PATENT CLAIM ANALYSIS

Application Number: 15904993
Application Type: Utility
Filing Date: 2018-02
Publication Date: 2018-07
Patent Classification: ["514", "210010"]

Abstract:
Provided herein are novel substituted bicyclic aza-heterocycle sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Claim (Index 3):
A method for treating a subject suffering from or susceptible to diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, chemotherapeutic-induced neuropathy, neuropathy associated with an ischemic event, ocular diseases and/or disorders, cardiovascular disease, blood clotting disorders, inflammation, and/or flushing, comprising administering to the subject in need thereof of a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound of formula (I): wherein:\n one of D and E is N and the other is C; and \n when D is N, one of A and B is N and the other is CR; and \n when E is N, B is N and A is N or CR; or \n a salt thereof, wherein:\n each R is independently selected from hydrogen, halo, OH, C\u2261N, C 1 -C 4  alkyl, halo-substituted C 2 -C 4  alkyl, C 1 -C 4  alkoxy-substituted C 1 -C 4  alkyl, hydroxy-substituted C 1 -C 8  alkyl, OR 3 , O\u2014(C 1 -C 4  alkyl)-OR 3 , S\u2014(C 1 -C 2  alkyl), S-(halo-substituted C 1 -C 4  alkyl), N(hydroxy-substituted C 1 -C 4  alkyl) 2 , N(methoxy-substituted C 1 -C 4  alkyl) 2 , N(C 1 -C 4  alkyl)(hydroxy-substituted C 1 -C 4  alkyl), N(C 1 -C 4  alkyl)(methoxy-substituted C 1 -C 4  alkyl), N(hydroxy-substituted C 1 -C 4  alkyl)(methoxy-substituted C 1 -C 4  alkyl), C 5 -C 7  cycloalkyl, and 4- to 8-membered non-aromatic heterocycle, and when one or both of E and A is N, then R can additionally be selected from halo-substituted methyl and C 3 -C 4  cycloalkyl; \n R 1  is an aromatic heterocycle or a fused carbocycle, wherein R 1  is optionally substituted with one or more substituents independently selected from halo, C\u2261N, C 1 -C 4  alkyl, halo-substituted C 1 -C 4  alkyl, C 1 -C 4  alkoxy-substituted C 1 -C 4  alkyl, hydroxy-substituted C 1 -C 8  alkyl, O\u2014R 3 , O\u2014(C 1 -C 4  alkyl)-OR 3 , \u2550O, C 3 -C 7  cycloalkyl, SO 2 R 3 , S\u2014R 3 , (C 1 -C 4  alkyl)-N(R 3 )(R 3 ), N(R 3 )(R 3 ), O\u2014(C 1 -C 4  alkyl)-N(R 3 )(R 3 ), O\u2014(C 0 -C 4  alkyl)-CR 3 R 3 (C 0 -C 4  alkyl), (C 1 -C 4  alkyl)-O\u2014(C 1 -C 4  alkyl)-N(R 3 )(R 3 ), C(\u2550O)\u2014N(R 3 )(R 3 ), (C 1 -C 4  alkyl)-C(\u2550O)\u2014N(R 3 )(R 3 ), O\u2014(C 0 -C 4  alkyl)-CR x R x \u2014(C 0 -C 4  alkyl), CR x R x , phenyl, O-phenyl, second heterocycle, O-(second heterocycle), 3,4-methylenedioxy, halo-substituted 3,4-methylenedioxy, 3,4-ethylenedioxy, and halo substituted 3,4-ethylenedioxy, wherein any phenyl, saturated heterocycle, or second heterocycle substituent of R 1  is optionally substituted with one or more substituents independently selected from halo, C\u2261N, C 1 -C 4  alkyl, halo-substituted C 1 -C 4  lkyl, O-(halo-substituted C 1 -C 4  alkyl), O\u2014(C 1 -C 4  alkyl), S\u2014(C 1 -C 4  alkyl), and S-(halo-substituted C 1 -C 4  alkyl); \n R 2  is a carbocycle or a heterocycle, wherein R 2  is optionally substituted