PATENT CLAIM ANALYSIS

Application Number: 15999117
Application Type: Utility
Filing Date: 2018-08
Publication Date: 2019-02
Patent Classification: ["424", "001890"]

Abstract:
Provided herein are monoacylglycerol lipase (MGLL) occupancy probes comprising a MGLL inhibitor containing a positron emission tomography (PET) tracer radionuclide. Also provided are methods of assessing MGLL enzyme occupancy of a MGLL inhibitor using the radiolabeled occupancy probes described herein.

Claim (Index 6):
A radiolabeled monoacylglycerol lipase (MGLL) occupancy probe, comprising an MGLL inhibitor containing a positron emission tomography (PET) tracer radionuclide, wherein the MGLL inhibitor has the structure of Formula (I): wherein\n T is CX 3  or \n X is selected independently, for each occurrence, from H, F, Cl or Br; wherein at least three occurrences of X are F; V is O or NR a ; R V  is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3-6 cycloalkyl, phenyl, heteroaryl, and heterocyclyl, or when R a  and R v  occur together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring which may have an additional heteroatom selected from O, S, and N; wherein C 1 -C 6 alkyl, C 2 -C 6 alkenyl, phenyl, heterocyclic ring and heterocyclyl are optionally substituted by one, two, or three moieties independently selected from the group consisting of halogen, hydroxyl, C 1 -C 6 alkyl, cyano, and phenyl; and wherein a)\n R 1  and R 2  taken together with the nitrogen to which they are attached form a moiety selected from: \n a 4-7 membered heterocyclic ring B having an additional nitrogen; or \n a 4-7 membered heterocyclic ring A; \n wherein one carbon of ring A has a substituent represented by: \n L 2  is C 1 -C 6 alkylene or C 1 -C 6 alkylene-NR a \u2014; R 3  and R 5  are each independently selected from phenyl, naphthyl, a mono or bicyclic heteroaryl and a mono or bicyclic heterocycle, wherein the heterocycle or heteroaryl has 1, 2 or 3 heteroatoms independently selected from O, S, and N; and wherein R 3  and R 5  may be independently and optionally substituted by one, two, three, or four moieties each independently selected from R g ; R 4  is selected from the group consisting of H, halogen, hydroxyl, cyano, and C 1 -C 5 alkoxy; A is optionally substituted on another carbon by one, two, three, or four substituents each independently selected from R d ; the additional nitrogen of ring B has a substituent represented by: L 3  is selected from the group consisting of: a bond, C 1 -C 6 alkylene, \u2014C(O)\u2014, C 1 -C 6 alkylene-C(O)\u2014, C(O)\u2014C 1 -C 6 alkylene-, NR a \u2014C(O)\u2014C 1 -C 6 alkylene-, C 1 -C 6 alkylene-O\u2014C(O)\u2014, \u2014S(O) w \u2014, and C 1 -C 6 alkylene-S(O) w \u2014, wherein w is 0, 1, or 2, and wherein C 1 -C 6 alkylene is optionally substituted by one or two substituents selected from the group consisting of: halogen, hydroxyl, cyano, and an additional R 7 , wherein when L 3  is \u2014S(O) w \u2014, then R 7  is not H; R 7  is selected from the group consisting of: H, phenyl, naphthyl, mono or bicyclic heteroaryl, and mono or bicyclic heterocyclyl, wherein the heteroaryl or the heterocyclyl has 1, 2 or 3 heteroatoms independently selected from O, S, and N; wherein R 7  is optionally substituted by one, two, three, or four moieties independently selected from R h ; B is optionally substituted on one or more carbons by one, two, three, or four moieties each independently selected from R d ; or b)\n R 1  is-L 1 -R 6 ; \n R 2  is H or C 1 -C 6 alkyl; \n L 1  is C 1 -C 6 alkylene or a bond; \n R 6  is selected from the group consisting of phenyl, naphthyl, a mono or bicyclic heteroaryl, and a mono or bicyclic heterocycle, wherein the heteroaryl or heterocycle has 1, 2 or 3 heteroatoms independently selected from O, S, and N; and R 6  is optionally substituted by one, two, three, or four moieties independently selected from the group consisting of: halogen, phenyl (optionally substituted by one, two, or three moieties independently selected from R c ), phenyloxy (optionally substituted by one, two, or three moieties independently selected from R c ), anilinyl (optionally substituted on a carbon by one, two or three moieties independently selected from R c ), hydroxyl, cyano, C 1-6 alkyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 1-6 alkoxy (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), R a R b N\u2014, R a R b N\u2014SO 2 \u2014, R a R b N\u2014C(O)\u2014, C 1-6 alkyl-C(O)NR a \u2014, R a \u2014S(O) w \u2014, R a \u2014S(O) w \u2014NR b \u2014 (wherein w is 0, 1, or 2), heteroaryl (optionally substituted by one, two, or three moieties independently selected from R c ), and heteroaryloxy; \n R a  and R b  may be independently selected, for each occurrence, from the group consisting of hydrogen and C 1-3 alkyl; wherein C 1-3 alkyl may optionally be