# US 12,215,095 B2 · Compounds for the treatment of respiratory diseases > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,215,095 B2 - Document ID: US12215095B2 - Status: Granted - Kind: B2 - Application number: 17/291,707 - Filed: 2019-11-07 - Published: 2022-01-06 - Granted: 2025-02-04 - Earliest claimed: 2018-11-07 - Assignees: The University of Melbourne - Applicants: Tianli Biotech Pty Ltd - Inventors: Alastair Stewart; Spencer Williams; Zalihe Hakki - Web page: https://patentgrep.com/patent/US12215095B2 ## CPC - C07D 403/04: directly linked by a ring-member-to-ring-member bond - A61P 11/00: Drugs for disorders of the respiratory system - C07D 401/14: containing three or more hetero rings - C07D 403/14: containing three or more hetero rings - C07D 405/14: containing three or more hetero rings - C07D 409/14: containing three or more hetero rings - C07B 2200/05: Isotopically modified compounds, e.g. labelled - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract The present invention relates to new compounds that are useful in the prevention or treatment of respiratory diseases, such as asthma, acute and chronic inflammatory conditions, and fibrotic diseases or conditions in which fibrosis contributes to the pathology of the condition. The invention also relates to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing respiratory diseases, acute and chronic inflammatory conditions, and fibrotic diseases or conditions in which fibrosis contributes to the pathology of the condition. ## Claims ### Claim 1 A compound of formula (I) or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof: wherein: R1 is C1-3alkylC3-6cycloalkyl; R2 is H; R3 is selected from the group consisting of H, F, Cl and CH3; R4 is selected from the group consisting of —C0-3alkylC3-12cycloalkyl and C1-12alkyl; wherein each of R1 and R4 is optionally substituted. ### Claim 2 (depends on 1) The compound according to claim 1 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is selected from the following groups: wherein each R5 is selected from the group consisting of C1-6alkyl, C1-6haloalkyl, C1-6 haloalkoxy, C1-6hydroxyalkyl, C3-7heterocyclyl, C3-7cycloalkyl, C2-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfenyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, arylsulfonoamino, alkylcarboxy, alkylcarboxyamide, oxo, hydroxy, mercapto, amino, acyl, carboxy, carbamoyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aroyl, aroylamino, heteroaroyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl, nitro, cyano, fluoro, iodo, bromo, ureido or C1-6 perfluoroalkyl, each of which may be optionally substituted; L is (CR7R8)m; R7 and R8 are independently selected from H and optionally substituted C1-6alkyl; n is selected from 0, 1, 2 and 3; and m is selected from 1, 2 and 3. ### Claim 3 (depends on 2) The compound according to claim 2 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein n is 0, 1 or 2. ### Claim 4 (depends on 2) The compound according to claim 2 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is G4. ### Claim 5 (depends on 2) The compound according to claim 2 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is G3. ### Claim 6 (depends on 2) The compound according to claim 2 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R4 is selected from —C0alkylC3-12cycloalkyl and C1-12alkyl, wherein R4 is optionally substituted with halo. ### Claim 7 (depends on 1) The compound according to claim 1 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is substituted C1-3alkylC3-6cycloalkyl. ### Claim 8 (depends on 1) The compound according to claim 1 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R3 is F. ### Claim 9 (depends on 1) The compound according to claim 1 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R4 is C0-3alkylC3-12cycloalkyl. ### Claim 10 (depends on 9) The compound according to claim 9 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R4 is C3-12cycloalkyl. ### Claim 11 (depends on 1) The compound of formula (I) according to claim 1 wherein the compound is selected from: or a pharmaceutically acceptable salt, solvate, N-oxide, tautomer, stereoisomer, prodrug and/or polymorph thereof. ### Claim 12 (depends on 1) A pharmaceutical composition comprising the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt, solvate, N-oxide, tautomer, stereoisomer, prodrug and/or polymorph thereof, and a pharmaceutically acceptable excipient. ### Claim 13 (depends on 1) A method of treating or preventing a respiratory disease, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) as defined in claim 1 or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof. ### Claim 14 (depends on 1) A compound according to claim 1, or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R4 is optionally substituted with a substituent selected from the group consisting of C1-6haloalkyl, C1-6haloalkoxy, C1-6hydroxyalkyl, C3-7heterocyclyl, C3-7cycloalkyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfenyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, arylsulfonoamino, alkylcarboxy, alkylcarboxyamide, oxo, hydroxy, mercapto, amino, acyl, carboxy, carbamoyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aroyl, aroylamino, heteroaroyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl, nitro, cyano, halo, ureido, C1-6perfluoroalkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxyaryl, ester, substituted amino, disubstituted amino, acyl, ketone, substituted ketone, amide, aminoacyl, substituted amide, disubstituted amide, thiol, alkylthio, thioxo, sulfate, sulfonate, sulfinyl, substituted sulfinyl, sulfonyl, substituted sulfonyl, sulfonylamide, substituted sulfonamide, disubstituted sulfonamide, arylC1-6alkyl and C3-7cycloalkylC1-6alkyl. ### Claim 15 (depends on 1) A compound according to claim 1, or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein the C1-3alkyl of the C1-3alkylC3-6cycloalkyl is straight chain. ### Claim 16 (depends on 15) A compound according to claim 15, or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is optionally substituted with a substituent selected from the group consisting of C1-6haloalkyl, C1-6haloalkoxy, C1-6hydroxyalkyl, C3-7heterocyclyl, C3-7cycloalkyl, C1-6alkoxy, C1-6alkylsulfanyl, C1-6alkylsulfenyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, arylsulfonoamino, alkylcarboxy, alkylcarboxyamide, oxo, hydroxy, mercapto, amino, acyl, carboxy, carbamoyl, aryl, aryloxy, heteroaryl, aminosulfonyl, aroyl, aroylamino, heteroaroyl, acyloxy, aroyloxy, heteroaroyloxy, alkoxycarbonyl, nitro, cyano, halo, ureido, C1-6perfluoroalkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxyaryl, ester, substituted amino, disubstituted amino, acyl, ketone, substituted ketone, amide, aminoacyl, substituted amide, disubstituted amide, thiol, alkylthio, thioxo, sulfate, sulfonate, sulfinyl, substituted sulfinyl, sulfonyl, substituted sulfonyl, sulfonylamide, substituted sulfonamide, disubstituted sulfonamide, arylC1-6alkyl, heterocyclylC1-6alkyl, and C3-7cycloalkylC1-6alkyl. ### Claim 17 (depends on 1) A compound according to claim 1, or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is substituted C1alkylC3-6cycloalkyl. ### Claim 18 (depends on 1) A compound according to claim 1, or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is optionally substituted C1alkylC6cycloalkyl. ### Claim 19 (depends on 17) A compound according to claim 17, or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof, wherein R1 is substituted with one or more halo groups. ### Claim 20 (depends on 11) A compound according to claim 11, wherein the compound is: or a salt, solvate, N-oxide, tautomer, stereoisomer, polymorph and/or prodrug thereof.