新型基于双（芳基磺酰胺）异羟肟酸酯的选择性基质金属蛋白酶抑制剂。
Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.
作者信息
Subramaniam Rajesh, Haldar Manas K, Tobwala Shakila, Ganguly Bratati, Srivastava D K, Mallik Sanku
机构信息
Department of Pharmaceutical Sciences, North Dakota State University, 1401 Albrecht Blvd, Fargo, ND 58105, USA.
出版信息
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. doi: 10.1016/j.bmcl.2008.04.035. Epub 2008 Apr 16.
Abstract
A series of bis-(arylsulfonamide) hydroxamate inhibitors were synthesized. These compounds exhibit good potency against MMP-7 and MMP-9 depending on the nature, steric bulk, and substitution pattern of the substituents in the benzene ring. In general, the preliminary structure-activity relationships (SAR) suggest that among the DAPA hydroxamates (i) electron-rich benzene rings of the sulfonamides may produce better inhibitors than electron-poor analogs. However, potential H-bond acceptors can reverse the trend depending on the isozyme; (ii) isozyme selectivity between MMP-7 and -9 can be conferred through steric bulk and substitution pattern of the substituents in the benzene ring, and (iii) the MMP-10 inhibition pattern of the compounds paralleled that for MMP-9.
摘要
合成了一系列双（芳基磺酰胺）异羟肟酸酯抑制剂。根据苯环上取代基的性质、空间位阻和取代模式，这些化合物对基质金属蛋白酶-7（MMP-7）和基质金属蛋白酶-9（MMP-9）表现出良好的活性。一般来说，初步的构效关系（SAR）表明，在二氨基苯丙氨酸异羟肟酸酯中：（i）磺酰胺的富电子苯环比缺电子类似物可能产生更好的抑制剂。然而，潜在的氢键受体可根据同工酶逆转这一趋势；（ii）MMP-7和MMP-9之间的同工酶选择性可通过苯环上取代基的空间位阻和取代模式来赋予，并且（iii）这些化合物对MMP-10的抑制模式与对MMP-9的抑制模式相似。
相似文献
1
Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.新型基于双（芳基磺酰胺）异羟肟酸酯的选择性基质金属蛋白酶抑制剂。
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. doi: 10.1016/j.bmcl.2008.04.035. Epub 2008 Apr 16.
2
A novel series of highly selective inhibitors of MMP-3.一系列新型的基质金属蛋白酶-3高选择性抑制剂。
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6750-3. doi: 10.1016/j.bmcl.2007.10.042. Epub 2007 Oct 17.
3
beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: part 1. Design, synthesis, and lead identification.β-N-二芳基醚磺酰胺异羟肟酸酯作为有效的明胶酶抑制剂：第1部分。设计、合成及先导物鉴定。
Bioorg Med Chem Lett. 2008 Feb 1;18(3):1135-9. doi: 10.1016/j.bmcl.2007.11.119. Epub 2007 Dec 5.
4
Design, synthesis and biological evaluation of bifunctional inhibitors of membrane type 1 matrix metalloproteinase (MT1-MMP).设计、合成及膜型 1 基质金属蛋白酶（MT1-MMP）双功能抑制剂的生物学评价。
Bioorg Med Chem. 2019 Jan 1;27(1):196-207. doi: 10.1016/j.bmc.2018.11.041. Epub 2018 Nov 29.
5
Carbonic anhydrase and matrix metalloproteinase inhibitors: sulfonylated amino acid hydroxamates with MMP inhibitory properties act as efficient inhibitors of CA isozymes I, II, and IV, and N-hydroxysulfonamides inhibit both these zinc enzymes.碳酸酐酶和基质金属蛋白酶抑制剂：具有基质金属蛋白酶抑制特性的磺酰化氨基酸异羟肟酸酯可作为碳酸酐酶同工酶I、II和IV的有效抑制剂，且N-羟基磺酰胺可抑制这两种锌酶。
J Med Chem. 2000 Oct 5;43(20):3677-87. doi: 10.1021/jm000027t.
6
Tetrahydroisoquinoline based sulfonamide hydroxamates as potent matrix metalloproteinase inhibitors.基于四氢异喹啉的磺酰胺异羟肟酸酯作为强效基质金属蛋白酶抑制剂
Bioorg Med Chem Lett. 2004 Jan 5;14(1):47-50. doi: 10.1016/j.bmcl.2003.10.026.
7
N-O-Isopropyl Sulfonamido-Based Hydroxamates as Matrix Metalloproteinase Inhibitors: Hit Selection and in Vivo Antiangiogenic Activity.基于N-O-异丙基磺酰胺基的异羟肟酸酯作为基质金属蛋白酶抑制剂：活性筛选及体内抗血管生成活性
J Med Chem. 2015 Sep 24;58(18):7224-40. doi: 10.1021/acs.jmedchem.5b00367. Epub 2015 Aug 28.
8
Sultam hydroxamates as novel matrix metalloproteinase inhibitors.磺酰胺异羟肟酸酯作为新型基质金属蛋白酶抑制剂。
J Med Chem. 2004 Jun 3;47(12):2981-3. doi: 10.1021/jm049833g.
9
The discovery of anthranilic acid-based MMP inhibitors. Part 1: SAR of the 3-position.基于邻氨基苯甲酸的基质金属蛋白酶抑制剂的发现。第1部分：3位的构效关系。
Bioorg Med Chem Lett. 2001 Jan 22;11(2):235-8. doi: 10.1016/s0960-894x(00)00642-9.
