Title:
NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
Document Type and Number:
WIPO Patent Application WO/2014/007412
Kind Code:
A1
Abstract:
The present invention relates to a novel compound inhibiting Hsp 90 and to a pharmaceutical composition including same as an active ingredient. Compounds of formula 1 and formula 2 according to the present invention inhibit the accumulation of HIF-1α protein, which is an Hsp90 client protein, by suppressing Hsp90 expression, and effectively inhibit the activity of vascular endothelial growth factor (VEGF). Furthermore, said compounds have low cytotoxicity and can thus be used as an active ingredient for the treatment of diabetic retinopathy and arthritis.
Inventors:
SUH YOUNG-GER (KR)
CHANG DONG-JO (KR)
AN HONGCHAN (KR)
KIM KYU-WON (KR)
KIM YOUNG-MYEONG (KR)
LEE HO-YOUNG (KR)
CHANG DONG-JO (KR)
AN HONGCHAN (KR)
KIM KYU-WON (KR)
KIM YOUNG-MYEONG (KR)
LEE HO-YOUNG (KR)
Application Number:
PCT/KR2012/005309
Publication Date:
January 09, 2014
Filing Date:
July 04, 2012
Export Citation:
Assignee:
SNU R&DB FOUNDATION (KR)
SUH YOUNG-GER (KR)
CHANG DONG-JO (KR)
AN HONGCHAN (KR)
KIM KYU-WON (KR)
KIM YOUNG-MYEONG (KR)
LEE HO-YOUNG (KR)
SUH YOUNG-GER (KR)
CHANG DONG-JO (KR)
AN HONGCHAN (KR)
KIM KYU-WON (KR)
KIM YOUNG-MYEONG (KR)
LEE HO-YOUNG (KR)
International Classes:
C07D493/12; A61K31/366; A61P35/00; C07D493/04
Foreign References:
| US7410998B2 | 2008-08-12 |
Other References:
KIM, W.-Y. ET AL.: "A novel derivative of the natural agent deguelin for cancer chemoprevention and therapy.", CANCER PREVENTION RESEARCH., vol. 1, 2008, pages 577 - 587, XP055170109
GARCIA, J. ET AL.: "Synthesis of deguelin-biotin conjugates and investigation into deguelin's interactions.", BIOORGANIC & MEDICINAL CHEMISTRY., vol. 20, January 2012 (2012-01-01), pages 672 - 680, XP028442303
FANG, N. ET AL.: "Anticancer action of cube insecticide: correlation for rotenoid constituents between inhibition ofNADH: ubiquinone oxidoreductase and induced ornithine decarboxylase activities.", PROC. NATL. ACAD. SCI. USA., vol. 95, 1998, pages 3380 - 3384, XP055170117
GRANADIOS-COVARRUBIAS, E.H. ET AL.: "Protected cyanohydrins in the synthesis of rotenoids: (+-)-munduserone and (+-)-cis-12a-hydroxymunduserone.", J. ORG. CHEM., vol. 74, 2009, pages 5097 - 5099, XP055170109
FANG, Y-T. ET AL.: "Total synthesis of (+-)-glyfavanone by a rigid quaternary ammonium salt.", JOURNAL OF THE CHINESE CHEMICAL SOCIETY., vol. 54, 2007, pages 817 - 822, XP055170374
BAGATELL, R.; WHITESELL, L.: "Altered Hsp90 function in cancer: A unique therapeutic opportunity", MOL. CANCER THER., vol. 3, 2004, pages 1021 - 1030, XP002445055
EUSTACE, B. K.; SAKURAI, T.; STEWART, J. K.; YIMLAMAI, D.; UNGER, C.; ZEHETMEIER, C.; LAIN, B.; TORELLA, C.; HENNING, S. W.; BESTE: "Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness", NAT. CELL BIOL., vol. 6, 2004, pages 507 - 514, XP002492122, DOI: doi:10.1038/ncb1131
ECCLES, S.; MASSEY, A.; RAYNAUD, F.; SHARP, S.; BOX, G.; VALENTI, M.; PATTERSON, L.; DE HAVEN BRANDON, A.; GOWAN, S.; BOXALL, F.: "NVP-AUY922: a heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis", CANCER RES., vol. 68, 2008, pages 2850, XP002609857, DOI: doi:10.1158/0008-5472.CAN-07-5256
