Title:
TARGETED DELIVERY OF 1, 2, 4, 5-TETRAOXANE COMPOUNDS AND THEIR USES
Document Type and Number:
WIPO Patent Application WO/2022/161490
Kind Code:
A1
Abstract:
1, 2, 4, 5-tetraoxane compounds and derivatives thereof that have anticancer properties are disclosed. Pharmaceutical compositions and pharmaceutical formulations in unit dosage form suitable for the delivery of the compounds to a subject in need thereof are disclosed. The pharmaceutical compositions or formulations may include one or more active agents in addition to the compounds, such as one or more additional anticancer agents. Methods for treating a cancer, reducing a cancer, or treating or ameliorating one or more symptoms associated with a cancer in a subject are also disclosed. The methods include (i) administering to a subject in need thereof an effective amount of the compound (s). The compound (s) can be administered by oral administration, parenteral administration, inhalation, mucosal administration, or a combination thereof. The compound can selectively kill cancer cells and/or cancer stem cells over non-cancerous cells by triggering ferroptosis in the cancer cells and/or cancer stem cells.
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Inventors:
YANG DAN (CN)
WONG MING KWAN (CN)
WONG MING KWAN (CN)
Application Number:
PCT/CN2022/074975
Publication Date:
August 04, 2022
Filing Date:
January 29, 2022
Export Citation:
Assignee:
YANG DAN (CN)
WONG MING KWAN (CN)
WONG MING KWAN (CN)
International Classes:
C07D323/04; A61K31/357; A61P35/00
Domestic Patent References:
| WO2008038030A2 | 2008-04-03 |
Foreign References:
| CN104771392A | 2015-07-15 |
Other References:
YANG JING, TU ZHENGCHAO, XU XIN, LUO JINFENG, YAN XING, RAN CHONGZHAO, MAO XINLIANG, DING KE, QIAO CHUNHUA: "Novel conjugates of endoperoxide and 4-anilinoquinazoline as potential anticancer agents", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 27, no. 6, 1 March 2017 (2017-03-01), Amsterdam NL , pages 1341 - 1345, XP055953628, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2017.02.023
AMEWU RICHARD K.; CHADWICK JAMES; HUSSAIN AFTHAB; PANDA SOMNATH; RINKI RINKI; JANNEH OMAR; WARD STEPHEN A.; MIGUEL CANDEL; BURRELL: "Synthesis and evaluation of the antimalarial, anticancer, and caspase 3 activities of tetraoxane dimers", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 21, no. 23, 1 October 2013 (2013-10-01), AMSTERDAM, NL, pages 7392 - 7397, XP028760010, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2013.09.047
CAPELA RITA, MAGALHÃES JOANA, MIRANDA DANIELA, MACHADO MARTA, SANCHES-VAZ MARGARIDA, ALBUQUERQUE INÊS S., SHARMA MONI, GUT JIRI, R: "Endoperoxide-8-aminoquinoline hybrids as dual-stage antimalarial agents with enhanced metabolic stability", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 149, 1 April 2018 (2018-04-01), AMSTERDAM, NL , pages 69 - 78, XP055953633, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2018.02.048
O'NEILL PAUL M., AMEWU RICHARD K., NIXON GEMMA L., BOUSEJRA ELGARAH FATIMA, MUNGTHIN MATHIRUT, CHADWICK JAMES, SHONE ALISON E., VI: "Identification of a 1,2,4,5-Tetraoxane Antimalarial Drug-Development Candidate (RKA 182) with Superior Properties to the Semisynthetic Artemisinins", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VERLAG CHEMIE, vol. 49, no. 33, 2 August 2010 (2010-08-02), pages 5693 - 5697, XP055953637, ISSN: 1433-7851, DOI: 10.1002/anie.201001026
OPSENICA IGOR, OPSENICA DEJAN, SMITH KIRSTEN S., MILHOUS WILBUR K., ŠOLAJA BOGDAN A.: "Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 51, no. 7, 1 April 2008 (2008-04-01), US , pages 2261 - 2266, XP055953641, ISSN: 0022-2623, DOI: 10.1021/jm701417a
CVIJETIĆ ILIJA N., ŽIŽAK ŽELJKO P., STANOJKOVIĆ TATJANA P., JURANIĆ ZORICA D., TERZIĆ NATAŠA, OPSENICA IGOR M., OPSENICA DEJAN M.,: "An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 45, no. 10, 1 October 2010 (2010-10-01), AMSTERDAM, NL , pages 4570 - 4577, XP055953642, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2010.07.019
