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US-20260124181-A1 - AGENT FOR REDUCING BLOOD MYOSTATIN LEVEL

US20260124181A1US 20260124181 A1US20260124181 A1US 20260124181A1US-20260124181-A1

Abstract

A novel preventive and/or therapeutic agent useful in the prevention and/or treatment of a disease whose symptom is alleviated or improved by the inhibition of myostatin. The present invention relates to an agent for preventing and/or treating a disease whose symptom is alleviated or improved by the inhibition of myostatin, the agent including a therapeutically effective dose of (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, a salt thereof, or a solvate thereof.

Inventors

  • Ryohei TANIGAWA

Assignees

  • KOWA COMPANY, LTD.

Dates

Publication Date
20260507
Application Date
20230705
Priority Date
20220706

Claims (7)

  1. 1 - 5 . (canceled)
  2. 6 . A method of inhibiting or reducing a blood myostatin level, comprising administering an effective dose of (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, a salt thereof, or a solvate thereof to a subject in need thereof.
  3. 7 . The method of claim 6 which comprises inhibiting myostatin, comprising administering an effective dose of (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, a salt thereof, or a solvate thereof to a subject in need thereof.
  4. 8 . A method of preventing and/or treating an amyotrophic disease, comprising administering an effective dose of (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, a salt thereof, or a solvate thereof to a subject in need thereof.
  5. 9 . The method according to claim 8 , wherein the amyotrophic disease is Duchenne muscular dystrophy.
  6. 10 . The method according to claim 8 , wherein the amyotrophic disease is sarcopenia.
  7. 11 - 20 . (canceled)

Description

FIELD OF THE INVENTION The present invention relates to an agent for reducing a blood myostatin level. BACKGROUND OF THE INVENTION Myostatin (another name: growth differentiation factor-8 (GDF8)) is a secretory protein produced from a skeletal muscle cell and suppresses the growth of a skeletal muscle, and the protein belongs to a TGF-β superfamily. It has been known from the phenotype of myostatin gene abnormality in an animal and a human, and observation with an animal model that the inhibition of myostatin shows muscle hypertrophy. Attention has been paid to the function of myostatin, and the application of its inhibition to the treatment of an amyotrophic disease such as muscular dystrophy has been expected. An attempt has heretofore been made to develop a drug that exhibits muscle hypertrophy in an animal model, such as a neutralizing antibody for myostatin, an antagonist for myostatin such as a soluble activin IIB receptor, or an analog of follistatin serving as a physiological antagonist in the TGF-β superfamily. However, no drug has been known that was put into practical use as a therapeutic drug for a human. As other approaches, attention has been paid to the fact that fenofibrate known as a PPARα agonist suppresses the expression of myostatin (Non Patent Document 1), and an investigation on its effect on a Duchenne muscular dystrophy model animal has been reported (Non Patent Document 2). However, each of those investigations is an investigation in a rodent animal model, and hence a clinical effect of fenofibrate in a human is uncertain. Meanwhile, Patent Document 1 discloses that a compound represented by the following formula (1), a salt thereof, or a solvate thereof has a selective PPARα-activating effect, and is hence useful as a preventive and/or therapeutic drug for hyperlipidemia, arteriosclerosis, diabetes, a diabetic complication (e.g., diabetic nephropathy), inflammation, a heart disease, or the like that is not accompanied by a weight gain or obesity in a mammal including a human: where R1 and R2 may be identical to or different from each other, and each represents a hydrogen atom, a methyl group, or an ethyl group, R3a, R3b, R4a, and R4b may be identical to or different from each other, and each represents a hydrogen atom, a halogen atom, a nitro group, a hydroxy group, a C1-4 alkyl group, a trifluoromethyl group, a C1-4 alkoxy group, a C1-4 alkylcarbonyloxy group, a di-C1-4 alkylamino group, a C1-4 alkylsulfonyloxy group, a C1-4 alkylsulfonyl group, a C1-4 alkylsulfinyl group, or a C1-4 alkylthio group, or R3a and R3b, or R4a and R4b are bonded to each other to represent an alkylenedioxy group, X represents an oxygen atom, a sulfur atom, or N—R5 (R5 represents a hydrogen atom, a C1-4 alkyl group, a C1-4 alkylsulfonyl group, or a C1-4 alkyloxycarbonyl group), Y represents an oxygen atom, a S(O)l group (“l” represents a number of from 0 to 2), a carbonyl group, a carbonylamino group, an aminocarbonyl group, a sulfonylamino group, an aminosulfonyl group, or an NH group, Z represents CH or N, “n” represents a number of from 1 to 6, and “m” represents a number of from 2 to 6. However, there is no description or suggestion of what effect such a compound has on myostatin. PRIOR ART DOCUMENTS Patent Document [Patent Document 1] WO 2005/023777 A1 Non Patent Documents [Non Patent Document 1] Am J Physiol-Endoclinol Metab. (2011) 300, E790-E799[Non Patent Document 2] Br J Pharmacol. (2021) 179, 1237-1250 SUMMARY OF THE INVENTION An objective of the present invention is to provide a novel preventive and/or therapeutic agent useful in the prevention and/or treatment of a disease on which a therapeutic effect can be expected by inhibition of myostatin. To achieve the above objective, the present inventors made energetic investigations, and as a result, found that to their complete surprise, a compound disclosed as Example 85 in Patent Document 1 described above, that is, (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid (hereinafter may be referred to as “compound A” or “pemafibrate”) reduced a blood myostatin concentration, and was hence useful in the prevention and/or treatment of a disease on which a therapeutic effect was expected by the inhibition of myostatin. In this way, the inventors completed the present invention. That is, the present invention provides the following [1] to. [1] An agent for reducing a blood myostatin level, comprising, as an active ingredient, (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, a salt thereof, or a solvate thereof.[2] An inhibitor of myostatin, comprising (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyric acid, a salt thereof, or a solvate thereof, as an active ingredient.[3] An agent for preventing and/or treating an amyotrophic disease, comprising (R)-2-[3-[[N-(benzoxazol-2-yl)-N-3-(4-methoxyphenoxy)propyl]aminomethyl]phenoxy]butyr