199864-86-3

199864-86-3结构式

常用中文名：RS 127445
常用英文名：RS 127445
CAS号：199864-86-3
分子式：C₁₇H₁₇ClFN₃
分子量：317.78800
相关类别：信号通路 G 蛋白偶联受体/G 蛋白 5-HT受体
发布时间：2018-06-25 11:00:13
更新时间：2024-01-03 09:11:27
RS 127445 是一种选择性的 5-HT2B 受体拮抗剂,pKi 为 9.5。

化源商城直购

中文名	2-氨基-4-(4-氟萘-1-基)-6-异丙基嘧啶盐酸盐
英文名	4-(4-Fluoronaphthalen-1-yl)-6-isopropylpyrimidin-2-amine hydrochloride
英文别名	RS-127445 Hydrochloride 2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine hydrochloride RS 127445

描述	RS 127445 是一种选择性的 5-HT2B 受体拮抗剂,pKi 为 9.5。
相关类别	信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体信号通路 >> 神经信号通路 >> 5-HT受体研究领域 >> 神经疾病
靶点	5-HT1A Receptor:5.5 (pKi) 5-HT1B/D Receptor:<6 (pKi) 5-HT3 Receptor:<6 (pKi) 5-HT5 Receptor:<6 (pKi) 5-HT6 Receptor:<6 (pKi) 5-HT2A Receptor:6.3 (pKi) 5-HT2C Receptor:6.4 (pKi) 5-HT2B Receptor:9.5 (pKi)
体外研究	发现RS-127445对5-HT2B受体具有纳摩尔亲和力(pKi = 9.5±0.1),并且与许多其他受体和离子通道结合位点相比,对该受体具有1,000倍的选择性。 RS-127445有效地置换CHO-K1细胞中表达的人重组5-HT2B受体的[3H] -5-HT。 RS-127445对5-HT2B受体的亲和力(pKi值)为9.5±0.1(n = 9)。 RS-127445对5-HT2B受体具有选择性,对人重组5-HT2A,5-HT2C,5-HT5,5-HT6和5-HT7受体的亲和力约为1000倍,大鼠中的5-HT1A受体脑膜,牛尾状核中的5-HT1B/D受体和兔血小板中的单胺摄取位点。 RS-127445有效阻断表达5-HT2B受体的HEK-293细胞中5-HT(10nM)引起的细胞内钙浓度的增加(pIC50为10.4±0.1)。在表达人重组5-HT2B受体的细胞中,RS-127445有效拮抗5-HT诱发的肌醇磷酸形成(pKB = 9.5±0.1)和5-HT诱发的细胞内钙增加(pIC10 = 10.4±0.1)。 RS-127445还可阻断5-HT诱发的大鼠离体胃底部收缩(pA2B = 9.5±1.1)和(±)α-甲基-5-HT介导的大鼠颈静脉松弛(pA2 = 9.9±0.3)[ 1]。
体内研究	在大鼠中,通过口服或腹膜内途径生物可利用的RS-127445的比例分别为14％和60％。腹膜内施用RS-127445(5mg/kg)产生的血浆浓度预计可使可接近的5-HT2B受体完全饱和至少4小时。通过口服,腹膜内和静脉内途径给予大鼠RS-127445(5mg/kg) 。在静脉内和腹膜内给药后(0.08小时)和通过口服给药途径给药后0.25小时测量的第一时间点发现最高浓度,迅速达到峰值血浆浓度。从等离子体中清除RS-127445,估计终末消除半衰期约为1.7小时。当通过口服和腹膜内途径给药时,RS-127445的生物利用度约为静脉内给药所得的生物利用度的14％和62％。大约60％的腹膜内剂量和14％的口服剂量RS-127445(5 mg/kg)是生物可利用的[1]。 RS-127445(1-30 mg/kg),剂量依赖性地减少粪便输出,在10和30 mg/kg(n = 6-11)时达到显着性。在血液和大脑中,> 98％的RS-127445是蛋白质结合的[2]。
