- GALNAC-TGFBR1 INHIBITOR CONJUGATES FOR THE TREATMENT OF LIVER DISEASES
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Conjugates comprising GalNAc moiety and a TGFβR1 inhibitor are provided. In some embodiments, the conjugates are useful for the treatment of viral infections, cancer, and fibrosis.
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Page/Page column 228; 237
(2021/04/17)
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- Palladium-Catalyzed Decarboxylative Synthesis of Arylamines
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A novel approach has been developed for the synthesis of arylamines via the palladium-catalyzed intramolecular decarboxylative coupling (IDC) of aroyloxycarbamates, obtained in situ by reacting aryl carboxylic acids with hydroxycarbamates. The reaction offers facile access to structurally diverse arylamines with the site-specific formation of the C(sp2)-N bond under mild conditions.
- Dai, Qipu,Li, Peihe,Ma, Nuannuan,Hu, Changwen
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supporting information
p. 5560 - 5563
(2016/11/17)
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- A suitable hydrobromidum fertile for method for synthesizing west sandbank industrial production (by machine translation)
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The invention provides a novel method for preparing vortioxetine hydrobromide, and belongs to the technical field of medicine synthesis. The method uses 2-fluoroaniline as a starting material to prepare the clinical medicinal vortioxetine hydrobromide by Boc protection, condensation, deprotection condensation, cyclization and other 4 steps of reaction. The method has the advantages of easy obtained raw material, low price, simple synthesis operation, mild reaction condition, easy control, no high pressure, good reaction selectivity, high yield and suitability for industrial production.
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Paragraph 0042-0046; 0060-0062
(2019/10/04)
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- Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles
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Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class of ligands that promote meta-C-H arylation of anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as a transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables a wide substrate and coupling partner scope. Meta-C-H arylation with heterocyclic aryl iodides as coupling partners is also realized for the first time using this ligand. The utility for this transformation for drug discovery is showcased by allowing the meta-C-H arylation of a lenalidomide derivative. The first steps toward a silver-free protocol for this reaction are also demonstrated.
- Wang, Peng,Farmer, Marcus E.,Huo, Xing,Jain, Pankaj,Shen, Peng-Xiang,Ishoey, Mette,Bradner, James E.,Wisniewski, Steven R.,Eastgate, Martin D.,Yu, Jin-Quan
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supporting information
p. 9269 - 9276
(2016/08/05)
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- MUTANT IDH1 INHIBITORS USEFUL FOR TREATING CANCER
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Compounds of Formula I and Formula II and the pharmaceutically acceptable salts thereof are disclosed The variables A, B, Y, Z, X1, X2, R1-4 and R13-18 are disclosed herein. The compounds are useful for treating cancer disorders, especially those involving mutant IDH1 enzymes. Pharmaceutical compositions containing compounds of Formula I or Formula II and methods of treatment comprising administering compounds of Formula I and Formula II are also disclosed.
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Paragraph 0225
(2016/07/27)
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- Homogenous suspension of immunopotentiating compounds and uses thereof
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The present invention generally relates to homogeneous suspensions of small molecule immune potentiators (SMIPs) that are capable of stimulating or modulating an immune response in a subject in need thereof. The homogeneous suspensions may be used in combinations with various antigens or adjuvants for vaccine therapies.
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Page/Page column 62; 63
(2016/09/12)
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- Palladium-catalyzed annulation of haloanilines and halobenzamides using norbornadiene as an acetylene synthon: A route to functionalized indolines, isoquinolinones, and indoles
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A general procedure for the palladium-catalyzed annulation of substituted haloanilines with norbornadiene gives functionalized indolines in 51-98% yield. These indolines can be rapidly converted to benzenoid- substituted indoles and tricyclic indolines. Extension to the use of substituted halobenzamides gives functionalized isoquinolinones in up to 86% yield.
- Thansandote, Praew,Hulcoop, David G.,Langer, Michael,Lautens, Mark
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supporting information; experimental part
p. 1673 - 1678
(2009/07/17)
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- COMPOUNDS AND COMPOSITIONS AS TLR ACTIVITY MODULATORS
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The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with Toll-Like Receptors, including TLR7 and TLR8. In one aspect, the compounds are useful as adjuvants for enhancing the effectiveness of a vaccine (formula I) wherein: X3 is N; X4 is N Or CR3; X5 is -CR4=CR5.
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Page/Page column 168-169
(2009/10/22)
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- Palladium-catalyzed aryl amination-heck cyclization cascade: A one-flask approach to 3-substituted indoles
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(Chemical Equation Presented) Two for the price of one: A Pd/dppf-based catalyst provides access to the title compounds from 1,2-dihalogenated aromatic compounds and allylic amines in a single reaction flask. The initial aryl amination step occurs with excellent selectivity for the aryl iodide to ensure the formation of a single indole regioisomer, which can be functionalized in situ by N-arylation (see scheme). dba = dibenzylideneacetone, dppf = 1,1′-bis(diphenylphospanyl)ferrocene.
