N-((2-羟基-6-甲基-4-丙基-3-吡啶基)甲基)-1-异丙基-6-(2-(4-甲基-1-哌嗪基)-4-吡啶基)-1H-吲唑-4-甲酰胺 | 1346704-33-3

• 物质功能分类: 生物化工 - 抑制剂 - 表观遗传学(Epigenetics)
• 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: N-((2-羟基-6-甲基-4-丙基-3-吡啶基)甲基)-1-异丙基-6-(2-(4-甲基-1-哌嗪基)-4-吡啶基)-1H-吲唑-4-甲酰胺
• 中文别名: 1-异丙基-N-[(6-甲基-2-氧代-4-丙基-1,2-二氢-3-吡啶基)甲基]-6-[2-(4-甲基-1-哌嗪基)-4-吡啶基]-1H-吲唑-4-甲酰胺
• 英文名称: N-[(1,2-dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1- methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4- carboxamide
• 英文别名: 1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-d ihydro-3-pryidinyl)methyl]-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide；1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide；N-[(1,2-dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole-4-carboxamide；N-[(6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1-(propan-2-yl)-1H-indazole-4-carboxamide；1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-indazole-4-carboxamide；N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1-propan-2-ylindazol-4-carboxamide；Gsk343；N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-1-propan-2-ylindazole-4-carboxamide
• CAS: 1346704-33-3
• 化学式: C₃₁H₃₉N₇O₂
• 分子量: 541.696
• InChiKey: ULNXAWLQFZMIHX-UHFFFAOYSA-N

物化性质

• 沸点：
  797.4±60.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO：可溶15mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  95.4
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• WGK Germany：
  3
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : GSK343
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 1346704-33-3
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xn Harmful R22
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
Precautionary statement(s) none
Supplemental Hazard none
Statements
Other hazards - none

---

SECTION 3: Composition/information on ingredients
Substances
Synonyms : N-[(1,2-Dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-
methylethyl)-6-[2-(4-methyl-1-piperazinyl)-4-pyridinyl]-1H-indazole
N-[(6-Methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl]-6-[2-(4-
methylpiperazin-1-yl)pyridin-4-yl]-1-(propan-2-yl)-1H-indazole-4
Formula : C31H39N7O2
Molecular Weight : 541,69 g/mol
CAS-No. : 1346704-33-3
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
N-[(1,2-dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-
piperazinyl)-4-pyridinyl]-1H-indazole
CAS-No. 1346704-33-3 Acute Tox. 4; H302 <= 100 %
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
N-[(1,2-dihydro-6-methyl-2-oxo-4-propyl-3-pyridinyl)methyl]-1-(1-methylethyl)-6-[2-(4-methyl-1-
piperazinyl)-4-pyridinyl]-1H-indazole
CAS-No. 1346704-33-3 Xn, R22 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

---

SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
no data available

---

SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

---

SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: 2 - 8 °C
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

---

SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

---

SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evapouration rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Auto-ignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

---

SECTION 10: Stability and reactivity
Reactivity
no data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

---

SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

---

SECTION 12: Ecological information
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
no data available

---

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

---

SECTION 14: Transport information
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

---

SECTION 15: Regulatory information
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

---

SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
Acute Tox. Acute toxicity
H302 Harmful if swallowed.
Full text of R-phrases referred to under sections 2 and 3
Xn Harmful
R22 Harmful if swallowed.
Further information
Copyright 2013 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

生物活性 GSK343是一种有效的、选择性EZH2抑制剂，无细胞试验中IC50为4 nM，比作用于EZH1的选择性高60倍，比其他组蛋白甲基转移酶的选择性高1000倍以上。此外，它还能诱导自噬。

靶点

Target	Value
EZH2 (Cell-free assay)	4 nM
EZH1 (Cell-free assay)	240 nM

体外研究 GSK343能够抑制H3K27（H3K27me3）的三甲基化，在HCC1806肺癌细胞中，IC50为174 nM。该化合物有效抑制乳腺癌和前列腺癌细胞的增殖，其中LNCaP前列腺癌细胞系对GSK343最敏感，其IC50值为2.9 μM。此外，GSK343显著抑制EOC细胞的生长，并在模拟肿瘤体内微环境的3D人工基底膜细胞外基质（ECM）中培养时诱导这些细胞凋亡，同时也显著抑制了它们的侵袭能力。

特征 一种SGC表观遗传学整合的化学探针，在多种实体瘤中具有潜在用途。

反应信息

• 作为产物：
  描述：

  6-溴-4-吲唑甲酸甲酯 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium hydride 、 碳酸氢钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.58h， 生成 N-((2-羟基-6-甲基-4-丙基-3-吡啶基)甲基)-1-异丙基-6-(2-(4-甲基-1-哌嗪基)-4-吡啶基)-1H-吲唑-4-甲酰胺
  参考文献：
  名称：

  Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2

  摘要：

  The histone H3-lysine 27 (H3K27) methyltransferase EZH2 plays a critical role in regulating gene expression, and its aberrant activity is linked to the onset and progression of cancer. As part of a drug discovery program targeting EZH2, we have identified highly potent, selective, SAM-competitive, and cell-active EZH2 inhibitors, including GSK926 (3) and GSK343 (6). These compounds are small molecule chemical tools that would be useful to further explore the biology of EZH2.

