Title:
PYRAZOLE-AMIDE COMPOUND AND MEDICINAL USES THEREFOR
Document Type and Number:
WIPO Patent Application WO/2014/142290
Kind Code:
A1
Abstract:
Provided is a compound as represented by formula [I] [in which n indicates 1 or 2], formula [II] or [IIh], or formula [III], or a pharmaceutically acceptable salt thereof. Also provided are medicinal uses for the compound or the salt thereof.
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Inventors:
MOTOMURA TAKAHISA (JP)
SHOMI GAKUJUN (JP)
SHOMI GAKUJUN (JP)
Application Number:
PCT/JP2014/056825
Publication Date:
September 18, 2014
Filing Date:
March 14, 2014
Export Citation:
Assignee:
JAPAN TOBACCO INC (JP)
International Classes:
C07D231/12; A61K31/415; A61P3/00; A61P3/04; A61P3/10; A61P9/04; A61P9/10; A61P11/00; A61P13/12; A61P25/00; A61P27/02; A61P27/12; A61P43/00
Domestic Patent References:
| WO2010041748A1 | 2010-04-15 | |||
| WO2010123016A1 | 2010-10-28 | |||
| WO2003011844A2 | 2003-02-13 | |||
| WO2010041748A1 | 2010-04-15 |
Other References:
KARPOV,V.M. ET AL.: "SKELETAL TRANSFORMATIONS OF PERFLUORO-1-PHENYLINDAN UNDER THE ACTION OF ANTIMONYPENTAFLUORIDE", JOURNAL OF FLUORINE CHEMISTRY, vol. 107, no. 11, 2001, pages 53 - 57, XP004228143
REED LJ; HACKERT ML.: "Structure-function relationships in dihydrolipoamide acyltransferases", J BIOL CHEM., vol. 265, no. 16, 5 June 1990 (1990-06-05), pages 8971 - 4
PATEL MS; ROCHE TE.: "Molecular biology and biochemistry of pyruvate dehydrogenase complexes", FASEB J., vol. 4, no. 14, November 1990 (1990-11-01), pages 3224 - 33
SUGDEN MC; HOLNESS MJ.: "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs", AM J PHYSIOL ENDOCRINOL METAB., vol. 284, no. 5, May 2003 (2003-05-01), pages E855 - 62, XP008101778, DOI: doi:10.1152/ajpendo.00526.2002
BOWKER-KINLEY MM; DAVIS WI; WU P; HARRIS RA; POPOV KM.: "Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex", BIOCHEM J., vol. 329, 1 January 1998 (1998-01-01), pages 191 - 6
KIM JW; TCHERNYSHYOV I; SEMENZA GL; DANG CV.: "HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia", CELL METAB., vol. 3, no. 3, March 2006 (2006-03-01), pages 177 - 85
MORINO K; PETERSEN KF; DUFOUR S; BEFROY D; FRATTINI J; SHATZKES N ET AL.: "Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents", J CLIN INVEST., vol. 115, no. 12, December 2005 (2005-12-01), pages 3587 - 93
CATERSON ID; FULLER SJ; RANDLE PJ.: "Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats", BIOCHEM J., vol. 208, no. 1, 15 October 1982 (1982-10-15), pages 53 - 60
BODEN G; CHEN X; STEIN TP.: "Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus", AM J PHYSIOL ENDOCRINOL METAB., vol. 280, no. 1, January 2001 (2001-01-01), pages E23 - 30
SHANGRAW RE; FISHER DM.: "Pharmacokinetics and pharmacodynamics of dichloroacetate in patients with cirrhosis", CLIN PHARMACOL THER., vol. 66, no. 4, October 1999 (1999-10-01), pages 380 - 90
STACPOOLE PW; MOORE GW; KORNHAUSER DM.: "Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia", N ENGL J MED., vol. 298, no. 10, 9 March 1978 (1978-03-09), pages 526 - 30
