Title:
COMPOUND OF HEPARIN TRISACCHARIDE STRUCTURE AND PHARMACEUTICAL USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/185505
Kind Code:
A1
Abstract:
A compound of a heparin trisaccharide structure and a preparation method therefor. The compound of the heparin trisaccharide structure has a single optical activity, and the core structure is Glc(1→4)IdoA(1→4)GlcNS. The compound can treat or prevent sepsis, reduce mortality, protect the organs of a sepsis patient, and reduce cytokines in patients. The compound barely has anticoagulant activity, is resistant to HPA hydrolysis, and has no binding activity for platelet factor-4; therefore, the risk of bleeding is extremely low in therapeutic use. The structure of the compound of formula A is specific, which favors preparation and quality control.
Inventors:
ZHAO WEI (CN)
JIN HONGZHEN (CN)
WANG DANYANG (CN)
WANG KAIXUAN (CN)
JIN HONGZHEN (CN)
WANG DANYANG (CN)
WANG KAIXUAN (CN)
Application Number:
PCT/CN2023/082124
Publication Date:
October 05, 2023
Filing Date:
March 17, 2023
Export Citation:
Assignee:
UNIV NANKAI (CN)
International Classes:
A61K31/702; C07H15/04; A61P31/00; A61P31/04; C07H1/00; C07H11/00; C07H15/18
Domestic Patent References:
| WO2021055933A1 | 2021-03-25 |
Foreign References:
| CN110494145A | 2019-11-22 |
Other References:
KE, W. WHITFIELD, D.M. BRISSON, J.-R. ENRIGHT, G. JARRELL, H.C. WU, W.-G.: "Development of specific inhibitors for heparin-binding proteins based on the cobra cardiotoxin structure: an effective synthetic strategy for rationally modified heparin-like disaccharides and a trisaccharide", CARBOHYDRATE RESEARCH, PERGAMON, GB, vol. 340, no. 3, 28 February 2005 (2005-02-28), GB , pages 355 - 372, XP004744231, ISSN: 0008-6215, DOI: 10.1016/j.carres.2004.11.029
XU PENG, LAVAL STEPHANE, GUO ZHENG, YU BIAO: "Microwave-assisted simultaneous O,N-sulfonation in the synthesis of heparin-like oligosaccharides", ORGANIC CHEMISTRY FRONTIERS, vol. 3, no. 1, 1 January 2016 (2016-01-01), pages 103 - 109, XP093095053, DOI: 10.1039/C5QO00320B
XU PENG, XU WEICHANG, DAI YUANWEI, YANG YOU, YU BIAO: "Efficient synthesis of a library of heparin tri- and tetrasaccharides relevant to the substrate of heparanase", ORG. CHEM. FRONT., vol. 1, no. 4, 1 January 2014 (2014-01-01), pages 405 - 414, XP093095058, DOI: 10.1039/C4QO00039K
MUNOZ-GARCIA J. C., CORZANA F., DE PAZ J. L., ANGULO J., NIETO P. M.: "Conformations of the iduronate ring in short heparin fragments described by time-averaged distance restrained molecular dynamics", GLYCOBIOLOGY, OXFORD UNIVERSITY PRESS, US, vol. 23, no. 11, 1 November 2013 (2013-11-01), US , pages 1220 - 1229, XP093095064, ISSN: 0959-6658, DOI: 10.1093/glycob/cwt058
TEN DAM GERDY B. ET AL.,: "3-O-Sulfated Oligosaccharide Structures Are Recognized by Anti-heparan Sulfate Antibody HS4C3", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 281, no. 8, 24 February 2006 (2006-02-24), XP093076937, DOI: 10.1074/jbc.M506357200