AMINAKE MAKOAH N., MAHAJAN AMAN, KUMAR VIPAN, HANS RENATE, WIESNER LUBBE, TAYLOR DALE, DE KOCK CARMEN, GROBLER ANNE, SMITH PETER J: "Synthesis and evaluation of hybrid drugs for a potential HIV/AIDS-malaria combination therapy", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 20, no. 17, 1 September 2012 (2012-09-01), AMSTERDAM, NL, pages 5277 - 5289, XP055953645, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2012.06.038
AMEWU RICHARD, ET AL: "Design and synthesis of orally active dispiro-1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin", ORGANIC & BIOMOLECULAR CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, vol. 4, no. 24, 1 January 2006 (2006-01-01), pages 4431 - 4436, XP002465730, ISSN: 1477-0520, DOI: 10.1039/b613565j
FATIMA BOUSEJRA-EL GARAH, MICHAEL HE-LONG WONG, RICHARD K. AMEWU, SANT MUANGNOICHAROEN, JAMES L. MAGGS, JEAN-LUC STIGLIANI, B. KEV: "Comparison of the Reactivity of Antimalarial 1,2,4,5-Tetraoxanes with 1,2,4-Trioxolanes in the Presence of Ferrous Iron Salts, Heme, and Ferrous Iron Salts/Phosphatidylcholine", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 54, no. 19, 13 October 2011 (2011-10-13), US , pages 6443 - 6455, XP055402535, ISSN: 0022-2623, DOI: 10.1021/jm200768h
XIAOFANG WANG, YUXIANG DONG, SERGIO WITTLIN, SUSAN A. CHARMAN, FRANCIS C. K. CHIU, JACQUES CHOLLET, KASIRAM KATNENI, JANNE MANNILA: "Comparative Antimalarial Activities and ADME Profiles of Ozonides (1,2,4-trioxolanes) OZ277, OZ439, and Their 1,2-Dioxolane, 1,2,4-Trioxane, and 1,2,4,5-Tetraoxane Isosteres", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 56, no. 6, 28 March 2013 (2013-03-28), US , pages 2547 - 2555, XP055752228, ISSN: 0022-2623, DOI: 10.1021/jm400004u
RUDI OLIVEIRA, RITA C. GUEDES, PATRíCIA MEIRELES, INêS S. ALBUQUERQUE, LíDIA M. GONçALVES, ELISABETE PIRES, MA: "Tetraoxane–Pyrimidine Nitrile Hybrids as Dual Stage Antimalarials", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 57, no. 11, 12 June 2014 (2014-06-12), US , pages 4916 - 4923, XP055619732, ISSN: 0022-2623, DOI: 10.1021/jm5004528
MIRANDA DANIELA, CAPELA RITA, ALBUQUERQUE INÊS S., MEIRELES PATRÍCIA, PAIVA ISA, NOGUEIRA FÁTIMA, AMEWU RICHARD, GUT JIRI, ROSENTH: "Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities", ACS MEDICINAL CHEMISTRY LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 5, no. 2, 13 February 2014 (2014-02-13), US , pages 108 - 112, XP055953650, ISSN: 1948-5875, DOI: 10.1021/ml4002985
CABRAL LÍLIA I. L., POMEL SÉBASTIEN, COJEAN SANDRINE, AMADO PATRÍCIA S. M., LOISEAU PHILIPPE M., CRISTIANO MARIA L. S.: "Synthesis and Antileishmanial Activity of 1,2,4,5-Tetraoxanes against Leishmania donovani", MOLECULES, SPRINGER VERLAG, BERLIN, DE, vol. 25, no. 3, 1 February 2020 (2020-02-01), DE , pages 465 - 8, XP055953651, ISSN: 1433-1373, DOI: 10.3390/molecules25030465
AMEWU RICHARD K.; CHADWICK JAMES; HUSSAIN AFTHAB; PANDA SOMNATH; RINKI RINKI; JANNEH OMAR; WARD STEPHEN A.; MIGUEL CANDEL; BURRELL: "Synthesis and evaluation of the antimalarial, anticancer, and caspase 3 activities of tetraoxane dimers", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 21, no. 23, 1 October 2013 (2013-10-01), AMSTERDAM, NL, pages 7392 - 7397, XP028760010, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2013.09.047
CAPELA RITA, MAGALHÃES JOANA, MIRANDA DANIELA, MACHADO MARTA, SANCHES-VAZ MARGARIDA, ALBUQUERQUE INÊS S., SHARMA MONI, GUT JIRI, R: "Endoperoxide-8-aminoquinoline hybrids as dual-stage antimalarial agents with enhanced metabolic stability", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 149, 1 April 2018 (2018-04-01), AMSTERDAM, NL , pages 69 - 78, XP055953633, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2018.02.048
