糖基化三氮唑水杨酸衍生物的合成及PTP1B抑制活性

利用Click chemistry将叠氮糖和炔丙基取代水杨醛分子通过Cu催化的1,3偶极环加成反应、氧化和水解3步反应得到8个糖基化三氮唑水杨酸衍生物,并利用1HNMR、IR、ESI-MS和元素分析对其结构进行了表征。通过对目标化合物进行PTP1B抑制活性测定,结果显示,所有化合物对PTP1B显示出一定的抑制活性,其中化合物Ⅳa活性最佳,IC50为(54.52±0.79)μmol/L。     

糖基化三氮唑香草酸衍生物的合成及酪氨酸酶抑制活性研究

以叠氮糖、炔丙基溴和香草醛为原料,通过醚化、"Click chemistry"、氧化、水解4步反应得到一系列标题化合物,产物结构经1HNMR、IR、EI-MS和元素分析确认。通过对目标化合物进行酪氨酸酶抑制活性筛选,结果表明,所得目标化合物均具有较强的酪氨酸酶抑制活性,其中3-甲氧基-4-((1-((2R,3R,4S,5S,6R)-3,4,5-三羟基-6-(羟基甲基)四氢-2H-吡喃-2-基)-1H-1,2,3-三唑-4-基)甲氧基)苯甲酸活性最佳,IC50为0.12±0.04 mmol/L。     

糖基化三氮唑鹰嘴豆芽素A衍生物的合成与抗缺氧活性研究

以叠氮糖、炔丙基溴和鹰嘴豆芽素A为原料,利用"Click chemistry"将糖基化三氮唑药效基团与鹰嘴豆芽素A巧妙结合,得到4种新的标题化合物,产物结构经1HNMR、13CNMR、IR、EI-MS和元素分析确认。通过小鼠常压密闭耐缺氧模型对其药理活性进行评价,结果表明:4个目标化合物均不同程度地延长小鼠的存活时间,其中半乳糖苷三氮唑鹰嘴豆芽素A和木糖苷三氮唑鹰嘴豆芽素A的活性优于乙酰唑胺。     

糖基化三氮唑香草酸白杨素酯的合成与结构表征

以叠氮糖、炔丙基溴、香草醛和白杨素为原料,通过醚化、Click chemistry氧化、酯化4步反应得到4个糖基化三氮唑香草酸白杨素酯,反应路线简单,条件温和,收率较高,总收率为51%~62%(以香草醛计),产物结构通过1H NMR、IR、ESI-MS和元素分析确认。     

合成1-(4-苯基-1,2,3-三氮唑-1-亚甲基)苯并三氮唑的新方法

三氮唑类衍生物具有抗菌、抗炎、抑制病毒生长等广泛的生物活性。从苯并三氮唑出发,通过点击化学反应在水相中合成了1-(4-苯基-1,2,3-三氮唑-1-亚甲基)苯并三氮唑,产率为91%;该合成方法具有简便快速、产率高等优点。     

三氮唑类衍生物的合成及其对幽门螺杆菌体外抑制活性研究

设计并合成了15个未曾见文献报道的1-(2-(4-取代)苯氧乙基)-1H-1,2,3-三氮唑衍生物,并通过NMR、IR、MS确认了它们的结构.幽门螺旋杆菌(HP)体外抑制活性测试结果表明,4个化合物对16株HP表现出一定的抑制活性.     

三氮唑葡萄糖苷化白杨素衍生物的合成研究

以葡萄糖、炔丙基溴和白杨素为原料,利用"Click chemistry"将糖基化三氮唑药效基团巧妙地引入白杨素分子结构中,得到一种三氮唑葡萄糖苷化白杨素衍生物,反应条件温和,操作简便,收率较高。产物结构经1H NMR、IR、EI-MS和元素分析确认。     

联吡啶羧酸铜配合物的合成及其抑制PTP1B活性研究

以一种柔性紫精衍生物1,1′-双(4-羧苄基)-4,4′-联吡啶二氯化物为配体,合成一种新型联吡啶羧酸铜配合物{[Cu(Bpybc)_(1.5)(H_2O)_2]·SO_4}_n,对其结构和组成进行红外光谱、X-射线单晶衍射和元素分析表征。该配合物属于三方晶系,空间群R-3,晶胞参数为:a=17.823 2(14)?,b=17.823 2(14)?,c=26.987(2)?,α=90°,β=90°,γ=120°,V=7 424.3(13)?~3,Z=6,R_(int)=0.134 7,R_1=0.095 0,T=293(2) K。此外,通过体外抑制活性实验研究了该配合物对蛋白酪氨酸磷酸酶1B(PTP1B)的抑制作用,该配合物能够有效抑制PTP1B的活性,其IC_(50)值为0.095μmol/L。     

