# US 2016/0355464 A1 · Fumarate compounds, pharmaceutical compositions thereof, and methods of use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2016/0355464 A1 - Document ID: US20160355464A1 - Status: Published application - Kind: A1 - Application number: 14/732,752 - Filed: 2015-06-07 - Published: 2016-12-08 - Earliest claimed: 2015-06-07 - Assignees: Mark Quang Nguyen - Inventors: Mark Quang Nguyen - Web page: https://patentgrep.com/patent/US20160355464A1 ## CPC - C07C 235/06: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms - A61K 31/225: Polycarboxylic acids - A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - C07C 235/08: having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms - C07D 211/06: having no double bonds between ring members or between ring members and non-ring members - C07D 295/195: Radicals derived from nitrogen analogues of carboxylic acids - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS - 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) ## Abstract Fumarate compounds, pharmaceutical compositions comprising the fumarate compounds, and methods of using fumarate compounds and pharmaceutical compositions for treating neurodegenerative, inflammatory, and autoimmune disorders including multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are disclosed. ## Claims ### Claim 1 A compound according to Formula (I): or a pharmaceutically acceptable salt thereof, wherein: each R1 and R2 is independently chosen from hydrogen, C1-6 alkyl, substituted C1-6 alkyl, C1-6 heteroalkyl, substituted C1-6 heteroalkyl, C3-12 cycloalkyl, substituted C3-12 cycloalkyl, C4-12 cycloalkylalkyl, substituted C4-12 cycloalkylalkyl, C6-10 aryl, substituted C6-10 aryl, C7-12 arylalkyl, and substituted C7-12 arylalkyl; or each R1 and R2 together with the nitrogen to which they are bonded independently forms a ring chosen from a C3-12 heterocycloalkyl, substituted C3-12 heterocycloalkyl, C5-10 heteroaryl, and substituted C5-10 heteroaryl; and each R3 and R4 is independently chosen from hydrogen, C1-6 alkyl, and substituted C1-6 alkyl; wherein each substituent group is independently chosen from halogen, —OH, —CN, —CF3, ═O, —NO2, benzyl, —C(O)NR212, —R21, —OR21, —C(O)R21, —C(O)OR21, —NR212, —NR21C(O)R21, and —O(O)R21, wherein each R21 is independently chosen from hydrogen and C1-4 alkyl. ### Claim 2 (depends on 1) The compound according to claim 1, wherein each R1 and R2 is independently chosen from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, phenyl, benzyl, 2-methoxyethyl, and 2-ethoxyethyl. ### Claim 3 (depends on 1) The compound according to claim 1, wherein each R1 and R2 is independently chosen from methyl and ethyl. ### Claim 4 (depends on 1) The compound according to claim 1, wherein each R1 and R2 is ethyl. ### Claim 5 (depends on 1) The compound according to claim 1, wherein each R1 and R2 together with the nitrogen to which they are bonded independently forms a ring chosen from morpholin-4-yl, piperazinyl, N-substituted piperazinyl, and piperidyl. ### Claim 6 (depends on 1) The compound according to claim 1, wherein each R1 and R2 together with the nitrogen to which they are bonded independently forms a ring chosen from morpholin-4-yl. ### Claim 7 (depends on 1) The compound according to claim 1, wherein each R3 and R4 is independently chosen from hydrogen, methyl, ethyl, n-propyl, and isopropyl. ### Claim 8 (depends on 1) The compound according to claim 1, wherein each R3 is hydrogen and each R4 is methyl. ### Claim 9 (depends on 1) The compound according to claim 1, wherein each R3 and R4 is hydrogen. ### Claim 10 (depends on 1) The compound according to claim 1, wherein each R1 and R2 is methyl; and each R3 and R4 is hydrogen. ### Claim 11 (depends on 1) The compound according to claim 1, wherein each R1 and R2 is ethyl; and each R3 and R4 is hydrogen. ### Claim 12 (depends on 1) The compound according to claim 1, wherein each R1 and R2 together with the nitrogen to which they are bonded forms a ring chosen from morpholin-4-yl; and each R3 and R4 is hydrogen. ### Claim 13 (depends on 1) The compound according to claim 1, wherein the compound is chosen from the compounds of Formula (I-A-2), Formula (I-A-3), Formula (I-A-8), Formula (I-A-11), Formula (I-A-12), Formula (I-A-16), Formula (I-A-21), Formula (I-A-23), Formula (I-A-51), and Formula (I-A-52): ### Claim 14 (depends on 1) The compound according to claim 1, wherein the compound is Formula (I-A-12): ### Claim 15 (depends on 13) A pharmaceutical composition comprising a pharmaceutically acceptable vehicle and a therapeutically effective amount of a compound selected from the compounds listed in claim 13. ### Claim 16 (depends on 15) The pharmaceutical composition according to claim 15, wherein the composition is suitable for oral administration. ### Claim 17 (depends on 15) The pharmaceutical composition according to claim 15, wherein the compound is present in an amount that is effective for the treatment of a disease chosen from a neurodegenerative disease, an inflammatory disease, and an autoimmune disease. ### Claim 18 (depends on 15) The pharmaceutical composition according to claim 15, wherein the compound is present in an amount that is effective for the treatment of a disease chosen from multiple sclerosis, psoriasis, irritable bowel disorder, ulcerative colitis, arthritis, chronic obstructive pulmonary disease, asthma, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. ### Claim 19 (depends on 15) The pharmaceutical composition according to claim 15, wherein the composition is suitable for sustained release formulation or controlled release formulation. ### Claim 20 (depends on 15) The pharmaceutical composition according to claim 15, comprising a second therapeutic agent selected from a non-steroidal anti-inflammatory agent, an antihistamine, a selective serotonin reuptake inhibitor (SSRI), a norepinephrine, serotonin reuptake inhibitor (NSRI), a salicylate, and a cox-2 inhibitor.