substituted by one or more substituents selected from halogen, cyano, oxo, hydroxyl, heterocycle, and phenyl; \n or R a  and R b , when they occur together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring or a 9-10 membered bicyclic heterocycle or spirocyclic ring, which may have an additional heteroatom selected from O, S, and N; wherein the 4-6 membered heterocyclic ring or 9-10 membered bicyclic heterocycle or spirocycle may optionally be substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, C 1-6 alkyl, C 1-6 haloalkyl, \u2014S(O) w \u2014C 1-6 alkyl (where w is 0, 1, or 2), hydroxyl, \u2014C(O)\u2014C 1-6 alkyl, \u2014NH 2 , and \u2014NH\u2014C(O)\u2014C 1-6 alkyl; \n R c  is selected from the group consisting of halogen, cyano, hydroxyl, nitro, C 1-6 alkyl (optionally substituted by one, two, or three halogens, cyano, or hydroxyl), C 2-6 alkenyl (optionally substituted by one, two, or three halogens), C 2-6 alkynyl (optionally substituted by one, two, or three halogens), C 3-6 cycloalkyl, C 1-6 alkoxy (optionally substituted by one, two, or three halogens), R a R b N\u2014, R a R b N\u2014SO 2 \u2014, R a R b N\u2014C(O)\u2014, R a \u2014C(O)\u2014NR a \u2014, R a \u2014C(O)\u2014, R a \u2014S(O) w \u2014NR b \u2014 (wherein w is 0, 1, or 2), and R a \u2014S(O) w \u2014 (wherein w is 0, 1, or 2); \n R d  is selected from the group consisting of: H, C 1-6 alkyl (optionally substituted by one, two, or three halogens, or hydroxyl) and R a R b N\u2014C(O)\u2014; \n R g  is selected from the group consisting of: halogen, phenyl, phenyloxy, anilinyl, hydroxyl, cyano, C 1-6 alkyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 3-6 cycloalkyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 2-6 alkenyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 2-6 alkynyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 1-6 alkoxy (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), R a \u2014C(O)NR a \u2014, R a R b N\u2014, R a R b N\u2014SO 2 \u2014, R a \u2014S(O) w \u2014 (wherein w is 0, 1, or 2), R a \u2014SO 2 \u2014NR b \u2014, R a R b N\u2014C(O)\u2014, heterocycle (optionally substituted by one, two, or three moieties each independently selected from R c , and connected to R 3  or R 5  through a carbon or heteroatom), and heteroaryl (optionally substituted by one, two, or three moieties each independently selected from R c , and connected to R 3  or R 5  through a carbon or heteroatom), or two adjacent R g  groups, along with the carbons to which they are attached, can be taken together to form a 5- or 6-member heterocyclic or heteroaryl ring optionally substituted with 0, 1 or 2 halogens selected from F or Cl and which may have one or two additional heteroatoms selected from O, S, and N; \n R h  is selected from the group consisting of: halogen, phenyl (optionally substituted by one, two, or three moieties each independently selected from R c ), phenyloxy (optionally substituted by one, two, or three moieties each independently selected from R c ), hydroxyl, cyano, C 1-6 alkyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 2-6 alkenyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 2-6 alkynyl (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), C 1-6 alkoxy (optionally substituted by cyano, hydroxyl, or one, two, or three halogens), R a R b N\u2014, R a \u2014C(O)NR a \u2014, R a R b N\u2014SO 2 \u2014, R a R b N\u2014C(O)\u2014, R a \u2014S(O) w \u2014 (wherein w is 0, 1, or 2), R a \u2014SO 2 \u2014NR b \u2014, heteroaryl (optionally substituted by one, two, or three moieties each independently selected from R c , and connected to R 7  through a carbon or heteroatom), heterocycle (optionally substituted by one, two, or three moieties each independently selected from R c , and connected to R 7  through a carbon or heteroatom), and heteroaryloxy (optionally substituted by one, two, or three moieties each independently selected from R c ), or two adjacent R h  groups, along with the carbons to which they are attached, can be taken together to form a 5- or 6-member heterocyclic or heteroaryl ring optionally substituted with 0, 1 or 2 halogens selected from F or Cl and which may have one or two additional heteroatoms selected from O, S, and N; \n or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.

Metadata:
- Claim Count in Document: 53.0
- Percentile: 96.0
- Lexical Diversity: 1.48387
- Patent Class: 424.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['13043956', '13479826', '14003547', '14764426', '13391402']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7205294131980308
- 35 USC 102 Novelty (BERT): 0.5046589614437991
- Combined Prediction Score: 0.6989423680226076
- Mean Citation Score: 262.048626
- Max Citation Score: 265.28232
- Similarity Product: 186.8866085726452

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