激酶实验	使用磷酸盐缓冲盐水中的2mM EDTA收获表达人5-HT2A，5-HT2B或5-HT2C受体的CHO-K1细胞。通过四个均质化循环（Brinkman P10破碎剂）和离心（48,000×g，15分钟）制备细胞膜。如前所述，建立每个测定以实现稳态条件并优化特异性结合。对于5-HT2A受体，将来自1×10 6个细胞的膜与0.2nM [3H] - 酮色林在32℃下孵育60分钟。使用10μM甲基麦角酰胺测定非特异性结合。对于5-HT2B受体，将来自1.5×10 6个细胞的膜与0.2nM [3H] -5-HT在4℃温育120分钟。使用10μM5-HT测定非特异性结合。对于5-HT2C受体，将来自3×10 5个细胞的膜与0.5nM [3H] - 美舒麦白在32℃温育60分钟。使用10μM甲基麦角酰胺测定非特异性结合。通过已经用0.1％聚乙烯亚胺预处理的玻璃纤维过滤器（GF / B）进行真空过滤来终止测定。通过液体闪烁计数测定总和结合放射性。在这些测定中的每一种中实现大于90％的特异性结合。通过在超过100个额外的离子通道或受体结合位点测试化合物的亲和力，进一步检查RS-127445对5-HT2B受体的选择性。这些研究由Cerep使用标准方案[1]进行。
细胞实验	将表达人5-HT2B受体的HEK-293细胞与[3H] - 肌醇（1.67μCi/ mL）在162cm 2烧瓶中在37℃下在含有10％透析的胎牛血清的无肌醇的Ham's F12培养基中温育过夜。收获细胞，用磷酸盐缓冲盐水洗涤五次，并以约3×10 6个细胞/ mL的密度重悬于无肌醇的Ham's F12培养基中。 RS-127445（10μM）最初溶解于10％（v / v）DMSO和90％无肌醇的Ham's F12培养基中。随后用不含肌醇的Ham's F12培养基稀释。将5-HT溶于含有100mM LiCl和1mM抗坏血酸的无肌醇的Ham's F12培养基中。将RS-127445，载体或其他拮抗剂与240μL细胞悬浮液在37℃预温育20分钟。通过添加5-HT引发反应。 60分钟后，通过加入50μL冰冷的20％高氯酸终止反应，在冰水浴中冷却10分钟，然后用160μL1NKOH中和。每种样品在室温下用2ml 50mM Tris-HCl，pH 7.4稀释。将含水部分（2.2mL）转移到已用5ml蒸馏水洗涤的Dowex AG1X8柱（1ml，1：1，w / v）上。然后用18ml蒸馏水洗涤柱子，用3ml 1N HCl洗脱肌醇磷酸酯。使用Packard 1900CA分析仪[1]通过液体闪烁光谱测定洗脱的放射性。
动物实验	大鼠[1]使用雄性Sprague-Dawley大鼠（200g）。为了比较不同给药途径后RS-127445的血浆动力学，将90只大鼠分成三个治疗组，每组30只大鼠。向每只大鼠施用单剂量的RS-127445（5mg / kg）溶解（2.5mg / mL）的乙醇：丙二醇：水（10：50：40，v：v：v）。在给药后0.08,0.25,0.5,1,2,4,8和24小时，将大鼠麻醉并通过心脏穿刺收集血液样品。小鼠[2]使用成年雄性C57BL / 6J小鼠（25-30g）。 RS-127445（1nM-10μM，每组织单一浓度，15分钟接触时间）或载体（5或50μLDMSO）的作用表示为与四种前药的平均振幅相比的振幅变化百分比。，EFS后的收缩反应。使用双样本等方差t检验分析结果。
参考文献	[1]. Bonhaus DW, et al. RS-127445: a selective, high affinity, orally bioavailable 5-HT2B receptor antagonist. Br J Pharmacol. 1999 Jul;127(5):1075-82. [2]. Bassil AK, et al. Inhibition of colonic motility and defecation by RS-127445 suggests an involvement of the 5-HT2B receptor in rodent large bowel physiology. Br J Pharmacol. 2009 Sep;158(1):252-8

分子式	C₁₇H₁₇ClFN₃
分子量	317.78800
精确质量	317.11000
PSA	51.80000
LogP	5.52470
储存条件	2-8℃

Section1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name: RS-127445 Hydrochloride
CAS-No.: 199864-86-3
Relevant identified uses of the substance or mixture and uses advised against
Identified uses: Laboratory chemicals, Manufacture of substances

