[미국특허]
TREATMENT OF HUTCHINSON-GILFORD PROGERIA SYNDROME AND DISEASES RELATED TO VASCULAR AGEING
원문보기
IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
A61K-031/505
A61K-031/16
A61K-031/381
A61K-009/00
A61K-031/54
C12N-015/113
G01N-033/68
G01N-033/50
C12Q-001/68
A61K-031/506
출원번호
US-0543703
(2016-01-15)
공개번호
US-0000817
(2018-01-04)
우선권정보
PT-108150 (2015-01-15)
국제출원번호
PCT/IB2016/050208
(2016-01-15)
발명자
/ 주소
DA SILVA FERREIRA, Lino
PINHEIRO PITREZ PEREIRA, Patricia Raquel
ESMERALDO DE CAMPOS VAZÃO, Helena Sofia
출원인 / 주소
DA SILVA FERREIRA, Lino
인용정보
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초록▼
The present disclosure relates to the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS) and diseases related to vascular ageing and in the treatment of smooth muscle cells diseases, in particular an inhibitor of a metalloprotease the treatment of smooth muscle cells diseases. The disclosure s
The present disclosure relates to the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS) and diseases related to vascular ageing and in the treatment of smooth muscle cells diseases, in particular an inhibitor of a metalloprotease the treatment of smooth muscle cells diseases. The disclosure subject matter describes a more effective therapies for the treatment of Hutchinson-Gilford Progeria Syndrome and diseases related to vascular ageing, or namely by the use of an inhibitor of a metalloprotease.
대표청구항▼
1. A method for treating Hutchinson-Gilford Progeria Syndrome or vascular ageing diseases comprising administering an effective amount of a metalloprotease inhibitor comprising a zinc endopeptidase, wherein said inhibitor is selected from the following compounds: pyrimidine-4,6-dicarboxylic acid, bi
1. A method for treating Hutchinson-Gilford Progeria Syndrome or vascular ageing diseases comprising administering an effective amount of a metalloprotease inhibitor comprising a zinc endopeptidase, wherein said inhibitor is selected from the following compounds: pyrimidine-4,6-dicarboxylic acid, bis-(4-fluoro-3-methyl-benzylamide); pyrimidine-4,6-dicarboxylic acid, bis-(3-methyl-benzylamide);pyrimidine-4,6-dicarboxylic acid, bis-(benzylamide);pyrimidine-4,6-dicarboxylic acid bis-[(Pyridin-3-YL-Methyl)-Amide;(2R,3S)-N4-Hydroxy-2-isobutyl-N1-[(2S)-1-(methylamino)-1-oxo-3-phenyl-2-propanyl]-3-[(2-thienylsulfanyl)methyl]succinamide;N-[2,2-dimethyl-1-(methylcarbamoyl)propyl]-2-[hydroxy-(hydroxycarbamoyl)methyl]-4-methyl-pentanamide;N-hydroxy-4-((4-((4-hydroxy-2-butynyl)oxy)phenyl)sulfonyl)-2,2-dimethyl-3-thiomorpholinecarboxamide;MMP-13 siRNA, and mixtures thereof,to a patient in need thereof. 2. The method according to claim 1 wherein said inhibitor is an inhibitor of MMP-1, MMP-7, MMP-13 or MMP-14. 3. The method according to claim 1 wherein said inhibitor is an inhibitor of MMP-13. 4. (canceled) 5. The method according to claim 1 wherein said inhibitor is selected from the following compounds: (2R,3S)-N4-Hydroxy-2-isobutyl-N1-[(2S)-1-(methylamino)-1-oxo-3-phenyl-2-propanyl]-3-[(2-thienylsulfanyl)methyl]succinamide;N-[2,2-dimethyl-1-(methylcarbamoyl)propyl]-2-[hydroxy-(hydroxycarbamoyl)methyl]-4-methyl-pentanamide;N-hydroxy-4-((4-((4-hydroxy-2-butynyl)oxy)phenyl)sulfonyl)-2,2-dimethyl-3-thiomorpholinecarboxamide;MMP-13 siRNA; and mixtures thereof. 6. The method according to claim 1 wherein the pyrimidine-4,6-dicarboxylic acid, bis-(4-fluoro-3-methyl-benzylamide) is an inhibitor of MMP-13. 7. The method according to claim 5 wherein the (2R,3S)-N4-Hydroxy-2-isobutyl-N1-[(2S)-1-(methylamino)-1-oxo-3-phenyl-2-propanyl]-3-[(2-thienylsulfanyl)methyl]succinamide is an inhibitor of MMP-1, MMP-2, MMP-3, MMP-7 or MMP-9. 8. A method for treating smooth muscle diseases comprising administering an effective amount of a metalloprotease inhibitor wherein said inhibitor is selected from the following compounds: pyrimidine-4,6-dicarboxylic acid, bis-(4-fluoro-3-methyl-benzylamide);pyrimidine-4,6-dicarboxylic acid, bis-(3-methyl-benzylamide);pyrimidine-4,6-dicarboxylic acid, bis-(benzylamide);pyrimidine-4,6-dicarboxylic acid bis-[(Pyridin-3-YL-Methyl)-Amide;(2R,3S)-N4-Hydroxy-2-isobutyl-N1-[(2S)-1-(methylamino)-1-oxo-3-phenyl-2-propanyl]-3-[(2-thienylsulfanyl)methyl]succinamide;N-[2,2-dimethyl-1-(methylcarbamoyl)propyl]-2-[hydroxy-(hydroxycarbamoyl)methyl]-4-methyl-pentanamide;N-hydroxy-4-((4-((4-hydroxy-2-butynyl)oxy)phenyl)sulfonyl)-2,2-dimethyl-3-thiomorpholinecarboxamide;MMP-13 siRNA; and mixtures thereof. 9. A pharmaceutical composition comprising at least one metalloprotease inhibitor as described in claim 1 in a therapeutically effective amount and a pharmaceutically acceptable carrier, adjuvant, excipient, or mixtures thereof. 10. The composition according to claim 9, wherein the composition is an injectable formulation, in particular an intraperitoneal injection. 11. The composition according to claim 9, wherein the inhibitor concentration is between 5 nM-7000 nM. 12. The composition according to claim 9, wherein the inhibitor concentration is between 5 nM-240 nM. 13. The composition according to claim 9, wherein the inhibitor concentration is between 5 nM-100 nM. 14. The composition according to claim 9, wherein the inhibitor concentration is between5 nM-50 nM. 15. The composition according to claim 9, wherein the inhibitor concentration is between 8 nM-20 nM. 16. A kit for drug screening for the treatment or diagnosis of Hutchinson-Gilford Progeria Syndrome or for the treatment or diagnosis of vascular ageing diseases or for the treatment or diagnosis of smooth muscle cells diseases, comprising: at least one metalloprotease inhibitor of claim 1;a fluidic system suitable for screening therapeutic drugs; anda Hutchinson-Gilford Progeria Syndrome smooth muscle cell population.
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