WATER-SOLUBLE ALLOPREGNENOLONE DERIVATIVE AND USE THEREOF

• US 20190322698A1
• Filed: 12/05/2017
• Published: 10/24/2019
• Est. Priority Date: 12/05/2016
• Status: Abandoned Application

• Current Assignee: Jiangsu Nhwaluokang Pharmceutical Research and Development Co., Ltd.
• Original Assignee: Jiangsu Nhwaluokang Pharmceutical Research and Development Co., Ltd.
• Inventors: LI, Qingeng, WANG, Tao, CHEN, Gang, REN, Liang, LIU, Xin
• Application Number:
  US16/466,819
• Publication Number:
  US 20190322698A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07C 211/63 having quaternised nitrogen atoms bound to acyclic carbon atoms
• CPC Class Codes: C07C 211/64 having quaternised nitrogen atoms bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 279/14 being further substituted by carboxyl groups
• CPC Class Codes: C07C 309/04 containing only one sulfo group
• CPC Class Codes: C07C 309/29 of non-condensed six-membered aromatic rings
• CPC Class Codes: C07C 57/145 Maleic acid
• CPC Class Codes: C07J 41/005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
• CPC Class Codes: C07J 43/003 not condensed
• CPC Class Codes: C07J 51/00 Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
• CPC Class Codes: C07J 7/002 : not substituted in position 16

Abstract

The present invention relates to the field of medicine, and particularly relates to a water-soluble allopregnenolone (3β,5α-tetrahydroprogesterone) derivative, a pharmaceutical composition comprising the same, and use thereof in prevention or treatment of central nervous system diseases, in sedation and hypnosis, in treatment of Alzheimer'"'"'s disease, in treatment of epilepsy or in treatment of depression, especially postpartum depression.

Claims

1. A compound of formula (I), or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof:

2. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein Y is F, CF₃, CH₂F or CHF₂.

3. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein when X is different from Y, the carbon atom to which both X and Y are attached is in a single R configuration, in a single S configuration, or in a mixture of R and S configurations.

4. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein R¹ and R² are each independently H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

5. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein the metal ion is a lithium ion, a sodium ion, a potassium ion, a magnesium ion, a zinc ion, a calcium ion or an aluminum ion.

6. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein the ammonium ion is (NR³R⁴R⁵R⁶)⁺ or

7. The compound of formula (I) according to claim 6, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein R³, R⁴, R⁵ and R⁶ are each independently H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, phenyl, benzyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

8. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein the basic amino acid cation is arginine+H⁺, lysine+H⁺ or histidine+H⁺.

9. The compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, wherein R is selected from the group consisting of:

10. A pharmaceutical composition comprising a prophylactically or therapeutically effective amount of the compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof, and one or more pharmaceutically acceptable carriers.

11. A method for preventing or treating central nervous system diseases, for treating Alzheimer'"'"'s disease, for treating epilepsy, or for treating depression, comprising administering a prophylactically or therapeutically effective amount of the compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt, a stereoisomer, a polymorph, or a solvate thereof.

12. The method according to claim 11, wherein the central nervous system diseases are selected from the group consisting of traumatic brain injury, essential tremor, epilepsy (including refractory status epilepticus and rare genetic epilepticus (e.g., Dravet syndrome and Rett syndrome)), depression (including postpartum depression), and Alzheimer'"'"'s disease.