PATENT CLAIM ANALYSIS

Application Number: 15989015
Application Type: Utility
Filing Date: 2018-05
Publication Date: 2019-02
Patent Classification: ["514", "210180"]

Abstract:
Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer, isotopic form or prodrug thereof, wherein R 1 , R 2a , R 2b , R 2c , R 3a , R 3b , R 4a , R 4b , R 5 , L 1 , L 2 , L 3 , E, m 1 , m 2  and * are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

Claim (Index 1):
A compound having the following structure (I): or a pharmaceutically acceptable salt, isotopic form, stereoisomer or prodrug thereof, wherein:\n G 1  and G 2  are each independently N or CH; \n L 1  is a bond or \u2014NR 6 \u2014; \n L 2  is a bond or alkylene; \n L 3  is a bond, \u2014O\u2014, \u2014NR 6 \u2014, \u2014S\u2014, \u2014S(\u2550O)\u2014 or \u2014S(\u2550O) 2 \u2014; \n R 1  is unsubstituted naphthyl or optionally substituted quinolinyl when at least one or R 3a , R 3b , R 4a  and R 4b  is not H; or R 1  has the following structure (R 1 \u2032): \n wherein:\n each \n \u2003represents an aromatic ring; A 1 , A 2 , A 3  and A 4  are each independently C or N; X is O, S, N, NH, C(\u2550O), CR 1e  or NR 1e\u2032 ; Y is O, S, N, NH, C(\u2550O), CR 1f  or NR 1f\u2032 ; Z is O, S, N, NH, C(\u2550O), CR 1g  or NR 1g\u2032 ; one of R 1a , R 1b , R 1c  and R 1d  is a covalent bond to the carbon marked with *, and the other of R 1a , R 1b , R 1c  and R 1d  are each independently H, amino, cyano, halo, hydroxyl, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, alkylaminyl, C 1 -C 6  haloalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy; cycloalkyl, heterocyclyl, aminylalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl; R 1e , R 1f  and R 1g  are each independently H, amino, cyano, halo, hydroxyl, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, alkylaminyl, C 1 -C 6  haloalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy, cycloalkyl, cycloalkylalkyl, cycloalkylalkylaminyl, cycloalkylaminyl, alkylcarbonylaminyl, heterocyclyl, aminylalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl, and R 1e\u2032 , R 1f\u2032  and R 1g\u2032  are each independently C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl or heterocyclylalkyl, provided that when each of A 1 , A 2 , A 3  and A 4  are C, R 1a  is a covalent bond to the carbon marked with *, one of R 1b , R 1c  and R 1d  is methyl and: i) X is NH, Y is N and Z is CR 1g ; ii) Y is N and Z is NH; iii) X is NH, Y is CR 1f  and Z is CR 1g ; or iv) X is NH, Y is CR 1f  and Z is N, then at least one of R 1b , R 1c , R 1d , R 1e , R 1f  and R 1g  is not H, or at least one of R 3a , R 3b , R 4a  and R 4b  is C 1 -C 6  cyanoalkyl, and provided that at least one of X, Y and Z is O, N or NH; R 2a , R 2b  and R 2c  are each independently H, amino, cyano, halo, hydroxyl, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkylaminyl, C 1 -C 6  haloalkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkoxy; cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonylalkyl, aminylcarbonyl, heteroaryl or aryl; R 3a  and R 3b  are, at each occurrence, independently H, \u2014OH, \u2014NH 2 , \u2014CO 2 H, halo, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, C 1 -C 6  hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl; or R 3a  and R 3b  join to form oxo, a carbocyclic or heterocyclic ring; or R 3a  is H, \u2014OH, \u2014NH 2 , \u2014CO 2 H, halo, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, C 1 -C 6  hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl, and R 3b  joins with R 4b  to form a carbocyclic or heterocyclic ring; R 4a  and R 4b  are, at each occurrence, independently H, \u2014OH, \u2014NH 2 , \u2014CO 2 H, halo, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, C 1 -C 6  hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl; or R 4a  and R 4b  join to form oxo, a carbocyclic or heterocyclic ring; or R 4a  is H, \u2014OH, \u2014NH 2 , \u2014CO 2 H, halo, cyano, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkoxy, C 1 -C 6  hydroxylalkyl, alkoxyalkyl, aminylalkyl, alkylaminylalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  carboxyalkyl, aminylcarbonylalkyl or aminylcarbonyl, and R 4b  joins with R 3b  to form a carbocyclic or heterocyclic ring; R 5  is amino, cyano, hydroxyl, C 1 -C 6  alkyl, C 2 -C 6  alkynyl; C 1 -C 6  haloalkyl, C 1 -C 6  hydroxylalkyl, C 1 -C 6  cyanoalkyl, alkoxy, aminylalkyl, aminylalkynyl, alkoxyalkyl, alkoxyalkynyl, alkylcarbonylaminyl, aminylalkylcarbonylaminyl, aminylcarbonylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylcarbonylalkyl, aryl, aralkyl, heteroaryl, heteroarylalkyl; \u2014NR a R b , C 1 -C 6  alkylphosphoryl, C 1 -C 6  alkylphosphorylaminyl, heteroarylalkyloxy or heteroarylalkylaminyl, wherein R a  is H or C 1 -C 6  alkyl, and R b  is C 1 -C 6  alkyl; R 6  is, at each occurrence, independently H or C 1 -C 6  alkyl; m 1  and m 2  are each independently 1, 2 or 3; and E is an electrophilic moiety capable of forming a covalent bond with the cysteine residue at position 12 of a KRAS, HRAS or NRAS G12C mutant protein, wherein each occurrence of alkyl, alkynyl, alkenyl, alkylene, aryl, aralkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, alkylaminyl, haloalkyl, hydroxylalkyl, alkoxy, alkoxyalkyl, haloalkoxy, heterocyclylalkyl, aminylalkyl, alkylaminylalkyl, cyanoalkyl, carboxyalkyl, aminylcarbonyl, aminylcarbonylalkyl, and carbocyclic and heterocyclic rings is optionally substituted with one or more substituents unless otherwise specified.

Metadata:
- Claim Count in Document: 2.0
- Percentile: 93.0
- Lexical Diversity: 1.78873
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: False
- Related Applications: ['15353402', '15093951', '15805716', '14511425', '15721021']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8368531053942467
- 35 USC 102 Novelty (BERT): 0.6125712708580621
- Combined Prediction Score: 0.8144249219406283
- Mean Citation Score: 559.354686
- Max Citation Score: 612.11615
- Similarity Product: 482.5503750203192

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

Dataset: test