3beta-(benzyloxy)-17alpha-methyl-pregn-5-en-20-one for use in the treatment of cognitive disorders

Patent metadata

Field	Value
Publication number	US-2022017562-A1
Application number	US-201917414826-A
Country	US
Kind code	A1
Filing date	Dec 18, 2019
Priority date	Dec 18, 2018
Publication date	Jan 20, 2022
Grant date	—

Abstract

The present invention generally relates to a specific pregnenolone derivative for its use for the treatment of a cognitive disorders. More particularly, the invention relates to a compound of Formula (I)for its use in the treatment of cognitive disorders. Indeed, the compound of the invention is in vivo very potent in correcting the cognitive impairments observed in cognitive disorders.

First claim

1 . A method of treating a cognitive disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to Formula (I):

.

2 . The method of claim 1 , wherein the cognitive disorder is a neurocognitive disorder selected from the group consisting of delirium, major neurocognitive disorder, and mild neurocognitive disorder.

3 . The method of claim 2 , wherein the neurocognitive disorder is related to a pathology or disorder selected from the group consisting of a neurodegenerative disease, frontotemporal lobar degeneration, Lewy body degeneration, Parkinson's disease, Huntington's disease, vascular disease, traumatic brain injury, substance or medication abuse, human immunodeficiency virus (HIV) infection, and prion disease.

4 . The method of claim 2 , wherein the neurocognitive disorder is related to a neurodegenerative disease selected from the group consisting of Alzheimer's disease, frontotemporal lobar degeneration, Lewy body degeneration, Parkinson's disease, and Huntington's disease.

5 . The method of claim 2 , wherein the neurocognitive disorder is related to Alzheimer's disease.

6 . The method of claim 2 , wherein the neurocognitive disorder is related to Parkinson's disease.

7 . The method of to claim 1 , wherein the cognitive disorder is related to age-related cognitive decline.

8 . The method of claim 1 , wherein the cognitive disorder is a neurodevelopmental disorder.

9 . The method of claim 8 , wherein the neurodevelopmental disorder is related to a pathology or medical condition selected from the group consisting of: a genetic disease, epilepsy, a metabolic disease, a developmental anomaly, a maternal disease, and a disorder caused by perinatal environmental factors.

10 . The method of claim 8 , wherein the neurodevelopmental disorder is related to an intellectual disability, an intellectual developmental disability, a communication disorder, autism spectrum disorder, Attention-Deficit/Hyperactivity Disorder (ADHD), a specific learning disorder, or a neurodevelopmental motor disorder.

11 . The method of claim 8 , wherein the neurodevelopmental disorder is related to a genetic disease.

12 . The method of claim 8 , wherein the neurodevelopmental disorder is related to Down syndrome.

13 . The method of claim 8 , wherein the neurodevelopmental disorder is related to Fragile X syndrome.

14 . The method of claim 1 , wherein the compound according to Formula (I) is administered to the subject by a route selected from the group consisting of an oral route, a parenteral route, an intravenous route, a subcutaneous route, an intranasal route, and an intramuscular route.

15 . The method of claim 1 , wherein the compound according to Formula (I) is administered to the subject at a dose of between 1 μg to 1000 mg.

16 . The method of claim 9 , wherein the developmental anomaly comprises brain malformation.

17 . The method of claim 9 , wherein the maternal disease comprises a placental disease.

18 . The method of claim 9 , wherein the perinatal environmental factors comprise fetal exposure to alcohol, toxins, or teratogens.

19 . The method of claim 11 , wherein the genetic disease is Down syndrome, fragile X syndrome, tuberous sclerosis, Rett syndrome, William syndrome, or spina bifida.

20 . A process for the manufacture of a compound of Formula (I):

comprising:
(a) converting pregnenolone to an enol acetate intermediate, followed by reaction of the enol acetate intermediate with a Grignard reagent to form a compound of Formula (II):

 and benzylating the compound of Formula (II) under acidic or basic conditions to provide the compound of Formula (I); or
(b) converting pregnenolone to a compound of Formula (III):

 benzylating the compound of Formula (III) under acidic or basic conditions to provide a compound of Formula (IV):

 reacting the compound of Formula (IV) with an acid to provide a compound of Formula (V):

 and methylating the compound of Formula (V) to provide the compound of Formula (I); or
(c) benzylating pregnenolone to form the compound of Formula (V), and then methylating the compound of Formula (V) to provide the compound of Formula (I).

Assignees

• Aelis Farma
• Univ Bordeaux
• Inst Nat Sante Rech Med

Inventors

• Piazza Pier Vincenzo
• Fabre Sandy
• Monlezun Stéphanie
• Metna Mathilde
• Vallee Monique
• Revest Jean-Michel
• Cota Daniela
• Marsicano Giovanni
• Marighetto Aline
• Ozaita Andrés
• Maldonado Rafael

Classifications

• A61K31/573

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/57 Primary

  substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• C07J7/009 Primary

  by only one oxygen atom doubly bound · CPC title