Methods for treating post traumatic stress disorder

Inventors

Brownstein, Michael J.

Assignees

Azevan Pharmaceuticals Inc

Abstract

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

Core Innovation

The invention relates to a method for treating post-traumatic stress disorder in a host animal by administering to the host animal a therapeutically effective amount of one or more compounds of formulae (I) and (II), or salts thereof. The compounds are defined by amide-containing structural parameters in which A and A' are independently selected amides, with Q as oxygen, or sulfur or disulfide, or an oxidized derivative thereof.

Additional structural diversity is provided through R5', an integer n selected from 0 to 3, and the allowed definitions for R1, R2, R3, and R4, together with optional substituent selections including halogen, hydroxy, alkyl, alkoxy, and amino-containing groups. The document also describes selective vasopressin V1a receptor antagonists and relates the intended therapeutic use in PTSD to selective antagonism of the vasopressin V1a receptor.

The disclosure includes chemical-definition detail, formula definitions, and experimental support relating to human V1a receptor binding, including a human V1a cell line and a 3H-AVP binding assay, together with V1a/V1b/V2 binding affinities for illustrative compounds. It also presents preclinical evaluation directed to vasopressin receptor selectivity and antagonist characterization, including V1a competitive binding assay measurement, V1b binding assays, and V1a/V1b functional IP turnover assays.

Preclinical efficacy is described in rodent neuroimaging and behavioral models, including predatory fear conditioning with fMRI, resident-intruder stress/aggression with functional imaging while preserving sexual motivation, hamster resident-intruder aggression, a social interaction depression model, and a light/dark shuttle box anxiolysis model. The document further includes a synthetic strategy concept as a diversity platform using proximal amide and distal amide approaches, supported by scheme images, example synthesis descriptions, and a large set of compound examples with stereochemical labeling.

Claims Coverage

The independent claims cover a method of treating post-traumatic stress disorder by administering therapeutically effective amounts of compounds of formulae (I)/(II) or salts, with the main inventive scope being a specific set of structural parameters for selective vasopressin V1a antagonists. Six inventive features are repeated across the claims, with dependent claims narrowing the structure by formula selection, Q restriction, and salt form.

Overall, the claims cover a PTSD treatment method based on administering therapeutically effective amounts of defined vasopressin V1a antagonists from formulae (I)/(II) and pharmaceutically acceptable salts, with dependent claims narrowing the approach by specifying V1a selectivity, selecting formula (II) with a restricted n range, defining A as a amide from optionally substituted arylalkylamine, restricting Q, and in some instances requiring a hydrochloride salt form.

Stated Advantages

Documented Applications