with one or more substituents independently selected from halo, C\u2261N, C 1 -C 4  alkyl, halo-substituted C 1 -C 4  alkyl, C 1 -C 4  alkoxy-substituted C 1 -C 4  alkyl, hydroxy-substituted C 1 -C 8  alkyl, O\u2014R 3 , \u2014O\u2014(C 1 -C 4  alkyl)-OR 3 , \u2550O, C 3 -C 7  cycloalkyl, SO 2 R 3 , S\u2014R 3 , (C 1 -C 4  alkyl)-N(R 3 )(R 3 ), N(R 3 )(R 3 ), O\u2014(C 1 -C 4  alkyl)-N(R 3 )(R 3 ), O\u2014(C 0 -C 4  alkyl)-CR 3 R 3 (C 0 -C 4  alkyl), (C 1 -C 4  alkyl)-O\u2014(C 1 -C 4  alkyl)-N(R 3 )(R 3 ), C(\u2550O)\u2014N(R 3 )(R 3 ), (C 1 -C 4  alkyl)-C(\u2550O)\u2014N(R 3 )(R 3 ), O-phenyl, O-(second heterocycle), 3,4-methylenedioxy, halo-substituted 3,4-methylenedioxy, 3,4-ethylenedioxy, and halo-substituted 3,4-ethylenedioxy, and when E is N, substituents on R 2  can additionally be selected from a second heterocycle, and when both D and A are N, substituents on R 2  can additionally be selected from phenyl and a second heterocycle, wherein any phenyl, saturated heterocycle or second heterocycle substituent of R 2  is optionally substituted with one or more substituents independently selected from halo, C\u2261N, C 1 -C 4  alkyl, halo-substituted C 1 -C 4  alkyl, O-(halo-substituted C 1 -C 4  alkyl), O\u2014(C 1 -C 4  alkyl), S\u2014(C 1 -C 4  alkyl), and S-(halo-substituted C 1 -C 4  alkyl); \n each R 3  is independently selected from hydrogen and C 1 -C 4  alkyl optionally substituted with one or more of OH, O\u2014(C 1 -C 4  alkyl), halo, NH 2 , NH(C 1 -C 4  alkyl), N(C 1 -C 4  alkyl) 2 , NH(methoxy-substituted C 1 -C 4  alkyl), NH(hydroxy-substituted C 1 -C 4  alkyl), N(hydroxy-substituted C 1 -C 4  alkyl) 2  and N(methoxy-substituted C 1 -C 4  alkyl) 2 ; or \n two R 3  are taken together with the nitrogen or carbon atom to which they are bound to form a 4- to 8-membered saturated heterocycle optionally comprising one additional heteroatom independently selected from N, S, S(\u2550O), S(\u2550O) 2 , and O, wherein the heterocycle formed by two R 3  is optionally substituted at any carbon atom with one or more of OH, halo, C 1 -C 4  alkyl, halo-substituted C 1 -C 4  alkyl, NH 2 , NH(C 1 -C 4  alkyl), N(C 1 -C 4  alkyl) 2 , \u2014O(C 1 -C 4  alkyl), NH(hydroxy-substituted C 1 -C 4  alkyl), N(hydroxy-substituted C 1 -C 4  alkyl) 2 NH(methoxy-substituted C 1 -C 4  alkyl), or N(methoxy-substituted C 1 -C 4  alkyl) 2 , and optionally substituted at any substitutable nitrogen atom with C 1 -C 4  alkyl or halo-substituted C 1 -C 4  alkyl; \n two R x  taken together with the carbon atom to which they are bound form a 4- to 8-membered carbocycle or heterocycle optionally comprising one or two heteroatoms independently selected from N, S, S(\u2550O), S(\u2550O) 2 , and O, wherein the carbocycle or heterocycle is optionally substituted at any carbon atom with one or more of OH, halo, C 1 -C 4  alkyl, halo-substituted C 1 -C 4  alkyl, NH 2 , and N(R 3 )(R 3 ) and optionally substituted at any substitutable nitrogen atom with C 1 -C 4  alkyl or halo-substituted C 1 -C 4  alkyl; and \n when D is N, A is CR and B is N, then X is selected from