Title:
PREVENTIVES/REMEDIES FOR LIVER DISEASES
Document Type and Number:
WIPO Patent Application WO/2000/064478
Kind Code:
A1
Abstract:
Preventives/remedies for liver diseases which contain compounds having an Rho kinase inhibitory activity; and liver astrocyte activation inhibitors. Because of having excellent effects of inhibiting the activation of liver astrocytes, preventing the fibrosis of liver tissues, etc., compounds having an Rho kinase inhibitory activity (for example, (+)- trans-4-(1-aminoethyl)-1-(4-pyridylcarbamoyl) cyclohexane) are useful in preventing and treating various liver diseases such as hepatitis, hepatic fibrosis, liver cirrhosis and liver cancer.
Inventors:
NAKAMUTA MAKOTO (JP)
NAWATA HAJIME (JP)
UEHATA MASAYOSHI (JP)
NAWATA HAJIME (JP)
UEHATA MASAYOSHI (JP)
Application Number:
PCT/JP2000/002797
Publication Date:
November 02, 2000
Filing Date:
April 27, 2000
Export Citation:
Assignee:
WELFIDE CORP (JP)
NAKAMUTA MAKOTO (JP)
NAWATA HAJIME (JP)
UEHATA MASAYOSHI (JP)
NAKAMUTA MAKOTO (JP)
NAWATA HAJIME (JP)
UEHATA MASAYOSHI (JP)
International Classes:
A61K31/16; A61K31/437; A61K31/44; A61K31/4409; A61P1/16; A61P29/00; A61P35/00; C07D213/75; C07D471/04; (IPC1-7): A61K45/00; A61K31/27; A61K31/415; A61K31/437; A61K31/44; A61K31/4409; A61K31/443; A61K31/4433; A61K31/4439; A61K31/445; A61K31/4545; A61K31/455; A61K31/501; A61K31/505; A61K31/519; A61P1/16; A61P29/00; A61P35/00
Domestic Patent References:
| WO1998006433A1 | 1998-02-19 | |||
| WO1998006433A1 | 1998-02-19 | |||
| WO1995028387A1 | 1995-10-26 | |||
| WO1997023222A1 | 1997-07-03 | |||
| WO1997028130A1 | 1997-08-07 |
Foreign References:
| JPH10113187A | 1998-05-06 | |||
| JPH10201480A | 1998-08-04 | |||
| JPS63185921A | 1988-08-01 | |||
| JPH0597834A | 1993-04-20 | |||
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| JPH03218356A | 1991-09-25 | |||
| JPH04273821A | 1992-09-30 | |||
| JPH05194401A | 1993-08-03 | |||
| JPH0641080A | 1994-02-15 | |||
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| JPH0680569A | 1994-03-22 | |||
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| JPH09227381A | 1997-09-02 | |||
| JPH1045598A | 1998-02-17 | |||
| JPH1087491A | 1998-04-07 |
Other References:
YEE H.F. JR.: "Rho directs activation-associated changes in rat hepatic stellate cell morphology via regulation of the actin cytoskelton", HEPATOLOGY,, vol. 28, no. 3, 1998, pages 843 - 850, XP002929559
ITOH K. ET AL.: "An essential part for Rho-associated kinase in the transcellular invasion of tumor cells", NATURE MEDICINE,, vol. 5, no. 2, February 1999 (1999-02-01), pages 221 - 225, XP002929607
KAWADA N. ET AL.: "ROCK inhibitor Y-27632 attenuates stellate cell contraction and portal pressure increase induction by endothelin-1", BIOCHEM. BIOPHYS. RES. COMMUN.,, vol. 266, 1999, pages 296 - 300, XP002929608
GENDA T. ET AL.: "Cell motility mediated by Rho and Rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma", HEPATOLOGY,, vol. 30, 1999, pages 1027 - 1036, XP002929609
KATO M. ET AL.: "Role of Rho small GTP binding protein in the regulation of actin cytoskelton in hepatic stellate cells", J. HEPATOLOGY,, vol. 31, 1999, pages 91 - 99, XP002929610
SHIMIZU, I., GUT, vol. 44, no. 1, 1999, pages 127 - 136
NAUNYN- SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, vol. 385, no. 1, 1998, pages R219
NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, vol. 385, no. 1, 1998, pages R219
LEUNG, T. ET AL., J. BIOL. CHEM., vol. 270, 1995, pages 29051 - 29054
ISHIZAKI, T. ET AL., THE EMBO J., vol. 15, no. 8, 1996, pages 1885 - 1893
FRIEDMAN S.L ET AL., PROC NATL ACAD SCI USA, vol. 82, 1985, pages 8681 - 8685
MOSHAGE H ET AL., HEPATOLOGY, vol. 12, 1990, pages 511 - 518
MIZOBUCHI M ET AL., J HEPATOL, vol. 29, 1998, pages 933 - 943
ITOH K. ET AL.: "An essential part for Rho-associated kinase in the transcellular invasion of tumor cells", NATURE MEDICINE,, vol. 5, no. 2, February 1999 (1999-02-01), pages 221 - 225, XP002929607
KAWADA N. ET AL.: "ROCK inhibitor Y-27632 attenuates stellate cell contraction and portal pressure increase induction by endothelin-1", BIOCHEM. BIOPHYS. RES. COMMUN.,, vol. 266, 1999, pages 296 - 300, XP002929608
GENDA T. ET AL.: "Cell motility mediated by Rho and Rho-associated protein kinase plays a critical role in intrahepatic metastasis of human hepatocellular carcinoma", HEPATOLOGY,, vol. 30, 1999, pages 1027 - 1036, XP002929609
KATO M. ET AL.: "Role of Rho small GTP binding protein in the regulation of actin cytoskelton in hepatic stellate cells", J. HEPATOLOGY,, vol. 31, 1999, pages 91 - 99, XP002929610
SHIMIZU, I., GUT, vol. 44, no. 1, 1999, pages 127 - 136
NAUNYN- SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, vol. 385, no. 1, 1998, pages R219
NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, vol. 385, no. 1, 1998, pages R219
LEUNG, T. ET AL., J. BIOL. CHEM., vol. 270, 1995, pages 29051 - 29054
ISHIZAKI, T. ET AL., THE EMBO J., vol. 15, no. 8, 1996, pages 1885 - 1893
FRIEDMAN S.L ET AL., PROC NATL ACAD SCI USA, vol. 82, 1985, pages 8681 - 8685
MOSHAGE H ET AL., HEPATOLOGY, vol. 12, 1990, pages 511 - 518
MIZOBUCHI M ET AL., J HEPATOL, vol. 29, 1998, pages 933 - 943
Attorney, Agent or Firm:
Takashima, Hajime (Fushimimachi 4-chome Chuo-ku Osaka-shi, Osaka, JP)
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