  DOI：

  10.1021/ml3003346

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS UTILISATIONS
  申请人：INFINITY PHARMACEUTICALS INC

  公开号：WO2016054491A1

  公开（公告）日：2016-04-07

  Compounds of formula I' and formula II' and their pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity for the treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity.

  式I'和式II'的化合物及其调节激酶活性的药物组合物，包括用于治疗与激酶活性相关的疾病和状况，包括PI3激酶活性。
• INDAZOLES
  申请人：Duquenne Celine

  公开号：US20130053383A1

  公开（公告）日：2013-02-28

  Herein are disclosed indazoles of formula (I) where the various groups are defined herein, and which are useful for treating cancer.

  本文披露了式(I)中各种基团的吲唑类化合物，这些化合物对于治疗癌症是有用的。
• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：INFINITY PHARMACEUTICALS, INC.

  公开号：US20150111874A1

  公开（公告）日：2015-04-23

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

  本文描述了调节激酶活性，包括PI3激酶活性的化合物和制药组合物，以及与激酶活性，包括PI3激酶活性相关的疾病和状况的治疗方法、化合物和制药组合物。
• [EN] TETRAHYDROQUINAZOLINE DERIVATIVES AS SELECTIVE CYTOTOXIC AGENTS<br/>[FR] DÉRIVÉS DE TÉTRAHYDROQUINAZOLINE UTILISÉS EN TANT QU'AGENTS CYTOTOXIQUES SÉLECTIFS
  申请人：MERCK SHARP & DOHME

  公开号：WO2022125412A1

  公开（公告）日：2022-06-16

  The present disclosure is directed to tetrahydroquinazoline derivatives of Formula (I) and their use for selectively killing HIV infected GAG-POL expressing cells without concomitant cytotoxicity to HIV naive cells, and for the treatment or prophylaxis of infection by HIV, or for the treatment, prophylaxis or delay in the onset or progression of AIDS or AIDS Related Complex (ARC).

  本公开涉及式(I)的四氢喹唑啉衍生物及其用于选择性杀死表达GAG-POL的HIV感染细胞，而不对HIV原始细胞产生细胞毒性，以及用于治疗或预防HIV感染，或用于治疗、预防或延迟AIDS或AIDS相关综合症（ARC）的发作或进展。
• CULTURE SYSTEM FOR CHEMICALLY INDUCING GENERATION OF PLURIPOTENT STEM CELLS AND CHEMICAL REPROGRAMMING METHOD USING SAME
  申请人：Guangzhou Institutes Of Biomedicine And Health Chinese Academy Of Sciences

  公开号：EP3760709A1

  公开（公告）日：2021-01-06

  Disclosed herein is a culture system for chemical induction of pluripotent stem cells, comprising a basic culture medium and a composition for performing chemical induction of reprogramming process. The said composition comprises a thymine analogue, a cAMP activator, a TGF-β receptor inhibitor, a bone morphogenetic protein, a RA receptor activator, a GSK3 inhibitor and a basic fibroblast growth factor. And the said culture system is free of serum. By using the culture system as described herein, there is no need to frequently replate cells during culture, such that culturing process is simplified and loss of cells resulting from replating cells is reduced. As the culture system is free of serum, subsequent collection of pluripotent stem cells and molecular mechanism analysis are simplified, thereby facilitating establishment of no animal origin culture systems for induction of pluripotent stem cells.

  本文公开了一种用于化学诱导多能干细胞的培养系统，该系统包括一种基本培养基和一种用于执行化学诱导重编程过程的组合物。所述组合物包括胸腺嘧啶类似物、cAMP 激活剂、TGF-β 受体抑制剂、骨形态发生蛋白、RA 受体激活剂、GSK3 抑制剂和碱性成纤维细胞生长因子。上述培养系统不含血清。使用本文所述的培养体系，在培养过程中无需频繁地进行细胞复制，从而简化了培养过程，减少了因细胞复制而造成的细胞损失。由于该培养体系不含血清，因此简化了后续的多能干细胞收集和分子机理分析，从而有利于建立无动物源培养体系来诱导多能干细胞。