Section2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP]
Acute toxicity, Oral (Category 3)
Skin irritation (Category 2)
Eye irritation (Category 2)
Specific target organ toxicity - single exposure (Category 3)
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Toxic if swallowed. Irritating to eyes, respiratory system and skin.
Label elements
Labelling according Regulation (EC) No 1272/2008 [CLP]
Pictogram
Signal wordDanger
Hazard statement(s)
H301Toxic if swallowed.
H315Causes skin irritation.
H319Causes serious eye irritation.
H335May cause respiratory irritation.
Precautionary statement(s)
P261Avoid breathing dust/ fume/ gas/ mist/ vapours/ spray.
P301 + P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/
physician.
P305 + P351 + P338IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazardnone
Statements
According to European Directive 67/548/EEC as amended.
Hazard symbol(s)
R-phrase(s)
R25Toxic if swallowed.
R36Irritating to eyes.
S-phrase(s)
S26In case of contact with eyes, rinse immediately with plenty of water and
seek medical advice.
S45In case of accident or if you feel unwell, seek medical advice immediately
(show the label where possible).
Other hazards - none

Section3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms: 2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine Hydrochloride
Formula: C17H16FN3 · HCl
Molecular Weight: 317,79 g/mol
ComponentConcentration
2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine hydrochloride
CAS-No.199864-86-3-

Section4. 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. Take victim immediately to hospital. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
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
To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly
investigated.
Indication of any immediate medical attention and special treatment needed
no data available

Section5. FIRE-FIGHTING 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 chloride gas, Hydrogen fluoride
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

Section6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate
ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
Environmental precautions
Prevent further leakage or spillage if safe to do so. 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.

Section7. 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.
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 uses
no data available

Section8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the
product.
Personal protective equipment
Eye/face protection
Face shield and safety glasses 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
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such as
NIOSH (US) or CEN (EU).

Section9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) AppearanceForm: solid
b) Odourno data available
c) Odour Thresholdno data available
d) pHno data available
e) Melting point/freezingMelting point/range: 156 - 158 °C
point
f) Initial boiling point and no data available
boiling range
g) Flash pointno data available
h) Evaporation rateno data available
i) Flammability (solid, gas) no data available
j) Upper/lowerno data available
flammability or
explosive limits
k) Vapour pressureno data available
l) Vapour densityno data available
m) Relative densityno data available
n) Water solubilityno data available
o) Partition coefficient: n- log Pow: 4,381
octanol/water
p) Autoignitionno data available
temperature
q) Decompositionno data available
temperature
r) Viscosityno data available
s) Explosive propertiesno data available
t) Oxidizing propertiesno data available
Other safety information
no data available

Section10. 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
Other decomposition products - no data available

Section11. 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 sensitization
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
Inhalation - May cause respiratory irritation.
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation
May be harmful if inhaled. Causes respiratory tract irritation.
IngestionToxic if swallowed.
SkinMay be harmful if absorbed through skin. Causes skin irritation.
EyesCauses serious eye irritation.
Signs and Symptoms of Exposure
To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly
investigated.
Additional Information
RTECS: Not available

Section12. 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
no data available
Other adverse effects
no data available

Section13. 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.

Section14. TRANSPORT INFORMATION
UN number
ADR/RID: 2811IMDG: 2811IATA: 2811
UN proper shipping name
ADR/RID: TOXIC SOLID, ORGANIC, N.O.S. (2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine
hydrochloride)
IMDG: TOXIC SOLID, ORGANIC, N.O.S. (2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine
hydrochloride)
IATA:Toxic solid, organic, n.o.s. (2-Amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine
hydrochloride)
Transport hazard class(es)
ADR/RID: 6.1IMDG: 6.1IATA: 6.1
Packaging group
ADR/RID: IIIIMDG: IIIIATA: III
Environmental hazards
ADR/RID: noIMDG Marine pollutant: noIATA: no
Special precautions for user
no data available

Section15. 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
no data available

Section16. OTHER INFORMATION
Further information
Copyright 2011 Co. 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. Co., shall not be held liable for any damage
resulting from handling or from contact with the above product. See reverse side of invoice or packing slip
for additional terms and conditions of sale.

符号	GHS06
信号词	Danger
危害声明	H301-H315-H319-H335
警示性声明	P261-P301 + P310-P305 + P351 + P338
危险品运输编码	UN 2811 6.1 / PGIII
海关编码	2933599090

海关编码	2933599090
中文概述	2933599090. 其他结构上有嘧啶环的化合物(包括其他结构上有哌嗪环的化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933599090. other compounds containing a pyrimidine ring (whether or not hydrogenated) or piperazine ring in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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