O'NEILL PAUL M., AMEWU RICHARD K., NIXON GEMMA L., BOUSEJRA ELGARAH FATIMA, MUNGTHIN MATHIRUT, CHADWICK JAMES, SHONE ALISON E., VI: "Identification of a 1,2,4,5-Tetraoxane Antimalarial Drug-Development Candidate (RKA 182) with Superior Properties to the Semisynthetic Artemisinins", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, VERLAG CHEMIE, vol. 49, no. 33, 2 August 2010 (2010-08-02), pages 5693 - 5697, XP055953637, ISSN: 1433-7851, DOI: 10.1002/anie.201001026
OPSENICA IGOR, OPSENICA DEJAN, SMITH KIRSTEN S., MILHOUS WILBUR K., ŠOLAJA BOGDAN A.: "Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 51, no. 7, 1 April 2008 (2008-04-01), US , pages 2261 - 2266, XP055953641, ISSN: 0022-2623, DOI: 10.1021/jm701417a
CVIJETIĆ ILIJA N., ŽIŽAK ŽELJKO P., STANOJKOVIĆ TATJANA P., JURANIĆ ZORICA D., TERZIĆ NATAŠA, OPSENICA IGOR M., OPSENICA DEJAN M.,: "An alignment independent 3D QSAR study of the antiproliferative activity of 1,2,4,5-tetraoxanes", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 45, no. 10, 1 October 2010 (2010-10-01), AMSTERDAM, NL , pages 4570 - 4577, XP055953642, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2010.07.019
AMINAKE MAKOAH N., MAHAJAN AMAN, KUMAR VIPAN, HANS RENATE, WIESNER LUBBE, TAYLOR DALE, DE KOCK CARMEN, GROBLER ANNE, SMITH PETER J: "Synthesis and evaluation of hybrid drugs for a potential HIV/AIDS-malaria combination therapy", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 20, no. 17, 1 September 2012 (2012-09-01), AMSTERDAM, NL, pages 5277 - 5289, XP055953645, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2012.06.038
AMEWU RICHARD, ET AL: "Design and synthesis of orally active dispiro-1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin", ORGANIC & BIOMOLECULAR CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, vol. 4, no. 24, 1 January 2006 (2006-01-01), pages 4431 - 4436, XP002465730, ISSN: 1477-0520, DOI: 10.1039/b613565j
FATIMA BOUSEJRA-EL GARAH, MICHAEL HE-LONG WONG, RICHARD K. AMEWU, SANT MUANGNOICHAROEN, JAMES L. MAGGS, JEAN-LUC STIGLIANI, B. KEV: "Comparison of the Reactivity of Antimalarial 1,2,4,5-Tetraoxanes with 1,2,4-Trioxolanes in the Presence of Ferrous Iron Salts, Heme, and Ferrous Iron Salts/Phosphatidylcholine", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 54, no. 19, 13 October 2011 (2011-10-13), US , pages 6443 - 6455, XP055402535, ISSN: 0022-2623, DOI: 10.1021/jm200768h
XIAOFANG WANG, YUXIANG DONG, SERGIO WITTLIN, SUSAN A. CHARMAN, FRANCIS C. K. CHIU, JACQUES CHOLLET, KASIRAM KATNENI, JANNE MANNILA: "Comparative Antimalarial Activities and ADME Profiles of Ozonides (1,2,4-trioxolanes) OZ277, OZ439, and Their 1,2-Dioxolane, 1,2,4-Trioxane, and 1,2,4,5-Tetraoxane Isosteres", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 56, no. 6, 28 March 2013 (2013-03-28), US , pages 2547 - 2555, XP055752228, ISSN: 0022-2623, DOI: 10.1021/jm400004u
RUDI OLIVEIRA, RITA C. GUEDES, PATRíCIA MEIRELES, INêS S. ALBUQUERQUE, LíDIA M. GONçALVES, ELISABETE PIRES, MA: "Tetraoxane–Pyrimidine Nitrile Hybrids as Dual Stage Antimalarials", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 57, no. 11, 12 June 2014 (2014-06-12), US , pages 4916 - 4923, XP055619732, ISSN: 0022-2623, DOI: 10.1021/jm5004528
MIRANDA DANIELA, CAPELA RITA, ALBUQUERQUE INÊS S., MEIRELES PATRÍCIA, PAIVA ISA, NOGUEIRA FÁTIMA, AMEWU RICHARD, GUT JIRI, ROSENTH: "Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities", ACS MEDICINAL CHEMISTRY LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 5, no. 2, 13 February 2014 (2014-02-13), US , pages 108 - 112, XP055953650, ISSN: 1948-5875, DOI: 10.1021/ml4002985
CABRAL LÍLIA I. L., POMEL SÉBASTIEN, COJEAN SANDRINE, AMADO PATRÍCIA S. M., LOISEAU PHILIPPE M., CRISTIANO MARIA L. S.: "Synthesis and Antileishmanial Activity of 1,2,4,5-Tetraoxanes against Leishmania donovani", MOLECULES, SPRINGER VERLAG, BERLIN, DE, vol. 25, no. 3, 1 February 2020 (2020-02-01), DE , pages 465 - 8, XP055953651, ISSN: 1433-1373, DOI: 10.3390/molecules25030465
Attorney, Agent or Firm:
SHANGCHENG & PARTNERS (CN)
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