Title:
2-((1-(6-METHYL-4-OXO-3,4-DIHYDROQUINAZOLIN-8-YL)ETHYL)AMINO)BENZOIC ACID DERIVATIVES AND SIMILAR COMPOUNDS AS PI3K INHIBITORS FOR THE TREATMENT OF E.G. CANCER
Document Type and Number:
WIPO Patent Application WO/2024/000401
Kind Code:
A1
Abstract:
The present invention relates to compounds of formula (I) preferred compounds are e.g. 2-((l-(4-oxo-3,4-dihydroquinazolin-8-yl)ethyl)amino)benzoic acid derivatives of formula (ll-A) an exemplary compound is e.g. 2-((l-(2-(isoindolin-2-yl)-6-methyl-4-oxo-3, 4-dihydroquinazolin-8-yl)ethyl)amino)benzoic acid (example 1) The present compounds are PI3K inhibitors for the treatment of cancer, CLOVES syndrome (congenital lipomatous overgrowth, syndrome) or PIK3CA-related overgrowth syndrome (PROS). Results of biological assays are provided.
Inventors:
WANG KAILIANG (CN)
ZHONG WENGE (CN)
WANG ZHENGLIN (CN)
FENG TENG (CN)
WU TIANLUN (CN)
HUA XIN (CN)
ZHONG WENGE (CN)
WANG ZHENGLIN (CN)
FENG TENG (CN)
WU TIANLUN (CN)
HUA XIN (CN)
Application Number:
PCT/CN2022/102810
Publication Date:
January 04, 2024
Filing Date:
June 30, 2022
Export Citation:
Assignee:
QILU REGOR THERAPEUTICS INC (CN)
WANG KAILIANG (CN)
ZHONG WENGE (CN)
WANG ZHENGLIN (CN)
FENG TENG (CN)
WU TIANLUN (CN)
HUA XIN (CN)
WANG KAILIANG (CN)
ZHONG WENGE (CN)
WANG ZHENGLIN (CN)
FENG TENG (CN)
WU TIANLUN (CN)
HUA XIN (CN)
International Classes:
C07D403/04; A61P35/00; A61P35/02; A61P35/04; A61P43/00; C07D239/90; C07D401/04; C07D401/14; C07D405/14
Other References:
YANG HUARONG ET AL: "Design, synthesis, and biological evaluation of novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives as potential anticancer agents via PI3K inhibition", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 46, no. 116346, 8 August 2021 (2021-08-08) - 2021, pages 1 - 11, XP086796645, ISSN: 0968-0896, DOI: 10.1016/J.BMC.2021.116346
PENG WEI ET AL: "Discovery of 2-(2-aminopyrimidin-5-yl)-4-morpholino-N-(pyridin-3-yl)quinazolin-7-amines as novel PI3K/mTOR inhibitors and anticancer agents", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 108, 2 December 2015 (2015-12-02), pages 644 - 654, XP029383491, ISSN: 0223-5234, DOI: 10.1016/J.EJMECH.2015.11.038
GONCALVES MDHOPKINS BDCANTIEY LC: "Phosphatidylinositoi 3-Kinase, Growth Disorders", CANCER. N ENGL J MED., vol. 379, no. 21, 22 November 2018 (2018-11-22), pages 2052 - 2062
GRAUPERA ET AL., NATURE, vol. 453, 2008, pages 662 - 6
BUSAIDY NL ET AL.: "Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt- mTOR pathway", J. CLIN. ONCOL., vol. 30, 2012, pages 2919 - 28, XP055341230, DOI: 10.1200/JCO.2011.39.7356
BLOUIN M-J ET AL.: "Abstract 4615: the hyperinsulinemia caused by PI3K inhibitors attenuates their antineoplastic efficacy, but can be minimized by co administration of metformin", CANCER RES, vol. 73, 2013, pages 4615
OKKENHAUG KGRAUPERA MVANHAESEBROECK B: "Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis", IMMUNOTHERAPY. CANCER DISCOV., vol. 6, no. 10, October 2016 (2016-10-01), pages 1090 - 1105
ARIELLA B. HANKER ET AL.: "Challenges for the clinical development of PI3K inhibitors: Strategies to improve their impact in solid tumors", CANCER DISCOV, vol. 9, no. 4, April 2019 (2019-04-01), pages 482 - 491
S. M. BERGE ET AL.: "describes pharmacologically acceptable salts", J. PHARM. SCI., vol. 66, 1977, pages 1 - 19
SMITH, ROGER M.: "Chromatographic Science Series", vol. 75, 1998, LOUGHBOROUGH UNIVERSITY, pages: 223 - 249
FINNINMORGAN, J. PHARM. SCI., vol. 88, 1999, pages 955 - 958
HOOVER, JOHN E.: "Remington's Pharmaceutical Sciences", 1975, MACK PUBLISHING CO.
