Title:
SATURATED RING-CONDENSED DIHYDROPYRIMIDINONE OR DIHYDROTRIAZINONE COMPOUND, AND PHARMACEUTICAL USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2019/167982
Kind Code:
A1
Abstract:
The present invention pertains to: a saturated ring-condensed dihydropyrimidinone or dihydrotriazinone compound having RORγ antagonist activity or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing same; and a pharmaceutical use thereof. Provided are: a compound of formula [I] or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing same; and a pharmaceutical use thereof. [In the formula, the respective substituent groups are as defined in the description of the present application.]
Inventors:
YOKOTA MASAHIRO (JP)
SEKI NORIYOSHI (JP)
WATANABE EIICHI (JP)
FUJIOKA SHINGO (JP)
SEKI NORIYOSHI (JP)
WATANABE EIICHI (JP)
FUJIOKA SHINGO (JP)
Application Number:
PCT/JP2019/007435
Publication Date:
September 06, 2019
Filing Date:
February 27, 2019
Export Citation:
Assignee:
JAPAN TOBACCO INC (JP)
International Classes:
C07D239/70; A61K31/517; A61K31/519; A61K31/53; A61P3/00; A61P27/02; A61P35/00; A61P37/06; A61P37/08; C07D239/80; C07D253/10; C07D487/04; C07D491/048; C07D491/052
Domestic Patent References:
| WO2016093342A1 | 2016-06-16 |
Other References:
ZIGEUNER, G.; EISENREICH, V.; IMMEL, W.: "Heterocycles. XXVI. Hexahydro-2 (1H)-quinazolines and -thiones = Über Hexahydro-2(1H)-chinazolinone bzw.-thione", MONATSHEFTE FÜR CHEMIE, vol. 101, no. 6, 1970, pages 1745 - 1750, XP009523213, ISSN: 0026-9247, DOI: 10.1007/BF01152088
KOENDERS ET AL.: "Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour necrosis factor and IL-1 in experimental arthritis", ANN. RHEUM. DIS., vol. 65, 2006, pages iii29 - 33
SCHMIDT-WEBER ET AL.: "Thl7 cells in the big picture of immunology", J. ALLERGY CLIN. IMMUNOL., vol. 120, 2007, pages 247 - 54, XP022199073, DOI: 10.1016/j.jaci.2007.06.039
MEISSBURGER ET AL.: "Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma", EMBO MOL. MED., vol. 3, 2011, pages 637 - 51
KELCHTERMANS ET AL.: "Effector mechanisms of interleukin-17 in collagen-induced arthritis in the absence of interferon-y and counteraction by interferon-y", ARTHRITIS RES. THER., vol. 11, no. 4, 2009, pages R122, XP021061277, DOI: 10.1186/ar2787
NAKAE ET AL.: "Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice", J. IMMUNOL., vol. 171, 2003, pages 6173 - 6177
HUEBER ET AL.: "Effects of AIN457, a Fully Human Antibody to Interleukin-17A, on Psoriasis, Rheumatoid Arthritis, and Uveitis", SCI. TRANSL. MED., vol. 2, no. 52, 2010, pages 52ra72
SANFORD ET AL.: "Secukinumab: first global approval", DRUGS, vol. 75, no. 3, 2015, pages 329 - 338, XP009507136, DOI: 10.1007/s40265-015-0359-0
LEPPKES ET AL.: "RORy-Expressing Thl7 Cells Induce MurineChronic Intestinal Inflammation via Redundant Effects of IL-17A and IL-17F", GASTROENTEROLOGY, vol. 136, no. 1, 2009, pages 257 - 267
IVANOV ET AL.: "The Orphan Nuclear Receptor RORyt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells", CELL, vol. 126, no. 6, 2006, pages 1121 - 1133, XP008091324, DOI: 10.1016/j.cell.2006.07.035
STEINMETZ ET AL.: "The Thl7-Defining Transcription Factor RORyt Promotes Glomerulonephritis", J. AM. SOC. NEPHROL., vol. 22, no. 3, 2011, pages 472 - 483
CRISPIN ET AL.: "Interleukin-17-producing T cells in lupus", CURR. OPIN. RHEUMATOL., vol. 22, no. 5, 2010, pages 499 - 503
BAETEN ET AL.: "Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial", LANCET, vol. 382, no. 9906, 2013, pages 1705 - 1713, XP002726555, DOI: 10.1016/S0140-6736(13)61134-4
