Chemical compounds as antibiotics
Inventors
LEIRIS, Simon • Davies, David Thomas • EVERETT, Martin • SPRYNSKI, Nicolas • Sutton, Jonathan Mark • BODNARCHUK, Michael Steven • Pallin, Thomas David • Cridland, Andrew Peter • Blench, Toby Jonathan • Clark, David Edward • Elliott, Richard Leonard • BEYRIA, Lilha
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11000511-B2
Publication Date
2021-05-11
Expiration Date
Abstract
The invention relates to a compound which is an indane derivative according to Formula (I), or a pharmaceutically acceptable salt thereof, [FORMULA (I)] wherein R1, R2, R3, n, R4, p, q, L, X and m are as defined herein. The compounds are useful in the treatment of antibacterial infection either as stand alone antibiotics, or in combination with further antibiotics. The compounds can also be used in vitro, for example in cleaning compositions.
Core Innovation
The invention relates to indane derivative compounds according to Formula (I), including pharmaceutically acceptable salts. The compounds are defined by extensive substituent-selection rules for R1, R2, R3, n, R4, p, q, the linker moiety L, the cyclic group {circle around (A)}, X, and the moiety -M-Q-, together with constraints on nitrogen atom(s) in heterocyclic or heteroaryl groups.
The core structure includes an indane scaffold with linker moiety L selected from -CH2-CH2-, -CH2-NH-, and -CH2-O-, and a bonding proviso depending on q. The cyclic group {circle around (A)} is selected from C6 to C10 aryl, 5- to 14-membered heteroaryl, and 4- to 14-membered carbocyclic and heterocyclic groups, and when nitrogen atom(s) are present they are independently selected from secondary, tertiary and quaternary nitrogen atom(s).
The disclosed compound space further includes defined substituent classes for R3 and X, with R3 selected from halogen, hydroxy, amino, methyl and CF3, and X selected from nitrogen-containing heterocyclic groups and related substituted alkyl and carbocyclyl frameworks. The document also describes indane-based benzothiazole carbamoyl acetic acid derivatives, including cationic and amino-substituted side chains and named specific compound examples.
Claims Coverage
The provided content centers on a single independent claim, clm-00001, defining an indane derivative according to Formula (I) or a pharmaceutically acceptable salt thereof. The claim coverage combines extensive substituent-selection rules with parameter constraints for the scaffold, linker moiety, cyclic group, and substituent classes.
Indane derivative according to Formula (I)
A compound which is an indane derivative according to Formula (I), or a pharmaceutically acceptable salt thereof, with selection rules for R1, R2, R3, n, R4, p, q, L, {circle around (A)}, X, and -M-Q-.
Linker moiety L and -M-Q- connectivity
L is selected from moieties including -CH2-CH2-, -CH2-NH-, and -CH2-O-, and -M-Q- is selected from -CH2-CH2-, -CH2-NH-, and -CH2-O-, with a bonding proviso when q is 0.
Cyclic group {circle around (A)} and X selection
{circle around (A)} is selected from C6 to C10 aryl, 5- to 14-membered heteroaryl, and 4- to 14-membered carbocyclic and heterocyclic groups, with nitrogen atom(s), when present, independently selected from secondary, tertiary and quaternary nitrogen atom(s); X is selected from nitrogen-containing heterocyclic group classes and related substituted alkyl and carbocyclyl frameworks.
Defined substituent and parameter limits
R3 is selected from halogen, hydroxy, amino, methyl and CF3, and the claim includes parameter limits for n, p, q, r, and m, together with defined options for R10, R11, R12, R13, R14, and RX.
Claim coverage is centered on Formula (I) indane derivatives and pharmaceutically acceptable salts, defined by parameterized substituent selection, linker and bonding rules, and cyclic-group and X restrictions.
Stated Advantages
Inhibits LasB (Pseudomonas aeruginosa).
Reduces biofilm formation.
Disrupts established biofilms.
Acts alone or with antibiotics.
Reduces hydrolysis of host proteins.
Used for bacterial infection/pneumonia, including in cystic fibrosis.
Documented Applications
Treatment or prevention of bacterial infection in a subject using an effective amount of a compound of claim 1 or a pharmaceutical composition comprising the compound.
Use in pneumonia.
Use in cystic fibrosis.
Therapeutic use for bacterial infection/pneumonia, including inhaled (aerosolised) administration, notably in cystic fibrosis.
Standalone antibiotic use and combination therapies.
Example chemical structures are tested in an “Elastic hydrolysis” assay, with activity reported as % inhibition and corresponding Ki (μM) values.
Interested in licensing this patent?