4-(6-(4-(哌嗪-1-基)苯基)吡唑并[1,5-a]嘧啶-3-基)喹啉 | 1062368-24-4

• 物质功能分类: 生物化工 - 抑制剂 - TGF-beta/Smad信号通路抑制剂(TGF-beta/Smad)
• 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-(6-(4-(哌嗪-1-基)苯基)吡唑并[1,5-a]嘧啶-3-基)喹啉
• 中文别名: BMPI型受体激酶抑制剂(LDN193189)；化合物LDN-193189；4-[6-(4-(哌嗪-1-基)苯基]吡唑并[1,5-A]嘧啶-3-基)喹啉；厚朴酚.木兰醇；LDN-193189,一种选择性BMP信号转导抑制剂
• 英文名称: LDN-193189
• 英文别名: 4-(6-(4-(piperazin-1-yl)phenyl)pyrazolo[1,5-a]pyrimidin-3-yl)quinoline；4-[6-[4-(1-piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline；4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline；LDN 193189；LDN193189；DM-3189
• CAS: 1062368-24-4
• 化学式: C₂₅H₂₂N₆
• 分子量: 406.49
• InChiKey: CDOVNWNANFFLFJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.33
• 溶解度：
  H2O中可溶 5mg/mL，澄清（加热）

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 海关编码：
  29339900
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : LDN193189 dihydrochloride
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.
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
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 : 4-[6-[4-(1-Piperazinyl)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-quinoline
dihydrochloride
Formula : C25H22N6.2HCl
Molecular Weight : 479,40 g/mol
No components need to be disclosed according to the applicable regulations.

---

SECTION 4: First aid measures
Description of first aid measures
no data available
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
no data available
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas
Advice for firefighters
no data available
Further information
no data available

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
For personal protection see section 8.
Environmental precautions
no data available
Methods and materials for containment and cleaning up
no data available
Reference to other sections
For disposal see section 13.

---

SECTION 7: Handling and storage
Precautions for safe handling
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Recommended storage temperature: -20 °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
no data available

---

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
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
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
no data available

---

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

制备方法与用途

生物活性

LDN-193189 是一种选择性的BMP信号通路抑制剂，在C2C12细胞中IC50分别为5 nM（ALK2）和30 nM（ALK3），其对BMP的选择性比TGF-β高200倍。

体外研究

LDN193189有效抑制了BMP4介导的Smad1、Smad5和Smad8的活化，IC50为5 nM，并有效地抑制BMP I型受体ALK2和ALK3的转录活性，IC50分别为5 nM和30 nM。此外，该化合物还抑制了组成型活性ALK2^R206H或ALK2^Q207D突变蛋白诱导的转录活性。

最近的一项研究表明，在动脉粥样硬化形成的人主动脉内皮细胞中，LDN-193189能够阻止氧化低密度脂蛋诱导的活性氧生成。

体内研究

在利用Ad.Cre条件性caALK2转基因小鼠中，从7日龄（P7）开始使用LDN-193189（3 mg/kg,腹腔注射），导致邻近的左胫骨和腓骨在P13出现轻度钙化，并防止了P15时放射线病变的发生，不会造成体重减轻或生长迟缓、自发性骨折、骨质密度下降或行为异常。LDN-193189通过抑制BMP6诱导的信号转导途径使斑马鱼胚胎背部化，但对血管发育没有影响。

在含PCa-118b瘤小鼠中，LDN-193189削弱了肿瘤生长并降低了肿瘤中的骨形成。在低密度脂蛋白受体缺陷（LDLR-/-）小鼠中，该化合物有效地抑制动脉粥样硬化的进展。此外，LDN-193189还表现出对相关血管炎、成骨活性和钙化的抑制作用。

靶点

Target	Value
ALK2 (C2C12 cells)	5 nM
ALK3 (C2C12 cells)	30 nM

反应信息

• 作为产物：
  描述：

  2-(喹啉-4-基)乙腈 在 tris-(dibenzylideneacetone)dipalladium(0) 、 5%-palladium/activated carbon 、 2-(二叔丁基膦)联苯 氢溴酸肼 、 potassium tert-butylate 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 1,1-二氯乙烷 、 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0~170.0 ℃ 、101.33 kPa 条件下， 反应 35.08h， 生成 4-(6-(4-(哌嗪-1-基)苯基)吡唑并[1,5-a]嘧啶-3-基)喹啉
  参考文献：
  名称：

  [EN] INHIBITORS OF THE BMP SIGNALING PATHWAY
  [FR] INHIBITEURS DE LA VOIE DE SIGNALISATION BMP

  摘要：

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号通路相关的疾病或症状，包括炎症、心血管疾病、血液学疾病、癌症和骨骼疾病，以及调节细胞分化和/或增殖。

