PATENT CLAIM ANALYSIS

Application Number: 16162835
Application Type: Utility
Filing Date: 2018-10
Publication Date: 2019-06
Patent Classification: ["544", "360000"]

Abstract:
The invention relates to triazole compounds of formula I and I′ or pharmaceutically acceptable salts thereof, useful as modulators of demyelinating diseases: The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention, methods of using the compositions and kits thereof in the treatment of various demyelinating and neurodegenerative diseases, including multiple sclerosis.

Claim (Index 6):
A method of promoting remyelination of demyelinated axons comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I\u2032), or a pharmaceutically acceptable salt thereof, wherein: X 1  is CH; X 2  is CR X2 ; X 3  is CR 3 ; where R 3  and R X2  are each independently selected from the group consisting of hydrogen, halogen, C 1-4 alkyl, C 1-4 haloalkyl, \u2014OC 1-4 alkyl, and cyano; L 1  is a bond, \u2014O\u2014, \u2014NR 5 \u2014, \u2014NR 5 \u2014C 1-4 alkylene-, \u2014O\u2014C 1-4 alkylene-, \u2014C 1-4 alkylene-, \u2014C(O)\u2014, \u2014NR 5 C(O)\u2014, \u2014OC(O)\u2014, \u2014NR 5 C(O)NR 5 \u2014, \u2014NR 5 C(O)O\u2014, \u2014NR 5 \u2014C 1-4 alkylene-C(O)\u2014, \u2014O\u2014C 1-4 alkylene-C(O)\u2014, \u2014C 1-4 alkylene-C(O)\u2014, \u2014NR 5 C(O)\u2014C 1-4 alkylene-, \u2014OC(O)\u2014C 1-4 alkylene-, \u2014NR 5 C(O)NR 5 \u2014C 1-4 alkylene-, \u2014NR 5 C(O)O\u2014C 1-4 alkylene-, or \u2014NR 5 \u2014C 1-4 alkylene-O\u2014, wherein each R 5  is independently hydrogen or C 1-4 alkyl, and the C 1-4 alkylene of \u2014NR 5 \u2014C 1-4 alkylene-, \u2014O\u2014C 1-4 alkylene-, \u2014C 1-4 alkylene-, NR 5 \u2014C 1-4 alkylene-C(O)\u2014, \u2014O\u2014C 1-4 alkylene-C(O)\u2014, \u2014C 1-4 alkylene-C(O)\u2014, \u2014NR 5 C(O)\u2014C 1-4 alkylene-, \u2014OC(O)\u2014C 1-4 alkylene-, \u2014NR 5 C(O)NR 5 \u2014C 1-4 alkylene-, \u2014NR 5 C(O)O\u2014C 1-4 alkylene-, or \u2014NR 5 \u2014C 1-4 alkylene-O\u2014 is optionally substituted with 1-6 halogens; R 1  is -G 1 -L 2 -R 6 , -G 1 -L 2 -R 7 , G 2 , G 3 , G 4 , G 6 , or -\u2261-G 5 ;\n G 1  is \n i) a 4- to 8-membered monocyclic heterocycle containing 1-2 heteroatoms independently selected from oxygen, nitrogen, and sulfur, the monocyclic heterocycle optionally containing one double bond and/or a C 1-3 alkylene bridge between two non-adjacent ring atoms, G 1  being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, and oxo; or \n ii) a 3- to 8-membered cycloalkyl optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, and oxo;\n L 2  is a bond, a \u2014C 1-6 alkylene-, \u2014C(O)\u2014, \u2014O\u2014, or \u2014NR 5\u2032 \u2014, wherein the \u2014C 1-6 alkylene- is optionally substituted with 1-6 halogens and 1-2 C 1 alkylene units of the \u2014C 1-6 alkylene- are optionally replaced with \u2014C(O)\u2014, \u2014O\u2014, or \u2014NR 5\u2032 \u2014, wherein each R 5\u2032  is independently hydrogen or C 1-4 alkyl; \n R 6  is \n a) a 4- to 8-membered monocyclic heterocycle containing 1-2 heteroatoms independently selected from oxygen, nitrogen, and sulfur, the monocyclic heterocycle optionally containing one double bond and/or a C 1-3 alkylene bridge between two non-adjacent