PATENT CLAIM ANALYSIS

Application Number: 16244876
Application Type: Utility
Filing Date: 2019-01
Publication Date: 2019-05
Patent Classification: ["514", "196000"]

Abstract:
The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, R A , X 1 , X 2  and R 1  are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

Claim (Index 1):
A compound of Formula I or a pharmaceutically acceptable salt thereof, wherein: X 1  is N or CH; X 2  is N or CH; Z is tetrazolyl, wherein Z is linked through a carbon to carbon bond to the six-membered core ring having X 1  and X 2 ; R A  is \u2014(CH 2 ) n -AryA1, \u2014(CH 2 ) n -HetA1, \u2014(CH 2 ) n \u2014C 4 -C 6 cycloalkyl, or \u2014(CH 2 ) n \u2014C 4 -C 6 cycloalkenyl, wherein said \u2014(CH 2 ) n \u2014C 4 -C 6 cycloalkyl and \u2014(CH 2 ) n \u2014C 4 -C 6 cycloalkenyl are optionally substituted with 1, 2, or 3 substituents independently selected from \u2014NH 2 , \u2014OH, \u2014F, and \u2014NR a C(O)C 1 -C 6 alkyl optionally substituted with 1 or 2 substituents independently selected from \u2014F, \u2014CF 3 , \u2014NR a R b , and \u2014OR a ; R 1  is\n 1) \u2014NH 2 ; \n 2) \u2014NR a \u2014C 1 -C 6 alkyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from: \u2014F, \u2014CF 3 , C 1 -C 6 alkyl, \u2014CH(NH 2 )C(O)NH 2 , \u2014C(O)NR a R b , \u2014C(O)OH, \u2014(CH 2 ) 1-2 NH 2 , \u2014NR a (CH 2 ) 2-3 NH 2 , \u2014NR a R b , \u2014N + R a R b CH 3 , \u2014NHCH 2 CH 2 OCH 3 , \u2014OR a , and \u2014O(CH 2 ) 2-3 NH 2 ; \n 3) \u2014NR a C(O)C 1 -C 6 alkyl optionally substituted with 1 or 2 substituents independently selected from: \u2014F, \u2014CF 3 , \u2014C(O)NR a R b , \u2014C(O)OH, \u2014NR a R b , \u2014N + R a R b CH 3 , \u2014NHCH 2 CH 2 OCH 3 , \u2014OR a , and \u2014O(CH 2 ) 2-3 NH 2 ; \n 4) \u2014NR a (CH 2 ) n \u2014C 3 -C 6 cycloalkyl, wherein the C 3 -C 6 cycloalkyl is optionally substituted with \u2014CH 2 OH or \u2014NH 2 ; \n 5) a nitrogen-linked 4-6 membered monocyclic heterocycloalkyl with 0, 1, or 2, additional heteroatom ring atoms independently selected from N, O and S, or a nitrogen-linked 6- to 10-membered bicyclic heterocycloalkyl with 0, 1, 2, or 3 additional heteroatom ring atoms selected from N, O and S wherein the bicyclic ring may be bridged, fused or spirocyclic, wherein the 4-6 membered monocyclic heterocycloalkyl and the 6- to 10-membered bicyclic heterocycloalkyl are optionally substituted with one to three substituents, independently selected from: \u2014F, \u2014NR a R b , oxo, \u2014(CH 2 ) 1-2 OH, \u2014CH 2 NH 2 , \u2014SO 2 CH 3 , and C 1 -C 6  alkyl and wherein a ring sulfur atom is optionally substituted with one or two oxo; \n 6) \u2014NR a \u2014(C 1 -C 3 alkyl) n -AryB1, wherein the C 1 -C 3 alkyl is optionally substituted with \u2014NH 2 ; and \n 7) \u2014NR a \u2014(C 1 -C 3 alkyl) n -HetB1; \n AryA1 is an aromatic ring system selected from:\n 1) a 5-6 membered monocyclic ring with 0, 1, 2, or 3 heteroatom ring atoms independently selected from N, O, and S, optionally substituted with 1, 2, or 3 substituents independently selected from:\n a) halogen, \n b) \u2014C 1 -C 6 alkyl, \n c) \u2014CN, \n d) \u2014CH 2 OH, \n e) \u2014C(O)NR a R b , \n f) \u2014C(O)NH(CH 2 ) 2-4 NH 2  optionally substituted with one or two substituents independently selected from \u2014NR a R b  and \u2014(CH 2 ) n OR a , \n g) \u2014C(O)OR a , \n h) \u2014(CH 2 ) p NHR a  optionally substituted with one or two substituents independently selected from \u2014NR a R b  or \u2014OR a , \n i) \u2014(CH 2 ) p NR a C(\u2550NH)NH 2 , \n j) \u2014NR a C(O)C 1 -C 6  alkyl optionally substituted with one or two substituents independently selected from \u2014NR a R b  or \u2014OR a , \n k) \u2014NR a SO 2 \u2014C 1 -C 6 alkyl, \n l) \u2014NR a SO 2 -cyclopropyl, \n m) \u2014OR a , \n n) oxo, \n o) \u2014SC 