PATENT CLAIM ANALYSIS

Application Number: 15770369
Application Type: Utility
Filing Date: 2018-04
Publication Date: 2019-01
Patent Classification: ["514", "255050"]

Abstract:
Described are methods of use of compounds that inhibit PIF-mediated substrate binding by PDK1, which are useful as inhibitors of cancer growth or proliferation that is RSK2-dependent or AKT-independent. Also described are compositions of such compounds for use in such methods of treating cancer.

Claim (Index 1):
A method of treating cancer in a subject in need thereof, in which cancer growth or survival is dependent on a PDK1-PIF-mediated substrate interaction, comprising administering to said subject a therapeutically effective amount of a compound of Formula I as described herein: I or a pharmaceutically acceptable salt thereof, in which: R 1  is hydrogen or optionally substituted C1-6 aliphatic, or:\n R 1  and a substituent on Ring A 4  are taken together with their intervening atoms to form an optionally substituted 5-7 membered partially unsaturated or aromatic fused ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; \n X is \u2014C(O)\u2014 or \u2014S(O) 2 \u2014, L 1  is a covalent bond or an optionally substituted bivalent group selected from C 1-4  alkylene, C 2-4  alkenylene, or C 2-4  alkynylene wherein one or more methylene units of L 1  are optionally and independently replaced\n by -Cy 1 -, \u2014O\u2014, \u2014S\u2014, \u2014N(R 2 )\u2014, \u2014C(O)\u2014, \u2014C(O)N(R 2 )\u2014, \u2014N(R 2 )C(O)N(R 2 )\u2014, \u2014N(R 2 )C(O)\u2014, \u2014N(R 2 )C(O)O\u2014, \u2014OC(O)N(R 2 )\u2014, \u2014S(O) 2 \u2014, \u2014S(O) 2 N(R 2 )\u2014, \u2014N(R 2 )S(O) 2 \u2014, \u2014OC(O)\u2014, or \u2014C(O)O\u2014; \n Cy 1  is an optionally substituted bivalent ring selected from phenylene, 3-7 membered saturated or partially unsaturated carbocyclylene, 4-7 membered saturated or partially unsaturated heterocyclylene having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroarylene having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R 2  is hydrogen or optionally substituted C 1-6  aliphatic; A 1  is a covalent bond or an optionally substituted bivalent ring selected from 3-7 membered saturated or partially unsaturated monocyclic carbocyclylene, 7-10 membered saturated or partially unsaturated bicyclic carbocyclylene, 4-7 membered saturated or partially unsaturated monocyclic heterocyclylene having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, 7-10 membered saturated or partially unsaturated bicyclic heterocyclylene having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenylene, 8-10 membered bicyclic arylene, 5-6 membered monocyclic heteroarylene having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 8-10 membered bicyclic heteroarylene having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; L 2  is a covalent bond, alkylidenylene, or an optionally substituted alkylene chain in which one or more methylene units of L 2  are optionally and independently replaced by \u2014O\u2014, \u2014S\u2014, \u2014N(R 2 )\u2014, \u2014C(O)\u2014, \u2014C(O)N(R 2 )\u2014, \u2014N(R 2 )C(O)N(R 2 )\u2014, \u2014N(R 2 )C(O)\u2014, \u2014N(R 2 )C(O)O\u2014, \u2014OC(O)N(R 2 )\u2014, \u2014S(O) 2 \u2014, \u2014S(O) 2 N(R 2 )\u2014, \u2014N(R 2 )S(O) 2 \u2014, \u2014OC(O)\u2014, or \u2014C(O)O\u2014; Ring A 2  is a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-10 membered saturated or partially unsaturated bicyclic carbocyclic ring, a 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a phenyl ring, an 8-10 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 10-16 membered saturated, partially unsaturated, or aromatic tricyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein Ring A 2  is optionally substituted with 1-4 R x  groups; each R x  is independently \u2014R, optionally substituted alkylidenyl, oxo, halo, \u2014NO 2 , \u2014CN, \u2014OR, \u2014SR, \u2014N(R\u2032) 2 , \u2014C(O)R, \u2014CO 2 R, \u2014C(O)C(O)R, \u2014C(O)CH 2 C(O)R, \u2014S(O)R, \u2014S(O) 2 R, \u2014C(O)N(R\u2032) 