EMAMAULLEE ET AL.: "Inhibition of Thl7 Cells Regulates Autoimmune Diabetes in NOD Mice", DIABETES, vol. 58, 2009, pages 1302 - 1311, XP055052644, DOI: 10.2337/db08-1113
TILLEY ET AL.: "Retinoid-Related Orphan Receptor γ Controls Immunoglobulin Production and Thl/Th2 Cytokine Balance in the Adaptive Immune Response to Allergen", J. IMMUNOL., vol. 178, 2007, pages 3208 - 3218
"ClinicalTrials.gov information for Clinical Trials Identifier NCT01250171", 4 December 2012, U.S. NATIONAL INSTITUTES OF HEALTH, article "The Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients"
MI ET AL.: "Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-(31-Dependent and -Independent Mechanisms", J. IMMUNOL., vol. 187, 2011, pages 3003 - 3014
"ClinicalTrials.gov information for Clinical Trials Identifier NCT01389973", 2 April 2015, U.S. NATIONAL INSTITUTES OF HEALTH, article "A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid"
FULTON ET AL.: "Attenuation of Acute Graft-versus-Host Disease in the Absence of the Transcription Factor RORyt", J. IMMUNOL., vol. 189, no. 4, 2012, pages 1765 - 1772
BRIAN G FEAGAN ET AL.: "Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study", THE LANCET, vol. 389, no. 10080, 2017, pages 1699 - 1709, XP029988821, DOI: 10.1016/S0140-6736(17)30570-6
EVA HAVRDOVA ET AL.: "Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study", J. NEUROL., vol. 263, no. 7, 2016, pages 1287 - 1295, XP035993925, DOI: 10.1007/s00415-016-8128-x
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02044848", U.S. NATIONAL INSTITUTES OF HEALTH, article "Study of Secukinumab in Patients With Newly-diagnosed Type 1 Diabetes Mellitus"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02594098", U.S. NATIONAL INSTITUTES OF HEALTH, article "Secukinumab for Treatment of Atopic Dermatitis"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02443298", U.S. NATIONAL INSTITUTES OF HEALTH, article "Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02599129", U.S. NATIONAL INSTITUTES OF HEALTH, article "A Study of Secukinumab for the Treatment of Alopecia Areata"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT03137160", U.S. NATIONAL INSTITUTES OF HEALTH, article "An Open-Label, Proof-of-Concept Study of Ixekizumab in the Treatment of Pyoderma Gangrenosum"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02733094", U.S. NATIONAL INSTITUTES OF HEALTH, article "Single-arm Study to Assess a Potential Effect of Anti-IL-17 (Secukinumab) in the Treatment of Pyoderma Gangrenosum"
Q ZHANG ET AL.: "Targeting Thl7-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model", PROSTATE, vol. 77, no. 8, 2017, pages 888 - 899
W SHI ET AL.: "Anti-IL-17 Antibody Improves . Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism", CLIN. DEV. IMMUNOL., vol. 2013, 2013, XP055385426, DOI: 10.1155/2013/253046
R XU ET AL.: "Neutralization of interleukin-17 attenuates high fat diet-induced non-alcoholic fatty liver disease in mice", ACTA BIOCHIM. BIOPHYS. SIN. (SHANGHAI, vol. 45, no. 9, 2013, pages 726 - 733
Y.H. LIAL ET AL.: "Interleukin-17A Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Cardiomyocyte Apoptosis and Neutrophil Infiltration", J. AM. COLL. CARDIOL., vol. 59, no. 4, 2012, pages 420 - 429, XP028444164, DOI: 10.1016/j.jacc.2011.10.863
M.A. SALEH ET AL.: "Inhibition of Interleukin 17-A but not Interleukin-17F Signaling Lowers Blood Pressure and Reduces End-organ Inflammation in Angiotensin II-induced Hypertension", JACC BASIC TRANSL. SCI., vol. 1, no. 7, 2016, pages 606 - 616
