5-[[7-[3-[乙基(2-羟基乙基)氨基]丙氧基]-4-喹唑啉]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺 | 722544-51-6

• 物质功能分类: 生物化工 - 抑制剂 - 细胞周期(Cell Cycle)
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 5-[[7-[3-[乙基(2-羟基乙基)氨基]丙氧基]-4-喹唑啉]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺
• 中文别名: 巴拉塞替
• 英文名称: N-(3-fluorophenyl)-2-{3-[(7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazolin-4-yl)amino]-1H-pyrazol-5-yl}acetamide
• 英文别名: AZD1152HQPA；2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3 -fluorophenyl)acetamide；2-(3-((7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-yl)amino)-1H-pyrazol-5-yl)-N-(3-fluorophenyl)acetamide；3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-fluorophenyl)-1H-pyrazole-5-acetamide；AZD-1152-HQPA；barasertib；Azd-1152hqpa；2-[3-[[7-[3-[ethyl(2-hydroxyethyl)amino]propoxy]quinazolin-4-yl]amino]-1H-pyrazol-5-yl]-N-(3-fluorophenyl)acetamide
• CAS: 722544-51-6
• 化学式: C₂₆H₃₀FN₇O₃
• 分子量: 507.568
• InChiKey: QYZOGCMHVIGURT-UHFFFAOYSA-N

物化性质

• 沸点：
  796.7±60.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>15mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  9

安全信息

• WGK Germany：
  3
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  2-8°C

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : AZD1152-HQPA
: SML0268
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. : 722544-51-6

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
This substance is not classified as dangerous according to Directive 67/548/EEC.
Other hazards - none

---

SECTION 3: Composition/information on ingredients
Substances
Synonyms : 3-[[7-[3-[Ethyl(2-hydroxyethyl)amino]propoxy]-4-quinazolinyl]amino]-N-(3-
fluorophenyl)-1H-pyrazole-5-acetamide
Formula : C26H30FN7O3
Molecular Weight : 507,56 g/mol
CAS-No. : 722544-51-6
No components need to be disclosed according to the applicable regulations.

---

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), Hydrogen fluoride
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. 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 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
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
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. 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

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Barasertib (AZD1152-HQPA, AZD2811, INH-34) 是一种高度选择性的 Aurora B 抑制剂，在无细胞试验中 IC50 为 0.37 nM，对 Aurora B 的作用比对 Aurora A 高约 3700 倍。

体外研究

AZD1152 对 Aurora B 的作用比对 Aurora A 高出 3000 多倍，IC50 为 1.368 μM。AZD1152 对 50 种其他丝-苏氨酸和酪氨酸激酶的活性较低，包括 FLT3、JAK2 和 Abl。

AZD1152 抑制造血恶性细胞增殖，如 HL-60、NB4、MOLM13、PALL-1、PALL-2、MV4-11、EOL-1、THP-1 和 K562 细胞，IC50 为 3-40 nM。其效果比另一种 Aurora 激酶抑制剂 ZM334739 高约 100 倍（IC50 为 3-30 μM）。

AZD1152 抑制 MOLM13 和 MV4-11 细胞克隆生长，IC50 分别为 1 nM 和 2.8 nM。它也抑制新分离的抗 Imatinib 的白血病细胞，IC50 为 1-3 nM，比作用于骨髓单核细胞更有效（IC50 > 10 nM）。AZD1152 诱导携带 4N/8N DNA 的细胞累积，并随后凋亡，这种作用存在剂量和时间依赖性。

体内研究

AZD1152 按 25 mg/kg 剂量单独处理 MOLM13 移植瘤，显著抑制肿瘤生长。平均肿瘤体积从 1261 mm³ 减少到 71 mm³，平均肿瘤重量从 583 mg 减少到 78 mg，并观察到坏死组织被吞噬细胞浸润。

此外，AZD1152 每天按 10-150 mg/kg 剂量处理多种人类实体瘤移植瘤，包括结肠癌、乳腺癌和肺癌，显著抑制肿瘤生长。这种作用存在剂量依赖性。

反应信息

• 作为反应物：
  描述：

  5-[[7-[3-[乙基(2-羟基乙基)氨基]丙氧基]-4-喹唑啉]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺 在 四氮唑 、 盐酸 、 氧化环己烯 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 5-[[7-[3-[乙基[2-(磷酰氧基)乙基]氨基]丙氧基]-4-喹唑啉基]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺
  参考文献：
  名称：

  新型吡唑并喹唑啉类化合物作为极光B激酶的选择性抑制剂的发现，合成和体内活性。

  摘要：

  作为开发新的抗癌剂的靶标，极光激酶已成为引起人们极大兴趣的主题。尽管有证据表明抑制Aurora B激酶会引起更明显的抗增殖表型，但迄今为止，据报道，临床上最先进的药物通常同时抑制Aurora A和B。我们发现了一系列吡唑并喹唑啉，其中有些显示超过1000倍在重组酶分析中对Aurora B的选择性高于Aurora A激酶活性。这些化合物已被设计用于肠胃外给药，并由于其以易于活化的磷酸酯衍生物形式传递的能力而实现了高水平的溶解性。前药在体内被完全转化为脱磷酸形式，并且活性物质具有有利的药代动力学性质和安全药理学特性。这些化合物具有惊人的体内活性，已经选择了化合物5（AZD1152）进行临床评估，目前处于1期临床试验中。