2 , \u2014S(O) 2 N(R\u2032) 2 , \u2014OC(O)R, \u2014N(R\u2032)C(O)R, \u2014N(R\u2032)N(R\u2032) 2 , \u2014N(R\u2032)OR, \u2014N(R\u2032) C(\u2550NR\u2032)N(R\u2032) 2 , \u2014C(\u2550NR\u2032)N(R\u2032) 2 , \u2014C\u2550NOR, \u2014N(R\u2032)C(O)N(R\u2032) 2 , \u2014N(R\u2032)S(O) 2 N(R\u2032) 2 , \u2014N(R\u2032)S(O) 2 R, or \u2014OC(O)N(R\u2032) 2 ; each R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-10 membered saturated or partially unsaturated bicyclic carbocyclic ring, a 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a phenyl ring, an 8-10 membered bicyclic aryl ring, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R\u2032 is independently \u2014R, or two R\u2032 groups on the same nitrogen are taken together with their intervening atoms to form an optionally substituted 5-8 membered saturated, partially unsaturated, or aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; L 3  is a covalent bond or an optionally substituted C 1-4  alkylene chain in which one or more methylene units of L 3  are optionally and independently replaced by \u2014O\u2014, \u2014S\u2014, \u2014N(R 2 )\u2014, \u2014C(O)\u2014, \u2014C(O)N(R 2 )\u2014, \u2014N(R 2 )C(O)N(R 2 )\u2014, \u2014N(R 2 )C(O)\u2014, \u2014N(R 2 )C(O)O\u2014, \u2014OC(O)N(R 2 )\u2014, \u2014S(O) 2 \u2014, \u2014S(O) 2 N(R 2 )\u2014, \u2014N(R 2 )S(O) 2 \u2014, \u2014OC(O)\u2014, or \u2014C(O)O\u2014; Ring A 3  is an optionally substituted ring selected from a 3-7 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 7-10 membered saturated or partially unsaturated bicyclic carbocyclic ring, a 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a phenyl ring, an 810 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Ring A 4  is a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein any substitutable carbon on Ring A 4  is optionally substituted with R 3 , R 4 , or R 5 , and any substitutable nitrogen on Ring A 4  is optionally substituted with R 6 ; each of R 3 , R 4 , and R 5  is\n independently \u2014R, -halo, \u2014NO 2 , \u2014CN, \u2014OR, \u2014SR, \u2014N(R\u2032) 2 , \u2014C(O)R, \u2014CO 2 R, \u2014C(O)C(O)R, \u2014C(O) CH 2 C(O)R, \u2014S(O)R, \u2014S(O) 2 R, \u2014C(O)N(R\u2032) 2 , \u2014S(O) 2 N(R\u2032) 2 , \u2014OC(O)R, \u2014N(R\u2032)C(O)R, \u2014N(R\u2032)N(R\u2032) 2 , \u2014N(R\u2032)OR, \u2014N(R\u2032)C(\u2550NR\u2032)N(R\u2032) 2 , \u2014C(\u2550NR\u2032)N(R\u2032) 2 , \u2014C\u2550NOR, \u2014N(R\u2032)C(O)N(R\u2032) 2 , \u2014N(R\u2032)S(O) 2 N(R\u2032) 2 , \u2014N(R\u2032)S(O) 2 R, or \u2014OC(O)N(R\u2032) 2 ; or: \n R 3  and R 4  or R 4  and R 5  are taken together with their intervening atoms to form an optionally substituted fused ring selected from a 4-7 membered partially unsaturated carbocyclic ring, phenyl, a 5-6 membered partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; each R 6  is\n independently \u2014R, \u2014C(O)R, \u2014CO 2 R, \u2014C(O)C(O)R, \u2014C(O)CH 2 C(O)R, \u2014S(O)R, \u2014S(O) 2 R, \u2014C(O) N(R\u2032) 2 , or \u2014S(O) 2 N(R\u2032) 2 ; or: \n R 3  and R 6  are taken together with their intervening atoms to form an optionally substituted fused ring selected from a 5-6 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; provided that: when A 1  is a bivalent monocyclic ring and L 1  is a covalent bond, L 2  is not \u2014O\u2014; when A 1  is a bivalent monocyclic or bicyclic ring, L 1  and L 2  are not simultaneously a covalent bond; and L 1 , A 1 , and L 2  are not simultaneously a covalent bond.

Metadata:
- Claim Count in Document: 15.0
- Percentile: 91.0
- Lexical Diversity: 1.42424
- Patent Class: 514.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['14966821', '10949714', '10350806', '13124773', '10922575']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8122144764996042
- 35 USC 102 Novelty (BERT): 0.5459280974525624
- Combined Prediction Score: 0.7855858385949
- Mean Citation Score: 397.804354
- Max Citation Score: 416.61884
- Similarity Product: 308.7911670588064

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

Dataset: test