PATENT CLAIM ANALYSIS

Application Number: 15575903
Application Type: Utility
Filing Date: 2018-04
Publication Date: 2018-08
Patent Classification: ["514", "230800"]

Abstract:
The present invention discloses a pyrido-azacyclic compound represented by formula I, an isomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, a preparation process thereof and a composition comprising the compound, and a use thereof as a multi-target protein kinase inhibitor in the preparation of a medicament for the treatment of diseases that are associated with protein kinase, especially c-Met, such as cancer and the like. The compound represented by formula I has potent inhibitory activity on tumor cells with overexpression of c-Met kinase, can effectively target c-Met-mediated signaling pathway, and can be used in the treatment of diseases such as cancer and the like that is caused by the overexpression of c-Met kinase.

Claim (Index 5):
The compound, the isomer thereof and the pharmaceutically acceptable salt or the pharmaceutically acceptable solvate thereof according to  claim 1 , wherein, the compound is one selected from the following compounds: Cpd. No. Name Structure 1S N-(4-((7-chloro-1,6-naphthyridin-4- yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   2S N-(4-((7-(dimethylamino)-1,6- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   3S N-(4-((7-methoxy-1,6-naphthyridin-4- yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   6S N-(4-((8-bromo-7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)-3- fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   7S N-(3-fluoro-4-((7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   8S N-(3-fluoro-4-((7-(2- morpholinopropoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   9S N-(3-fluoro-4-((7-((1-methylpiperidin-4- yl)methoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   10S N-(4-((8-bromo-7-(2-(4-methylpiperazin- 1-yl)ethoxy)-1,6-naphthyridin-4-yl)oxy)- 3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   11S N-(3-fluoro-4-((7-(2-(4-methylpiperazin- 1-yl)ethoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   12S N-(4-fluorophenyl)-N-(4-((7-(2- morpholinoethoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)cyclopropyl-1,1- dicarboxamide   13S N-(4-fluorophenyl)-N-(4-((7-(2- morpholinoethoxy)-1,6-naphthyridin-4- yl)amino)phenyl)cyclopropyl-1,1- dicarboxamide   14S N-(3-fluoro-4-((7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)-N-methylcyclopropyl-1,1- dicarboxamide   15S N-(3-fluoro-4-((7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)phenyl)-1-(4- fluorophenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide   16S 1-(3-fluoro-4-((7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide   17S methyl 1-(3-fluoro-4-((7-(2- morpholinoethoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-2-oxo-1,2- dihydropyridine-3-carboxylate   18S N-(4-((8-bromo-7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)-3- fluorophenyl)-2-phenylacetamide   19S N-(4-((8-bromo-7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)-3- fluorophenyl)-4-oxo-5-phenyl-1,4- dihydropyridine-3-carboxamide   20S N-(3-fluoro-4-((7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)phenyl)-4- oxo-5-phenyl-1,4-dihydropyridine-3- carboxamide   21S N-(4-((8-bromo-7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)-3- fluorophenyl)-5-(4-fluorophenyl)-4-oxo- 1,4-dihydropyridine-3-carboxamide   22S N-(3-fluoro-4-((7-(2-morpholinoethoxy)- 1,6-naphthyridin-4-yl)oxy)phenyl)-5-(4- fluorophenyl)-4-oxo-1,4- dihydropyridine-3-carboxamide   23S N-(3,4-difluorophenyl)-N-(3-fluoro-4- ((7-(2-morpholinoethoxy)-1,6- naphthyridin-4- yl)oxy)phenyl)cyclopropyl-1,1- dicarboxamide   24S N-(4-fluoro-3-methoxyphenyl)-N-(3- fluoro-4-((7-(2-morpholinoethoxy)-1,6- naphthyridin-4- yl)oxy)phenyl)cyclopropyl-1,1- dicarboxamide   25S N-(3-fluoro-4-((7-(2-(pyridin-4- yl)ethoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   26S N-(3-fluoro-4-((7-((1-morpholinopropan- 2-yl)oxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   27S N-(3-fluoro-4-((7-morpholino-1,6- naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   28S N-(3-fluoro-4-((7-(4- morpholinopiperidin-1-yl)-naphthyridin- 4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   29S (S)-N-(3-fluoro-4-((7-(2-(3- methylmorpholino)ethoxy)-naphthyridin- 4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   30S (R)-N-(3-fluoro-4-((7-(2-(3- methylmorpholino)ethoxy)-naphthyridin- 4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   31S N-(4-((7-(2-(1H-imidazol-1-yl)ethoxy)- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   32S N-(4-((7-(4-benzylpiperazin-1-yl)- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   33S N-(3-fluoro-4-((3-oxo-3,4- dihydropyrido[2,3-b]pyrazin-8- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   34S