  DOI：

  10.1021/jm061335f
• 作为产物：
  描述：

  4-amino-7-{3-[ethyl(2-hydroxyethyl)amino]propoxy}quinazoline 在 四丁基硫酸氢铵 、 sodium hydroxide 作用下， 以 水 为溶剂， 生成 5-[[7-[3-[乙基(2-羟基乙基)氨基]丙氧基]-4-喹唑啉]氨基]-N-(3-氟苯基)-1H-吡唑-3-乙酰胺
  参考文献：
  名称：

  巴拉塞替的制备方法

  摘要：

  本发明公开了巴拉塞替的制备方法，所述巴拉塞替化学名称为2‑{5‑[（7‑{3‑[乙基(2‑羟基乙基)氨基]丙氧基}喹唑啉‑4‑基)氨基]‑1H‑吡唑‑3‑基}‑N‑(3‑氟苯基)乙酰胺，其化学式为C26H30FN7O3；本发明制备工艺过程简洁，原料易得，经济环保，有利于实现工业化，可促进巴拉塞替原料药的经济技术发展，降低了生成成本，适于大批量生产。

  公开号：

  CN107641115A

文献信息

• ANTIPROLIFERATIVE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE
  申请人：Celgene Corporation

  公开号：US20200215060A1

  公开（公告）日：2020-07-09

  Provided herein are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof, in combination with a second active agent for treating, preventing or managing multiple myeloma. The second active agent is one or more of a BTK inhibitor, an mTOR inhibitor, a PIM inhibitor, an IGF-1R inhibitor, an MEK inhibitor, an XPO1 inhibitor, a DOT1L inhibitor, an EZH2 inhibitor, a JAK2 inhibitor, a BRD4 inhibitor, a PLK 1 inhibitor, an NEK2 inhibitor, an AURKB inhibitor, a BIRC5 inhibitor, a BET inhibitor, or a DNA methyltransferase inhibitor.

  本文提供了使用4-(4-(4-(((2-(2,6-二氧代哌啶-3-基)-1-氧代异吲哚啉-4-基)氧基)甲基)苄基)哌嗪-1-基)-3-氟苯甲腈，或其对映体、对映体混合物、互变异构体或其药学上可接受的盐，与第二活性剂结合用于治疗、预防或管理多发性骨髓瘤的方法。第二活性剂是BTK抑制剂、mTOR抑制剂、PIM抑制剂、IGF-1R抑制剂、MEK抑制剂、XPO1抑制剂、DOT1L抑制剂、EZH2抑制剂、JAK2抑制剂、BRD4抑制剂、PLK1抑制剂、NEK2抑制剂、AURKB抑制剂、BIRC5抑制剂、BET抑制剂或DNA甲基转移酶抑制剂中的一个或多个。
• PROCESS AND INTERMEDIATE
  申请人：Pittam John David

  公开号：US20070270384A1

  公开（公告）日：2007-11-22

  The invention relates to a new process useful in the preparation of pharmaceutical compounds such as 2-ethyl[3-(4-[(5-2-[(3-fluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-3-yl)amino]quinazolin-7-yl}oxy)propyl]amino}ethyl dihydrogen phosphate (AZD1152) and intermediates used therein.

  本发明涉及一种新的工艺，用于制备药物化合物，例如2-乙基[3-(4-[(5-2-[(3-氟苯基)氨基]-2-氧代乙基}-1H-吡唑-3-基)氨基]喹唑啉-7-基}氧基)丙基]氨基}乙酸二氢磷酸盐（AZD1152）及其中使用的中间体。
• [EN] FORMULATIONS FOR IMPROVING THE EFFICACY OF HYDROPHOBIC DRUGS<br/>[FR] FORMULATIONS PERMETTANT D'AMÉLIORER L'EFFICACITÉ DES MÉDICAMENTS HYDROPHOBES
  申请人：PEPTINOVO BIOPHARMA LLC

  公开号：WO2017011312A1

  公开（公告）日：2017-01-19

  Novel amphiphilic peptide, peptide amphiphile lipid micelles, processes for making peptide amphiphile lipid micelles comprising an amphiphilic peptide and phospholipid and optionally comprising a cargo molecule, and methods of use.

  小说性两性肽，肽两性脂质微粒，制备肽两性脂质微粒的方法包括两性肽和磷脂质，并可选地包括载荷分子，以及使用方法。
• COMBINATION THERAPY FOR THE TREATMENT OF CANCER
  申请人：Keen Nicholas John

  公开号：US20090253616A1

  公开（公告）日：2009-10-08

  A combination comprising an aurora kinase inhibitor and an efflux transporter inhibitor wherein the aurora kinase inhibitor is a compound of formula (I) or pharmaceutically acceptable salt thereof for use in the treatment of hyperproliferative diseases such as cancer.

  一种组合物，包括一个极化激酶抑制剂和一个外排转运蛋白抑制剂，其中极化激酶抑制剂是式（I）的化合物或其药学上可接受的盐，用于治疗癌症等高增殖性疾病。
• Phosphonooxy quinazoline derivatives and their pharmaceutical use
  申请人：Heron Murdoch Nicola

  公开号：US20060116357A1

  公开（公告）日：2006-06-01

  Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a nitrogen atom and one or two further nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.

  公式（I）中的喹唑啉衍生物，其中A是含有一个或两个进一步的氮原子的5-成员杂环芳基；包含它们的组合物，它们的制备过程以及它们在治疗中的用途。