- Deuterated lucitanib compounds and use thereof
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The invention discloses a compound represented by the formula (I) or optical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, wherein R-R are independently selected from H and D respectively, and are not H at the same time. The deuterated lucitanib compounds and the optical isomers, pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereofprovided by the invention not only have the anticancer activity of lucitanib, but also have significant improvement in pharmacokinetics, have the metabolic stability obviously improved, are better than a nondeuterated compound lucitanib, and are indicated to have better safety and effectiveness, high bioavailability and good application prospect.
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Paragraph 0054; 0055; 0057
(2019/12/25)
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- Naphthyridine compound and pharmaceutical composition as well as applications thereof
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The invention relates to the field of biological medicines and discloses a naphthyridine compound and a pharmaceutical composition as well as applications thereof. The naphthyridine compound has a structure shown in a formula (I) or a stereisomer, a geometric isomer, a tautomer, nitric oxide, hydrate, solvate, metabolite, a pharmaceutically acceptable salt or a prodrug. The naphthyridine compound disclosed by the invention has an anti-tumor effect which is obviously superior to the anti-tumor effect of the prior art. And moreover, the naphthyridine compound disclosed by the invention can treat diseases mediated by protein kinase.
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- THERAPEUTIC COMPOUNDS AND USES THEREOF
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Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.
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- Design, synthesis, and biological evaluation of potent c-Met inhibitors
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c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo.
- D'Angelo, Noel D.,Bellon, Steven F.,Booker, Shon K.,Cheng, Yuan,Coxon, Angela,Dominguez, Celia,Fellows, Ingrid,Hoffman, Douglas,Hungate, Randall,Kaplan-Lefko, Paula,Lee, Matthew R.,Li, Chun,Liu, Longbin,Rainbeau, Elizabeth,Reider, Paul J.,Rex, Karen,Siegmund, Aaron,Sun, Yaxiong,Tasker, Andrew S.,Xi, Ning,Xu, Shimin,Yang, Yajing,Zhang, Yihong,Burgess, Teresa L.,Dussault, Isabelle,Kim, Tae-Seong
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experimental part
p. 5766 - 5779
(2009/07/25)
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- Quinoline derivatives inhibiting the effect of growth factors such as VEGF
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Compounds of the formula (I): wherein: R2represents hydroxy, halogeno, C1-3alkyl, C1-3alkoxy, C1-3alkanoyloxy, trifluoromethyl, cyano, amino or nitro; n is an integer from 0 to 5; Z represents —O—, —NH—, —S— or —CH2—; G1represents phenyl or a 5-10 membered heteroaromatic cyclic or bicyclic group; Y1, Y2, Y3and Y4each independently represents carbon or nitrogen; R1represents fluoro or hydrogen; m is an integer from 1 to 3; R3represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C1-3alkyl, —NR4R5(wherein R4and R5, can each be hydrogen or C1-3alkyl), or a group R6—X1— wherein X1represents —CH2— or a heteroatom linker group and R6is an alkyl, alkenyl or alkynyl chain optionally substituted by for example hydroxy, amino, nitro, alkyl, cycloalkyl, alkoxyalkyl, or an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring, which alkyl, alkenyl or alkynyl chain may have a heteroatom linker group, or R6is an optionally substituted group selected from pyridone, phenyl and a heterocyclic ring and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals such as humans, processes for the preparation of such derivatives, pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula I. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
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Page column 40
(2010/02/08)
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- QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES
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An object of the present invention is to provide compounds which have antitumor activity and do not change cytomorphosis. Disclosed are compounds represented by formula (I) and a pharmaceutically acceptable salts and solvates thereof and pharmaceutical compositions comprising said compounds: wherein X and Z each independently represent CH or N; R1 to R3 represent H, substituted alkoxy, unsubstituted alkoxy or the like; R4 represents H; R5 to R8 represent H, halogen, alkyl, alkoxy, alkylthio, nitro, or amino, provided that R5 to R8 do not simultaneously represent H; R9 and R10 represent H, alkyl, or alkylcarbonyl; and R11 represents alkyl, alkenyl, alkynyl, or aralkyl.
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