MAYERS RM; LEIGHTON B; KILGOUR E.: "PDH kinase inhibitors: a novel therapy for Type II diabetes?", BIOCHEM SOC TRANS., vol. 33, April 2005 (2005-04-01), pages 367 - 70, XP003021543, DOI: doi:10.1042/BST0330367
JEOUNG NH; RAHIMI Y; WU P; LEE WN; HARRIS RA.: "Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice", BIOCHEM J., vol. 443, no. 3, 1 May 2012 (2012-05-01), pages 829 - 39
ZHOU YP; BERGGREN PO; GRILL V.: "A fatty acid-induced decrease in pyruvate dehydrogenase activity is an important determinant of beta-cell dysfunction in the obese diabetic db/db mouse", DIABETES, vol. 45, no. 5, May 1996 (1996-05-01), pages 580 - 6
XU J; HAN J; EPSTEIN PN; LIU YQ.: "Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets", BIOCHEM BIOPHYS RES COMMUN., vol. 344, no. 3, 9 June 2006 (2006-06-09), pages 827 - 33, XP024924968, DOI: doi:10.1016/j.bbrc.2006.03.211
"Benfotiamine", MONOGRAPH. ALTERN MED REV., vol. 11, no. 3, September 2006 (2006-09-01), pages 238 - 42
VALLIANOU N; EVANGELOPOULOS A; KOUTALAS P.: "Alpha-lipoic Acid and diabetic neuropathy", REV DIABET STUD., vol. 6, no. 4, 2009, pages 230 - 6
USSHER JR; LOPASCHUK GD.: "The malonyl CoA axis as a potential target for treating ischaemic heart disease", CARDIOVASC RES., vol. 79, no. 2, 15 July 2008 (2008-07-15), pages 259 - 68
WARGOVICH TJ; MACDONALD RG; HILL JA; FELDMAN RL; STACPOOLE PW; PEPINE CJ.: "Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease", AM J CARDIOL., vol. 61, no. 1, 1 January 1988 (1988-01-01), pages 65 - 70, XP023276043, DOI: doi:10.1016/0002-9149(88)91306-9
TANIGUCHI M; WILSON C; HUNTER CA; PEHOWICH DJ; CLANACHAN AS; LOPASCHUK GD.: "Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak", AM J PHYSIOL HEART CIRC PHYSIOL., vol. 280, no. 4, April 2001 (2001-04-01), pages H1762 - 9
STACPOOLE PW; NAGARAJA NV; HUTSON AD.: "Efficacy of dichloroacetate as a lactate-lowering drug", J CLIN PHARMACOL., vol. 43, no. 7, July 2003 (2003-07-01), pages 683 - 91
BONNET S; ARCHER SL; ALLALUNIS-TURNER J; HAROMY A; BEAULIEU C; THOMPSON R ET AL.: "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth", CANCER CELL, vol. 11, no. 1, January 2007 (2007-01-01), pages 37 - 51, XP009133827, DOI: doi:10.1016/j.ccr.2006.10.020
MCMURTRY MS; BONNET S; WU X; DYCK JR; HAROMY A; HASHIMOTO K ET AL.: "Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis", CIRC RES., vol. 95, no. 8, 15 October 2004 (2004-10-15), pages 830 - 40, XP003001198
SAXENA U.: "Bioenergetics breakdown in Alzheimer's disease: targets for new therapies", INT J PHYSIOL PATHOPHYSIOL PHARMACOL., vol. 3, no. 2, 2011, pages 133 - 9
STACPOOLE PW.: "The pyruvate dehydrogenase complex as a therapeutic target for age-related diseases", AGING CELL, vol. 11, no. 3, June 2012 (2012-06-01), pages 371 - 7
MARANGOS PJ; TURKEL CC; DZIEWANOWSKA ZE; FOX AW.: "Dichloroacetate and cerebral ischaemia therapeutics", EXPERT OPIN INVESTIG DRUGS., vol. 8, no. 4, April 1999 (1999-04-01), pages 373 - 82
