Methods for the prevention or treatment of pulmonary arterial hypertension by the use of 7-dehydrocholesterol or its salts, oxides, metabolites or derivatives.

Abstract

A method is provided for preventing or treating pulmonary arterial hypertension in a subject in need, comprising administering an effective amount of 7-dehydrocholesterol or its salts, oxides, metabolites, or derivatives to the subject.

Claims

1. A method for preventing or treating pulmonary arterial hypertension in a person in need, A method characterized by administering to a target a pharmaceutical composition comprising an effective amount of a TGF-β receptor inhibitor and a pharmaceutically acceptable excipient thereof.

2. The method according to claim 1, characterized in that the TGF-β receptor inhibitor is 7-dehydrocholesterol, its salt, oxide, metabolite, or derivative.

3. The method according to 2, characterized in that the salt of 7-dehydrocholesterol includes an acetate or benzoate of (3β)-7-dehydrocholesterol or a derivative thereof.

4. The method according to claim 2, characterized in that the derivative of 7-dehydrocholesterol includes cholecalciferol or a compound represented by formula (I). 【Chemistry 1】 (In the formula, R １ CR ５ or N; R ３ is selected from the group consisting of -O(CR ５ ), -OC(-O)(CR ｎ R ６ ), -OC(=O)(CR ５ ), ｎ R ６ ), -OC(=O)(CR ５ ), ｎ OR ５ and -OC(=O)C(R ５ )=C(R ５ ); ２ and is selected from the group consisting of; R ２ is oxygen, sulfur, C(R) ４ ) ２ , and N(R ４ Selected from the group consisting of; R ４ In each occurrence, independently, hydrogen, alkyl group, substituted alkyl group, cycloalkyl group, substituted cycloalkyl group, alkenyl group, substituted alkenyl group, alkynyl group, substituted alkynyl group, aryl group, substituted aryl group, aralkyl group, substituted aralkyl group, heteroaryl group, substituted heteroaryl group, heteroarylalkyl group, substituted heteroarylalkyl group, OR ５ and N(R ５ ) ２ Selected from the group consisting of; R ５ Each occurrence is independently selected from the group consisting of hydrogen, alkyl groups, substituted alkyl groups, cycloalkyl groups, substituted cycloalkyl groups, alkenyl groups, substituted alkenyl groups, alkynyl groups, substituted alkynyl groups, aryl groups, substituted aryl groups, aralkyl groups, substituted aralkyl groups, heteroaryl groups, substituted heteroaryl groups, heteroarylalkyl groups, and substituted heteroarylalkyl groups; R ６ Fluorine, chlorine, bromine, iodine, methanesulfonyl group, toluenesulfonyl group, -OSi(R) ５ ) ３ , -C (=O) OR ５ and -C(=O)R ５ Selected from the group consisting of; Dashed lines represent single or double bonds; n is an integer between 1 and 10.

5. The method according to 4, characterized in that the compound represented by formula (I) is the compound represented by formula (Ia) or a salt or solvate thereof. 【Chemistry 2】 (In the formula, R １ ~R ３ (This is as defined in claim 4.)

6. The method according to 5, characterized in that the compound represented by formula (I) is the compound represented by formula (Ib) or a salt or solvate thereof. 【Transformation 3】 (In the formula, R １ ~R ３ (This is as defined in claim 4.)

7. The aforementioned R １ The method according to 4, characterized in that N is present.

8. The aforementioned R ２ N(R) ４ ) and R ４ The method according to claim 7, characterized in that it is as defined in claim 4.

9. The method according to 8, characterized in that the compound represented by formula (I) is a compound represented by formula (Ic) or a salt or solvate thereof. 【Chemistry 4】 (In the formula, R ３ and R ４ (This is as defined in claim 4.)

10. The method according to 9, characterized in that the compound represented by formula (I) is the compound represented by formula (Id) or a salt or solvate thereof. 【Transformation 5】 (In the formula, R ３ and R ４ (This is as defined in claim 4.)

11. The compound represented by formula (I) is 【Transformation 6】 The method according to 4, characterized in that...

12. The method according to 4, characterized in that the subject is a mammal.

13. The compound represented by formula (I) is 【Transformation 7】 The method according to 4, characterized in that...

14. The method according to claim 2, characterized in that the 7-dehydrocholesterol or its salt, oxide, metabolite, or derivative is administered to the subject in a dose ranging from 1 mg / kg to 50 mg / kg.

15. The method according to claim 1, characterized in that the 7-dehydrocholesterol or its salt, oxide, metabolite, or derivative is a single active ingredient in a pharmaceutical composition for preventing or treating pulmonary arterial hypertension.

16. The method according to claim 1, wherein the pharmaceutical composition further comprises other active ingredients selected from the group consisting of calcium blockers, anticoagulants, diuretics, cardiac stimulants, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, prostacyclin analogs, and any combination thereof.

17. The method according to claim 1, characterized in that the TGF-β receptor inhibitor reduces the proliferation of pulmonary artery endothelial cells, smooth muscle cells, or a combination thereof in the subject.

18. The method according to claim 1, characterized in that the pharmaceutical composition is administered to the subject subcutaneously, intravenously, intradermally, intraperitoneally, orally, intrabuccally, sublingually, intramuscularly, intra-airway, or intra-lungally.

19. The method according to claim 1, characterized in that the pharmaceutical composition is administered to the subject at least once a day.

20. The method according to claim 1, characterized in that the pharmaceutical composition is administered to the subject for at least one month.

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