N-(3-fluoro-4-((2-oxo-1,2- dihydropyrido[2,3-b]pyrazin-8- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   35S N-(4-((7-((1-ethyl-3-fluoropiperidin-4- yl)amino)-1,6-naphthyridin-4-yl)oxy)-3- fluorophenyl)-2-(4-fluorophenyl)-3-oxo- 2,3-dihydropyridazine-4-carboxamide   36S N-(3-fluoro-4-((7-(2-morpholino-2- acetoxy)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   37S N-(3-fluoro-4-((7-(2-(3- oxomorpholino)ethoxy)-1,6- naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   38S N-(3-fluoro-4-((7-(1-methyl-1H-pyrazol- 4-yl)-1,6-naphthyridin-4-yl)oxy)phenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   39S N-(4-((7-(1H-pyrazol-4-yl)-1,6- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   40S N-(3-fluoro-4-((7-(1-(methylsulfonyl)- 1H-pyrazol-4-yl)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   41S N-(3-fluoro-4-((7-(1-isopropyl-1H- pyrazol-4-yl)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   42S N-(3-fluoro-4-((7-(1-(piperidin-4-yl)-1H- pyrazol-4-yl)-1,6-naphthyridin-4- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   43S N-(3-fluoro-4-((7-(1-(1- isopropylpiperidin-4-yl)-1H-pyrazol-4- yl)-1,6-naphthyridin-4-yl)oxy)phenyl)-N- (4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   44S N-(4-((7-((1H-imidazol-1-yl)methyl)-1,6- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   45S N-(4-((7-(3,5-dimethylisoxazol-4-yl)-1,6- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   46S N-(3-fluoro-4-((7-(pyridin-4-yl)-1,6- naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   47S N-(3-fluoro-4-((7-(pyrimidin-5-yl)-1,6- naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   48S N-(3-fluoro-4-((7-(4-nitrophenyl)-1,6- naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   49S N-(3-fluoro-4-((7-(3,4-difluorophenyl)- 1,6-naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   50S N-(3-fluoro-4-((7-(4-morpholinophenyl)- 1,6-naphthyridin-4-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   51S N-4-((7-(isoxazol-4-yl)-1,6-naphthyridin- 4-yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   52S N-4-((7-(isothiazol-3-yl)-1,6- naphthyridin-4-yl)oxy)-3-fluorophenyl)- N-(4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   53S N-(3-fluoro-4-((7-(1-methyl-1H-pyrazol- 4-yl)-1,6-naphthyridin-4-yl)oxy)phenyl)- 1-(4-fluorophenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide   54S N-(3-fluoro-4-((7-(1-methyl-1H-pyrazol- 4-yl)-1,6-naphthyridin-4-yl)oxy)phenyl)- 5-(4-fluorophenyl)-4-oxo-1,4- dihydropyridine-3-carboxamide   55S N-(4-((3-chloropyrido[2,3-b]pyrazin-8- yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   56S N-(4-(2-chloropyrido[2,3-b]pyrazin-8- yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   57S N-4-((3-morpholinopyrido[2,3-b]pyrazin- 8-yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   58S N-4-((2-morpholinopyrido[2,3-b]pyrazin- 8-yl)oxy)-3-fluorophenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   59S N-(3-fluoro-4-((3-(4-methylpiperazin-1- yl)pyrido[2,3-b]pyrazin-8- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   60S N-(3-fluoro-4-((3-(2- morpholinoethoxy)pyrido[2,3-b]pyrazin- 8-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   61S N-(3-fluoro-4-((3-(2- morpholinopropoxy)pyrido[2,3- b]pyrazin-8-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   62S N-(3-fluoro-4-((3-((3- morpholinopropyl)amino)pyrido[2,3- b]pyrazin-8-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   63S N-(3-fluoro-4-((2-((3- morpholinopropyl)amino)pyrido[2,3- b]pyrazin-8-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   64S N-(4-((3-piperazinyl-pyrido[2,3- b]pyrazin-8-yl)oxy)-3-fluorophenyl)-N- (4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   65S N-(4-((2-piperazinyl-pyrido[2,3- b]pyrazin-8-yl)oxy)-3-fluorophenyl)-N- (4-fluorophenyl)cyclopropyl-1,1- dicarboxamide   66S N-(3-fluoro-4-((2-(2-(4-methylpiperazin- 1-yl)ethoxy)pyrido[2,3-b]pyrazin-8- yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   67S N-(3-fluoro-4-((2-(2- morpholinoethoxy)pyrido[2,3-b]pyrazin- 8-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide   68S N-(3-fluoro-4-((2-(3- morpholinopropoxy)pyrido[2,3- b]pyrazin-8-yl)oxy)phenyl)-N-(4- fluorophenyl)cyclopropyl-1,1- dicarboxamide

Metadata:
- Claim Count in Document: 11.0
- Percentile: 91.0
- Lexical Diversity: 1.92424
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['14916177', '14763468', '13509442', '13801753', '14383803']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7545805603244263
- 35 USC 102 Novelty (BERT): 0.5462442159674498
- Combined Prediction Score: 0.7337469258887287
- Mean Citation Score: 360.248268
- Max Citation Score: 382.27582
- Similarity Product: 287.86203994215725

Labels:
- Claim Label 101: 1
- Claim Label 102: 1
- Claim Label 103: 1
- Claim Label 112: 0
- Combined Label: 1
- Label 101 Adjusted: 1

Dataset: test