ZHU SANYONG, LI JIAYI, LOKA RAVI S., SONG ZHENFENG, VLODAVSKY ISRAEL, ZHANG KEZHONG, NGUYEN HIEN M.: "Modulating Heparanase Activity: Tuning Sulfation Pattern and Glycosidic Linkage of Oligosaccharides", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 63, no. 8, 23 April 2020 (2020-04-23), US , pages 4227 - 4255, XP093095067, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.0c00156
REMKO MILAN, VON DER LIETH CLAUS-WILHELM: "Conformational Structure of Some Trimeric and Pentameric Structural Units of Heparin", THE JOURNAL OF PHYSICAL CHEMISTRY A, WASHINGTON DC, US, vol. 111, no. 51, 1 December 2007 (2007-12-01), US , pages 13484 - 13491, XP093095070, ISSN: 1089-5639, DOI: 10.1021/jp075330l
DATABASE Registry STNext; ANONYMOUS : "a-D-Glucopyranoside, methyl O-2-deoxy-3,4,6-tri-O-sulfo-2(sulfoamino)-a-D-glucopyranosyl-(1^4)-0-2,3-di-0-sulfoa-L-idopyranuronosy l-( 1 >4)-2-deoxy-2(sulfoamino)-,3,6-bis(hydrogen sulfate)", XP093104962
XU PENG, LAVAL STEPHANE, GUO ZHENG, YU BIAO: "Microwave-assisted simultaneous O,N-sulfonation in the synthesis of heparin-like oligosaccharides", ORGANIC CHEMISTRY FRONTIERS, vol. 3, no. 1, 1 January 2016 (2016-01-01), pages 103 - 109, XP093095053, DOI: 10.1039/C5QO00320B
XU PENG, XU WEICHANG, DAI YUANWEI, YANG YOU, YU BIAO: "Efficient synthesis of a library of heparin tri- and tetrasaccharides relevant to the substrate of heparanase", ORG. CHEM. FRONT., vol. 1, no. 4, 1 January 2014 (2014-01-01), pages 405 - 414, XP093095058, DOI: 10.1039/C4QO00039K
MUNOZ-GARCIA J. C., CORZANA F., DE PAZ J. L., ANGULO J., NIETO P. M.: "Conformations of the iduronate ring in short heparin fragments described by time-averaged distance restrained molecular dynamics", GLYCOBIOLOGY, OXFORD UNIVERSITY PRESS, US, vol. 23, no. 11, 1 November 2013 (2013-11-01), US , pages 1220 - 1229, XP093095064, ISSN: 0959-6658, DOI: 10.1093/glycob/cwt058
TEN DAM GERDY B. ET AL.,: "3-O-Sulfated Oligosaccharide Structures Are Recognized by Anti-heparan Sulfate Antibody HS4C3", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 281, no. 8, 24 February 2006 (2006-02-24), XP093076937, DOI: 10.1074/jbc.M506357200
ZHU SANYONG, LI JIAYI, LOKA RAVI S., SONG ZHENFENG, VLODAVSKY ISRAEL, ZHANG KEZHONG, NGUYEN HIEN M.: "Modulating Heparanase Activity: Tuning Sulfation Pattern and Glycosidic Linkage of Oligosaccharides", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 63, no. 8, 23 April 2020 (2020-04-23), US , pages 4227 - 4255, XP093095067, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.0c00156
REMKO MILAN, VON DER LIETH CLAUS-WILHELM: "Conformational Structure of Some Trimeric and Pentameric Structural Units of Heparin", THE JOURNAL OF PHYSICAL CHEMISTRY A, WASHINGTON DC, US, vol. 111, no. 51, 1 December 2007 (2007-12-01), US , pages 13484 - 13491, XP093095070, ISSN: 1089-5639, DOI: 10.1021/jp075330l
DATABASE Registry STNext; ANONYMOUS : "a-D-Glucopyranoside, methyl O-2-deoxy-3,4,6-tri-O-sulfo-2(sulfoamino)-a-D-glucopyranosyl-(1^4)-0-2,3-di-0-sulfoa-L-idopyranuronosy l-( 1 >4)-2-deoxy-2(sulfoamino)-,3,6-bis(hydrogen sulfate)", XP093104962
Attorney, Agent or Firm:
BEIJING YUNJIN IP LAW FIRM (CN)
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