Title:
SAFE CHEMICAL UNCOUPLERS FOR THE TREATMENT OF OBESITY
Document Type and Number:
WIPO Patent Application WO2004041256
Kind Code:
A3
Abstract:
This invention relates to chemical uncouplers with a broader safety window making the use of them in treating obesity and, consequently, in the treatment of obesity related dis-eases and conditions such as atherosclerosis, hypertension, diabetes, especially type 2 dia-betes (NIDDM (non-insulin dependent diabetes mellitus)), impaired glucose tolerance, dyslip-idemia, coronary heart disease, gallbladder disease, osteoarthritis and various types of can-cer such as endometrial, breast, prostate and colon cancers and the risk for premature death as well as other conditions, such as diseases and disorders, which conditions are improved by an increase in mitochondrial respiration, more attractive.
Inventors:
HANSEN BIRGIT SEHESTED
TULLIN SOEREN
HANSEN THOMAS KRUSE
COLDING-JOERGENSEN MORTEN
TULLIN SOEREN
HANSEN THOMAS KRUSE
COLDING-JOERGENSEN MORTEN
Application Number:
PCT/DK2003/000742
Publication Date:
September 02, 2004
Filing Date:
October 31, 2003
Export Citation:
Assignee:
NOVO NORDISK AS (DK)
International Classes:
A61K31/166; A61K31/17; A61K31/19; A61K31/216; A61K31/40; A61K31/404; C07D213/70; C07D277/32; C07D295/192; C07D295/26; C07D307/28; C07D307/38; C07D311/16; C07D333/34; (IPC1-7): A61K31/04; A61K31/06; C12Q1/00; C07C205/12; G01N33/50; C12N5/00
Domestic Patent References:
| WO2000006143A1 | 2000-02-10 | |||
| WO2001051923A2 | 2001-07-19 |
Foreign References:
| US5240962A | 1993-08-31 | |||
| GB2284153A | 1995-05-31 | |||
| GB2312375A | 1997-10-29 | |||
| US4673691A | 1987-06-16 | |||
| US20010046664A1 | 2001-11-29 | |||
| US6183948B1 | 2001-02-06 |
Other References:
ROBERT M. DRUMMOND ET AL: "Release of Ca2+ from the sarcoplasmic reticulum increases mitochondrial (Ca2+) in rat pulmonary artery smooth muscle cells", JOURNAL OF PHYSIOLOGY, vol. 516, no. 1, 1999, pages 139 - 147, XP002271195
ROLF ALTENBURGER ET AL: "Predictability of the toxicity of multiple chemical mixtures to vibrio fischeri: mixtures composed of similarly acting chemicals", ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, vol. 19, no. 9, 2000, pages 2341 - 2347, XP002271196
WOO L W ET AL: "Steroidal and nonsteroidal sulfamates as potent inhibitors of steroid sulfatase.", JOURNAL OF MEDICINAL CHEMISTRY. UNITED STATES 26 MAR 1998, vol. 41, no. 7, 26 March 1998 (1998-03-26), pages 1068 - 1083, XP002271197, ISSN: 0022-2623
HUANG SHU-GUI: "Development of a high throughput screening assay for mitochondrial membrane potential in living cells.", JOURNAL OF BIOMOLECULAR SCREENING: THE OFFICIAL JOURNAL OF THE SOCIETY FOR BIOMOLECULAR SCREENING. UNITED STATES AUG 2002, vol. 7, no. 4, August 2002 (2002-08-01), pages 383 - 389, XP002271198, ISSN: 1087-0571
TERADA H ET AL: "Structural requirements of salicylanilides for uncoupling activity in mitochondria: quantitative analysis of structure-uncoupling relationships.", BIOCHIMICA ET BIOPHYSICA ACTA. NETHERLANDS 7 DEC 1988, vol. 936, no. 3, 7 December 1988 (1988-12-07), pages 504 - 512, XP002271199, ISSN: 0006-3002
SABU KURUVILLA ET AL: "Effects of Minimally Toxic Levels of Carbonyl Cyanide P-(Trifluoromethoxy) Phenylhydrazone (FCCP), Elucidated through differential Gene Expression with Biochemical and Morphological Correlations", TOXICOLOGICAL SCIENCES, vol. 73, 2003, pages 348 - 361, XP002271200
ROLF ALTENBURGER ET AL: "Predictability of the toxicity of multiple chemical mixtures to vibrio fischeri: mixtures composed of similarly acting chemicals", ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY, vol. 19, no. 9, 2000, pages 2341 - 2347, XP002271196
WOO L W ET AL: "Steroidal and nonsteroidal sulfamates as potent inhibitors of steroid sulfatase.", JOURNAL OF MEDICINAL CHEMISTRY. UNITED STATES 26 MAR 1998, vol. 41, no. 7, 26 March 1998 (1998-03-26), pages 1068 - 1083, XP002271197, ISSN: 0022-2623
HUANG SHU-GUI: "Development of a high throughput screening assay for mitochondrial membrane potential in living cells.", JOURNAL OF BIOMOLECULAR SCREENING: THE OFFICIAL JOURNAL OF THE SOCIETY FOR BIOMOLECULAR SCREENING. UNITED STATES AUG 2002, vol. 7, no. 4, August 2002 (2002-08-01), pages 383 - 389, XP002271198, ISSN: 1087-0571
TERADA H ET AL: "Structural requirements of salicylanilides for uncoupling activity in mitochondria: quantitative analysis of structure-uncoupling relationships.", BIOCHIMICA ET BIOPHYSICA ACTA. NETHERLANDS 7 DEC 1988, vol. 936, no. 3, 7 December 1988 (1988-12-07), pages 504 - 512, XP002271199, ISSN: 0006-3002
SABU KURUVILLA ET AL: "Effects of Minimally Toxic Levels of Carbonyl Cyanide P-(Trifluoromethoxy) Phenylhydrazone (FCCP), Elucidated through differential Gene Expression with Biochemical and Morphological Correlations", TOXICOLOGICAL SCIENCES, vol. 73, 2003, pages 348 - 361, XP002271200
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