THERAPEUTIC COMPOUNDS

• US 20190330157A1
• Filed: 06/03/2019
• Published: 10/31/2019
• Est. Priority Date: 01/13/2017
• Status: Active Application

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: More, Swati S., Vince, Robert
• Application Number:
  US16/429,507
• Publication Number:
  US 20190330157A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: C07C 279/06 being further substituted by halogen atoms, or by nitro or nitroso groups
• CPC Class Codes: C07C 279/08 being further substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 279/18 having nitrogen atoms of guanidine groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 279/22 Y being a hydrogen or a carbon atom, e.g. benzoylguanidines
• CPC Class Codes: C07C 281/14 the carbon atom being further bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 281/16 Compounds containing any of the groups , e.g. aminoguanidine
• CPC Class Codes: C07C 281/18 the other nitrogen atom being further doubly-bound to a carbon atom, e.g. guanylhydrazones
• CPC Class Codes: C07C 335/04 Derivatives of thiourea
• CPC Class Codes: C07C 335/12 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 335/40 having nitrogen atoms of thiourea or isothiourea groups further bound to other hetero atoms
• CPC Class Codes: C07D 213/61 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 231/38 Nitrogen atoms nitro radicals C07D231/16
• CPC Class Codes: C07D 233/44 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 233/50 with carbocyclic radicals directly attached to said nitrogen atoms
• CPC Class Codes: C07D 233/52 with hetero atoms directly attached to said nitrogen atoms
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 239/06 : having one double bond between ring members or between a ring member and a non-ring member
• CPC Class Codes: C07D 239/18 : with hetero atoms attached to said nitrogen atoms, except nitro radicals, e.g. hydrazine radicals
• CPC Class Codes: C07D 239/22 : with hetero atoms directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/47 : One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine

Abstract

The invention provides methods for producing analgesia in an animal comprising administering to the animal a compound of the formula Ia′, Ib′, Ic′, and Id′:

and pharmaceutically acceptable salts thereof, wherein the variables A, R⁶, R⁷, R⁸, R⁹, R^x, L, X, Y, and Z have the meaning as described herein.

Claims

1. A method for producing analgesia in an animal comprising administering to the animal a compound of formula Ia′

, Ib′

Ic′

, or Id′

;

2. The method of claim 1, wherein the compound is selected from the group consisting of:

3. The method of claim 1, wherein the compound is

4. The method of claim 1, further comprising administering morphine to the animal.

5. The method of claim 1, wherein the compound is a compound of formula Ia:

6. The method of claim 1, wherein the compound is a compound of the following formula:

7. The method of claim 1, wherein the compound is

8. The method of claim 1, wherein the analgesia is produced for synergy in antinociception with reduced sedation or cardiovascular effects.

9. The method of claim 1, further comprising administering acetaminophen to the animal.

10. The method of claim 1, wherein the compound of formula Ia′

, Ib′

Ic′

, or Id′

, or a pharmaceutically acceptable salt thereof is E-guanabenz or Z-guanabenz, or a pharmaceutically acceptable salt thereof.

11. A method for treating a condition in an animal wherein the condition is selected from the group consisting of reducing endoplasmic reticulum stress and reducing drug-induced toxicity comprising administering to the animal a compound of formula Ia′

, Ib′

Ic′

, or Id′

;

13. The method of claim 11, wherein the drug is acetaminophen.

12. (canceled)

14. A method for treating a disease selected from the group consisting of diabetes, viral infection, liver disease, and cancer in an animal comprising administering to the animal a compound of formula Ia′

, Ib′

Ic′

, or Id′

;

15. The method of claim 14, wherein the compound is selected from the group consisting of:

16. The method of claim 14, wherein the compound is

19. The method of claim 14, wherein the liver disease is NASH/NAFLD.

17. (canceled)

18. (canceled)