1 -C 6  alkyl optionally substituted with one or two substituents independently selected from \u2014NR a R b  or \u2014OR a ; \n p) \u2014SO 2 R a , \n q) \u2014SO 2 NR a R b , \n r) \u2014SO 2 NH-cyclopropyl, \n s) -AryA2, \n t) \u2014(CH 2 ) n NR a AryA2, \n u) \u2014C(O)NR a HetA2 and \n v) -HetA2, and \n \n 2) an 8- to 10-membered bicyclic ring with 1, 2, 3 or 4 heteroatom ring atoms selected from N, O and S, wherein an S atom optionally has one or two oxo substituents and a N atom is optionally in the form of an N-oxide, and wherein the ring is optionally substituted with 1 or 2 substituents independently selected from\n a) halogen; b) C 1 -C 6 alkyl optionally substituted with one to three substituents independently selected from \u2014NR a R b , \u2014F and \u2014OR a ; c) \u2014(CH 2 ) n CF 3 ; d) \u2014C(\u2550NH)NH 2 ; e) \u2014CN; f) \u2014C(O)CF 3 ; g) \u2014C(O)NR a R b ; h) \u2014C(O)NHCH 2 C(O)OR a ; i) \u2014C(O)NH\u2014C 2 -C 4 alkyl-NH 2 , j) \u2014C(O)OR a ; k) \u2014NR a R b ; l) \u2014NHCH 2 SO 3 H; m) \u2014(CH 2 ) n NHC(\u2550NH)NH 2 ; n) \u2014NHC(O)C 1 -C 6 alkyl; o) \u2014NHC(O)NH 2 ; p) \u2014NHC(O)OR a ; q) \u2014NHSO 2 CH 3 ; r) \u2014OR a ; s) oxo; t) \u2014SO 2 R a , u) \u2014CH 2 -phenyl-OCH 3 ; and v) -HetA2; \n HetA1 is dihydrothiopyranyl or tetrahydropyranyl; AryA2 is a 5-6-membered aromatic monocyclic ring with 1, 2, or 3 heteroatom ring atoms independently selected from N, N as a quaternary salt, and S, or 4 N ring atoms, optionally substituted with \u2014CH 2 OH, \u2014COOH, \u2014CONH 2 , \u2014C(O)OC 1 -C 6 alkyl, and \u2014(CH 2 ) p NHR a  optionally substituted with one or two substituents independently selected from \u2014NR a R b  and \u2014OR a ; HetA2 is a 4-6-membered saturated monocyclic ring with 1 or 2 heteroatom ring atoms independently selected from N, O and S, wherein the S is optionally substituted with two oxo groups, and wherein the ring is optionally substituted with 1 or 2 substituents independently selected from C 1 -C 6 alkyl, \u2014CN, \u2014OH, and oxo; AryB1 is an aromatic ring selected from:\n 1) a 5-6 membered monocyclic aromatic ring with 0, 1, 2, or 3 N ring atoms, optionally substituted with 1 substituent selected from \u2014CF 3 , C 1 -C 6  alkyl, \u2014(CH 2 ) n NH 2  and \u2014OCH 3 ; or \n 2) a 9-membered bicyclic ring with 2 N ring atoms; \n HetB1 is a saturated ring selected from:\n 1) a 4-6 membered saturated monocyclic ring with 1 or 2 heteroatom ring atoms independently selected from N, O and S, wherein a N ring atom is optionally in the form of a quaternary amine, wherein the S is substituted with two oxo groups, and wherein the ring is optionally substituted with 1 or 2 substituents independently selected from \u2014F, C 1 -C 6  alkyl, C 1 -C 6  hydroxyalkyl, \u2014C(O)OR a , \u2014(CH 2 ) k NR a R b , \u2014OR a , and oxo; or \n 2) a 6-10-membered bicyclic ring with 1 or 2 heteroatom ring atoms independently selected from N and O, optionally substituted with \u2014OH or \u2014NH 2 , wherein the bicyclic ring is bridged or fused; \n R a  and R b  are independently H or C 1 -C 6  alkyl; k is 0, 1, 2, 3, or 4; each n is independently 0 or 1; and each p is independently 0, 1, 2, or 3.

Metadata:
- Claim Count in Document: 59.0
- Percentile: 99.0
- Lexical Diversity: 2.14493
- Patent Class: 514.0
- Transitional Phrase Type: none
- Component Type: 0
- Foreign Priority: True
- Related Applications: ['15737351', '15737334', '15110431', '15309533', '16076781']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.8091262944266692
- 35 USC 102 Novelty (BERT): 0.6312755692054156
- Combined Prediction Score: 0.7913412219045439
- Mean Citation Score: 479.64314800000005
- Max Citation Score: 571.37726
- Similarity Product: 568.9602192037522

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