PATENT CLAIM ANALYSIS

Application Number: 16175895
Application Type: Utility
Filing Date: 2018-10
Publication Date: 2019-05
Patent Classification: ["514", "318000"]

Abstract:
The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

Claim (Index 1):
A compound of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof; wherein:\n B ring is a 5- to 8-membered bridged cycloalkyl or cycloheteroalkyl; and the point of attachment to L 1  or Z is a carbon atom; \n X 1  and X 4  are each independently C or N; \n X 2  and X 3  are each independently CR 3 , N, NR 4 , O, or S; \n E 1  and E 3  are each independently a covalent bond, O, S, N, NR 6 , CR 5 , or CR 5a R 5b ; \n E 2  is O, S, N, NR 8 , CR 7 , or CR 7a R 7b ; wherein (E 1  and E 2 ) or (E 3  and E 2 ) forms a single bond or double bond; provided that (1) the bonds between (E 1  and E 2 ) and (E 3  and E 2 ) are not both double bonds; and (2) not more than one of E 1 , E 2 , and E 3  is O, S, N, or NR 8 ; \n L 1  is a covalent bond, O, S, NR 16 , \u2014C(S)NH\u2014, C 1-3  alkylene, C 1-3  heteroalkylene, C 2-4  alkenylene, C 2-4  alkynylene, aryl, or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms independently selected from N, O, and S; wherein the alkylene, heteroalkylene, aryl, and heteroaryl are each independently substituted with 0 to 3 R 9 ; \n Z is 6- to 10-membered aryl, 5- to 10-membered heteroaryl, 3- to 10-membered carbocyclyl, or 4- to 10-membered heterocyclyl, wherein the aryl, heteroaryl carbocyclyl, and heterocyclyl are independently substituted with 0 to 5 R 10 ; \n L 2  are each independently a covalent bond, O, S, NR 17 , C 1-3  alkylene, or C 1-3  heteroalkylene, wherein the alkylene and heteroalkylene are independently substituted with 0 to 3 R 11 ; \n R X  is \u2014(CR 12a R 12b ) e \u2014R Z  or \u2014O(CR 12a R 12b ) e \u2014R Z ; \n e is 0 or 1; \n R Z  is selected from \u2014CN, \u2014OH, \u2014C(O)OR 13 , \u2014C(O)NR 14a R 14b , \n R e  is C 1-6  alkyl, C 3-6  cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, or phenyl; R 1  is C 1-6  alkyl, C 3-5  cycloalkyl, or C 4-6  heterocyclyl, wherein the alkyl, cycloalkyl, and heterocyclyl are each independently substituted with 0 to 3 R 15 ; R 2  is 6- to 10-membered aryl, 5- to 10-membered heteroaryl, 3- to 10-membered carbocyclyl, or 4- to 10-membered heterocyclyl, wherein the aryl, heteroaryl, carbocyclyl, and heterocyclyl are independently substituted with 0 to 5 R 16 ; R 3  and R 7  are each independently hydrogen, halo, cyano, hydroxyl, amino, C 1-6  alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R 4 , R 6 , R 8 , R 16  and R 17  are each independently hydrogen, C 1-6  alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R 5  is hydrogen, C 1-6  alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; R 5a , R 5b , R 7a  and R 7b  are each independently hydrogen, halo, cyano, hydroxyl, amino, C 1-6  alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R 9  and R 11  are each independently halo, oxo, cyano, hydroxyl, amino, C 1-6  alkyl, C 3-6  cycloalkyl, C 4-6  heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; a is an integer of 0, 1, 2, or 3; R 10  and R 16  are each independently halo, cyano, hydroxyl, amino, oxo, \u2014OR a , \u2014SR a , \u2550S, \u2014NR c R c , \u2550NH, \u2550N\u2014OH, \u2550NR a , \u2550N\u2014OR a , \u2014NO 2 , \u2014S(O) 2 R a , \u2014S(O) 2 NHR b , \u2014S(O) 2 NR c R c , \u2014S(O) 2 OR b , \u2014OS(O) 2 R b , \u2014OS(O) 2 OR b , \u2014P(O)(OR b )(OR b ), \u2014C(O)R b , \u2014C(NR b )R b , \u2014C(O)OR b , \u2014C(O)NR c R c , \u2014C(NR b )NR c R c , \u2014OC(O)R b , \u2014NR b C(O)R b , \u2014OC(O)OR b , \u2014NR b C(O)OR b , \u2014OC(O)NR c R c , \u2014NR b C(O)NR c R c , \u2014NR b C(NR b )R b , \u2014NR b C(NR b )NR c R c , C 1-6  alkyl, C 1-6  haloalkyl, aryl, arylalkyl, heteroaryl, carbocyclyl, or heterocyclyl; wherein the alkyl, aryl, heteroaryl, carbocyclyl, and heterocyclyl, by themselves or as part of another group, are each independently substituted with 0 to 5 R d ; R a  is selected from C 1-6  alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, and heterocyclylalkyl; R b  is each independently hydrogen or R a ; R c  is each independently R b  or alternatively, the two R c  are taken together with the nitrogen atom to which they are bonded form a 4-, 5-, 6- or 7-membered heterocyclyl; R d  is each independently selected from R a , alkoxy, haloalkoxy, alkylamino, cycloalkylamino, heterocyclylamino, haloalkyl, hydroxyalkyl, aminoalkyl, cycloalkoxy, heterocyclyloxy, haloalkoxy, alkoxyalkoxy, haloalkylamino, alkoxyalkylamino, haloalkoxyalkylamino, arylamino, aralkylamino, aryloxy, aralkyloxy, heteroaryloxy, heteroarylalkyloxy, alkylthio, halo, cyano, hydroxyl, amino, oxo, \u2014OR a , \u2014SR a , \u2014S, \u2014NR c R c , \u2550NH, \u2550N\u2014OH, \u2550NR a , \u2550N\u2014OR a , \u2014NO 2 , \u2014S(O) 2 R a , \u2014S(O) 2 NHR b , \u2014S(O) 2 NR c R c , \u2014S(O) 2 OR b , \u2014OS(O) 2 R b , \u2014OS(O) 2 OR b , \u2014P(O)(OR b )(OR b ), \u2014C(O)R b , \u2014C(NR b )R b , \u2014C(O)OR b , \u2014C(O)NR c R c , \u2014C(NR b )NR c R c , \u2014OC(O)R b , \u2014NR b C(O)R b , \u2014OC(O)OR b , \u2014NR b C(O)OR b , \u2014NR b C(O)NR c R c , \u2014NR b C(NR b )R b , and \u2014NR b C(NR b )NR c R c ; R 12a  and R 12b  are each independently hydrogen, halo, cyano, hydroxyl, amino, C 1-6  alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; or alternatively, R 12a  and R 12b  together with the atom(s) to which they are attached, form a 3- or 4-membered carbocyclic or heterocyclic ring; R 13  is hydrogen, C 1-10  alkyl, or glycosyl; R 14a  and R 14b  are each independently hydrogen, C 1-6  alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R 15  is hydrogen, halo, cyano, hydroxyl, amino, C 1-6  alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy.

Metadata:
- Claim Count in Document: 5.0
- Percentile: 97.0
- Lexical Diversity: 1.5
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: False
- Related Applications: ['14971875', '15541018', '14971825', '16322945', '12377307']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8047910920897589
- 35 USC 102 Novelty (BERT): 0.5325498383822516
- Combined Prediction Score: 0.7775669667190082
- Mean Citation Score: 329.48176399999994
- Max Citation Score: 338.1815
- Similarity Product: 277.2684527332187

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