Title:
ANISOMYCIN DERIVATIVE AND USE OF ANISOMYCIN AND DERIVATIVE THEREOF AS GLP-1R AGONIST
Document Type and Number:
WIPO Patent Application WO/2022/160530
Kind Code:
A1
Abstract:
The present invention provides an anisomycin derivative represented by a general formula (I) or a pharmaceutically acceptable salt, solvate, and stereoisomer thereof. In the present invention, it is found that the anisomycin and derivatives thereof have the effect of promoting insulin secretion at high blood sugar concentration and can treat diabetes and prevent the occurrence of hypoglycemia. In the study on the mechanisms of action of the anisomycin and derivatives thereof, it is found that the anisomycin and derivatives thereof are highly related to GLP-1R, indicating that the anisomycin and derivatives thereof are a small molecule GLP-1R agonist and can effectively treat a variety of GLP-1R-mediated diseases comprising obesity and diabetes.
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Inventors:
ZHANG YI (CN)
XUE HUAN (CN)
ZHANG MIN (CN)
LU ZHIHONG (CN)
ZHI LINPING (CN)
WEN ZHITONG (CN)
CUI LIJUAN (CN)
BAI TAO (CN)
LIU YUNFENG (CN)
XUE HUAN (CN)
ZHANG MIN (CN)
LU ZHIHONG (CN)
ZHI LINPING (CN)
WEN ZHITONG (CN)
CUI LIJUAN (CN)
BAI TAO (CN)
LIU YUNFENG (CN)
Application Number:
PCT/CN2021/096473
Publication Date:
August 04, 2022
Filing Date:
May 27, 2021
Export Citation:
Assignee:
UNIV SHANXI MEDICAL (CN)
International Classes:
A61K31/40; C07D207/12; A61P3/00; A61P3/10
Foreign References:
| JPS6289659A | 1987-04-24 | |||
| US5463078A | 1995-10-31 |
Other References:
JI LI; YAN HUA FENG; XIN BAI LI; WEI HAN; HUAN QIU LIU; GUO GUANG SHAO;: "Concise synthesis of ()-anisomycin", CHINESE CHEMICAL LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 23, no. 6, AMSTERDAM, NL , pages 647 - 649, XP028505434, ISSN: 1001-8417, DOI: 10.1016/j.cclet.2012.03.029
SILVIA KADEN; MIRJAM BROCKMANN; HANS‐ULRICH REISSIG: "Syntheses of Enantiomerically Pure 2‐Substituted Pyrrolidin‐3‐ones via Lithiated Alkoxyallenes – An Auxiliary‐Based Synthesis of both Enantiomers of the Antibiotic Anisomycin", HELVETICA CHIMICA ACTA, VERLAG HELVETICA CHIMICA ACTA., HOBOKEN, USA, vol. 88, no. 7, 20 July 2005 (2005-07-20), Hoboken, USA, pages 1826 - 1838, XP071269068, ISSN: 0018-019X, DOI: 10.1002/hlca.200590143
EDWARD M. ROSSER, SIMON MORTON, KATE S. ASHTON, PHILIP COHEN, ALISON N. HULME: "SYNTHETIC ANISOMYCIN ANALOGUES ACTIVATING THE JNK/SAPK1 AND P38/SAPK2 PATHWAYS", ORGANIC & BIOMOLECULAR CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, vol. 02, no. 1, 1 January 2004 (2004-01-01), pages 142 - 149, XP009055070, ISSN: 1477-0520, DOI: 10.1039/b311242j
SCHWARDT OLIVER, VEITH ULRICH, GASPARD CHRISTIANE, JÄGER VOLKER: "Stereoselective Synthesis and Biological Evaluation of Anisomycin and 2-Substituted Analogues", SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE., vol. 1999, no. S1, 1 August 1999 (1999-08-01), STUTTGART, DE. , pages 1473 - 1490, XP055953542, ISSN: 0039-7881, DOI: 10.1055/s-1999-3661
MASAO TOKUDA ET AL: "New total synthesis of (+)-N-methylanisomycin by anodic cyclization of delta-alkenylamine", TETRAHEDRON, ELSEVIER SIENCE PUBLISHERS, AMSTERDAM, NL, vol. 49, no. 12, 1 January 1993 (1993-01-01), AMSTERDAM, NL , pages 2413 - 2426, XP002154403, ISSN: 0040-4020, DOI: 10.1016/S0040-4020(01)86320-1