PTP1B抑制剂专利技术分析

蛋白酪氨酸磷酸酶1B(PTP1B)是治疗II型糖尿病的潜在的重要靶点,与肥胖、肿瘤也具有密切关系。本文以PTP1B抑制剂专利文献为基础,对其专利申请态势、地区分布、活跃度、重点申请人等进行了统计分析。     

A Novel PTP1B Inhibitor-Phosphate of Polymannuronic Acid Ameliorates Insulin Resistance by Regulating IRS-1/Akt Signaling

Protein tyrosine phosphatase 1B (PTP1B) is a critical negative modulator of insulin signaling and has attracted considerable attention in treating type 2 diabetes mellitus (T2DM). Low-molecular-weight polymannuronic acid phosphate (LPMP) was found to be a selective PTP1B inhibitor with an IC₅₀ of 1.02 ± 0.17 μM. Cellular glucose consumption was significantly elevated in insulin-resistant HepG2 cells after LPMP treatment. LPMP could alleviate oxidative stress and endoplasmic reticulum stress, which are associated with the development of insulin resistance. Western blot and polymerase chain reaction (PCR) analysis demonstrated that LPMP could enhance insulin sensitivity through the PTP1B/IRS/Akt transduction pathway. Furthermore, animal study confirmed that LPMP could decrease blood glucose, alleviate insulin resistance, and exert hepatoprotective effects in diabetic mice. Taken together, LPMP can effectively inhibit insulin resistance and has high potential as an anti-diabetic drug candidate to be further developed.     

蛋白酪氨酸磷酸酶1B(PTP1B)抑制剂的研究进展

2型糖尿病是一种代谢综合症,其特点是胰岛素抵抗、高胰岛素血症、高血糖。研究表明,蛋白酪氨酸磷酸酶1B(PTP1B)是胰岛素转导信号的负调节因子,已经是治疗2型糖尿病和肥胖症的一个新的靶点。PTP1B抑制剂能够有效地治疗2型糖尿病和肥胖症。本文综述了近年来PTP1B抑制剂的研究进展。     

申嗪霉素羟基苯甲酸衍生物的合成及生物活性

[目的]为了提高申嗪霉素的生物活性.[方法]以吩嗪-1-羧酸为原料,通过亲核取代、酯水解等反应,将羟基苯甲酸结构片段引入吩嗪-1-羧酸中.[结果]设计合成了6个新的申嗪霉素羟基苯甲酸衍生物4a～4c和5a～5c.生物活性测定结果表明:在80 mg/L下,化合物5a对水稻纹枯病的抑菌率为74.54％;在160 mg/L时...     

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.     

The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance

Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386). Palmitate acid (PA) impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance.     

水杨酸重排法制备对羟基苯甲酸

研究了反应诸因素对水杨酸重排法制备对羟基苯甲酸产率的影响，推荐的反应条件为：反应时间７０ｍｉｎ，反应温度２４０℃，水杨酸与ＫＯＨ的物质的量比为１：１．１。按重量法计对羟基苯甲酸的收率超过３７％。     

超高交联吸附树脂的合成及其对水杨酸的吸附性能

以甲苯、苯甲醇和氯甲醚为基本原料, 一锅法合成了极性超高交联吸附树脂HH-1;利用树脂HH-1上残留的大量未反应完全的氯甲基, 加入苯胺对树脂HH-1进行了后交联反应, 得到比表面积更大的超高交联吸附树脂HH-2。并对两种树脂进行了分析表征, 分析结果表明, 树脂HH-1和树脂HH-2的比表面积分别为67.85m²/g和555.22m²/g, 平均孔径分别为1.882nm和1.105nm。以亲水性小分子水杨酸作为吸附对象, 研究了两种树脂对水杨酸的吸附行为。结果表明, 交联后树脂HH-2对水杨酸的吸附能力是交联前树脂HH-1的5倍。主要原因是二次交联后, 树脂的比表面积得到了大幅度提高。