ring atoms and being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, \u2014CH 2 S(O) 2 phenyl, halogen, hydroxyl, oxo, \u2014OC 1-4 alkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, and \u2014C 1-6 alkylene-OH; \n b) a 5- or 6-membered monocyclic heteroaryl containing 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, the monocyclic heteroaryl being optionally substituted with 1-3 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, \u2014OC 1-4 alkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, and \u2014C 1-6 alkylene-OH; \n c) a 7- to 12-membered spiro heterocycle comprising a first ring and a second ring, the first ring being a 4- to 8-membered monocyclic heterocycle containing 1-2 heteroatoms independently selected from nitrogen and oxygen and being attached to L 2 , the second ring being a C 3-8 cycloalkyl or a 4- to 8-membered monocyclic heterocycle containing 1-2 oxygen atoms wherein two atoms of the second ring are attached to one carbon of the first ring to form a spirocycle optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, oxo, \u2014OC 1-4 alkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, and \u2014C 1-6 alkylene-OH; or \n d) a 7- to 12-membered fused bicyclic heterocycle containing 1-3 heteroatoms independently selected from oxygen, nitrogen, and sulfur and being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, oxo, \u2014OC 1-4 alkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, and \u2014C 1-6 alkylene-OH; \n R 7  is \n a) a 3- to 8-membered cycloalkyl optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, \u2014C(O)OC 1-4 alkyl, \u2014C(O)OH, oxo, \u2014OC 1-4 alkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, and \u2014C 1-6 alkylene-OH; or \n b) phenyl optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, \u2014C(O)OC 1-4 alkyl, \u2014C(O)OH, \u2014OC 1-4 alkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, and \u2014C 1-6 alkylene-OH; \n \n G 2  is a 4- to 8-membered monocyclic heterocycle containing 1-3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, the monocyclic heterocycle optionally containing one double bond and/or a C 1-3 alkylene bridge between two non-adjacent ring atoms, G 2  being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, oxo, cyano, \u2014C 1-6 alkylene-cyano, \u2014C(O)C 1-4 alkyl, \u2014C(O)\u2014C 1-6 alkylene-OC 1-4 alkyl, \u2014C(O)\u2014C 1-6 alkylene-OH, \u2014C(O)C 3-6 cycloalkyl, \u2014C(O)OC 1-4 alkyl, \u2014C(O)OC 1-4 haloalkyl, \u2014C(O)NH 2 , \u2014C(O)NH(C 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(C 1-4 alkyl), \u2014C(O)NH(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014C(O)NH(\u2014C 1-6 alkylene-OH), \u2014C(O)N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OH), \u2014NH(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014NH(\u2014C 1-6 alkylene-OH), \u2014N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OH), \u2014C(O)C 1-4 haloalkyl, \u2014OC 1-4 alkyl, \u2014OC 1-4 haloalkyl, \u2014C 1-6 alkylene-OC 1-4 alkyl, \u2014C 1-6 alkylene-OH, \u2014C 1-6 alkylene-NH 2 , \u2014C 1-6 alkylene-NH(C 1-4 alkyl), \u2014C 1-6 alkylene-N(C 1-4 alkyl)(C 1-4 alkyl), \u2014O\u2014C 1-6 alkylene-NH 2 , \u2014O\u2014C 1-6 alkylene-NH(C 