Pyrazole derivative and use thereof for medical purposes
Inventors
Isaji, Masayuki • Takemura, Masaaki • Isawa, Hidetoshi • Hotei, Yukihiko • Miyashita, Itaru
Assignees
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Publication Number
US-9273085-B2
Publication Date
2016-03-01
Expiration Date
Abstract
The present invention provides pyrazole derivatives, uses thereof for medical purposes and so on. More particularly, the present invention relates to pharmaceuticals useful for the prevention or treatment of constipation, which comprise as an active ingredient 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, or a pharmaceutically acceptable salt thereof. The pharmaceuticals of the present invention exert an effect of increasing the frequency of bowel movement or the like, and are useful for the prevention or treatment of constipation.
Core Innovation
The invention relates to a pharmaceutical composition for preventing or treating constipation by administering to a patient in need thereof 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, and/or a pharmaceutically acceptable salt thereof. The described pharmaceutical forms include pharmaceutically acceptable salts such as bis[...] monosebacate and hemifumarate dihydrate.
The background describes constipation as being related to different subtypes, including functional constipation, chronic idiopathic constipation, and drug-induced constipation. The document states a need for new mechanisms to prevent or treat constipation, and it distinguishes constipation from related conditions such as IBS-C.
The invention is presented as addressing this need through the use of the specified pyrazole derivative active ingredient and pharmaceutically acceptable salts. The described pharmacological effect is increased bowel movement frequency and improved stool properties.
The document provides preclinical and clinical evidence for the specified active ingredient forms. In a loperamide-induced dog constipation model and a low-fiber diet rat model, Compound 2 shows dose-dependent increases in bowel-movement frequency, fecal weight measures, and stool properties. In human studies and a clinical trial in chronic constipation patients, administration is described as increasing bowel-movement frequency and producing softer stool forms (Bristol 6–7).
Claims Coverage
The independent claim provides coverage for a method for the treatment of constipation by administering a pharmaceutical composition with a specifically defined pyrazole derivative active ingredient, or a pharmaceutically acceptable salt, and an appropriate pharmaceutical carrier. Across dependent claims, the inventive features are refined by selecting particular salt forms and narrowing the treated constipation subtype.
Constipation treatment by glucopyranosyloxy pyrazole derivative composition
A method for the treatment of constipation comprising administering to a patient a pharmaceutical composition having as an active ingredient 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide or a pharmaceutically acceptable salt thereof, together with an appropriate pharmaceutical carrier.
Use of bis[...] monosebacate salt form
The method includes administering a pharmaceutical composition where the active ingredient is 3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide in the form of bis[3-(3-{4-[3-(β-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide]monosebacate.
Functional constipation treatment
The method treats constipation wherein the constipation is functional constipation.
Chronic idiopathic constipation within functional constipation
The method treats constipation wherein the functional constipation is chronic idiopathic functional constipation.
Drug-induced constipation within functional constipation
The method treats constipation wherein the functional constipation is drug-induced constipation.
Overall, the claim set covers constipation treatment by administering a pharmaceutical composition containing the defined pyrazole derivative active ingredient, or pharmaceutically acceptable salt, with an appropriate carrier, with dependent claim refinements specifying a bis[...] monosebacate salt form and narrowing the treated condition to functional constipation subtypes including chronic idiopathic functional constipation and drug-induced constipation.
Stated Advantages
Increased bowel movement frequency.
Improved stool properties, including softer stool forms (Bristol 6–7).
Reported as not associated with hypoglycemia in the described clinical trial with Compound 2.
Documented Applications
Preventing or treating constipation in a patient in need thereof, including functional constipation, chronic idiopathic constipation, and drug-induced constipation.
Treatment of chronic constipation patients in a clinical trial context (improving spontaneous bowel-movement frequency and stool form).
Loperamide-induced dog constipation model used to evaluate constipation treatment effects.
Low-fiber diet rat constipation model used to evaluate constipation treatment effects.
Studies in healthy males to assess bowel-movement frequency and stool form after single-dose and multiple-dose administration.
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