4-(4-异丙基哌嗪)苯硼酸频那醇酯 | 1073354-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(4-异丙基哌嗪)苯硼酸频那醇酯
• 英文名称: 1-isopropyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine
• 英文别名: 4-(4-isopropylpiperazinyl)phenylboronic acid pinacol ester；1-(propan-2-yl)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine；4-(4-isopropylpiperizinyl)phenylboronic acid pinacol ester；1-propan-2-yl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine
• CAS: 1073354-18-3
• 化学式: C₁₉H₃₁BN₂O₂
• 分子量: 330.278
• InChiKey: CSORKGLMGUQQOY-UHFFFAOYSA-N

物化性质

• 沸点：
  440.7±40.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312+P330,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-(4-Isopropylpiperizinyl)phenylboronic acid, pinacol ester
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 4-(4-Isopropylpiperizinyl)phenylboronic acid, pinacol ester
CAS number: 1073354-18-3

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C19H31BN2O2
Molecular weight: 330.3

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4-(4-异丙基哌嗪)苯硼酸频那醇酯 在 二(氰基苯)二氯化钯 、 锂硼氢 、 氯化铵 、 caesium carbonate 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.34h， 生成 (Z)-5-(4-aminophenyl)-5-(4-(4-isopropylpiperazin-1-yl)phenyl)-4-phenylpent-4-en-1-ol dihydrochloride salt
  参考文献：
  名称：

  Discovery of Potent, Selective, and Orally Bioavailable Estrogen-Related Receptor-γ Inverse Agonists To Restore the Sodium Iodide Symporter Function in Anaplastic Thyroid Cancer

  摘要：

  An inverse agonist of estrogen-related receptor-gamma (ERR gamma), an orphan nuclear receptor encoded by Esrrg, enhances sodium iodide symporter-mediated radioiodine uptake in anaplastic thyroid cancer (ATC) cells, thereby facilitating responsiveness to radioiodine therapy in vitro. We synthesized potent, selective, and orally bioavailable ERR gamma-inverse agonists and evaluated their activity by analyzing in vitro pharmacology and absorption, distribution, metabolism, excretion, and toxicity profiles. X-ray crystallographic analysis of the ligand and ERR gamma complex showed that 35 completely binds to the target protein (PDB 6A6K). Our results showed improved radioiodine avidity in ATC cells through compound 35 mediated upregulation of iodide-handling genes, leading to enhanced responsiveness to radioiodine therapy in vitro. Importantly, in vivo I-124-positron emission tomography/computed tomography imaging revealed that 35 increases radioiodine avidity in CAL62 tumors. Collectively, these results demonstrated that 35 can be developed as a promising treatment for ERR gamma-related cancer in the future.

  DOI：

  10.1021/acs.jmedchem.8b01296
• 作为产物：
  描述：

  1-(4-溴苯基)哌嗪 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 27.0h， 生成 4-(4-异丙基哌嗪)苯硼酸频那醇酯
  参考文献：
  名称：

  [EN] HALO-SUBSTITUTED AMINO PYRIDINE COMPOUNDS AS INHIBITORS OF THE HAEMATOPOIETIC PROGENITOR KINASE 1 (HPK1)
  [FR] COMPOSÉS D'AMINO PYRIDINE HALO-SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE DES PROGÉNITEURS HÉMATOPOÏÉTIQUES 1 (HPK1)

  摘要：

  本申请涉及公式（I）的卤代杂环化合物或其药学上可接受的盐、溶剂或前药，以及包含这些化合物或药学上可接受的盐、溶剂或前药的组合物，以及在治疗可通过抑制HPK1来治疗的疾病、紊乱或情况方面的各种用途，例如癌症。

  公开号：

  WO2022226668A1

文献信息

• [EN] PYRROLO[3,2-C]PYRIDINE DERIVATIVES AS TLR INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLO[3,2-C]PYRIDINE COMME INHIBITEURS DE TLR
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2015088045A1

  公开（公告）日：2015-06-18

  The present invention provides a heterocyclic compound having a TLR7, TLR9, TLR7/8, TLR7/9 or TLR7/8/9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases, inflammatory diseases and the like, in particular, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.

  本发明提供了一种具有TLR7、TLR9、TLR7/8、TLR7/9或TLR7/8/9抑制作用的杂环化合物，该化合物可用作自身免疫性疾病、炎症性疾病等的预防或治疗剂，特别是系统性红斑狼疮、干燥综合征、类风湿关节炎、牛皮癣、炎症性肠病等。本发明是由式（1）表示的化合物：其中每个符号如说明书中所述，或其盐。
• PYRROLO[3,2-C]PYRIDINE DERIVATIVES AS TLR INHIBITORS
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20170008885A1

  公开（公告）日：2017-01-12

  The present invention provides a heterocyclic compound having a TLR7, TLR9, TLR7/8, TLR7/9 or TLR7/8/9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases, inflammatory diseases and the like, in particular, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease and the like. The present invention is a compound represented by the formula (1): wherein each symbol is as described in the specification, or a salt thereof.

