Methods for treating post traumatic stress disorder

• US 10,953,001 B2
• Filed: 05/23/2018
• Issued: 03/23/2021
• Est. Priority Date: 07/01/2010
• Status: Active Grant

• Current Assignee: Azevan Pharmaceuticals, Inc.
• Original Assignee: Azevan Pharmaceuticals, Inc.
• Inventors: Brownstein, Michael J.
• Primary Examiner(s): Valenrod, Yevgeny
• Application Number:
  US15/987,053
• Publication Number:
  US 20190099410A1
• Time in Patent Office: 1,035 Days
• Field of Search: 51421002
• CPC Class Codes: A61K 31/397 having four-membered rings, e.g. azetidine
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

Compounds and compositions are described herein for treating post traumatic stress disorder.

Claims

1. A method for treating post-traumatic stress disorder in a host animal, the method comprising administering to the host animal a therapeutically effective amount of one or more compounds of the formulae

2. The method of claim 1 wherein the patient also has one or more impulse control or anger disorders, one or more general anxiety disorders or related anxiety disorders, or one or more depression disorders, or a combination thereof.

3. The method of claim 1 wherein the compound is selective for the V1a receptor.

4. The method of claim 1 wherein the compound is of the formula (I)

5. The method of claim 4 wherein n is 1 or 2.

6. The method of claim 4 wherein A or A′

is an amide of an optionally substituted arylalkylamine.

7. The method of claim 4 wherein A or A′

is an amide of 1,2,3,4-tetrahydronaphth-1-ylamine, or A or A′

is of the formula

8. The method of claim 4 wherein A or A′

is an amide of an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl, or homopiperazinyl, where the substituent is heterocyclyl, heterocyclyl(C₁-C₄)alkyl, (C₃-C₁₂)cycloalkyl, (C₃-C₈)cycloalkyl(C₁-C₄)alkyl, aryl, or aryl(C₁-C₄)alkyl.

9. The method of claim 4 wherein R¹ or R² is hydrogen, or R¹ and R² are both hydrogen.

10. The method of claim 1 wherein the compound is of the formula (II)

11. The method of claim 10 wherein A is an amide of an optionally substituted arylalkylamine.

12. The method of claim 10 wherein A is an amide of 1,2,3,4-tetrahydronaphth-1-ylamine, or A is of the formula

13. The method of claim 10 wherein A is an amide of an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl, or homopiperazinyl, where the substituent is heterocyclyl, heterocyclyl(C₁-C₄)alkyl, (C₃-C₁₂)cycloalkyl, (C₃-C₈)cycloalkyl(C₁-C₄)alkyl, aryl, or aryl(C₁-C₄)alkyl.

14. The method of claim 10 wherein Q is oxygen or sulfur.

15. The method of claim 10 wherein R^5′

is optionally substituted aryl(C₁-C₂alkyl).

16. The method of claim 10 wherein R¹ or R² is hydrogen or both R¹ and R² are hydrogen.

17. The method of claim 10 wherein R³ is

18. The method of claim 1 wherein alkanoyloxy is C₁- C₆ alkanoyloxy, alkyl is C₁-C₆ alkyl, alkoxy is C₁-C₆ alkoxy, cycloalkyl is C₃-C₈ cycloalkyl, cycloalkoxy is C₃-C₈ cycloalkoxy, alkenyl is C₂-C₆ alkenyl, alkynyl is C₂-C₆ alkynyl, haloalkyl is C₁-C₆ haloalkyl, haloalkoxy is C₁-C₆ haloalkoxy, halocycloalkyl is C₃-C₈ halocycloalkyl, and halocycloalkoxy is C₃-C₈ halocycloalkoxy.

19. The method of claim 4 wherein R³ is

20. The method of claim 1 wherein R⁴ is optionally substituted arylalkenyl or optionally substituted arylhaloalkenyl.

21. The method of claim 1 wherein the compound is of the formula

22. The method of claim 1 wherein the compound is of the formula

23. The method of claim 22 wherein the salt form is a hydrochloride salt form.