Substituted 1-Arylalkyl-4-Acylaminopiperidine Compounds and Methods of Producing and Using the Same

• US 20180235949A1
• Filed: 05/04/2016
• Published: 08/23/2018
• Est. Priority Date: 08/22/2014
• Status: Abandoned Application

• Current Assignee: Arizona Board of Regents (University of Arizona)
• Original Assignee: Arizona Board of Regents (University of Arizona)
• Inventors: Vardanyan, Ruben S., Hruby, Victor J.
• Application Number:
  US15/756,014
• Publication Number:
  US 20180235949A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/4465 only substituted in position 4
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

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 C_1-10 alkyl, C_1-10 haloalkyl, optionally substituted aryl, or optionally substituted heteroaryl; R² is C_1-6 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 C_1-10 alkyl.

Claims

1. A method for treating a clinical condition associated with α

_2B adrenoreceptor activation, said method comprising administering a therapeutically effective amount of an α

_2B adrenoreceptor antagonist to a patient in need of such a treatment, wherein said α

_2B adrenoreceptor antagonist is of the formula;

2. 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.

3. The method of claim 1, wherein R² is ethylene.

4. 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 C_1-10 alkyl.

5. The method of claim 1, wherein said α

_2B 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.

6. A method for treating hemorrhagic shock, nicotine withdrawal symptoms, gastrointestinal side effects of opioids, cancer therapy, 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:

7. 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.

8. The method of claim 6, wherein R² is ethylene.

9. 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 C_1-10 alkyl.

10. The method of claim 6, wherein said α

_2B 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.