# US 11,440,885 B2 · Substituted 1-arylalkyl-4-acylaminopiperidine compounds and methods of producing and using the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,440,885 B2 - Document ID: US11440885B2 - Status: Granted - Kind: B2 - Application number: 16/829,299 - Filed: 2020-03-25 - Published: 2020-07-16 - Granted: 2022-09-13 - Earliest claimed: 2014-08-22 - Assignees: Arizona Board of Regents On Behalf of the Univeristy of Arizona - Applicants: Arizona Board of Regents on Behalf of the University of Arizona - Inventors: Ruben S. Vardanyan; Victor J. Hruby - Web page: https://patentgrep.com/patent/US11440885B2 ## CPC - C07D 211/58: attached in position 4 - A61K 31/16: Amides, e.g. hydroxamic acids - A61K 31/4465: only substituted in position 4 - A61K 31/4468: having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl - A61K 31/451: having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine - A61P 25/00: Drugs for disorders of the nervous system - C07D 405/12: linked by a chain containing hetero atoms as chain links - C07D 407/12: linked by a chain containing hetero atoms as chain links - C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms - C07D 409/12: linked by a chain containing hetero atoms as chain links - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - 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 invention provides using a substituted 1-arylalkyl-4-acylaminopiperidine compound of Formula I: to treat various clinical conditions including, but not limited to, hemorrhagic shock, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, cancer therapy, epithelial wounds, herpes zoster infection, or opioid-induced pruritus. In compound of Formula I, R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is C1-6 alkylene; Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(═O)—X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl. ## Claims ### Claim 1 A method for treating a clinical condition selected from the group consisting of dyskinesia associated with Parkinson's Disease, hemorrhagic shock, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, cancer therapy side effects, epithelial wounds, herpes zoster infection, and opioid-induced pruritus, said method comprising administering a therapeutically effective amount of an α2B adrenoreceptor antagonist to a patient in need of such a treatment, wherein said α2B adrenoreceptor antagonist is of the formula: wherein R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is C1-6 alkylene; Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(═O)X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl. ### Claim 2 (depends on 1) The method of claim 1, wherein R1 is selected from the group consisting of ethyl, 7-bromoheptyl, fur-2-yl, fur-3-yl, and phenyl. ### Claim 3 (depends on 1) The method of claim 1, wherein R2 is ethylene. ### Claim 4 (depends on 1) The method of claim 1, wherein Y is selected from the group consisting of phenyl, thiophen-2-yl, and a moiety of the formula —C(═O)—OR3, where R3 is C1-10 alkyl. ### Claim 5 (depends on 1) The method of claim 1, wherein said α2B adrenoreceptor antagonist compound is selected from the group consisting of N-(1-phenethylpiperidin-4-yl)propionamide, methyl 3-(4-propionamidopiperidin-1-yl)propanoate, N-(1-phenethylpiperidin-4-yl)furan-2-carboxamide, N-(1-phenethylpiperidin-4-yl)furan-3-carboxamide, N-(1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)propionamide, 8-bromo-N-(1-phenethylpiperidin-4-yl)octanamide, and N-(1-phenethylpiperidin-4-yl)benzamide. ### Claim 6 A method for treating dyskinesia associated with Parkinson's Disease, hemorrhagic shock, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, cancer therapy side effects, epithelial wounds, herpes zoster infection, or opioid-induced pruritus in a subject, said method comprising administering a therapeutically effective amount of an N-substituted piperidin-4-yl compound to a subject in need of such a treatment, wherein said N-substituted piperidin-4-yl compound is of the Formula: wherein R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is C1-6 alkylene; Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(═O)—X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl. ### Claim 7 (depends on 6) The method of claim 6, wherein R1 is selected from the group consisting of ethyl, 7-bromoheptyl, fur-2-yl, fur-3-yl, and phenyl. ### Claim 8 (depends on 6) The method of claim 6, wherein R2 is ethylene. ### Claim 9 (depends on 6) The method of claim 6, wherein Y is selected from the group consisting of phenyl, thiophen-2-yl, and a moiety of the formula —C(═O)—OR3, where R3 is C1-10 alkyl. ### Claim 10 (depends on 6) The method of claim 6, wherein said α2B adrenoreceptor antagonist compound is selected from the group consisting of N-(1-phenethylpiperidin-4-yl)propionamide, methyl 3-(4-propionamidopiperidin-1-yl)propanoate, N-(1-phenethylpiperidin-4-yl)furan-2-carboxamide, N-(1-phenethylpiperidin-4-yl)furan-3-carboxamide, N-(1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)propionamide, 8-bromo-N-(1-phenethylpiperidin-4-yl)octanamide, and N-(1-phenethylpiperidin-4-yl)benzamide. ### Claim 11 (depends on 6) The method of claim 6, wherein said method comprises treating dyskinesia associated with Parkinson's disease. ### Claim 12 A method for treating a clinical condition selected from the group consisting of dyskinesia associated with Parkinson's Disease, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, side-effects of cancer therapy, and opioid-induced pruritus in a subject, said method comprising administering a therapeutically effective amount of an N-substituted piperidin-4-yl compound to a subject in need of such a treatment, wherein said N-substituted piperidin-4-yl compound is of the Formula: wherein R1 is C1-10 alkyl, C1-10 haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R2 is C1-6 alkylene; Y is optionally substituted aryl, optionally substituted heteroaryl, or a moiety of the formula —C(═O)—X1, wherein X1 is —OR3 or —NR4R5, where each of R3, R4 and R5 is H or C1-10 alkyl. ### Claim 13 (depends on 12) The method of claim 12, wherein R1 is selected from the group consisting of ethyl, 7-bromoheptyl, fur-2-yl, fur-3-yl, and phenyl. ### Claim 14 (depends on 12) The method of claim 12, wherein R2 is ethylene. ### Claim 15 (depends on 12) The method of claim 12, wherein Y is selected from the group consisting of phenyl, thiophen-2-yl, and a moiety of the formula —C(═O)—OR3, where R3 is C1-10 alkyl. ### Claim 16 (depends on 12) The method of claim 12, wherein said α2B adrenoreceptor antagonist compound is selected from the group consisting of N-(1-phenethylpiperidin-4-yl)propionamide, methyl 3-(4-propionamidopiperidin-1-yl)propanoate, N-(1-phenethylpiperidin-4-yl)furan-2-carboxamide, N-(1-phenethylpiperidin-4-yl)furan-3-carboxamide, N-(1-(2-(thiophen-2-yl)ethyl)piperidin-4-yl)propionamide, 8-bromo-N-(1-phenethylpiperidin-4-yl)octanamide, and N-(1-phenethylpiperidin-4-yl)benzamide. ### Claim 17 (depends on 12) The method of claim 12, wherein said method comprises treating dyskinesia associated with Parkinson's disease.