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New combination of anti-MADCAM antibody and antifibrotic caspase inhibitor to treat liver fibrosis

A protease inhibitor and anti-fibrosis technology, applied in the direction of antibodies, anti-inflammatory agents, drug combinations, etc., can solve problems such as unmet medical needs

Inactive Publication Date: 2008-07-09
PFIZER INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Have a serious unmet medical need

Method used

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  • New combination of anti-MADCAM antibody and antifibrotic caspase inhibitor to treat liver fibrosis
  • New combination of anti-MADCAM antibody and antifibrotic caspase inhibitor to treat liver fibrosis
  • New combination of anti-MADCAM antibody and antifibrotic caspase inhibitor to treat liver fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0077] The combined anti-fibrotic agent of the present invention is preferably a protease inhibitor, more preferably a caspase inhibitor, further preferably a compound of formula I, or a pharmaceutically acceptable salt thereof

[0078]

[0079] Formula I

[0080] in,

[0081] A is a natural or unnatural amino acid of formula IIa-i:

[0082]

[0083] B is hydrogen atom, deuterium atom, alkyl, cycloalkyl, phenyl, substituted phenyl, naphthyl, substituted naphthyl, 2-benzoxazolyl, substituted 2-oxazolyl, (CH 2 ) n -Cycloalkyl, (CH 2 ) n -Phenyl, (CH 2 ) n -(substituted phenyl), (CH 2 ) n -(1 or 2-naphthyl), (CH 2 ) n -(substituted 1 or 2-naphthyl), (CH 2 ) n -(heteroaryl), (CH 2 ) n -(substituted heteroaryl), halomethyl, CO 2 R 12 、CONR 13 R 14 、CH 2 ZR 15 、CH 2 OCO (aryl), CH 2 OCO (heteroaryl) or CH 2 OPO(R 16 )R 17 , wherein Z is an oxygen or sulfur atom, or B is a group of formula IIIa-c:

[0084]

[0085] R 1 is al...

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Abstract

The present invention relates to novel combinations of anti-MAdCAM antibodies and anti-fibrotic agents such as protease inhibitors, preferably caspase inhibitors. The invention also relates to pharmaceutical compositions comprising the combination of the invention, and the use of the combination in the treatment of liver fibrosis.

Description

technical field [0001] The present invention relates to novel combinations of anti-MAdCAM antibodies and anti-fibrotic agents such as protease inhibitors, preferably caspase inhibitors. The invention also relates to pharmaceutical compositions comprising the combination of the invention, and the use of the combination in the treatment of liver fibrosis. Background technique [0002] Chronic liver disease causes more than 1.4 million deaths per year (WHO, World Health Report 2004) and is one of the top ten disease-related causes of death in the United States (CDC, National Center for Health Statistics, 2004). Hepatic fibrosis is a consequence of persistent hepatitis and, if uncontrolled, has serious long-term consequences for patient morbidity and mortality. [0003] Liver fibrosis is one of the processes that occurs when the liver is damaged. The cause of this damage can be, for example, viral activity (e.g. chronic hepatitis B or C) or other liver infections (e.g. parasit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K31/33A61K31/16A61P29/00
CPCA61K39/39541A61K45/06A61P1/16A61P29/00A61P43/00Y02A50/30A61K2300/00A61K39/395A61K31/16A61K31/33
Inventor G·C·伯吉斯R·凯丽
Owner PFIZER INC