CN-121985941-A - Methods of treating epilepsy and related disorders with potent and selective potassium channel activators

Abstract

A method of administering a Kv7 channel activator, or a pharmaceutically acceptable salt thereof, to a human without generating adverse events typically associated with antiepileptic drugs in said human is disclosed. Also disclosed is a method of treating a medical condition in a patient without producing adverse events normally associated with anti-epileptic drugs, the method comprising administering to the patient in need of such treatment a therapeutically effective amount of a Kv7 channel activator, or a pharmaceutically acceptable salt thereof.

Inventors

• B. Ovisel
• M.E. Bozk
• S. I. Dvoretsky
• I. Kuresh

Assignees

• 拜奥海芬治疗学有限公司

Dates

Publication Date

20260505

Application Date

20240913

Priority Date

20230915

Claims (20)

1. 1. A method of administering a Kv7 channel activator, or a pharmaceutically acceptable salt thereof, to a human without generating adverse events normally associated with antiepileptic drugs in said human.
2. 2. A method of treating a medical condition of a patient without producing adverse events normally associated with anti-epileptic drugs of said patient, said method comprising administering to said patient in need of such treatment a therapeutically effective amount of a Kv7 channel activator, or a pharmaceutically acceptable salt thereof.
3. 3. The method of claim 1 or 2, wherein the adverse event comprises somnolence, nausea, abdominal pain, balance disorder, dizziness, headache, irritability, anxiety, mood changes, memory disorder, sensory disorder, speech disorder, or a combination thereof.
4. 4. A method according to any one of claims 1 to 3, wherein the Kv7 channel activator is of the formula:
5. 5. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: , , , , , , , , , , , , , , , 、 、 、 、 、 、 、 、 、 、 、 And Or a pharmaceutically acceptable salt thereof.
6. 6. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: 、 、 And Or a pharmaceutically acceptable salt thereof.
7. 7. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Pharmaceutically acceptable salts.
8. 8. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: 、 、 、 、 、 、 、 、 And Or a pharmaceutically acceptable salt thereof.
9. 9. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
10. 10. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
11. 11. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
12. 12. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
13. 13. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
14. 14. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
15. 15. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
16. 16. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
17. 17. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
18. 18. The method of any one of claims 1 to 4, wherein the Kv7 channel activator is of the formula: Or a pharmaceutically acceptable salt thereof.
19. 19. The method of any one of claims 1 to 18, wherein the medical condition is an epileptic related condition.
20. 20. The method of any one of claims 19, wherein the epileptic related condition is focal epilepsy, pain, neuropathic pain, inflammatory pain, persistent pain, cancer pain, post-operative pain, tinnitus, epileptic encephalopathy, refractory epilepsy, congenital neurological disorder with intellectual impairment or epileptic encephalopathy, severe epileptic encephalopathy, congenital neurological developmental disorder with a phenotype of non-syndromic intellectual impairment or epileptic encephalopathy, epileptic spasticity, epileptic encephalopathy, early infant epileptic encephalopathy 7, early infant epileptic encephalopathy with a delay in psychomotor development, or a combination thereof.

Description

Methods of treating epilepsy and related disorders with potent and selective potassium channel activators Technical Field The present invention relates to methods of treating medical conditions with anti-epileptic drugs without adverse events. In particular, the present invention relates to a method of treating epilepsy with potassium voltage channel activators (Kv 7 channel activators) without the occurrence of adverse events commonly associated with antiepileptic drugs. Background Potassium channel activators become promising candidates for the treatment of epilepsy and other neurological disorders. However, elzogabine (ezogabine) and other molecules in this class are subject to dose limitations by Adverse Events (AEs) typical of antiepileptic drugs (ASM), including sleepiness, nausea, abdominal pain, balance disorders, dizziness, headache, irritability, anxiety, mood changes, memory disorders, sensory disorders, speech disorders. There remains a need for new and selective potassium channel activators that can be safely administered without adverse events in the patient. Disclosure of Invention The present invention relates to the treatment and prevention of medical conditions without the occurrence of adverse events associated with antiepileptic drugs. In one embodiment, a method of administering a Kv7 channel activator, or a pharmaceutically acceptable salt thereof, to a human without generating adverse events typically associated with antiepileptic drugs in humans is provided. In another embodiment, there is provided a method of treating a medical condition in a patient, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a Kv7 channel activator, or a pharmaceutically acceptable salt thereof, wherein the treatment does not result in adverse events in the patient. Drawings These and/or other aspects will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings, in which: FIGS. 1A-1C are graphs of power ((mV 2/m 4)/Hz) versus frequency (Hz) showing spectral power in a resting state EEG. Variation of spectral power at baseline (day-1; blue) and compound 1 at 50-mg dose (red). The hatching indicates confidence intervals. Fig. 2 is a graph showing the effect of compound 1 on EEG power spectrum. The absolute power increases most significantly at the alpha, beta and gamma frequencies following the compound 1-mg dose and decreases with decreasing plasma concentrations. The total absolute power during open eyes was calculated as the difference in power per band for compound 1-mg dose compared to baseline at pre-dose, tmax and 6 hours. Tmax, time to maximum drug concentration. Fig. 3 is a graph showing the frequency band of the dose-dependent effect of compound 1 on EEG band power versus spectral power variation from baseline. Changes in spectral power of the band at maximum response relative to baseline (day-1) after single dose of compound 1 (10 mg, 25 mg, and 50 mg). The box plot depicts the minimum, 25 th percentile, median, 75 th percentile, and maximum. Detailed Description The following detailed description is provided to assist those skilled in the art in practicing the invention. Exemplary embodiments will be described in detail below. However, these embodiments are merely exemplary and the disclosure is not limited thereto but is defined by the scope of the appended claims. Modifications and variations may be made in the embodiments described herein by those of ordinary skill in the art without departing from the spirit or scope of the present disclosure. Accordingly, the embodiments are described below by merely referring to structures and schemes to explain aspects of the present description. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items. The term "or" means "and/or". The expression "at least one of" when followed by a list of elements, modifies the entire list of elements without modifying the individual elements of the list. It will be understood that when an element is referred to as being "on" another element, it can be directly in contact with the other element or intervening elements may be present therebetween. In contrast, when an element is referred to as being "directly on" another element, there are no intervening elements present. It will be understood that, although the terms first, second, third, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or