technical filed of medicinal chemistry. The present disclosure provides a modulator of FXR receptor having a structural formula I or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, which can combine with FXR receptor (that is NR1H4) and be acted as a FXR agonist or a partial agonist for preventing and treating the disease mediated by FXR, such as chronic intrahepatic or extrahepatic cholestasis, hepatic fibrosis caused by chronic cholestasis or acute intrahepatic cholestasis, chronic hepatitis B, gallstone, hepatic carcinoma, colon cancer or intestinal inflammatory disease, etc. Specifically, for some chemical compounds, their EC50 for FXR agonist activity reach below 100nM, which show an excellent FXR agonist activity and an excellent prospect to provide a new pharmaceutical selection in clinical treatment for the disease mediated by FXR.
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Paragraph 0047; 0048; 0057; 0067; 0068
(2018/11/27)
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- B-LACTAMASE INHIBITOR AND APPLICATION THEREOF
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The present invention relates to a compound of Formula (I)-(IV) useful as β-lactamase inhibitor, a pharmaceutically acceptable salt, ester, solvate or stereoisomer thereof, wherein R1, R2, M and ring A have definitions as those in the specification. The present invention further relates to methods for preparing these compounds, pharmaceutical compositions comprising these compounds, and uses of these compounds. For example, the compounds of the present invention can be used as β-lactamase inhibitors, for treatment and/or prophylaxis of diseases caused by bacterial infections, solving drug-resistance problems caused by β-lactamases, especially bacterial drug-resistant diseases caused by type B metallo-β-lactamases.
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Paragraph 0105; 0106
(2018/03/07)
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- THIENOPYRIMIDINE DERIVATIVE AND USE THEREOF IN MEDICINE
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The present invention relates to a thienopyrimidine derivative and use thereof in medicine, and also to a pharmaceutical composition containing the compound. The compound or pharmaceutical composition is used for inhibiting acetyl-CoA carboxylase (ACC). The present invention also relates to a method of preparing such compound and pharmaceutical composition, as well as their use in the treatment or prevention of diseases regulated by acetyl-CoA carboxylase in mammals, especially in humans.
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Paragraph 00221
(2018/08/12)
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- Synthesis of Electron-Deficient Heteroaromatic 1,3-Substituted Cyclobutyls via Zinc Insertion/Negishi Coupling Sequence under Batch and Automated Flow Conditions
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Synthesis of 1,3-substituted cyclobutyls enabled by zinc insertion into functionalized iodocyclobutyl derivatives followed by Negishi coupling with halo-heteroaromatics is reported. Two distinct sets of conditions were developed; the first involved a two-step batch protocol using activated Rieke zinc, and the second involved a multistep continuous flow process. Both methods showed complementarity and allowed for rapid access to these medicinally relevant motifs, the possibility of scaling up, and automation for library synthesis.
- Tissot, Matthieu,Body, Nathalie,Petit, Sylvain,Claessens, Jehan,Genicot, Christophe,Pasau, Patrick
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supporting information
p. 8022 - 8025
(2019/01/04)
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- Sulfonamide derivative and application thereof in pharmacy
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The invention relates to a sulfonamide derivative and a pharmaceutical composition containing the same, and an application of the sulfonamide derivative and the pharmaceutical composition of the sulfonamide derivative in drug preparation, specifically the application in drug preparation of a BCL-2 family protein antagonist and the application in treatment of cancers.
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- 1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors with a Novel Monodentate Binding Interaction
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Herein we describe the identification of 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe2+ ion, while the benzonitrile group accepts a hydrogen-bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.
- Ahmed, Saleh,Ayscough, Andrew,Barker, Greg R.,Canning, Hannah E.,Davenport, Richard,Downham, Robert,Harrison, David,Jenkins, Kerry,Kinsella, Natasha,Livermore, David G.,Wright, Susanne,Ivetac, Anthony D.,Skene, Robert,Wilkens, Steven J.,Webster, Natalie A.,Hendrick, Alan G.
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supporting information
p. 5663 - 5672
(2017/07/22)
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- Baeyer–Villiger monooxygenase-catalyzed desymmetrizations of cyclobutanones. Application to the synthesis of valuable spirolactones
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A series of γ-butyrolactone derivatives, including some spiranic ones, was obtained through desymmetrization of the corresponding prochiral 3-substituted cyclobutanones via Baeyer–Villiger monooxygenase (BVMO)-catalyzed oxidation. After reaction optimization using several commercial enzymes, both antipodes of various lactones were synthesized in most cases with >90% conversion and >80% enantiomeric excess under mild reaction conditions. In some cases alcohol formation was also observed (up to 40% conversion) as an undesired side reaction due to the presence of alcohol dehydrogenases in these preparations. Selected transformations were achieved on a 100 mg scale showing the possibilities of these oxidative biocatalysts as a new source of highly interesting compounds.
- Rodríguez-Mata, María,Lavandera, Iván,Gotor-Fernández, Vicente,Gotor, Vicente,García-Cerrada, Susana,Mendiola, Javier,de Frutos, óscar,Collado, Iván
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supporting information
p. 7268 - 7275
(2016/10/26)
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- SPIROCYCLIC MOLECULES AS PROTEIN KINASE INHIBITORS
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The present invention relates to spirocyclic compounds of formula I, namely spirocyclic (1H-pyrazol-4-yl)-3-(1-(2,6-dichloro-3-fiuorophenyl) ethoxy)pyridin-2-amines having protein kinase inhibitory activity, and methods of synthesizing and using such compounds. Preferred compounds are c-Met and/or ALK inhibitors useful for the treatment of abnormal cell growth, such as cancers
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Paragraph 00178-00180
(2013/03/26)
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- 7-AZA-SPIRO[3.5]NONANE-7-CARBOXYLATE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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The invention relates to compounds of the general formula (I) where: R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy, or NR8R9 group; m, n, o and p ind
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Page/Page column 13
(2012/06/01)
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- DERIVATIVES OF AZASPIRANYL-ALKYLCARBAMATES OF 5-MEMBER HETEROCYCLIC COMPOUNDS, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
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The invention relates to a compound of the general formula (I) in which R2 is a hydrogen or fluorine atom or a hydroxyl, cyano, trifluoromethyl, C1-6-alkyl, C1-6-alkoxy, NR8R9 group; m, n, o and p are independently an integer equal to 0, 1, 2 or 3; A is a covalent bond or a C1-8-alkylene group; R1 is an optionally substituted aryl or heteroaryl group; R3 is a hydrogen or fluorine atom or a C1-6-alkyl group or a trifluoromethyl group; R4 is an optionally substituted 5-member heterocyclic compound; the compound being in the form of a base or acid addition salt. The invention also relates to the therapeutic use thereof.
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Page/Page column 15
(2012/01/13)
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- Synthesis of tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate
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Image Persented Two efficient and scaleable synthetic routes to previously unknown bifunctional tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate are described. This compound and related intermediates described herein are useful for further selective derivation on the azetidine and cyclobutane rings providing a convenient entry point to novel compounds accessing chemical space complementary to piperidine ring systems.
- Meyers, Marvin J.,Muizebelt, Inouk,Van Wiltenburg, Jim,Brown, David L.,Thorarensen, Atli
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supporting information; experimental part
p. 3523 - 3525
(2011/02/22)
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