# US 2025/0145604 A1 · Compounds and use thereof as hdac6 inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2025/0145604 A1 - Document ID: US20250145604A1 - Status: Published application - Kind: A1 - Application number: 19/016,827 - Filed: 2025-01-10 - Published: 2025-05-08 - Earliest claimed: 2021-12-22 - Assignees: Augustine Therapeutics - Applicants: Augustine Therapeutics - Inventors: Sylvain CELANIRE; Joao Fernando DOS SANTOS CARVALHO; Frederik Jan Rita ROMBOUTS; Peter Christian SENNHENN; Michele CURCIO; Joana Catarina REIS PEDRO - Web page: https://patentgrep.com/patent/US20250145604A1 ## CPC - A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline - C07D 413/14: containing three or more hetero rings - A61K 31/498: Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 35/00: Antineoplastic agents - A61P 37/00: Drugs for immunological or allergic disorders - C07D 409/12: linked by a chain containing hetero atoms as chain links - C07D 471/04: Ortho-condensed systems - C07D 487/04: Ortho-condensed systems - 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) - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, wherein Y1 is a 9- or 10-membered bicyclic heteroaryl, Y2 is a 5-membered heteroaryl, Z1 is selected from (C═O)—R9, S(O)—R9 and S(O2)—R9, L is an alkyl-, cycloalkyl- or heterocycloalkyl-based linker, and R1 and R9 may be various groups. The present invention further relates to a compound of formula (I) as HDAC6 inhibitor, typically for use in the treatment and/or the prevention of an HDAC6-associated disease, such as cancers, neurodegenerative diseases, neuropathies or cardiovascular diseases. ## Claims ### Claim 1 A compound or a salt and/or solvate thereof, which is a compound selected from the group consisting of: 2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: N-((5-(2-((6-chloro-7-fluoro-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: 2-hydroxy-N-((5-(2-((2-methyl-6-morpholinoquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: N-((5-(2-((5-fluoro-6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: and (R)-2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)propanamide: or a salt and/or solvate of any one thereof. ### Claim 2 (depends on 1) The compound according to claim 1, which is 2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: or a salt and/or solvate thereof. ### Claim 3 (depends on 1) The compound according to claim 1, which is N-((5-(2-((6-chloro-7-fluoro-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: or a salt and/or solvate thereof. ### Claim 4 (depends on 1) The compound according to claim 1, which is 2-hydroxy-N-((5-(2-((2-methyl-6-morpholinoquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: or a salt and/or solvate thereof. ### Claim 5 (depends on 1) The compound according to claim 1, which is N-((5-(2-((5-fluoro-6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: or a salt and/or solvate thereof. ### Claim 6 (depends on 1) The compound according to claim 1, which is (R)-2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)propanamide: or a salt and/or solvate thereof. ### Claim 7 (depends on 1) The compound according to claim 1, which is 2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: ### Claim 8 (depends on 1) The compound according to claim 1, which is N-((5-(2-((6-chloro-7-fluoro-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: ### Claim 9 (depends on 1) The compound according to claim 1, which is 2-hydroxy-N-((5-(2-((2-methyl-6-morpholinoquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: ### Claim 10 (depends on 1) The compound according to claim 1, which is N-((5-(2-((5-fluoro-6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: ### Claim 11 (depends on 1) The compound according to claim 1, which is (R)-2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)propanamide: ### Claim 12 (depends on 1) A pharmaceutical composition comprising the compound or a salt and/or solvate thereof according to claim 1 and at least one pharmaceutically acceptable carrier. ### Claim 13 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is 2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: or a salt and/or solvate thereof. ### Claim 14 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is N-((5-(2-((6-chloro-7-fluoro-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: or a salt and/or solvate thereof. ### Claim 15 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is 2-hydroxy-N-((5-(2-((2-methyl-6-morpholinoquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: or a salt and/or solvate thereof. ### Claim 16 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is N-((5-(2-((5-fluoro-6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: or a salt and/or solvate thereof. ### Claim 17 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is (R)-2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)propenamide: or a salt and/or solvate thereof. ### Claim 18 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is 2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: ### Claim 19 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is N-((5-(2-((6-chloro-7-fluoro-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: ### Claim 20 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is 2-hydroxy-N-((5-(2-((2-methyl-6-morpholinoquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)acetamide: ### Claim 21 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is N-((5-(2-((5-fluoro-6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)-2-hydroxyacetamide: ### Claim 22 (depends on 12) The pharmaceutical composition according to claim 12, wherein the compound or a salt and/or solvate thereof is (R)-2-hydroxy-N-((5-(2-((6-methoxy-2-methylquinazolin-4-yl)thio)acetyl)thiophen-2-yl)methyl)propenamide: ### Claim 23 (depends on 1) A method for treating a HDAC6 associated disease, comprising a step of administering to a subject in need thereof a therapeutically effective amount of the compound or a salt and/or solvate thereof according to claim 1. ### Claim 24 (depends on 23) The method according to claim 23, wherein said HDAC6 associated disease is selected from inflammatory diseases, autoimmune diseases, proliferative diseases, neurodegenerative diseases, pains, neuropathies, psychiatric diseases, neurodevelopmental disorders, sleep disorders, cardiovascular diseases and metabolic or hormonal disorders. ### Claim 25 (depends on 24) The method according to claim 24, wherein said HDAC6 associated disease is a neuropathy selected from Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), Charcot-Marie-Tooth disease, hereditary sensory and autonomic neuropathy, familial amyloidotic polyneuropathy, chemotherapy-induced peripheral neuropathy (CIPN) using chemotherapeutic anticancer agents, diabetic peripheral neuropathy (DPN), neuralgia, pain and/or neuropathic pain. ### Claim 26 (depends on 24) The method according to claim 24, wherein said HDAC6 associated disease is a cardiovascular disease selected from chronic heart failure or acute heart failure, acute decompensated heart failure, ischemic heart disease, cardiomyopathy, myocarditis, valvular disease, hypertension, cardiac disease, tachycardia and congestive cardiac failure. ### Claim 27 (depends on 24) The method according to claim 24, wherein said HDAC6 associated disease is a metabolic or hormonal disorder selected from obesity, diabetes, acromegaly, infertility and metabolic syndrome.