Title:
THIAZOLAMINE MBL INHIBITOR, AND PREPARATION METHOD THEREFOR AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2023/160582
Kind Code:
A1
Abstract:
Provided in the present invention are a thiazolamine MBL inhibitor, and a preparation method therefor and the use thereof, which belong to the field of medical chemistry. The thiazolamine MBL inhibitor is a compound represented by formula I, or a salt, an isomer, a hydrate, a solvate, or a prodrug thereof. The compound provided in the present invention has good inhibitory activity on metallo-β-lactamase (MBL), and particularly has good inhibitory activity on multiple clinically relevant MBL subtypes, such as the subtypes of VIM, NDM, IMP, etc., has high Gram-negative bacterial permeability, can be used for preparing a broad-spectrum MBL inhibitor, can be used as a drug molecule for overcoming bacteria resistance and drug resistance, and has a good development prospect.
Inventors:
LI GUOBO (CN)
YAN YUHANG (CN)
YAN YUHANG (CN)
Application Number:
PCT/CN2023/077670
Publication Date:
August 31, 2023
Filing Date:
February 22, 2023
Export Citation:
Assignee:
UNIV SICHUAN (CN)
International Classes:
C07D277/56; A61K31/426; A61P31/00
Domestic Patent References:
| WO2021252068A1 | 2021-12-16 |
Foreign References:
| US3282927A | 1966-11-01 | |||
| CN114230522A | 2022-03-25 | |||
| CN105658631A | 2016-06-08 |
Other References:
EI-KERDAWY MOHAMED M, EL-EMAM 1' ALI A, EL-SUBBAGH HUSSEIN I, ABUSHANAB ELIE: "Synthesis of Substituted 4H-Thiazolo[4,5-b] [1]benzothiopyran-4-ones as Possible Schistosomicidal Agents", MONATSHEFTE FÜR CHEMIE - CHEMICAL MONTHLY ; AN INTERNATIONAL JOURNAL OF CHEMISTRY, SPRINGER-VERLAG, AU, vol. 120, 30 November 1989 (1989-11-30), AU , pages 991 - 995, XP093088069, ISSN: 1434-4475, DOI: 10.1007/BF00808770
DATABASE REGISTRY STN CAS; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-(acetylamino)-5-(phenylmethyl)- ", XP093088113
DATABASE REGISTRY STN ; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-amino-5-(2-phenylethyl)-", XP093088145
DATABASE REGISTRY STN; ANONYMOUS : " 4-Thiazolecarboxylic acid, 2-amino-5-(2-furanyl)- (CA INDEX NAME)", XP093088150
DATABASE REGISTRY STN; ANONYMOUS : " 4-Thiazolecarboxylic acid, 2-amino-5-butyl- (CA INDEX NAME)", XP093088151
DATABASE REGISTRY STN; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-amino-5-hexyl- (CA INDEX NAME)", XP093088153
DATABASE REGISTRY STN; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-(acetylamino)-5-(2-phenylethyl)- (CA INDEX NAME)", XP093088155
DATABASE REGISTRY STN; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-amino-5-(phenylthio)- (CA INDEX NAME)", XP093088157
SEAN CONROY ET AL.: "Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y2 Receptor Based on AR -C118925", JOURNAL OF MEDICINAL CHEMISTRY, vol. 61, no. 7, 20 March 2018 (2018-03-20), pages 3089 - 3113, XP055666438, ISSN: 1520-4804, DOI: 10.1021/acs.jmedchem.8b00139
BADDI M, C. S. MAHAJANSHETTI: "ChemInform Abstract: Synthesis and Antimicrobial Activity of Some Ethyl 2-Amino/Acetamido-5- arylthiothiazole-4-carboxylates and Their Sulfones: An Attempted Synthesis of 2-Amino/Acetamido(1)benzothiopyrano(3,2-d)thiazole-9(H)- ones.", CHEMINFORM, vol. 27, no. 22, 28 May 1996 (1996-05-28), pages 1, XP093088164, DOI: 10.1002/chin.199622138
AN QIAOYU, LIU LEI, TANG ZONGYUAN, LUO HAN, LI YOU, XU MINGCHUAN, LI BAOSHENG: "Access to thiazoles via [3 + 2] cycloaddition of 1,2,3-thiadiazoles with isonitriles", ORGANIC CHEMISTRY FRONTIERS, vol. 8, no. 12, 14 June 2021 (2021-06-14), pages 2909 - 2913, XP093088173, DOI: 10.1039/D1QO00165E
CUI, Y.M. HUANG, Q.Q. XU, J. CHEN, L.L. LI, J.Y. YE, Q.Z. LI, J. NAN, F.J.: "Identification of potent type I MetAP inhibitors by simple bioisosteric replacement. Part 1: Synthesis and preliminary SAR studies of thiazole-4-carboxylic acid thiazol-2-ylamide derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 15, no. 16, 15 August 2005 (2005-08-15), Amsterdam NL , pages 3732 - 3736, XP004985340, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2005.05.055