CALVERT LD; SHELLEY R; SINGH SJ; GREENHAFF PL; BANKART J; MORGAN MD ET AL.: "Dichloroacetate enhances performance and reduces blood lactate during maximal cycle exercise in chronic obstructive pulmonary disease", AM J RESPIR CRIT CARE MED., vol. 177, no. 10, 15 May 2008 (2008-05-15), pages 1090 - 4
FLAVIN DF.: "Non-Hodgkin's Lymphoma Reversal with Dichloroacetate", J ONCOL. HINDAWI PUBLISHING CORPORATION JOURNAL OF ONCOLOGY, vol. 2010, pages 4
See also references of EP 2975028A4
REED LJ; HACKERT ML.: "Structure-function relationships in dihydrolipoamide acyltransferases", J BIOL CHEM., vol. 265, no. 16, 5 June 1990 (1990-06-05), pages 8971 - 4
PATEL MS; ROCHE TE.: "Molecular biology and biochemistry of pyruvate dehydrogenase complexes", FASEB J., vol. 4, no. 14, November 1990 (1990-11-01), pages 3224 - 33
SUGDEN MC; HOLNESS MJ.: "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs", AM J PHYSIOL ENDOCRINOL METAB., vol. 284, no. 5, May 2003 (2003-05-01), pages E855 - 62, XP008101778, DOI: doi:10.1152/ajpendo.00526.2002
BOWKER-KINLEY MM; DAVIS WI; WU P; HARRIS RA; POPOV KM.: "Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex", BIOCHEM J., vol. 329, 1 January 1998 (1998-01-01), pages 191 - 6
KIM JW; TCHERNYSHYOV I; SEMENZA GL; DANG CV.: "HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia", CELL METAB., vol. 3, no. 3, March 2006 (2006-03-01), pages 177 - 85
MORINO K; PETERSEN KF; DUFOUR S; BEFROY D; FRATTINI J; SHATZKES N ET AL.: "Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents", J CLIN INVEST., vol. 115, no. 12, December 2005 (2005-12-01), pages 3587 - 93
CATERSON ID; FULLER SJ; RANDLE PJ.: "Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats", BIOCHEM J., vol. 208, no. 1, 15 October 1982 (1982-10-15), pages 53 - 60
BODEN G; CHEN X; STEIN TP.: "Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus", AM J PHYSIOL ENDOCRINOL METAB., vol. 280, no. 1, January 2001 (2001-01-01), pages E23 - 30
SHANGRAW RE; FISHER DM.: "Pharmacokinetics and pharmacodynamics of dichloroacetate in patients with cirrhosis", CLIN PHARMACOL THER., vol. 66, no. 4, October 1999 (1999-10-01), pages 380 - 90
STACPOOLE PW; MOORE GW; KORNHAUSER DM.: "Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia", N ENGL J MED., vol. 298, no. 10, 9 March 1978 (1978-03-09), pages 526 - 30
MAYERS RM; LEIGHTON B; KILGOUR E.: "PDH kinase inhibitors: a novel therapy for Type II diabetes?", BIOCHEM SOC TRANS., vol. 33, April 2005 (2005-04-01), pages 367 - 70, XP003021543, DOI: doi:10.1042/BST0330367
JEOUNG NH; RAHIMI Y; WU P; LEE WN; HARRIS RA.: "Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice", BIOCHEM J., vol. 443, no. 3, 1 May 2012 (2012-05-01), pages 829 - 39
ZHOU YP; BERGGREN PO; GRILL V.: "A fatty acid-induced decrease in pyruvate dehydrogenase activity is an important determinant of beta-cell dysfunction in the obese diabetic db/db mouse", DIABETES, vol. 45, no. 5, May 1996 (1996-05-01), pages 580 - 6
