NZ733245B2 - 3.alpha.-ethynyl, 3.beta.-hydroxy-5.alpha.-pregnan-20-oxime for use in the treatment of cns disorders - Google Patents
3.alpha.-ethynyl, 3.beta.-hydroxy-5.alpha.-pregnan-20-oxime for use in the treatment of cns disordersInfo
- Publication number
- NZ733245B2 NZ733245B2 NZ733245A NZ73324516A NZ733245B2 NZ 733245 B2 NZ733245 B2 NZ 733245B2 NZ 733245 A NZ733245 A NZ 733245A NZ 73324516 A NZ73324516 A NZ 73324516A NZ 733245 B2 NZ733245 B2 NZ 733245B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- hepatic encephalopathy
- compound
- treatment
- alpha
- steroid
- Prior art date
Links
- 208000007386 hepatic encephalopathy Diseases 0.000 claims abstract 8
- 150000001875 compounds Chemical class 0.000 claims abstract 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 5
- 208000035475 disorder Diseases 0.000 claims abstract 5
- 201000010374 Down Syndrome Diseases 0.000 claims abstract 3
- 206010044688 Trisomy 21 Diseases 0.000 claims abstract 3
- 150000003839 salts Chemical class 0.000 claims abstract 3
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract 2
- 239000002671 adjuvant Substances 0.000 claims 5
- 208000015114 central nervous system disease Diseases 0.000 claims 5
- 150000003431 steroids Chemical class 0.000 claims 5
- 239000003085 diluting agent Substances 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 230000027758 ovulation cycle Effects 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 239000013066 combination product Substances 0.000 claims 3
- 229940127555 combination product Drugs 0.000 claims 3
- 230000000694 effects Effects 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- 208000016255 tiredness Diseases 0.000 claims 3
- 230000003867 tiredness Effects 0.000 claims 3
- 208000028698 Cognitive impairment Diseases 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 206010015037 epilepsy Diseases 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- 208000007848 Alcoholism Diseases 0.000 claims 1
- 208000012639 Balance disease Diseases 0.000 claims 1
- 206010052804 Drug tolerance Diseases 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
- 206010020710 Hyperphagia Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- 206010027940 Mood altered Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010036618 Premenstrual syndrome Diseases 0.000 claims 1
- 206010001584 alcohol abuse Diseases 0.000 claims 1
- 208000025746 alcohol use disease Diseases 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 230000001544 dysphoric effect Effects 0.000 claims 1
- 206010021654 increased appetite Diseases 0.000 claims 1
- 230000005906 menstruation Effects 0.000 claims 1
- 206010027599 migraine Diseases 0.000 claims 1
- 230000007510 mood change Effects 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 229940127234 oral contraceptive Drugs 0.000 claims 1
- 239000003539 oral contraceptive agent Substances 0.000 claims 1
- 235000020830 overeating Nutrition 0.000 claims 1
- 208000019116 sleep disease Diseases 0.000 claims 1
- 201000009032 substance abuse Diseases 0.000 claims 1
- 231100000736 substance abuse Toxicity 0.000 claims 1
- 208000011117 substance-related disease Diseases 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- 206010001497 Agitation Diseases 0.000 abstract 1
- 229940124277 aminobutyric acid Drugs 0.000 abstract 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 abstract 1
- 239000002555 ionophore Substances 0.000 abstract 1
- 230000000236 ionophoric effect Effects 0.000 abstract 1
- 210000005171 mammalian brain Anatomy 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention relates to 3a-ethynyl, 3ß-hydroxy, 5a-pregnan-20-oxime or a pharmaceutically acceptable salt thereof, which compounds and/or salts are useful as modulators of the mammal brain excitability via the gamma-5 aminobutyric acid receptor-chloride ionophore (GABAA-R) complex and in the treatment of disorders such as hepatic encephalopathy, Down's syndrome and Alzheimer's disease.
Claims (12)
1. 3a-ethynyl, roxy, 5a-pregnanoxime or a pharmaceutically acceptable salt thereof.
2. A pharmaceutical formulation comprising a compound as defined in Claim 1, in admixture with a pharmaceutically able adjuvant, diluent or carrier.
3. A compound as defined in Claim 1, for use in therapy.
4. Use of a compound as defined in Claim 1 for the cture of a medicament for the treatment of: (a) a d-related CNS disorder; (b) a condition or of symptoms caused by tolerance development after 15 exposure to 3-alpha-hydroxyalpha/beta-steroids; (c) a condition that is influenced by withdrawal/abstinence of exposure to 3- alpha-hydroxyalpha/beta-steroids; (d) one or more side effect of an anti-inflammatory d; (e) one or more side effect of postmenopausal therapy; and/or 20 (f) one or more side effect of an oral contraceptive.
5. A use as claimed in Claim 4, wherein the steroid-related CNS disorder is selected from the group consisting of epilepsy, menstruation cycle dependent epilepsy, sion, stress related depression, migraine and tiredness.
6. A use as claimed in Claim 4, wherein the steroid-related CNS disorder is selected from the group consisting of stress related tiredness, premenstrual syndrome, strual dysphoric disorder, menstrual cycle linked mood changes, minimal cognitive impairment, cognitive impairment, menstrual cycle 30 linked memory changes, stress related memory changes, stress related learning difficulties, hepatic encephalopathy, Down’s syndrome, Alzheimer’s e, menstrual cycle linked ulties in tration, menstrual cycle linked sleep disorders and tiredness, increased appetite, overeating and obesity, relapse of alcohol and substance abuse, balance disorders, moment disorders and co- 35 ordination difficulties.
7. A use as claimed in Claim 6, n the disorder is hepatic encephalopathy. 5 8. A use as claimed in Claim 7, wherein the hepatic encephalopathy is Type
A hepatic encephalopathy, Type B hepatic encephalopathy, Type C hepatic encephalopathy, minimal c alopathy, or overt hepatic encephalopathy. 10 9. A use as claimed in Claim 6, wherein the disorder is Down’s syndrome or
Alzheimer’s disease.
10. A combination product sing: (A) a compound as d in Claim 1; and 15 (B) at least one other therapeutic agent that is useful in the treatment of a steroid-related CNS disorder, wherein each of components (A) and (B) is formulated in admixture with a ceutically-acceptable adjuvant, diluent or carrier. 20
11. A combination product as claimed in Claim 10 which comprises a pharmaceutical formulation including a compound as defined in Claim 1, at least one other therapeutic agent that is useful in the treatment of a steroid-related CNS disorder, and a pharmaceutically-acceptable adjuvant, diluent or carrier. 25
12. A combination product as claimed in Claim 10 which comprises a kit of parts comprising components: (a) a pharmaceutical formulation comprising a compound of formula I as defined in Claim 1, in admixture with a pharmaceutically-acceptable adjuvant, diluent or carrier; and 30 (b) a pharmaceutical formulation comprising at least one other therapeutic agent that is useful in the treatment of a steroid-related CNS er in admixture with a pharmaceutically-acceptable adjuvant, t or carrier, which components (a) and (b) are each provided in a form that is le for administration in conjunction with the other.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE1500018 | 2015-01-12 | ||
| PCT/GB2016/050059 WO2016113549A1 (en) | 2015-01-12 | 2016-01-11 | 3.alpha.-ethynyl, 3.beta.-hydroxy-5.alpha.-pregnan-20-oxime for use in the treatment of cns disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ733245A NZ733245A (en) | 2024-01-26 |
| NZ733245B2 true NZ733245B2 (en) | 2024-04-30 |
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