- A Selective and Orally Bioavailable Quinoline-6-Carbonitrile-Based Inhibitor of CDK8/19 Mediator Kinase with Tumor-Enriched Pharmacokinetics
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Senexins are potent and selective quinazoline inhibitors of CDK8/19 Mediator kinases. To improve their potency and metabolic stability, quinoline-based derivatives were designed through a structure-guided strategy based on the simulated drug–target dockin
- Zhang, Li,Cheng, Chen,Li, Jing,Wang, Lili,Chumanevich, Alexander A.,Porter, Donald C.,Mindich, Aleksei,Gorbunova, Svetlana,Roninson, Igor B.,Chen, Mengqian,McInnes, Campbell
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supporting information
p. 3420 - 3433
(2022/02/16)
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- QUINOLINE-BASED COMPOUNDS AND METHODS OF INHIBITING CDK8/19
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Disclosed herein are quinoline-based compounds and method for inhibiting CDK8 or CDK19 for the intervention in diseases, disorders, and conditions. The quinoline-based composition comprise substituents at quinoline ring positions 4 and 6, wherein the substituent at position 4 is selected from a substituted or unsubstituted arylalkylamine or a substituted or unsubstituted arylhetrocyclylamine. Pharmaceutical compositions comprising the substituted qunioline compositions, methods of inhibiting CDK8 or CDK19, and methods of treating CDK8/19-associated diseases, disorders, or conditions are also disclosed.
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Paragraph 0108; 0117-0118; 0122
(2020/03/09)
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- CYCLOALKYL ACID DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF
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The present invention relates to a cycloalkyl acid derivative, a preparation method thereof, and a pharmaceutical application thereof, and in particular, the present invention relates to a cycloalkyl acid derivative represented by general formula (I) and a medical salt thereof, a preparation method thereof, and an application of the cycloalkyl acid derivative and the medical salt thereof as URAT1 inhibitors, and particularly as therapeutic agents for diseases related to an abnormal uric acid level, wherein definitions of substituent groups in general formula (I) are the same as definitions in the specifications.
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Paragraph 0188; 0191-0194
(2016/11/14)
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- CYCLOALKYL ACID DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL APPLICATION THEREOF
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Cycloalkyl acid derivatives, a preparation method thereof, and a pharmaceutical application thereof are described. In particular, a cycloalkyl acid derivative represented by general formula (I) and a medical salt thereof, a preparation method thereof, and an application of the cycloalkyl acid derivative and the medical salt thereof as URAT1 inhibitors, and particularly as therapeutic agents for diseases related to an abnormal uric acid level are described, wherein definitions of substituent groups in general formula (I) are the same as the definitions in the specification.
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Paragraph 0136-0137
(2016/05/24)
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- Efficient copper-catalyzed trifluoromethylation of aromatic and heteroaromatic iodides: The beneficial anchoring effect of borates
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Efficient copper-catalyzed trifluoromethylation of aromatic iodides was achieved with TMSCF3 in the presence of trimethylborate. The Lewis acid was used to anchor the in situ generated trifluoromethyl anion and suppress its rapid decomposition. Broad applicability of the new trifluoromethylating reaction was demonstrated in the functionalization of different aromatic and heteroaromatic iodides.
- Gonda, Zsombor,Kovacs, Szabolcs,Weber, Csaba,Gati, Tamas,Meszaros, Attila,Kotschy, Andras,Novak, Zoltan
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supporting information
p. 4268 - 4271
(2014/09/30)
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- Structural optimization of quinolon-4(1 H)-imines as dual-stage antimalarials: Toward increased potency and metabolic stability
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Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervent
- Ressurrei??o, Ana S.,Gon?alves, Daniel,Sitoe, Ana R.,Albuquerque, Ine?s S.,Gut, Jiri,Góis, Ana,Gon?alves, Lídia M.,Bronze, Maria R.,Hanscheid, Thomas,Biagini, Giancarlo A.,Rosenthal, Philip J.,Prude?ncio, Miguel,O'Neill, Paul,Mota, Maria M.,Lopes, Francisca,Moreira, Rui
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p. 7679 - 7690
(2013/11/06)
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- Synthesis of ring-substituted 4-aminoquinolines and evaluation of their antimalarial activities
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A simple two-step synthesis method was used to make 51 B-ring-substituted 4-hydroxyquinolines allowing analysis of the effect of ring substitutions on inhibition of growth of chloroquine sensitive and resistant strains of Plasmodium falciparum, the dominant cause of malaria morbidity. Substituted quinoline rings other than the 7-chloroquinoline ring found in chloroquine were found to have significant activity against the drug-resistant strain of P. falciparum W2.
- Madrid, Peter B.,Sherrill, John,Liou, Ally P.,Weisman, Jennifer L.,DeRisi, Joseph L.,Guy, R. Kiplin
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p. 1015 - 1018
(2007/10/03)
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