N. DUTZAN ET AL.: "A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans", SCI. TRANSL. MED., vol. 10, no. 463, 2018, pages eaat0797
R SPEECKAERT ET AL.: "The many faces of interleukin-17 in inflammatory skin diseases", BR. J. DERMATOL., vol. 175, no. 5, 2016, pages 892 - 901
BERGE ET AL., J. PHARM. SCI., vol. 66, 1977, pages l-19
STAHL ET AL.: "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", 2002, WILEY-VCH
PAULEKUHN ET AL., J. MED. CHEM., vol. 50, 2007, pages 6665 - 6672
F. DIEDERICHP. J. STANG: "Metal-catalyzed Cross-coupling Reactions", 1998, WILEY-VCH
See also references of EP 3760619A4
KOENDERS ET AL.: "Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour necrosis factor and IL-1 in experimental arthritis", ANN. RHEUM. DIS., vol. 65, 2006, pages iii29 - 33
SCHMIDT-WEBER ET AL.: "Thl7 cells in the big picture of immunology", J. ALLERGY CLIN. IMMUNOL., vol. 120, 2007, pages 247 - 54, XP022199073, DOI: 10.1016/j.jaci.2007.06.039
MEISSBURGER ET AL.: "Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma", EMBO MOL. MED., vol. 3, 2011, pages 637 - 51
KELCHTERMANS ET AL.: "Effector mechanisms of interleukin-17 in collagen-induced arthritis in the absence of interferon-y and counteraction by interferon-y", ARTHRITIS RES. THER., vol. 11, no. 4, 2009, pages R122, XP021061277, DOI: 10.1186/ar2787
NAKAE ET AL.: "Suppression of Immune Induction of Collagen-Induced Arthritis in IL-17-Deficient Mice", J. IMMUNOL., vol. 171, 2003, pages 6173 - 6177
HUEBER ET AL.: "Effects of AIN457, a Fully Human Antibody to Interleukin-17A, on Psoriasis, Rheumatoid Arthritis, and Uveitis", SCI. TRANSL. MED., vol. 2, no. 52, 2010, pages 52ra72
SANFORD ET AL.: "Secukinumab: first global approval", DRUGS, vol. 75, no. 3, 2015, pages 329 - 338, XP009507136, DOI: 10.1007/s40265-015-0359-0
LEPPKES ET AL.: "RORy-Expressing Thl7 Cells Induce MurineChronic Intestinal Inflammation via Redundant Effects of IL-17A and IL-17F", GASTROENTEROLOGY, vol. 136, no. 1, 2009, pages 257 - 267
IVANOV ET AL.: "The Orphan Nuclear Receptor RORyt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells", CELL, vol. 126, no. 6, 2006, pages 1121 - 1133, XP008091324, DOI: 10.1016/j.cell.2006.07.035
STEINMETZ ET AL.: "The Thl7-Defining Transcription Factor RORyt Promotes Glomerulonephritis", J. AM. SOC. NEPHROL., vol. 22, no. 3, 2011, pages 472 - 483
CRISPIN ET AL.: "Interleukin-17-producing T cells in lupus", CURR. OPIN. RHEUMATOL., vol. 22, no. 5, 2010, pages 499 - 503
BAETEN ET AL.: "Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial", LANCET, vol. 382, no. 9906, 2013, pages 1705 - 1713, XP002726555, DOI: 10.1016/S0140-6736(13)61134-4
EMAMAULLEE ET AL.: "Inhibition of Thl7 Cells Regulates Autoimmune Diabetes in NOD Mice", DIABETES, vol. 58, 2009, pages 1302 - 1311, XP055052644, DOI: 10.2337/db08-1113
TILLEY ET AL.: "Retinoid-Related Orphan Receptor γ Controls Immunoglobulin Production and Thl/Th2 Cytokine Balance in the Adaptive Immune Response to Allergen", J. IMMUNOL., vol. 178, 2007, pages 3208 - 3218
"ClinicalTrials.gov information for Clinical Trials Identifier NCT01250171", 4 December 2012, U.S. NATIONAL INSTITUTES OF HEALTH, article "The Effects of a Single Intravenous Administration of Secukinumab (AIN457) or Canakinumab (ACZ885) in Dry Eye Patients"
MI ET AL.: "Blocking IL-17A Promotes the Resolution of Pulmonary Inflammation and Fibrosis Via TGF-(31-Dependent and -Independent Mechanisms", J. IMMUNOL., vol. 187, 2011, pages 3003 - 3014
"ClinicalTrials.gov information for Clinical Trials Identifier NCT01389973", 2 April 2015, U.S. NATIONAL INSTITUTES OF HEALTH, article "A Study of Efficacy and Safety of Ustekinumab in Patients With Primary Biliary Cirrhosis (PBC) Who Had an Inadequate Response to Ursodeoxycholic Acid"
