PATENT CLAIM ANALYSIS

Application Number: 15903671
Application Type: Utility
Filing Date: 2018-02
Publication Date: 2018-07
Patent Classification: ["514", "248000"]

Abstract:
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Claim (Index 1):
A compound of Formula (I): or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof, wherein:\n ring A is independently selected from 6-membered aryl and 5- to 6-membered heterocyclyl, wherein said aryl and heterocyclyl are optionally substituted with, where valence allows, one or more R 4 ; \n ring B is 5- to 10-membered heterocyclyl optionally substituted with, where valence allows, one or more R 3  or 5- to 10-membered heterocyclyl comprising carbon atoms and 1-4 heteroatoms selected from N, NR 3c , O, and S(O) p  and optionally substituted with, where valence allows, one or more R 3 ; \n G 1  is independently selected from C 3-10  carbocyclyl and 5- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with, where valence allows, one or more R 8 ; \n X is independently selected from C 4-8  alkylene and C 4-8  alkenylene, wherein said alkylene and alkenylene are substituted with R 1  and R 2 ; alternatively one or more of the carbon atoms of said alkylene and alkenylene may be replaced by O, C\u2550O, S(\u2550O) p , S(\u2550O) p NH, and NR 15 ; \n Y is independently selected from \u2014CR 13 NH\u2014, \u2014NHC(\u2550O)\u2014, \u2014C(\u2550O)NH\u2014, \u2014S(\u2550O) p NH\u2014, \u2014NHS(\u2550O) p \u2014, and C 1-2  alkylene; \n R 1  and R 2  are independently selected from H, D, halogen, haloalkyl, C 1-6  alkyl (optionally substituted with R 6 ), hydroxyl, and alkoxy optionally substituted with R 6 , and C 3-6  cycloalkyl optionally substituted with R 6 ; optionally, when R 1  and R 2  are attached to the same carbon atom, together they form an oxo group or C 3-6  cycloalkyl; optionally, when R 1  and R 2  are attached to carbon atoms adjacent to each other, together they form a bond or carbocyclyl; optionally, R 1  and R 15  or R 2  and R 15  taken together form a ring; \n R 3  is independently selected from H, NO 2 , \u2550O, halogen, haloalkyl, C 1-4  alkyl (optionally substituted with R 6 ), C 2-4  alkenyl (optionally substituted with R 6 ), C 2-4  alkynyl (optionally substituted with R 6 ), CN, \u2014(CH 2 ) n \u2014OR 5 , \u2014(CH 2 ) n \u2014NR 5 R 5 , \u2014(CH 2 ) n \u2014C(\u2550O)R 5 , \u2014(CH 2 ) n \u2014C(\u2550O)OR 5 , \u2014(CH 2 ) n \u2014NR 9 C(\u2550O)OR 5 , \u2014(CH 2 ) n \u2014NR 9 C(\u2550O)R 5 , \u2014(CH 2 ) n \u2014NR 9 C(N\u2014CN)NHR 5 , \u2014(CH 2 ) n \u2014NR 9 C(NH)NHR 5 , \u2014(CH 2 ) n \u2014N\u2550CR 9 NR 5 R 5 , \u2014(CH 2 ) n \u2014NR 9 C(\u2550O)NR 5 R 5 , \u2014(CH 2 ) n \u2014C(\u2550O)NR 5 R 5 , \u2014(CH 2 ) n \u2014NR 9 C(\u2550S)NR 9 C(\u2550O)R 5 , \u2014(CH 2 ) n \u2014S(\u2550O) p R 5 , \u2014(CH 2 ) n \u2014S(\u2550O) p NR 5 R 5 , \u2014(CH 2 ) n \u2014NR 9 S(\u2550O) p NR 5 R 5 , \u2014(CH 2 ) n \u2014NR 9 S(\u2550O) p R 5 , \u2014(CH 2 ) n \u2014C 3-10  carbocyclyl and \u2014(CH 2 ) n -4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R 6 ; optionally, two adjacent R 3  groups on the heterocyclyl may form a ring optionally substituted with R 6 ; \n R 3c  is independently selected from H, haloalkyl, C 1-4  alkyl (optionally substituted with R 6 ), \u2014(CH 2 ) 1-2 \u2014OH, C(\u2550O)C 1-4  alkyl, \u2014(CH 2 ) 0-2 \u2014C(\u2550O)OH, \u2014C(\u2550O)OC 1-4  alkyl, S(\u2550O) p C 1-6  alkyl, \u2014(CH 2 ) n \u2014C 3-10  carbocyclyl and \u2014(CH 2 ) n -4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R 6 ; \n R 4  is independently selected from H, OH, NH 2 , halogen, CN, C 1-4  alkyl, C 1-4  haloalkyl, C 1-4  alkoxy, \u2014CH 2 OH, \u2014C(\u2550O)OH, \u2014CH 2 C(\u2550O)OH, \u2014CO 2 (C 1-4  alkyl), \u2014C(\u2550O)NH 2 , \u2014C(\u2550O)NH(C 1-4  alkyl), \u2014C(\u2550O)N(C 1-4  alkyl) 2 , \u2014S(\u2550O) 2 C 1-4  alkyl, \u2014S(\u2550O) 2 NH 2 , C 3-6  cycloalkyl, aryl, and 5- to 6-membered heterocyclyl, wherein said cycloalkyl, aryl and heterocyclyl are