C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)-\u2020, S(\u2550O)\u2014NH-\u2020, S(\u2550O) 2 \u2014NH-\u2020, and NH\u2014C(\u2550O)\u2014O\u2014CR 4 R 5 -\u2020; and \n when E is N, B is N and A is N or CR then X is selected from C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)-\u2020, S(\u2550O)\u2014NH-\u2020, S(\u2550O) 2 \u2014NH-\u2020, NH\u2014C(\u2550S)-\u2020, C(\u2550S)\u2014NH-\u2020, NH\u2014S(\u2550O)-\u2020, NH\u2014S(\u2550O) 2 -\u2020, NH\u2014S(\u2550O) 2 \u2014NR 4 -\u2020, NR 4 \u2014S(\u2550O) 2 \u2014NH-\u2020, NH\u2014C(\u2550O)\u2014O-\u2020, O\u2014C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2014NR 4 -\u2020, NR 4 \u2014C(\u2550O)\u2014NH-\u2020, CH 2 \u2014NH\u2014C(\u2550O)-\u2020, NH\u2014C(\u2550S)\u2014CR 4 R 5 -\u2020, CR 4 R 5 \u2014C(\u2550S)\u2014NH-\u2020, NH\u2014S(\u2550O)\u2014CR 4 R 5 -\u2020, CR 4 R 5 \u2014S(\u2550O)\u2014NH-\u2020, NH\u2014S(\u2550O) 2 \u2014CR 4 R 5 -\u2020, CR 4 R 5 \u2014S(\u2550O) 2 \u2014NH-\u2020, CR 4 R 5 \u2014O\u2014C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2014CR 4 R 5 -\u2020, NH\u2014C(\u2550O)\u2014CR 4 R 5 \u2014NH-\u2020, CR 4 R 5 \u2014NH\u2014C(\u2550O)\u2014O\u2014\u2020 and NH\u2014C(\u2550O)\u2014O\u2014CR 4 R 5 \u2014; and \n when D is N, A is N and B is CR then X is selected from C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2020, NH\u2014CR 4 R 5 -\u2020, C(\u2550O)\u2014NH\u2014CR 4 R 5 -\u2020, S(\u2550O)\u2014NH-\u2020, S(\u2550O) 2 \u2014NH-\u2020, CR 4 R 5 \u2014NH-\u2020, \u2014NH\u2014C(\u2550O)O\u2014CR 4 R 5 -\u2020, NH-\u2020, NH\u2014C(\u2550S)-\u2020, C(\u2550S)\u2014NH-\u2020, NH\u2014S(\u2550O)-\u2020, NH\u2014S(\u2550O) 2 -\u2020, NH\u2014S(\u2550O) 2 \u2014NR 4 -\u2020, NR 4 \u2014S(O) 2 \u2014NH-\u2020, NH\u2014C(\u2550O)\u2014O-\u2020, O\u2014C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2014NR 4 -\u2020, NR 4 \u2014C(\u2550O)\u2014NH-\u2020, CR 4 R 5 \u2014NH\u2014C(O)-\u2020, NH\u2014C(\u2550S)\u2014CR 4 R 5 -\u2020, CR 4 R 5 \u2014C(\u2550S)\u2014NH-\u2020, NH\u2014S(\u2550O)\u2014CR 4 R 5 -\u2020, CR 4 R 5 \u2014S(\u2550O)\u2014NH-\u2020, NH\u2014S(\u2550O) 2 \u2014CR 4 R 5 -\u2020, CR 4 R 5 \u2014S(\u2550O) 2 \u2014NH\u2014, CR 4 R 5 \u2014O\u2014C(\u2550O)\u2014NH-\u2020, NH\u2014C(\u2550O)\u2014CR 4 R 5 -\u2020, NH\u2014C(\u2550O)\u2014CR 4 R 5 \u2014NH\u2020 and CR 4 R 5 \u2014NH\u2014C(\u2550O)\u2014O-\u2020; \n wherein: \n \u2020 represents where X is bound to R 1 ; and \n each R 4  and R 5  is independently selected from hydrogen, C 1 -C 4  alkyl, CF 3  and (C 1 -C 3  alkyl)-CF 3 .

Metadata:
- Claim Count in Document: 18.0
- Percentile: 88.0
- Lexical Diversity: 1.47143
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['12999795', '12990339', '15528195', '13504134', '13121411']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7984242866377472
- 35 USC 102 Novelty (BERT): 0.5357202779511655
- Combined Prediction Score: 0.772153885769089
- Mean Citation Score: 370.57483
- Max Citation Score: 381.78717
- Similarity Product: 269.3767931527627

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

Dataset: test