- Jensen, Thomas,Pedersen, Henrik,Bang-Andersen, Benny,Madsen, Robert,Jorgensen, Morten
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p. 888 - 890
(2008/09/20)
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- Nucleus- and side-chain fluorinated 3-substituted indoles by a suitable combination of organometallic and radical chemistry
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Regioselectively fluoro-, trifluoromethyl- and trifluoromethoxy-substituted 3-methyleneindolines have been prepared using a four-step procedure involving metalation/bromination of fluorinated Boc-protected anilines, N-propargylation of the resulting o-bro
- Bellezza, Francesca,Cipiciani, Antonio,Ruzziconi, Renzo,Spizzichino, Sara
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- Discovery of (R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7- methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl) piperidine-1-carboxamide (BMS-694153): A potent antagonist of the human calcitonin gene-related peptide receptor for migraine with rapid and efficient intranasal exposure
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Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Early chemistry leads suffered from modest potency, significant CYP3A4 inhibition, and poor aqueous solubility. Herein, we describe the optimization of these leads to give 4 (BMS-694153), a molecule with outstanding potency, a favorable predictive toxicology profile, and remarkable aqueous solubility. Compound 4 has good intranasal bioavailablity in rabbits and shows dose-dependent activity in validated in vivo and ex vivo migraine models.
- Degnan, Andrew P.,Chaturvedula, Prasad V.,Conway, Charles M.,Cook, Deborah A.,Davis, Carl D.,Denton, Rex,Han, Xiaojun,Macci, Robert,Mathias, Neil R.,Moench, Paul,Pin, Sokhom S.,Ren, Shelly X.,Schartman, Richard,Signor, Laura J.,Thalody, George,Widmann, Kimberly A.,Xu, Cen,Macor, John E.,Dubowchik, Gene M.
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supporting information; experimental part
p. 4858 - 4861
(2009/08/09)
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- Copper(II) tetrafluoroborate as a novel and highly efficient catalyst for N-tert-butoxycarbonylation of amines under solvent-free conditions at room temperature
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Commercially available copper(II) tetrafluoroborate hydrate was found to be a highly efficient catalyst for chemoselective N-tert-butoxycarbonylation of amines with di-tert-butyl dicarbonate under solvent-free conditions and at room temperature. Various aromatic amines were protected as their N-tert-butyl carbamates in high yields and in short times. No competitive side reactions such as isocyanate, urea, and N,N-di-t-Boc formation was observed. Chemoselective N-tert-butoxycarbonylation was achieved with substrates bearing OH and SH groups. Chiral α-amino acid esters afforded the corresponding N-t-Boc derivatives in excellent yields.
- Chankeshwara, Sunay V.,Chakraborti, Asit K.
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p. 1087 - 1091
(2007/10/03)
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- In search of simplicity and flexibility: A rational access to twelve fluoroindolecarboxylic acids
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All twelve indolecarboxylic acids 1-12 carrying both a fluorine substituent and a carboxy group at the benzo ring have been prepared either directly from the corresponding fluoroindoles 13-16 or from the chlorinated derivatives 22, 23 and 25 by hydrogen/metal permutation ("metalation"), or from the bromo- or iodofluoroindoles 17-20 and 26, 27, 29 and 30 by halogen/metal permutation, the organometallic intermediate being each time trapped with carbon dioxide. In most, though not all cases, the nitrogen atom in the five-membered ring had to be protected by a trialkylsilyl group. Some of the bromo- or iodofluoroindoles (26 and 27) were successfully subjected to a basicity gradient-driven selective migration of the heavy halogen. An unexpected finding on the way to the target compounds were the rigorously site-selective metalation of the 5-fluoro-N-(trialkylsilyl)indole (14b; exclusive deprotonation of the 4-position). The fluoroindoles 13-16, although previously known, were accessed more conveniently from suitably substituted nitrobenzenes using the Bartoli or the Leimgruber-Batcho method. A new and very attractive indole synthesis was elaborated consisting of the ortho-lithiation of an N-acyl-protected aniline followed by ortho-formylation, Wittig chloromethylenation and base-catalyzed cyclization accompanied by dehydrochlorination. These five consecutive steps can be contracted to a convenient one-pot protocol. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Schlosser, Manfred,Ginanneschi, Assunta,Leroux, Frederic
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p. 2956 - 2969
(2007/10/03)
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- HETEROCYCLIC ANTI-MIGRAINE AGENTS
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The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.
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Page/Page column 35
(2008/06/13)
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- Novel therapeutic agents for the treatment of migraine
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The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their u
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Page/Page column 46
(2010/02/14)
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- Synthesis of regiospecifically substituted quinolines from anilines
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A protocol for the synthesis of quinolines substituted on both pyridine and benzo-fused rings is reported. The method is based on the formylation of a substituted N-(tert-butoxycarbonyl)aniline followed by direct cyclisation and aromatisation of the inter
- Chelucci, Giorgio,Manca, Ilaria,Pinna, Gerard A.
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p. 767 - 770
(2007/10/03)
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- Synthesis and Biological Evaluation of New 1,2-Dihydro-4-hydroxy-2-oxo-3-quinolinecarboxamides for Treatment of Autoimmune Disorders: Structure-Activity Relationship
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Roquinimex-related 3-quinolinecarboxamide derivatives were prepared and evaluated for treatment of autoimmune disorders. The compounds were tested in mice for their inhibitory effects on disease development in the acute experimental autoimmune encephalomyelitis model and selected compounds in the beagle dog for induction of proinflammatory reaction. Structure-activity relationships are discussed. Compound 8c, laquinimod, showed improved potency and superior toxicological profile compared to the lead compound roquinimex (1b, Linomide) and was selected for clinical studies (currently in phase II).
- J?nsson, Stig,Andersson, Gunnar,Fex, Tomas,Fristedt, Tomas,Hedlund, Gunnar,Jansson, Karl,Abramo, Lisbeth,Fritzson, Ingela,Pekarski, Olga,Runstr?m, Anna,Sandin, Helena,Thuvesson, Ingela,Bj?rk, Anders
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p. 2075 - 2088
(2007/10/03)
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- Calcitonin gene related peptide receptor antagonists
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The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.
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