CHANG SHEN, CHEN JIAN-YOU, CHUANG YUNG-JEN, CHEN BOR-SEN: "Systems Approach to Pathogenic Mechanism of Type 2 Diabetes and Drug Discovery Design Based on Deep Learning and Drug Design Specifications", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL (MDPI), BASEL, CH, vol. 22, no. 1, 1 January 2021 (2021-01-01), Basel, CH , pages 166 - 33, XP055953546, ISSN: 1422-0067, DOI: 10.3390/ijms22010166
DATABASE Registry STN; ANONYMOUS : "Butanoic acid, (2R,3S,4S)-4-hydroxy-2-[(4-methoxyphenyl)methyl]-3-pyrrolidinyl ester // Butanoic acid, 3-methyl-, (2R,3S,4S)-4-hydroxy-2-[(4-methoxyphenyl)methyl]-3-pyrrolidinyl ester // Butanoic acid, 4-hydroxy-2-[(4-methoxyphenyl)methyl]-3-pyrrolidinyl ester, hydrochloride, [2R-(2.alpha.,3.alpha.,", XP055953561
CAS, no. 22862-76-6
SILVIA KADEN; MIRJAM BROCKMANN; HANS‐ULRICH REISSIG: "Syntheses of Enantiomerically Pure 2‐Substituted Pyrrolidin‐3‐ones via Lithiated Alkoxyallenes – An Auxiliary‐Based Synthesis of both Enantiomers of the Antibiotic Anisomycin", HELVETICA CHIMICA ACTA, VERLAG HELVETICA CHIMICA ACTA., HOBOKEN, USA, vol. 88, no. 7, 20 July 2005 (2005-07-20), Hoboken, USA, pages 1826 - 1838, XP071269068, ISSN: 0018-019X, DOI: 10.1002/hlca.200590143
EDWARD M. ROSSER, SIMON MORTON, KATE S. ASHTON, PHILIP COHEN, ALISON N. HULME: "SYNTHETIC ANISOMYCIN ANALOGUES ACTIVATING THE JNK/SAPK1 AND P38/SAPK2 PATHWAYS", ORGANIC & BIOMOLECULAR CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, vol. 02, no. 1, 1 January 2004 (2004-01-01), pages 142 - 149, XP009055070, ISSN: 1477-0520, DOI: 10.1039/b311242j
SCHWARDT OLIVER, VEITH ULRICH, GASPARD CHRISTIANE, JÄGER VOLKER: "Stereoselective Synthesis and Biological Evaluation of Anisomycin and 2-Substituted Analogues", SYNTHESIS, GEORG THIEME VERLAG, STUTTGART, DE., vol. 1999, no. S1, 1 August 1999 (1999-08-01), STUTTGART, DE. , pages 1473 - 1490, XP055953542, ISSN: 0039-7881, DOI: 10.1055/s-1999-3661
MASAO TOKUDA ET AL: "New total synthesis of (+)-N-methylanisomycin by anodic cyclization of delta-alkenylamine", TETRAHEDRON, ELSEVIER SIENCE PUBLISHERS, AMSTERDAM, NL, vol. 49, no. 12, 1 January 1993 (1993-01-01), AMSTERDAM, NL , pages 2413 - 2426, XP002154403, ISSN: 0040-4020, DOI: 10.1016/S0040-4020(01)86320-1
CHANG SHEN, CHEN JIAN-YOU, CHUANG YUNG-JEN, CHEN BOR-SEN: "Systems Approach to Pathogenic Mechanism of Type 2 Diabetes and Drug Discovery Design Based on Deep Learning and Drug Design Specifications", INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL (MDPI), BASEL, CH, vol. 22, no. 1, 1 January 2021 (2021-01-01), Basel, CH , pages 166 - 33, XP055953546, ISSN: 1422-0067, DOI: 10.3390/ijms22010166
DATABASE Registry STN; ANONYMOUS : "Butanoic acid, (2R,3S,4S)-4-hydroxy-2-[(4-methoxyphenyl)methyl]-3-pyrrolidinyl ester // Butanoic acid, 3-methyl-, (2R,3S,4S)-4-hydroxy-2-[(4-methoxyphenyl)methyl]-3-pyrrolidinyl ester // Butanoic acid, 4-hydroxy-2-[(4-methoxyphenyl)methyl]-3-pyrrolidinyl ester, hydrochloride, [2R-(2.alpha.,3.alpha.,", XP055953561
CAS, no. 22862-76-6
Attorney, Agent or Firm:
BEIJING ZHONGZHI XINGYUAN IP LAW FIRM (CN)
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