4-(4-甲基哌嗪)苯甲酸甲酯 | 354813-14-2

• 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-甲基哌嗪)苯甲酸甲酯
• 英文名称: methyl 4-(4-methylpiperazin-1-yl)benzoate
• CAS: 354813-14-2
• 化学式: C₁₃H₁₈N₂O₂
• 分子量: 234.298
• InChiKey: LXCXOZWVDWCOCC-UHFFFAOYSA-N

物化性质

• 熔点：
  122-124°
• 沸点：
  362.4±37.0 °C(Predicted)
• 密度：
  1.112±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933599090

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: Methyl 4-(4-methylpiperazino)benzoate
Synonyms:

---

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

---

Section 3. Composition/information on ingredients.
Ingredient name: Methyl 4-(4-methylpiperazino)benzoate
CAS number: 354813-14-2

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C13H18N2O2
Molecular weight: 234.3

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

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

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4-(4-甲基哌嗪)苯甲酸甲酯 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 4-(4-methylpiperazin-1-yI)benzoic acid
  参考文献：
  名称：

  通过基于片段的虚拟筛选，设计和合成新型1H-1,2,4-三唑，苯并噻唑和吲唑基衍生物，作为有效的FGFR1抑制剂。

  摘要：

  成纤维细胞生长因子受体（FGFR）是癌症治疗的潜在靶标。通过基于片段的虚拟筛选，我们设计了三种新型的带有吲唑，苯并噻唑和1H-1,2,4-三唑支架的FGFR1抑制剂。在体外评估所有新合成的化合物对FGFR1的抑制活性。首先将带有吲唑支架的化合物9d鉴定为具有优良激酶抑制活性（IC50 = 15.0 nM）和适度的抗增殖活性（IC50 = 785.8 nM）的命中化合物。通过两轮优化，吲唑衍生物9 u是最强的FGFR1抑制剂，具有最佳的酶抑制活性（IC50 = 3.3 nM）和细胞活性（IC50 = 468.2 nM）。此外，9 u还表现出良好的激酶选择性。此外，

  DOI：

  10.1080/14756366.2019.1673745
• 作为产物：
  描述：

  N-甲基哌嗪 、 对溴苯甲酸甲酯 在 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 为溶剂， 以37.08%的产率得到4-(4-甲基哌嗪)苯甲酸甲酯
  参考文献：
  名称：

  [EN] C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS
  [FR] NOUVEAU TRITERPÉNONE EN C-3 AVEC DES DÉRIVÉS D'AMIDE INVERSE EN C-17 EN TANT QU'INHIBITEURS DU VIH

  摘要：

  本发明涉及具有式（I）的C-17反酰胺化合物的C-3新型三萜酮，及其药学上可接受的盐，其中环式（II），R1、R2、R3、R4、R5、R6、R7，'n'和'm'如式（I）中所定义。该发明还涉及C-3新型三萜酮与C-17反酰胺衍生物、相关化合物和用于治疗病毒性疾病，特别是HIV介导疾病的药物组合物。

  公开号：

  WO2018029604A1

文献信息

• [EN] C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS<br/>[FR] NOUVEAU TRITERPÉNONE EN C-3 AVEC DES DÉRIVÉS D'AMIDE INVERSE EN C-17 EN TANT QU'INHIBITEURS DU VIH
  申请人：HETERO LABS LTD

  公开号：WO2018029604A1

  公开（公告）日：2018-02-15

  The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

  本发明涉及具有式（I）的C-17反酰胺化合物的C-3新型三萜酮，及其药学上可接受的盐，其中环式（II），R1、R2、R3、R4、R5、R6、R7，'n'和'm'如式（I）中所定义。该发明还涉及C-3新型三萜酮与C-17反酰胺衍生物、相关化合物和用于治疗病毒性疾病，特别是HIV介导疾病的药物组合物。
• Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors
  作者：Jing Cui、Xia Peng、Dingding Gao、Yang Dai、Jing Ai、Yingxia Li

