# US 2021/0275514 A1 · Compounds for use in treating kidney disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275514 A1 - Document ID: US20210275514A1 - Status: Published application - Kind: A1 - Application number: 17/206,955 - Filed: 2021-03-19 - Published: 2021-09-09 - Earliest claimed: 2018-07-26 - Assignees: Hoffmann-La Roche Inc. - Applicants: Hoffmann-La Roche Inc. - Inventors: Alessia FORNONI - Web page: https://patentgrep.com/patent/US20210275514A1 ## CPC - A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof - A61K 31/455: Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 31/422: not condensed and containing further heterocyclic rings - A61K 31/4245: Oxadiazoles - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 13/12: of the kidneys - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present disclosure relates to ABCA1 inducer compounds for use in treating kidney disorders, and in particular, chronic kidney diseases, glomerular diseases or proteinuric kidney diseases such as Alport syndrome, focal segmental glomerulosclerosis, and diabetic kidney disease. ## Claims ### Claim 1 A compound for treating a kidney disease, wherein said compound is an ABCA1 inducer compound or a pharmaceutically acceptable salt thereof. ### Claim 2 (depends on 1) The compound according to claim 1, characterized in that it is represented by the formula I wherein: one of A1 and A2 is N and the other one of A1 and A2 is CH; R1 is selected from the group consisting of C1-7-alkyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-7-alkyl, C1-7-alkoxy-C1-7-alkyl, halogen-C1-7-alkyl, heterocyclyl-C1-7-alkyl wherein the heterocyclyl group is unsubstituted or substituted by oxo, and heteroaryl-C1-7-alkyl wherein the heteroaryl group is unsubstituted or mono- or di-substituted by lower alkyl; R2 and R6 independently from each other are hydrogen or halogen; R3 and R5 independently from each other are selected from the group consisting of hydrogen, C1-7-alkyl, C1-7-alkoxy, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxy and cyano; R4 is selected from the group consisting of hydrogen, C1-7-alkyl, C1-7-alkoxy, halogen, halogen-C1-7-alkyl, halogen-C1-7-alkoxy, amino and cyano; R7 is selected from the group consisting of C1-7-alkyl, C3-7-cycloalkyl, said cycloalkyl being unsubstituted or substituted by hydroxy, heterocyclyl, said heterocyclyl having 3 to 7 ring atoms, comprising one, two or three heteroatoms selected from N, O and S and being unsubstituted or substituted by hydroxy or oxo, phenyl, wherein phenyl is unsubstituted or substituted by one or two groups selected from the group consisting of C1-7-alkyl, hydroxy, C1-7-alkoxy, cyano, halogen and halogen-C1-7-alkyl, and heteroaryl, wherein heteroaryl is unsubstituted or substituted by one or two groups selected from the group consisting of C1-7-alkyl, hydroxy, C1-7-alkoxy, cyano, halogen and halogen-C1-7-alkyl, and G is selected from the group consisting of —(CH2)m-, wherein m is selected from 0 or 1, and —NR8—, wherein R8 is hydrogen or C1-7-alkyl, or a pharmaceutically acceptable salt thereof. ### Claim 3 (depends on 1) The compound according to claim 1, wherein G is a bond and R7 is C3-7-cycloalkyl, said cycloalkyl being unsubstituted or substituted by hydroxy. ### Claim 4 (depends on 3) The compound according to claim 3, wherein R7 is cyclohexyl substituted by hydroxy. ### Claim 5 (depends on 1) The compound according to claim 1, wherein R2 and R6 are each a hydrogen, R4 is halogen, and one of R3 and R5 is halogen and the other one of R3 and R5 is hydrogen. ### Claim 6 (depends on 1) The compound according to claim 1, wherein R1 is halogen-C1-7-alkyl. ### Claim 7 (depends on 6) The compound according to claim 6, wherein R1 is selected from —CF3, —CHF2, —CH2Cl, —CH2CF3, —CH(CF3)2, —CF2—CF3. ### Claim 8 (depends on 1) The compound according to claim 1, which is 6-(3,4-dichlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-5-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide. ### Claim 9 (depends on 1) The compound according to claim 1, which is 5-(3,4-dichloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide. ### Claim 10 (depends on 1) The compound according to claim 1, wherein said kidney disease is selected from chronic kidney diseases, primary or secondary glomerular diseases