XU J; HAN J; EPSTEIN PN; LIU YQ.: "Regulation of PDK mRNA by high fatty acid and glucose in pancreatic islets", BIOCHEM BIOPHYS RES COMMUN., vol. 344, no. 3, 9 June 2006 (2006-06-09), pages 827 - 33, XP024924968, DOI: doi:10.1016/j.bbrc.2006.03.211
"Benfotiamine", MONOGRAPH. ALTERN MED REV., vol. 11, no. 3, September 2006 (2006-09-01), pages 238 - 42
VALLIANOU N; EVANGELOPOULOS A; KOUTALAS P.: "Alpha-lipoic Acid and diabetic neuropathy", REV DIABET STUD., vol. 6, no. 4, 2009, pages 230 - 6
USSHER JR; LOPASCHUK GD.: "The malonyl CoA axis as a potential target for treating ischaemic heart disease", CARDIOVASC RES., vol. 79, no. 2, 15 July 2008 (2008-07-15), pages 259 - 68
WARGOVICH TJ; MACDONALD RG; HILL JA; FELDMAN RL; STACPOOLE PW; PEPINE CJ.: "Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease", AM J CARDIOL., vol. 61, no. 1, 1 January 1988 (1988-01-01), pages 65 - 70, XP023276043, DOI: doi:10.1016/0002-9149(88)91306-9
TANIGUCHI M; WILSON C; HUNTER CA; PEHOWICH DJ; CLANACHAN AS; LOPASCHUK GD.: "Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak", AM J PHYSIOL HEART CIRC PHYSIOL., vol. 280, no. 4, April 2001 (2001-04-01), pages H1762 - 9
STACPOOLE PW; NAGARAJA NV; HUTSON AD.: "Efficacy of dichloroacetate as a lactate-lowering drug", J CLIN PHARMACOL., vol. 43, no. 7, July 2003 (2003-07-01), pages 683 - 91
BONNET S; ARCHER SL; ALLALUNIS-TURNER J; HAROMY A; BEAULIEU C; THOMPSON R ET AL.: "A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth", CANCER CELL, vol. 11, no. 1, January 2007 (2007-01-01), pages 37 - 51, XP009133827, DOI: doi:10.1016/j.ccr.2006.10.020
MCMURTRY MS; BONNET S; WU X; DYCK JR; HAROMY A; HASHIMOTO K ET AL.: "Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis", CIRC RES., vol. 95, no. 8, 15 October 2004 (2004-10-15), pages 830 - 40, XP003001198
SAXENA U.: "Bioenergetics breakdown in Alzheimer's disease: targets for new therapies", INT J PHYSIOL PATHOPHYSIOL PHARMACOL., vol. 3, no. 2, 2011, pages 133 - 9
STACPOOLE PW.: "The pyruvate dehydrogenase complex as a therapeutic target for age-related diseases", AGING CELL, vol. 11, no. 3, June 2012 (2012-06-01), pages 371 - 7
MARANGOS PJ; TURKEL CC; DZIEWANOWSKA ZE; FOX AW.: "Dichloroacetate and cerebral ischaemia therapeutics", EXPERT OPIN INVESTIG DRUGS., vol. 8, no. 4, April 1999 (1999-04-01), pages 373 - 82
CALVERT LD; SHELLEY R; SINGH SJ; GREENHAFF PL; BANKART J; MORGAN MD ET AL.: "Dichloroacetate enhances performance and reduces blood lactate during maximal cycle exercise in chronic obstructive pulmonary disease", AM J RESPIR CRIT CARE MED., vol. 177, no. 10, 15 May 2008 (2008-05-15), pages 1090 - 4
FLAVIN DF.: "Non-Hodgkin's Lymphoma Reversal with Dichloroacetate", J ONCOL. HINDAWI PUBLISHING CORPORATION JOURNAL OF ONCOLOGY, vol. 2010, pages 4
See also references of EP 2975028A4
Attorney, Agent or Firm:
TAKASHIMA, HAJIME (JP)
Takashima 1 (JP)
Takashima 1 (JP)
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