  DOI：10.1016/j.bmcl.2017.06.068

  日期：2017.8

  Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological

  成纤维细胞生长因子受体（FGFR）由于其在促进癌症形成和发展中的关键作用而成为癌症治疗的潜在靶标。为了不断改善带有吲唑骨架的命中化合物7r的细胞活性（这是我们小组先前发现的），设计，合成了几种利用氟取代基的化合物，并对其进行了生物学评估。此外，还探索了向溶剂延伸至ATP结合口袋的区域。其中，含有2，6-二氟-3-甲氧基苯基残基的化合物2a表现出最强的活性（FGFR1：小于4.1nM，FGFR2：2.0±0.8nM）。更重要的是化合物2a结果显示对KG1细胞系和SNU16细胞系的抗增殖作用得到改善，IC 50值分别为25.3±4.6 nM和77.4±6.2 nM。
• Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer
  作者：Xin Han、Lijie Zhao、Weiguo Xiang、Chong Qin、Bukeyan Miao、Donna McEachern、Yu Wang、Hoda Metwally、Lu Wang、Aleksas Matvekas、Bo Wen、Duxin Sun、Shaomeng Wang

  DOI：10.1021/acs.jmedchem.1c00882

  日期：2021.9.9

  Proteolysis targeting chimera (PROTAC) small-molecule degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to

  蛋白水解靶向嵌合体 (PROTAC) 小分子降解剂已成为一种很有前途的新型治疗剂，但设计具有优异口服药代动力学的 PROTAC 降解剂是一项重大挑战。在这项研究中，我们提出了我们的策略，以发现具有出色口服药代动力学的高效雄激素受体 (AR) PROTAC 降解剂。使用沙利度胺募集 cereblon/cullin 4A E3 连接酶并通过连接器的刚性化，我们在小鼠中发现了具有良好口服药代动力学特性的高效 AR 降解剂，其中 ARD-2128 是最佳化合物。ARD-2128在小鼠中达到67%的口服生物利用度，有效降低AR蛋白并抑制肿瘤组织中的AR调节基因，导致有效抑制小鼠肿瘤生长而没有毒性迹象。本研究支持开发用于治疗前列腺癌的口服活性 PROTAC AR 降解剂，并为口服活性 PROTAC 降解剂的设计提供见解和指导。
• Design, synthesis and biological evaluation of novel 1<i>H</i>-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors <i>via</i>fragment-based virtual screening
  作者：Jian Liu、Yu Wen、Lina Gao、Liang Gao、Fengjun He、Jingxian Zhou、Junwei Wang、Rupeng Dai、Xiaojing Chen、Di Kang、Lihong Hu

  DOI：10.1080/14756366.2019.1673745

  日期：2020.1.1

  therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15

  成纤维细胞生长因子受体（FGFR）是癌症治疗的潜在靶标。通过基于片段的虚拟筛选，我们设计了三种新型的带有吲唑，苯并噻唑和1H-1,2,4-三唑支架的FGFR1抑制剂。在体外评估所有新合成的化合物对FGFR1的抑制活性。首先将带有吲唑支架的化合物9d鉴定为具有优良激酶抑制活性（IC50 = 15.0 nM）和适度的抗增殖活性（IC50 = 785.8 nM）的命中化合物。通过两轮优化，吲唑衍生物9 u是最强的FGFR1抑制剂，具有最佳的酶抑制活性（IC50 = 3.3 nM）和细胞活性（IC50 = 468.2 nM）。此外，9 u还表现出良好的激酶选择性。此外，
• NOVEL COMPOUNDS
  申请人：Buttar David

  公开号：US20080153812A1

  公开（公告）日：2008-06-26

  There is provided a compound of formula (I): or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula 1, and the use of a compound of Formula 1 as a medicament and in the treatment of cancer.

  提供了一个式(I)的化合物，或其药用可接受的盐。还提供了制备式1化合物的方法，以及将式1化合物用作药物和用于癌症治疗的用途。