or proteinuric kidney diseases. ### Claim 11 (depends on 10) The compound according to claim 10, wherein said glomerular disease is Alport syndrome or focal segmental glomerulosclerosis. ### Claim 12 (depends on 10) The compound according to claim 10, wherein said kidney disease is selected from diabetic kidney disease. ### Claim 13 (depends on 1) The compound according to claim 1, which is formulated for oral administration. ### Claim 14 (depends on 1) The compound according to claim 1, which is formulated for topical, intranasal, intraocular, intravenous, intramuscular, subcutaneous, intravitreal, intrathecal or transdermal administration. ### Claim 15 (depends on 1) The compound according to claim 1, wherein the daily dose is 20 to 800 mg/day. ### Claim 16 (depends on 1) The compound according to claim 1, wherein the daily dose is 200 mg/day. ### Claim 17 (depends on 1) The compound according to claim 1, wherein the dosing regimen is once daily, twice daily, three time a day, once per three days, once weekly, once every two weeks, or once monthly. ### Claim 18 (depends on 1) The compound according to claim 1, wherein the loading dose regimen double the dose for the first 7 days, 14 days, or 30 days. ### Claim 19 (depends on 1) The compound according to claim 1, for the simultaneous, sequential or separate use with a compound selected from the group consisting of angiotensin-converting enzyme (ACE) inhibitor drugs; RAS blockers; angiotensin receptor blockers (ARBs); protein kinase C (PKC) inhibitors; inhibitors of AGE-dependent pathways; anti-inflammatory agents; GAGs; pyridoxamine; endothelin antagonists, COX-2 inhibitors, PPAR-γ antagonists and other compounds like amifostine, captopril, cyclophosphamide, sodium thiosulfate, tranilast or cyclodextrins and their derivatives, vitamin D derivatives, anti-hyperglycemic agents and anti-hypercholesterolemic agents. ### Claim 20 (depends on 1) A compound of formula I according to claim 1 or a pharmaceutically acceptable salts, for the preparation of a medicament for the treatment and/or prophylaxis of kidney diseases. ### Claim 21 (depends on 1) A pharmaceutical composition, comprising a compound according to claim 1 and a pharmaceutically acceptable carrier and/or adjuvant. ### Claim 22 (depends on 1) A method for treating a kidney disease in a subject in need thereof, comprising administering a therapeutically effective amount of an ABCA1 inducer according to claim 1 or a pharmaceutically acceptable salt thereof. ### Claim 23 (depends on 22) The method according to claim 22, wherein said ABCA1 inducer is administrated by topical, oral, intranasal, intraocular, intravenous, intramuscular, subcutaneous, intravitreal, intrathecal or transdermal route. ### Claim 24 (depends on 22) The method according to claim 22, wherein the administration is once daily, twice daily, three time a day, once every three days, once weekly, once every two weeks, or once monthly, preferably one daily. ### Claim 25 (depends on 1, 22) The method according to claim 22, wherein the daily dose of ABCA1 inducer as defined according to claim 1, is in the range of 20 to 800 mg/day. ### Claim 26 (depends on 22) The method according to claim 22, wherein said ABCA1 inducer is administered simultaneously, separately or sequentially in combination with a therapeutically effective amount of an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker. ### Claim 27 (depends on 22) The method according to claim 22, wherein said ABCA1 inducer is administered simultaneously, separately or sequentially in combination with a therapeutically effective amount of a compound selected from the group consisting of angiotensin-converting enzyme (ACE) inhibitor drugs; RAS blockers; angiotensin receptor blockers (ARBs); protein kinase C (PKC) inhibitors; inhibitors of AGE-dependent pathways; anti-inflammatory agents, GAGs; pyridoxamine; endothelin antagonists, COX-2 inhibitors, PPAR-γ antagonists and other compounds like amifostine, captopril cyclophosphamide, sodium thiosulfate, tranilast, or cyclodextrins and their derivatives, vitamin D derivatives, anti-hyperglycemic agents and anti-hypercholesterolemic agents. ### Claim 28 A compound: 5-(3,4-dichloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide, or a pharmaceutically acceptable salt thereof.