1-4 alkyl), \u2014O\u2014C 1-6 alkylene-N(C 1-4 alkyl)(C 1-4 alkyl), \u2014O\u2014C 1-6 alkylene-OC 1-4 alkyl, \u2014O\u2014C 1-6 alkylene-OH, \u2014C 1-4 alkylene-O\u2014C 1-4 alkylene-OC 1-4 alkyl, \u2014C 1-4 alkylene-O\u2014C 1-4 alkylene-OH, \u2014C 1-4 alkylene-C(O)OC 1-4 alkyl, \u2014C 1-4 alkylene-C(O)OH, \u2014NHC(O)(C 1-4 alkyl), \u2014N(C 1-4 alkyl)C(O)(C 1-4 alkyl), \u2014NH 2 , \u2014NH(C 1-4 alkyl), \u2014N(C 1-4 alkyl)(C 1-4 alkyl), \u2014S(O) 1-2 C 1-4 alkyl, \u2014C 1-6 alkylene-S(O) 1-2 C 1-4 alkyl, and a \u2014C 1-6 alkylene substituted by 2 groups independently selected from hydroxyl, \u2014OC(O)C 1-4 alkyl, \u2014OC 1-4 alkyl, \u2014NH 2 , \u2014NH(C 1-4 alkyl), and \u2014N(C 1-4 alkyl)(C 1-4 alkyl); \n G 3  is a 7- to 12-membered spiro heterocycle comprising a first ring and a second ring, the first ring being a 4- to 8-membered monocyclic heterocycle containing 1-2 heteroatoms independently selected from nitrogen and oxygen and being attached to L 1 , the second ring being a C 3-8 cycloalkyl or a 4- to 8-membered monocyclic heterocycle containing 1-2 oxygen atoms wherein two atoms of the second ring are attached to one carbon of the first ring to form a spirocycle, and wherein G 3  is optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, and oxo; \n G 4  is a 7- to 12-membered fused bicyclic heterocycle containing 1-3 heteroatoms independently selected from oxygen, nitrogen, and sulfur, G 4  being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, and oxo; \n G 5  is 3- to 8-membered cycloalkyl optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, oxo, cyano, \u2014C(O)C 1-4 alkyl, \u2014C(O)C 3-6 cycloalkyl, \u2014C(O)OC 1-4 alkyl, \u2014C(O)OC 1-4 haloalkyl, \u2014C(O)NH 2 , \u2014C(O)NH(C 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(C 1-4 alkyl), \u2014C(O)NH(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014C(O)NH(\u2014C 1-6 alkylene-OH), \u2014C(O)N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OH), \u2014NH(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014NH(\u2014C 1-6 alkylene-OH), \u2014N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OH), \u2014C(O)C 1-4 haloalkyl, \u2014OC 1-4 alkyl, \u2014C 1-4 alkylene-OC 1-4 alkyl, \u2014C 1-6 alkylene-OH, \u2014C 1-6 alkylene substituted by 2 groups independently selected from hydroxyl and \u2014OC(O)C 1-4 alkyl, \u2014C 1-4 alkylene-C(O)OC 1-4 alkyl, \u2014C 1-4 alkylene-C(O)OH, \u2014NHC(O)(C 1-4 alkyl), \u2014N(C 1-4 alkyl)C(O)(C 1-4 alkyl), \u2014NH 2 , \u2014NH(C 1-4 alkyl), and \u2014N(C 1-4 alkyl)(C 1-4 alkyl); \n G 6  is a monocyclic or bicyclic heteroaryl containing 1-4 heteroatoms independently selected from oxygen, nitrogen, and sulfur, G 6  being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, cyano, phenyl, \u2014C(O)C 1-4 alkyl, \u2014C(O)C 3-6 cycloalkyl, \u2014C(O)OC 1-4 alkyl, \u2014C(O)OC 1-4 haloalkyl, \u2014C(O)NH 2 , \u2014C(O)NH(C 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(C 1-4 alkyl), \u2014C(O)NH(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014C(O)NH(\u2014C 1-6 alkylene-OH), \u2014C(O)N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OH), \u2014NH(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OC 1-4 