optionally substituted with R 6 ; \n R 5  is independently selected from H, C 1-4  alkyl (optionally substituted with halogen, hydroxyl, alkoxy, carboxy, hydroxycarbonyl, alkoxycarbonyl, amino, substituted amino), \u2014(CH 2 ) n \u2014C 3-10  carbocyclyl and \u2014(CH 2 ) n -4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R 6 ; alternatively, R 5  and R 5  together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with R 6 ; \n R 6  is independently selected from H, \u2014(CH 2 ) n \u2014OH, \u2550O, \u2014(CH 2 ) n NH 2 , \u2014(CH 2 ) n CN, halogen, C 1-6  alkyl, \u2014(CH 2 ) n \u2014C(\u2550O)OH, \u2014(CH 2 ) n \u2014C(\u2550O)NH 2 , \u2014(CH 2 ) n \u2014C(\u2550O)OC 1-4  alkyl, \u2014(CH 2 ) n \u2014OC 1-4  alkyl, \u2014(CH 2 ) n \u2014C 3-10  carbocyclyl, \u2014(CH 2 ) n -4- to 10-membered heterocyclyl, and \u2014O-4- to 10-membered heterocyclyl, wherein said carbocyclyl and heterocyclyl are optionally substituted with R 10 ; \n R 7  is independently selected from H, hydroxyl, alkoxy, halogen, amino, C 1-3 haloalkyl, and C 1-3  alkyl; \n R 8  is independently selected from H, halogen, \u2014(CH 2 ) n CN, C 1-6  alkyl, amino, aminoalkyl, haloalkyl, hydroxyl, alkoxy, haloalkoxy, alkylcarbonyl, carboxyl, carboxyl ester, amide, haloalkylaminocarbonyl, arylalkylaminocarbonyl, haloalkylaminocarbonyl, alkoxycarbonylamino, haloalkylcarbonylamino, arylamino, heteroarylamino, arylalkylcarbonyl, aryloxy, heteroaryloxy, alkylthio, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, sulfonamide, \u2014(CH 2 ) n -aryl, \u2014(CH 2 ) n \u2014C 3-6  cycloalkyl, and \u2014(CH 2 ) n -4- to 12-membered heterocyclyl, wherein said aryl, cycloalkyl, and heterocyclyl are optionally substituted with R 10 ; \n alternatively, two adjacent R 8  groups taken together form a heterocyclic ring optionally substituted with R 10 ; \n R 9  is H or C 1-6  alkyl; \n R 10  is independently selected from H, C 1-6  alkyl (optionally substituted with R 11 ), C 2-6  alkenyl, C 2-6  alkynyl, aryl (optionally substituted with R 11 ), \u2014(CH 2 ) n \u2014C 3-6  cycloalkyl (optionally substituted with R 11 ), \u2014(CH 2 ) n \u2014O-4- to 10-membered heterocyclyl (optionally substituted with R 11 ), halogen, \u2014(CH 2 ) n CN, NO 2 , \u2550O, C(\u2550O)NR 12 R 12 , \u2014(CH 2 ) n C(\u2550O)OR 12 , Si(C 1-4  alkyl) 3 , \u2014(CH 2 ) n \u2014OR 12 , \u2014(CH 2 ) n \u2014NR 12 R 12 , \u2014S(\u2550O) p C 1-6  alkyl, NR 12 S(\u2550O) p C 1-6  alkyl, S(\u2550O) p NR 12 R 12 , and C(\u2550NOH)NH 2 ; \n R 11 , at each occurrence, is independently selected from H, halogen, C 1-5  alkyl, \u2014(CH 2 ) n \u2014OH, C 3-6  cycloalkyl, phenyl, and heterocyclyl; \n R 12 , at each occurrence, is independently selected from H, C 1-5  alkyl optionally substituted with R 11 , C 3-6  cycloalkyl, phenyl, and heterocyclyl, or R 12  and R 12  together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C 1-4 alkyl; \n R 13  is, independently at each occurrence, selected from H, C 1-4  haloalkyl, C 1-4  alkyl, C(\u2550O)OH, C(\u2550O)O(C 1-4  alkyl), C(\u2550O)O(CH 2 ) 2 O(C 1-4  alkyl), C(\u2550O)O(C 1-4  haloalkyl), CH 2 C(\u2550O)OH, CH 2 C(\u2550O)O(C 1-4  alkyl), C(\u2550O)NH 2 , C(\u2550O)NH(C 1-4  alkyl), C(\u2550O)N(C 1-4  alkyl) 2 , and \u2014C(\u2550O)NH(C 1-4  alkoxy); \n R 15  is H or C 1-6  alkyl; \n n, at each occurrence, is an integer independently selected from 0, 1, 2, 3, and 4; and \n p, at each occurrence, is an integer independently selected from 0, 1, and 2.

Metadata:
- Claim Count in Document: 4.0
- Percentile: 88.0
- Lexical Diversity: 1.27778
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['14872546', '15115314', '15747867', '15205059', '15735322']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8073327563962643
- 35 USC 102 Novelty (BERT): 0.629187648227554
- Combined Prediction Score: 0.7895182455793933
- Mean Citation Score: 526.2841340000001
- Max Citation Score: 598.2743
- Similarity Product: 530.8630590333462

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

Dataset: test