10
Heteroaryl and cycloalkyl sulfonamide hydroxamic acid inhibitors of matrix metalloproteinases.基质金属蛋白酶的杂芳基和环烷基磺酰胺异羟肟酸抑制剂。
Bioorg Med Chem Lett. 2001 Jan 22;11(2):239-42. doi: 10.1016/s0960-894x(00)00644-2.
引用本文的文献
1
The Role of Extracellular Proteases in Tumor Progression and the Development of Innovative Metal Ion Chelators that Inhibit their Activity.细胞外蛋白酶在肿瘤进展中的作用和开发抑制其活性的创新金属离子螯合剂。
Int J Mol Sci. 2020 Sep 16;21(18):6805. doi: 10.3390/ijms21186805.
2
Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders.基质金属蛋白酶抑制剂作为无节制组织重塑和病理紊乱中的研究及治疗工具
Prog Mol Biol Transl Sci. 2017;148:355-420. doi: 10.1016/bs.pmbts.2017.04.003. Epub 2017 May 10.
3
Role of the Substrate Specificity-Defining Residues of Human SIRT5 in Modulating the Structural Stability and Inhibitory Features of the Enzyme.人类SIRT5中定义底物特异性的残基在调节酶的结构稳定性和抑制特性中的作用。
PLoS One. 2016 Mar 29;11(3):e0152467. doi: 10.1371/journal.pone.0152467. eCollection 2016.
4
Discovery of a New Class of Potent MMP Inhibitors by Structure-Based Optimization of the Arylsulfonamide Scaffold.通过基于结构的芳基磺酰胺骨架优化发现一类新型强效基质金属蛋白酶抑制剂。
ACS Med Chem Lett. 2013 May 14;4(6):565-9. doi: 10.1021/ml300446a. eCollection 2013 Jun 13.
5
Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins.基质金属蛋白酶作为与静脉曲张相关静脉扩张的潜在靶点。
Curr Drug Targets. 2013 Mar;14(3):287-324.
6
Matrix metalloproteinase inhibitors as investigative tools in the pathogenesis and management of vascular disease.基质金属蛋白酶抑制剂作为血管疾病发病机制及治疗研究的工具
Exp Suppl. 2012;103:209-79. doi: 10.1007/978-3-0348-0364-9_7.
本文引用的文献
1
Matrix metalloproteinase-9/gelatinase B is a putative therapeutic target of chronic obstructive pulmonary disease and multiple sclerosis.基质金属蛋白酶-9/明胶酶B是慢性阻塞性肺疾病和多发性硬化症的一个假定治疗靶点。
Curr Pharm Biotechnol. 2008 Feb;9(1):34-46. doi: 10.2174/138920108783497631.
2
MMP inhibitors in cardiac diseases: an update.心脏病中的基质金属蛋白酶抑制剂：最新进展
Recent Pat Cardiovasc Drug Discov. 2007 Nov;2(3):186-94. doi: 10.2174/157489007782418964.
3
beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: part 1. Design, synthesis, and lead identification.β-N-二芳基醚磺酰胺异羟肟酸酯作为有效的明胶酶抑制剂：第1部分。设计、合成及先导物鉴定。
Bioorg Med Chem Lett. 2008 Feb 1;18(3):1135-9. doi: 10.1016/j.bmcl.2007.11.119. Epub 2007 Dec 5.
4
beta-N-Biaryl ether sulfonamide hydroxamates as potent gelatinase inhibitors: part 2. Optimization of alpha-amino substituents.β-N-二芳基醚磺酰胺异羟肟酸酯作为有效的明胶酶抑制剂：第2部分。α-氨基取代基的优化。
Bioorg Med Chem Lett. 2008 Feb 1;18(3):1140-5. doi: 10.1016/j.bmcl.2007.11.129. Epub 2007 Dec 5.
5
The other side of MMPs: protective roles in tumor progression.基质金属蛋白酶的另一面：在肿瘤进展中的保护作用。
Cancer Metastasis Rev. 2007 Dec;26(3-4):717-24. doi: 10.1007/s10555-007-9089-4.
6
Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease.基质金属蛋白酶及其抑制剂在血管重塑和血管疾病中的作用
Biochem Pharmacol. 2008 Jan 15;75(2):346-59. doi: 10.1016/j.bcp.2007.07.004. Epub 2007 Jul 7.
7
Control of matrix metalloproteinase catalytic activity.基质金属蛋白酶催化活性的调控
Matrix Biol. 2007 Oct;26(8):587-96. doi: 10.1016/j.matbio.2007.07.001. Epub 2007 Jul 7.
8
Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: can MMPs be good for you?基质金属蛋白酶基因表达的信号转导及细胞类型特异性调控：基质金属蛋白酶对人体有益吗？
J Cell Physiol. 2007 Nov;213(2):355-64. doi: 10.1002/jcp.21208.
9
Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor.基质金属蛋白酶7通过ErbB4受体介导乳腺上皮细胞的肿瘤发生。
Cancer Res. 2007 Jul 15;67(14):6760-7. doi: 10.1158/0008-5472.CAN-07-0026.
10
Matrix metalloproteinases: useful and deleterious.基质金属蛋白酶：有益亦有害。
Biochem Soc Trans. 2007 Aug;35(Pt 4):689-91. doi: 10.1042/BST0350689.
Zotero 插件