alkyl), \u2014NH(\u2014C 1-6 alkylene-OH), \u2014N(C 1-4 alkyl)(\u2014C 1-6 alkylene-OH), \u2014C(O)C 1-4 haloalkyl, \u2014OC 1-4 alkyl, \u2014C 1-4 alkylene-OC 1-4 alkyl, \u2014C 1-6 alkylene-OH, \u2014C 1-6 alkylene substituted by 2 groups independently selected from hydroxyl and \u2014OC(O)C 1-4 alkyl, \u2014C 1-4 alkylene-C(O)OC 1-4 alkyl, \u2014C 1-4 alkylene-C(O)OH, \u2014NHC(O)(C 1-4 alkyl), \u2014N(C 1-4 alkyl)C(O)(C 1-4 alkyl), \u2014NH 2 , \u2014NH(C 1-4 alkyl), and \u2014N(C 1-4 alkyl)(C 1-4 alkyl); \n R 2  is C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, cyano, \u2014S(O) 2 C 1-4 alkyl, \u2014S(O)C 1-4 alkyl, \u2014SC 1-4 alkyl, \u2014OC 1-4 alkyl, \u2014OC 1-4 haloalkyl, \u2014C(O)C 1-4 alkyl, \u2014C(O)OC 1-4 alkyl, \u2014C(O)NH 2 , \u2014C(O)NH(C 1-4 alkyl), \u2014C(O)N(C 1-4 alkyl)(C 1-4 alkyl), \u2014C 1-4 alkylene-OC 1-4 alkyl, \u2014C 1-4 alkylene-OH, or G 10 , G 10  being a C 3-6 cycloalkyl, C 5-6 cycloalkenyl, or a 4- to 8-membered monocyclic heterocycle containing 1 to 2 heteroatoms independently selected from nitrogen and oxygen and optionally containing 1 double bond, G 10  being optionally substituted with 1-2 substituents independently selected from oxo, halogen, C 1-4 alkyl, C 1-4 haloalkyl, and G 20 , G 20  being a C 3-6 cycloalkyl or a 4- to 8-membered monocyclic heterocycle containing 1 to 2 heteroatoms independently selected from nitrogen and oxygen, G 20  being optionally substituted with 1-4 substituents independently selected from the group consisting of C 1-4 alkyl, C 1-4 haloalkyl, halogen, hydroxyl, and oxo; and R 4  is phenyl or a 6-membered heteroaryl containing 1-3 nitrogen atoms, R 4  being optionally substituted with 1-3 substituents independently selected from the group consisting of halogen, hydroxyl, cyano, \u2014S(O) 2 C 1-4 alkyl, \u2014S(O)C 1-4 alkyl, \u2014SC 1-4 alkyl, C 1-4 alkyl, C 1-4 haloalkyl, \u2014OC 1-4 alkyl, \u2014OC 1-4 haloalkyl, \u2014C 1-4 alkylene-OC 1-4 alkyl, \u2014C 1-4 alkylene-N(C 1-4 alkyl)(C 1-4 alkyl), \u2014NH(C 1-4 alkylene-OC 1-4 alkyl), \u2014NH(C 1-4 alkylene-OH), \u2014N(C 1-4 alkyl)(C 1-4 alkylene-OC 1-4 alkyl), \u2014N(C 1-4 alkyl)(C 1-4 alkylene-OH), \u2014NH 2 , \u2014NH(C 1-4 alkyl), \u2014N(C 1-4 alkyl)(C 1-4 alkyl), C 3-6 cycloalkyl, C 5-6 cycloalkenyl, or a 4- to 8-membered monocyclic heterocycle containing 1-2 nitrogen atoms, the C 3-6 cycloalkyl, the C 5-6 cycloalkenyl, and the 4- to 8-membered monocyclic heterocycle being independently optionally substituted with 1-2 substituents independently selected from the group consisting of halogen, hydroxyl, \u2014OC 1-4 alkyl, C 1-4 alkyl, C 1-4 haloalkyl, \u2014C 1-4 alkylene-OC 1-4 alkyl, and \u2014C 1-4 alkylene-OH.

Metadata:
- Claim Count in Document: 2.0
- Percentile: 97.0
- Lexical Diversity: 1.53846
- Patent Class: 544.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15173177', '15037090', '15287922', '14509793', '11703522']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.783560907059592
- 35 USC 102 Novelty (BERT): 0.6032071226938668
- Combined Prediction Score: 0.7655255286230196
- Mean Citation Score: 421.580412
- Max Citation Score: 592.3917
- Similarity Product: 448.26066857280136

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