  公开号：

  WO2009114180A1

文献信息

• [EN] COMPOSITIONS AND METHODS FOR INHIBITING BMP<br/>[FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE LA BMP
  申请人：BRIGHAM & WOMENS HOSPITAL

  公开号：WO2016011019A1

  公开（公告）日：2016-01-21

  The present invention provides small-molecule inhibitors of BMP signaling and compositions and methods for inhibiting BMP signaling. These compounds and compositions may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds and compositions may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

  本发明提供了BMP信号通路的小分子抑制剂，以及用于抑制BMP信号通路的组合物和方法。这些化合物和组合物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号通路相关的疾病或症状，包括炎症、心血管疾病、血液疾病、癌症和骨骼疾病，以及用于调节细胞分化和/或增殖。这些化合物和组合物还可用于降低ApoB-100或LDL的循环水平，并治疗或预防获得性或先天性高胆固醇血症或高脂蛋白血症；与脂质吸收或代谢缺陷相关的疾病、紊乱或综合征；或由高脂血症引起的疾病、紊乱或综合征。
• [EN] METHODS OF CULTURING AND/OR EXPANDING STEM CELLS AND/OR LINEAGE COMMITTED PROGENITOR CELLS USING AMIDO COMPOUNDS<br/>[FR] PROCÉDÉS DE CULTURE ET/OU D'EXPANSION DE CELLULES SOUCHES ET/OU DE CELLULES PROGÉNITRICES DÉTERMINÉES D'UNE LIGNÉE À L'AIDE DE COMPOSÉS AMIDO
  申请人：IDEAYA BIOSCIENCES INC

  公开号：WO2020018848A1

  公开（公告）日：2020-01-23

  Provided are methods for expanding stem cells and/or lineage committed progenitor cells, such as hematopoietic stems cells and/or lineage committed progenitor cells, at least in part, by using compounds that antagonize AhR. The compounds are represented by formulae (I) (II) (III) (IV), wherein the letters and symbols a, b, c, d, e, f, g, Z, R1b, R2a and R2b have the meanings provided in the specification. Also provided are compositions comprising stem cells and/or lineage committed progenitor cells expanded by methods disclosed herein and methods for the treatment of diseases treatable by same.

  提供了一种扩增干细胞和/或系谱承诺的前体细胞的方法，例如造血干细胞和/或系谱承诺的前体细胞，至少部分地通过使用拮抗AhR的化合物。这些化合物由公式 (I) (II) (III) (IV) 表示，其中字母和符号 a、b、c、d、e、f、g、Z、R1b、R2a 和 R2b 在说明书中有提供的含义。还提供了包含通过本文披露的方法扩增的干细胞和/或系谱承诺的前体细胞的组合物，以及用于治疗可通过相同方法治疗的疾病的方法。
• [EN] BMP INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE BMP ET LEURS PROCÉDÉS D'UTILISATION
  申请人：BRIGHAM & WOMENS HOSPITAL

  公开号：WO2014138088A1

  公开（公告）日：2014-09-12

  The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号相关的疾病或症状，包括炎症、心血管疾病、血液疾病、癌症和骨骼疾病，以及用于调节细胞分化和/或增殖。这些化合物还可用于降低ApoB-100或LDL的循环水平，并治疗或预防获得性或先天性高胆固醇血症或高脂蛋白血症；与脂质吸收或代谢缺陷相关的疾病、疾病或综合征；或由高脂血症引起的疾病、疾病或综合征。
• INHIBITORS OF THE BMP SIGNALING PATHWAY
  申请人：Yu Paul B.

  公开号：US20110053930A1

  公开（公告）日：2011-03-03

  The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可以用于调节细胞生长、分化、增殖和凋亡，因此可能有用于治疗与BMP信号通路相关的疾病或病症，包括炎症、心血管疾病、血液疾病、癌症和骨骼疾病，以及调节细胞分化和/或增殖。
• BMP INHIBITORS AND METHODS OF USE THEREOF
  申请人：THE BRIGHAM AND WOMEN'S HOSPITAL, INC.

  公开号：US20160046633A1

  公开（公告）日：2016-02-18

  The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

  本发明提供了BMP信号通路的小分子抑制剂。这些化合物可用于调节细胞生长、分化、增殖和凋亡，因此可用于治疗与BMP信号通路相关的疾病或病症，包括炎症、心血管疾病、血液病、癌症和骨病，以及调节细胞分化和/或增殖。这些化合物还可用于降低ApoB-100或LDL的循环水平，治疗或预防获得性或先天性高胆固醇血症或高脂蛋白血症；与脂质吸收或代谢缺陷相关的疾病、疾病或综合症；或由高脂血症引起的疾病、疾病或综合症。