"Pharmaceutical Dosage Forms", 1980, MARCEL DECKER
"Handbook of Pharmaceutical Excipients", 1999, AMERICAN PHARMACEUTICAL ASSOCIATION
GOODMANGILMAN: "Comprehensive Organic Transformations: A Guide to Functional Group Preparations", 1991, JOHN WILEY AND SONS
PENG WEI ET AL: "Discovery of 2-(2-aminopyrimidin-5-yl)-4-morpholino-N-(pyridin-3-yl)quinazolin-7-amines as novel PI3K/mTOR inhibitors and anticancer agents", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 108, 2 December 2015 (2015-12-02), pages 644 - 654, XP029383491, ISSN: 0223-5234, DOI: 10.1016/J.EJMECH.2015.11.038
GONCALVES MDHOPKINS BDCANTIEY LC: "Phosphatidylinositoi 3-Kinase, Growth Disorders", CANCER. N ENGL J MED., vol. 379, no. 21, 22 November 2018 (2018-11-22), pages 2052 - 2062
GRAUPERA ET AL., NATURE, vol. 453, 2008, pages 662 - 6
BUSAIDY NL ET AL.: "Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt- mTOR pathway", J. CLIN. ONCOL., vol. 30, 2012, pages 2919 - 28, XP055341230, DOI: 10.1200/JCO.2011.39.7356
BLOUIN M-J ET AL.: "Abstract 4615: the hyperinsulinemia caused by PI3K inhibitors attenuates their antineoplastic efficacy, but can be minimized by co administration of metformin", CANCER RES, vol. 73, 2013, pages 4615
OKKENHAUG KGRAUPERA MVANHAESEBROECK B: "Targeting PI3K in Cancer: Impact on Tumor Cells, Their Protective Stroma, Angiogenesis", IMMUNOTHERAPY. CANCER DISCOV., vol. 6, no. 10, October 2016 (2016-10-01), pages 1090 - 1105
ARIELLA B. HANKER ET AL.: "Challenges for the clinical development of PI3K inhibitors: Strategies to improve their impact in solid tumors", CANCER DISCOV, vol. 9, no. 4, April 2019 (2019-04-01), pages 482 - 491
S. M. BERGE ET AL.: "describes pharmacologically acceptable salts", J. PHARM. SCI., vol. 66, 1977, pages 1 - 19
SMITH, ROGER M.: "Chromatographic Science Series", vol. 75, 1998, LOUGHBOROUGH UNIVERSITY, pages: 223 - 249
FINNINMORGAN, J. PHARM. SCI., vol. 88, 1999, pages 955 - 958
HOOVER, JOHN E.: "Remington's Pharmaceutical Sciences", 1975, MACK PUBLISHING CO.
"Pharmaceutical Dosage Forms", 1980, MARCEL DECKER
"Handbook of Pharmaceutical Excipients", 1999, AMERICAN PHARMACEUTICAL ASSOCIATION
GOODMANGILMAN: "Comprehensive Organic Transformations: A Guide to Functional Group Preparations", 1991, JOHN WILEY AND SONS
Attorney, Agent or Firm:
LIU, SHEN & ASSOCIATES (CN)
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