2-(4-tert-butoxycarbonylaminobutoxy)-6-hydroxybenzoic acid methyl ester | 436864-52-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-tert-butoxycarbonylaminobutoxy)-6-hydroxybenzoic acid methyl ester
• 英文别名: methyl 2-{4-[(tert-butoxycarbonyl)amino]butoxy}-6-hydroxybenzoate；methyl 2-hydroxy-6-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butoxy]benzoate
• CAS: 436864-52-7
• 化学式: C₁₇H₂₅NO₆
• 分子量: 339.389
• InChiKey: JUFYUCBEBZVTME-UHFFFAOYSA-N

物化性质

• 沸点：
  487.3±35.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  94.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-tert-butoxycarbonylaminobutoxy)-6-hydroxybenzoic acid methyl ester 在 盐酸 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 methyl 2-{4-[(N-[(allyloxy)carbonyl]-4-{{2-[(benzhydryloxy)carbonyl]phenyl}[tert-butoxy(oxo)acetyl]amino}-L-phenylalanyl)amino]butoxy}-6-hydroxybenzoate
  参考文献：
  名称：

  Selective Protein Tyrosine Phosphatase 1B Inhibitors:  Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands

  摘要：

  Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling cascades. We identified several salicylic acid-based ligands for the second phosphotyrosine binding site of PTP1B using a NMR-based screening. Structure-based linking with a catalytic site-directed oxalylarylaminobenzoic acid-based pharmacophore led to the identification of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity over the highly homologous T-cell PTPase (TCPTP) and high selectivity over other phosphatases.

  DOI：

  10.1021/jm034088d
• 作为产物：
  描述：

  2,6-二羟基苯甲酸 在 氯化亚砜 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 2-(4-tert-butoxycarbonylaminobutoxy)-6-hydroxybenzoic acid methyl ester
  参考文献：
  名称：

  PTP1B 和 TCPTP 的收敛蛋白磷酸酶抑制剂设计：石墨烯量子点上的可交换钒配位配合物

  摘要：

  开发具有所需药物样特性的蛋白质酪氨酸磷酸酶 1B (PTP1B) 的有效和特异性抑制剂仍然是一个挑战。基于由钒酸肽组成的 PTP1B 过渡态类似物的晶体结构，提出了一种设计 PTP1B 抑制剂的新方法，其中 PTP1B 肽模拟物 (PL1) 的酪氨酰钒酸酯稳定地整合在膜可渗透石墨烯量子点上。 （GQD）。制备的钒酸盐复合物 ( GQD-PL1 - V V )在溶液和 HepG2 细胞中。GQD-PL1-V V的口服给药 db/db模型小鼠在肝脏和脂肪组织中显示出选择性 PTP1B 抑制作用，并且与双（麦芽糖醇）氧钒 (IV) 相比，显示出改善的抗糖尿病活性。此外，PL1 与 TCPTP 特异性配体 (PL2) 的交换导致有效的 TCPTP 抑制 ( K i  = 59 ± 12 × 10 -9 m )，正如预期的 SI ≈23 与 PTP1B 相比。总体而言，目前的结果提供了由 GQD、复合靶向配体和钒

  DOI：

  10.1002/adfm.202108645

文献信息

• Selective protein tyrosine phosphatatase inhibitors
  申请人：Liu Gang

  公开号：US06972340B2

  公开（公告）日：2005-12-06

  Compounds of formula (I) or therapeutically acceptable salts thereof, are selective protein tyrosine kinase-B (PTP1B) inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of disorders using the compounds are disclosed.

  化合物的分子式(I)或其治疗上可接受的盐是选择性蛋白酪氨酸激酶-B(PTP1B)抑制剂。该文披露了该类化合物的制备、含有该类化合物的组合物以及使用该类化合物治疗疾病的方法。
• Protein tyrosine phosphatase inhibitors and methods of use thereof
  申请人：Blaskovich Arnold Thomas Mark

  公开号：US20060142250A1

  公开（公告）日：2006-06-29

  The present invention provides compounds of Formula (I) and Formula (II) that are useful for modulating the biological activity of the protein tyrosine phosphatase-1b (PTP1B) enzyme. Compounds of this invention can be used to treat diseases and/or conditions in which the PTP1B enzyme is a factor. Such diseases and/or conditions include, but are not limited to, Type 1 diabetes, Type 2 diabetes, inadequate glucose tolerance, insulin resistance, obesity, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL levels, atherosclerosis, vascular restenosis, inflammatory bowel disease, pancreatitis, adipose cell tumors, adipose cell carcinoma, liposarcoma, dyslipidemia, cancer, and neurodegenerative diseases.

  本发明提供了式（I）和式（II）的化合物，这些化合物对于调节蛋白酪氨酸磷酸酶-1b（PTP1B）酶的生物活性是有用的。本发明的化合物可用于治疗PTP1B酶是因素的疾病和/或病况。这些疾病和/或病况包括但不限于1型糖尿病、2型糖尿病、葡萄糖耐量不足、胰岛素抵抗、肥胖症、高脂血症、高三酰甘油血症、高胆固醇血症、低高密度脂蛋白水平、动脉粥样硬化、血管再狭窄、炎症性肠病、胰腺炎、脂肪细胞肿瘤、脂肪细胞癌、脂肪肉瘤、脂质代谢异常、癌症和神经退行性疾病。
• PROTEIN TYROSINE PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
  申请人：Blaskovich Mark Arnold Thomas

  公开号：US20090131374A1

  公开（公告）日：2009-05-21

  The present invention provides compounds of Formula (I) and Formula (II) that are useful for modulating the biological activity of the protein tyrosine phosphatase-1b (PTP1B) enzyme. Compounds of this invention can be used to treat diseases and/or conditions in which the PTP1B enzyme is a factor. Such diseases and/or conditions include, but are not limited to, Type 1 diabetes, Type 2 diabetes, inadequate glucose tolerance, insulin resistance, obesity, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL levels, atherosclerosis, vascular restenosis, inflammatory bowel disease, pancreatitis, adipose cell tumors, adipose cell carcinoma, liposarcoma, dyslipidemia, cancer, and neurodegenerative diseases.

