1070879-27-4Relevant academic research and scientific papers
Quinoline Derivatives and Their Use as ALK and ALK L1196M Inhibitors
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Paragraph 0263-0264; 0310-0311, (2019/05/04)
The present invention relates to quinoline derivatives and a use thereof as inhibitors of ALK and mutated ALK. A pharmaceutical composition containing quinoline derivatives of chemical formula 1 or each of pharmaceutically acceptable salt thereof, has an effect of preventing or treating diseases associated with ALK and ALK L1196M, in other words, proliferative diseases caused by abnormal cell growth and function or behavior thereof.COPYRIGHT KIPO 2019
Identification of 4-Phenoxyquinoline Based Inhibitors for L1196M Mutant of Anaplastic Lymphoma Kinase by Structure-Based Design
Mah, Shinmee,Park, Jung Hee,Jung, Hoi-Yun,Ahn, Kukcheol,Choi, Soyeon,Tae, Hyun Seop,Jung, Kyung Hee,Rho, Jin Kyung,Lee, Jae Cheol,Hong, Soon-Sun,Hong, Sungwoo
, p. 9205 - 9221 (2017/11/30)
Dysregulation of anaplastic lymphoma kinase (ALK) has been detected in nonsmall cell lung cancer (NSCLC) in the form of EML4-ALK fusion. Secondary mutations opposing activity of the first-generation ALK inhibitor crizotinib came into existence, requiring mutation-targeting drug discovery for the powerful second-line treatment. In this study, we report 4-phenoxyquinoline-based inhibitors that overcome crizotinib resistance to ALK L1196M, discovered by the fragment-growing strategy. The protonation of 4-aminoquinoline core could interrupt the ability the N atom of quinoline to act as a hydrogen bond acceptor; therefore, the pKa and calculated ionization pH values of relevant pyridine-based core moieties were carefully analyzed. The replacement of amine linkage with ether resulted in single-digit nanomolar range inhibitors. The inhibitors exhibited significant antiproliferative effects on H2228 CR crizotinib-resistant cells by decreasing PI3K/AKT and MAPK signaling. This work constitutes the first example for systematic investigation of the effect of ionization pH on activity in this system.
Novel cyclic urea derivatives, preparation thereof and pharmaceutical use thereof as kinase inhibitors
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Page 105, (2010/02/09)
The present invention relates to a cyclic urea compound of formula I: as defined herein. The invention is also directed to the process for its preparation, pharmaceutical composition comprising it and its pharmaceutical use, as an inhibitor on a protein kinase. Thus, it is useful for preventing or treating a physiological disorder capable of being modulated by inhibiting the activity of a protein kinase, such as a solid tumor.
Process for piperidine intermediates for quinine, quinidine and analogs thereof
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, (2008/06/13)
Quinine, quinidine and analogs thereof, are prepared by reacting a 4-quinolyllithium compound with a 4,5-erythro-5-ethyl(or vinyl)-quinuclidine-2ε -carboxaldehyde or the corresponding quinuclidine-2-carboxylic acid alkyl ester. Also described, inter alia, is the preparation of a 4,5-erythro-5-ethyl(or vinyl)-quinuclidine-2ε-carboxaldehyde, and a 4,5-crythro-5-ethyl(or vinyl)-quinuclidine-2ε -carboxylic acid and esters thereof. The end products are useful as antimalarial and antiarrhythmic agents.