QOSAY AL-BALAS, NAHOUM G. ANTHONY, BILAL AL-JAIDI, AMANI ALNIMR, GRAINNE ABBOTT, ALISTAIR K. BROWN, REBECCA C. TAYLOR, GURDYAL S. : "Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH", PLOS ONE, vol. 4, no. 5, pages e5617, XP055103698, DOI: 10.1371/journal.pone.0005617
LI RONG; SU HUILIN; CHEN WEI; YAN YU-HANG; ZHOU CONG; MOU LUOHE; YANG HUAN; QIAN SHAN; WANG ZHOUYU; YANG LINGLING; LI GUO-BO: "Design, Synthesis, and Biological Evaluation of New 1H-Imidazole-2-Carboxylic Acid Derivatives as Metallo-β-Lactamase Inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 72, 5 September 2022 (2022-09-05), AMSTERDAM, NL, XP087181940, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2022.116993
DATABASE REGISTRY STN CAS; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-(acetylamino)-5-(phenylmethyl)- ", XP093088113
DATABASE REGISTRY STN ; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-amino-5-(2-phenylethyl)-", XP093088145
DATABASE REGISTRY STN; ANONYMOUS : " 4-Thiazolecarboxylic acid, 2-amino-5-(2-furanyl)- (CA INDEX NAME)", XP093088150
DATABASE REGISTRY STN; ANONYMOUS : " 4-Thiazolecarboxylic acid, 2-amino-5-butyl- (CA INDEX NAME)", XP093088151
DATABASE REGISTRY STN; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-amino-5-hexyl- (CA INDEX NAME)", XP093088153
DATABASE REGISTRY STN; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-(acetylamino)-5-(2-phenylethyl)- (CA INDEX NAME)", XP093088155
DATABASE REGISTRY STN; ANONYMOUS : "4-Thiazolecarboxylic acid, 2-amino-5-(phenylthio)- (CA INDEX NAME)", XP093088157
SEAN CONROY ET AL.: "Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y2 Receptor Based on AR -C118925", JOURNAL OF MEDICINAL CHEMISTRY, vol. 61, no. 7, 20 March 2018 (2018-03-20), pages 3089 - 3113, XP055666438, ISSN: 1520-4804, DOI: 10.1021/acs.jmedchem.8b00139
BADDI M, C. S. MAHAJANSHETTI: "ChemInform Abstract: Synthesis and Antimicrobial Activity of Some Ethyl 2-Amino/Acetamido-5- arylthiothiazole-4-carboxylates and Their Sulfones: An Attempted Synthesis of 2-Amino/Acetamido(1)benzothiopyrano(3,2-d)thiazole-9(H)- ones.", CHEMINFORM, vol. 27, no. 22, 28 May 1996 (1996-05-28), pages 1, XP093088164, DOI: 10.1002/chin.199622138
AN QIAOYU, LIU LEI, TANG ZONGYUAN, LUO HAN, LI YOU, XU MINGCHUAN, LI BAOSHENG: "Access to thiazoles via [3 + 2] cycloaddition of 1,2,3-thiadiazoles with isonitriles", ORGANIC CHEMISTRY FRONTIERS, vol. 8, no. 12, 14 June 2021 (2021-06-14), pages 2909 - 2913, XP093088173, DOI: 10.1039/D1QO00165E
CUI, Y.M. HUANG, Q.Q. XU, J. CHEN, L.L. LI, J.Y. YE, Q.Z. LI, J. NAN, F.J.: "Identification of potent type I MetAP inhibitors by simple bioisosteric replacement. Part 1: Synthesis and preliminary SAR studies of thiazole-4-carboxylic acid thiazol-2-ylamide derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 15, no. 16, 15 August 2005 (2005-08-15), Amsterdam NL , pages 3732 - 3736, XP004985340, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2005.05.055
QOSAY AL-BALAS, NAHOUM G. ANTHONY, BILAL AL-JAIDI, AMANI ALNIMR, GRAINNE ABBOTT, ALISTAIR K. BROWN, REBECCA C. TAYLOR, GURDYAL S. : "Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH", PLOS ONE, vol. 4, no. 5, pages e5617, XP055103698, DOI: 10.1371/journal.pone.0005617
LI RONG; SU HUILIN; CHEN WEI; YAN YU-HANG; ZHOU CONG; MOU LUOHE; YANG HUAN; QIAN SHAN; WANG ZHOUYU; YANG LINGLING; LI GUO-BO: "Design, Synthesis, and Biological Evaluation of New 1H-Imidazole-2-Carboxylic Acid Derivatives as Metallo-β-Lactamase Inhibitors", BIOORGANIC & MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 72, 5 September 2022 (2022-09-05), AMSTERDAM, NL, XP087181940, ISSN: 0968-0896, DOI: 10.1016/j.bmc.2022.116993
Attorney, Agent or Firm:
GAOYUNG INTELLECTUAL PROPERTY AGENCY (GENERAL PARTNERSHIP) (CN)
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