FULTON ET AL.: "Attenuation of Acute Graft-versus-Host Disease in the Absence of the Transcription Factor RORyt", J. IMMUNOL., vol. 189, no. 4, 2012, pages 1765 - 1772
BRIAN G FEAGAN ET AL.: "Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double-blind, placebo-controlled phase 2 study", THE LANCET, vol. 389, no. 10080, 2017, pages 1699 - 1709, XP029988821, DOI: 10.1016/S0140-6736(17)30570-6
EVA HAVRDOVA ET AL.: "Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study", J. NEUROL., vol. 263, no. 7, 2016, pages 1287 - 1295, XP035993925, DOI: 10.1007/s00415-016-8128-x
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02044848", U.S. NATIONAL INSTITUTES OF HEALTH, article "Study of Secukinumab in Patients With Newly-diagnosed Type 1 Diabetes Mellitus"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02594098", U.S. NATIONAL INSTITUTES OF HEALTH, article "Secukinumab for Treatment of Atopic Dermatitis"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02443298", U.S. NATIONAL INSTITUTES OF HEALTH, article "Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02599129", U.S. NATIONAL INSTITUTES OF HEALTH, article "A Study of Secukinumab for the Treatment of Alopecia Areata"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT03137160", U.S. NATIONAL INSTITUTES OF HEALTH, article "An Open-Label, Proof-of-Concept Study of Ixekizumab in the Treatment of Pyoderma Gangrenosum"
"ClinicalTrials.gov information for Clinical Trials Identifier NCT02733094", U.S. NATIONAL INSTITUTES OF HEALTH, article "Single-arm Study to Assess a Potential Effect of Anti-IL-17 (Secukinumab) in the Treatment of Pyoderma Gangrenosum"
Q ZHANG ET AL.: "Targeting Thl7-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model", PROSTATE, vol. 77, no. 8, 2017, pages 888 - 899
W SHI ET AL.: "Anti-IL-17 Antibody Improves . Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism", CLIN. DEV. IMMUNOL., vol. 2013, 2013, XP055385426, DOI: 10.1155/2013/253046
R XU ET AL.: "Neutralization of interleukin-17 attenuates high fat diet-induced non-alcoholic fatty liver disease in mice", ACTA BIOCHIM. BIOPHYS. SIN. (SHANGHAI, vol. 45, no. 9, 2013, pages 726 - 733
Y.H. LIAL ET AL.: "Interleukin-17A Contributes to Myocardial Ischemia/Reperfusion Injury by Regulating Cardiomyocyte Apoptosis and Neutrophil Infiltration", J. AM. COLL. CARDIOL., vol. 59, no. 4, 2012, pages 420 - 429, XP028444164, DOI: 10.1016/j.jacc.2011.10.863
M.A. SALEH ET AL.: "Inhibition of Interleukin 17-A but not Interleukin-17F Signaling Lowers Blood Pressure and Reduces End-organ Inflammation in Angiotensin II-induced Hypertension", JACC BASIC TRANSL. SCI., vol. 1, no. 7, 2016, pages 606 - 616
N. DUTZAN ET AL.: "A dysbiotic microbiome triggers TH17 cells to mediate oral mucosal immunopathology in mice and humans", SCI. TRANSL. MED., vol. 10, no. 463, 2018, pages eaat0797
R SPEECKAERT ET AL.: "The many faces of interleukin-17 in inflammatory skin diseases", BR. J. DERMATOL., vol. 175, no. 5, 2016, pages 892 - 901
BERGE ET AL., J. PHARM. SCI., vol. 66, 1977, pages l-19
STAHL ET AL.: "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", 2002, WILEY-VCH
PAULEKUHN ET AL., J. MED. CHEM., vol. 50, 2007, pages 6665 - 6672
F. DIEDERICHP. J. STANG: "Metal-catalyzed Cross-coupling Reactions", 1998, WILEY-VCH
See also references of EP 3760619A4
Attorney, Agent or Firm:
YAMAO, Norihito et al. (JP)
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