  本发明提供了公式（I）和公式（II）的化合物，这些化合物对于调节蛋白酪氨酸磷酸酶-1b（PTP1B）酶的生物活性是有用的。本发明的化合物可用于治疗PTP1B酶是因素的疾病和/或病况。这些疾病和/或病况包括但不限于1型糖尿病，2型糖尿病，不足的葡萄糖耐受性，胰岛素抵抗，肥胖症，高脂血症，高三酰甘油血症，高胆固醇血症，低高密度脂蛋白水平，动脉粥样硬化，血管再狭窄，炎症性肠病，胰腺炎，脂肪细胞肿瘤，脂肪细胞癌，脂肪肉瘤，脂质代谢异常，癌症和神经退行性疾病。
• 1-orthofluorophenyl substituted 1,2,5-thiazolidinedione derivatives as ptp-as inhibitors
  申请人：Barnes David

  公开号：US20100035942A1

  公开（公告）日：2010-02-11

  Compounds of the formula are inhibitors of protein tyrosine phosphatases (PTPases) and, thus, may be employed for the treatment of conditions mediated by PTPase activity. The compounds of the present invention may also be employed as inhibitors of other enzymes characterized with a phosphotyrosine binding region such as the SH2 domain. Accordingly, the compounds of formula (I) may be employed for prevention and/or treatment of insulin resistance associated with obesity, glucose intolerance, diabetes mellitus, hypertension and ischemic diseases of the large and small blood vessels, conditions that accompany type-2 diabetes, including hyperlipidemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, irritable bowel syndrome, pancreatitis, adipose cell tumors and carcinomas such as liposarcoma, dyslipidemia, and other disorders where insulin resistance is indicated. In addition, the compounds of the present invention may be employed to treat and/or prevent cancer, osteoporosis, neurodegenerative and infectious diseases, and diseases involving inflammation and the immune system.

  式（I）的化合物是蛋白酪氨酸磷酸酶（PTPase）的抑制剂，因此可用于治疗由PTPase活性介导的疾病。本发明的化合物也可用作其他酶的抑制剂，这些酶具有磷酸酪氨酸结合区域，例如SH2结构域。因此，式（I）的化合物可用于预防和/或治疗与肥胖相关的胰岛素抵抗、葡萄糖不耐受、糖尿病、高血压和大、小血管缺血性疾病，伴随2型糖尿病的疾病，包括高脂血症、高三酰甘油血症、动脉粥样硬化、血管再狭窄、肠易激综合征、胰腺炎、脂肪细胞肿瘤和脂肪肉瘤、脂质代谢异常以及其他表现为胰岛素抵抗的疾病。此外，本发明的化合物可用于治疗和/或预防癌症、骨质疏松症、神经退行性和传染性疾病以及涉及炎症和免疫系统的疾病。
• Organic compounds
  申请人：Novartis AG

  公开号：US08084448B2

  公开（公告）日：2011-12-27

  Compounds of the formula are inhibitors of protein tyrosine phosphatases (PTPases) and, thus, may be employed for the treatment of conditions mediated by PTPase activity. The compounds of the present invention may also be employed as inhibitors of other enzymes characterized with a phosphotyrosine binding region such as the SH2 domain. Accordingly, the compounds of formula (I) may be employed for prevention and/or treatment of insulin resistance associated with obesity, glucose intolerance, diabetes mellitus, hypertension and ischemic diseases of the large and small blood vessels, conditions that accompany type-2 diabetes, including hyperlipidemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, irritable bowel syndrome, pancreatitis, adipose cell tumors and carcinomas such as liposarcoma, dyslipidemia, and other disorders where insulin resistance is indicated. In addition, the compounds of the present invention may be employed to treat and/or prevent cancer, osteoporosis, musculoskeletal, neurodegenerative and infectious diseases, and diseases involving inflammation and the immune system.

  公式为的化合物是蛋白酪氨酸磷酸酶（PTPase）的抑制剂，因此可用于治疗PTPase活性介导的疾病。本发明的化合物也可用作其他酶的抑制剂，这些酶具有磷酸酪氨酸结合区域，如SH2结构域。因此，公式（I）的化合物可用于预防和/或治疗与肥胖、葡萄糖耐受性、糖尿病、高血压和大、小血管缺血性疾病相关的胰岛素抵抗，以及伴随2型糖尿病的情况，包括高脂血症、高三酰甘油血症、动脉粥样硬化、血管再狭窄、肠易激综合征、胰腺炎、脂肪细胞肿瘤和脂肪肉瘤、脂质代谢异常和其他表现为胰岛素抵抗的疾病。此外，本发明的化合物可用于治疗和/或预防癌症、骨质疏松症、肌肉骨骼、神经退行性和传染性疾病，以及涉及炎症和免疫系统的疾病。