CLARK, E.: "A relation between rotenone", DEGUELIN AND TEPHROSIN, vol. 73, 1931, pages 17 - 18
LEE, H.: "Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells", BIOCHEM. PHARMACOL., vol. 68, 2004, pages 1119 - 1124
CABONI, P.; SHERER, T.; ZHANG, N.; TAYLOR, G.; NA, H.; GREENAMYRE, J.; CASIDA, J. ROTENONE: "deguelin, their metabolites, and the rat model of Parkinson's disease", CHEM. RES. TOXICOL, vol. 17, 2004, pages 1540 - 1548
ANZEVENO, P.: "Rotenoid interconversion. Synthesis of deguelin from rotenone", J. ORG. CHEM., vol. 44, 1979, pages 2578 - 2580
See also references of EP 2871187A4
GARCIA, J. ET AL.: "Synthesis of deguelin-biotin conjugates and investigation into deguelin's interactions.", BIOORGANIC & MEDICINAL CHEMISTRY., vol. 20, January 2012 (2012-01-01), pages 672 - 680, XP028442303
FANG, N. ET AL.: "Anticancer action of cube insecticide: correlation for rotenoid constituents between inhibition ofNADH: ubiquinone oxidoreductase and induced ornithine decarboxylase activities.", PROC. NATL. ACAD. SCI. USA., vol. 95, 1998, pages 3380 - 3384, XP055170117
GRANADIOS-COVARRUBIAS, E.H. ET AL.: "Protected cyanohydrins in the synthesis of rotenoids: (+-)-munduserone and (+-)-cis-12a-hydroxymunduserone.", J. ORG. CHEM., vol. 74, 2009, pages 5097 - 5099, XP055170109
FANG, Y-T. ET AL.: "Total synthesis of (+-)-glyfavanone by a rigid quaternary ammonium salt.", JOURNAL OF THE CHINESE CHEMICAL SOCIETY., vol. 54, 2007, pages 817 - 822, XP055170374
BAGATELL, R.; WHITESELL, L.: "Altered Hsp90 function in cancer: A unique therapeutic opportunity", MOL. CANCER THER., vol. 3, 2004, pages 1021 - 1030, XP002445055
EUSTACE, B. K.; SAKURAI, T.; STEWART, J. K.; YIMLAMAI, D.; UNGER, C.; ZEHETMEIER, C.; LAIN, B.; TORELLA, C.; HENNING, S. W.; BESTE: "Functional proteomic screens reveal an essential extracellular role for hsp90 alpha in cancer cell invasiveness", NAT. CELL BIOL., vol. 6, 2004, pages 507 - 514, XP002492122, DOI: doi:10.1038/ncb1131
ECCLES, S.; MASSEY, A.; RAYNAUD, F.; SHARP, S.; BOX, G.; VALENTI, M.; PATTERSON, L.; DE HAVEN BRANDON, A.; GOWAN, S.; BOXALL, F.: "NVP-AUY922: a heat shock protein 90 inhibitor active against xenograft tumor growth, angiogenesis, and metastasis", CANCER RES., vol. 68, 2008, pages 2850, XP002609857, DOI: doi:10.1158/0008-5472.CAN-07-5256
CLARK, E.: "A relation between rotenone", DEGUELIN AND TEPHROSIN, vol. 73, 1931, pages 17 - 18
LEE, H.: "Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells", BIOCHEM. PHARMACOL., vol. 68, 2004, pages 1119 - 1124
CABONI, P.; SHERER, T.; ZHANG, N.; TAYLOR, G.; NA, H.; GREENAMYRE, J.; CASIDA, J. ROTENONE: "deguelin, their metabolites, and the rat model of Parkinson's disease", CHEM. RES. TOXICOL, vol. 17, 2004, pages 1540 - 1548
ANZEVENO, P.: "Rotenoid interconversion. Synthesis of deguelin from rotenone", J. ORG. CHEM., vol. 44, 1979, pages 2578 - 2580
See also references of EP 2871187A4
Attorney, Agent or Firm:
LEE, Won Hee (Yoksam-dong Kangnam-ku, Seoul 135-080, KR)
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