  本发明提供了一种具有TLR7、TLR9、TLR7/8、TLR7/9或TLR7/8/9抑制作用的杂环化合物，该化合物可用作自身免疫性疾病、炎症性疾病等的预防或治疗剂，特别是系统性红斑狼疮、干燥综合征、类风湿关节炎、牛皮癣、炎症性肠病等。本发明是由式（1）表示的化合物，其中每个符号如说明书中所述，或其盐。
• [EN] HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017038909A1

  公开（公告）日：2017-03-09

  The present invention provides a heterocyclic compound a TLR7 and/or TLR9 and/or TLR-7/8/9 and/or TLR-7/8 and/or TLR-7/9 inhibitory action, which is useful as an agent for the prophylaxis or treatment of autoimmune diseases and/or inflammatory diseases and the like, in particular, acute decompensated heart failure, non-alcoholic steatohepatitis (NASH), IgA nephropathy, Duchenne muscular dystrophy (DMD), systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, psoriasis, inflammatory bowel disease, asthma, type 1 diabetes, myasthenia gravis, hematopoetic disfunction, B-cell malignancies, transplant rejection and graft-versus-host disease, hepatocellular carcinoma (HCC) and the like. The present invention is a compound represented by the formula (1) : wherein each symbol is as described in the specification, or a salt thereof.

  本发明提供了一种杂环化合物，具有TLR7和/或TLR9和/或TLR-7/8/9和/或TLR-7/8和/或TLR-7/9的抑制作用，可用作自身免疫疾病和/或炎症性疾病等的预防或治疗剂，特别是急性失代偿性心力衰竭、非酒精性脂肪肝炎（NASH）、IgA肾病、杜兴氏肌肉萎缩症（DMD）、系统性红斑狼疮、干燥综合征、类风湿关节炎、银屑病、炎症性肠病、哮喘、1型糖尿病、重症肌无力、造血功能障碍、B细胞恶性肿瘤、移植排斥和移植物抗宿主病、肝细胞癌（HCC）等。本发明是一种由式（1）表示的化合物：其中每个符号如说明书中所述，或其盐。
• Discovery of GSK251: A Highly Potent, Highly Selective, Orally Bioavailable Inhibitor of PI3Kδ with a Novel Binding Mode
  作者：Kenneth Down、Augustin Amour、Niall A. Anderson、Nick Barton、Sebastien Campos、Edward P. Cannons、Cole Clissold、Maire A. Convery、John J. Coward、Kevin Doyle、Birgit Duempelfeld、Christopher D. Edwards、Michael D. Goldsmith、Jana Krause、David N. Mallett、Grant A. McGonagle、Vipulkumar K. Patel、James Rowedder、Paul Rowland、Andrew Sharpe、Srividya Sriskantharajah、Daniel A. Thomas、Douglas W. Thomson、Sorif Uddin、J. Nicole Hamblin、Edith M. Hessel

  DOI：10.1021/acs.jmedchem.1c01102

  日期：2021.9.23

  Optimization of a previously reported lead series of PI3Kδ inhibitors with a novel binding mode led to the identification of a clinical candidate compound 31 (GSK251). Removal of an embedded Ames-positive heteroaromatic amine by reversing a sulfonamide followed by locating an interaction with Trp760 led to a highly selective compound 9. Further optimization to avoid glutathione trapping, to enhance

  通过对先前报道的 PI3Kδ 抑制剂先导系列进行优化，采用新型结合模式，确定了临床候选化合物31 (GSK251)。通过逆转磺酰胺去除嵌入的 Ames 阳性杂芳胺，然后定位与 Trp760 的相互作用，产生高度选择性的化合物9 。进一步优化以避免谷胱甘肽捕获、增强效力和选择性以及优化口服药代动力学特征，发现了化合物31 (GSK215)，其具有较低的预测日剂量（45 mg，bid）和适合于大鼠的毒性特征。进一步发展。
• [EN] SUBSTITUTED HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF TLR9<br/>[FR] COMPOSÉS HÉTÉROARYLES SUBSTITUÉS UTILES EN TANT QU'INHIBITEURS DE TLR9
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2022040293A1

  公开（公告）日：2022-02-24

  Disclosed are compounds of Formulas (I) and (II): or a salt thereof, wherein X, Y, Q1, Q2, G, R1, and R3 are defined herein. Also disclosed are methods of using such compounds as inhibitors of TLR9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing fibrotic diseases.

  揭示的是以下化合物的结构（I）和（II）：或其盐，其中X、Y、Q1、Q2、G、R1和R3在此处有定义。还揭示了使用这些化合物作为TLR9抑制剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓纤维化疾病方面具有用处。