SB 222200; 3-甲基-2-苯基-N-((1S)-1-苯基丙基)喹啉-4-甲酰胺 | 174635-69-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: SB 222200; 3-甲基-2-苯基-N-((1S)-1-苯基丙基)喹啉-4-甲酰胺
• 中文别名: SB222200;3-甲基-2-苯基-N-((1S)-1-苯基丙基)喹啉-4-甲酰胺；3-甲基-2-苯基-N-((1S)-1-苯基丙基)喹啉-4-甲酰胺；3-甲基-2-苯基-N-[(1S)-1-苯基丙基]喹啉-4-甲酰胺
• 英文名称: (-)-(S)-N-(α-ethylbenzyl)-3-methyl-2-phenylquinoline-4-carboxamide
• 英文别名: SB 222200；3-methyl-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide
• CAS: 174635-69-9
• 化学式: C₂₆H₂₄N₂O
• 分子量: 380.489
• InChiKey: MQNYRKWJSMQECI-QFIPXVFZSA-N

物化性质

• 熔点：
  154℃
• 沸点：
  553.5±50.0 °C(Predicted)
• 密度：
  1.142
• 溶解度：
  DMSO：~28 mg/mL，可溶

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : SB 222200
CAS-No. : 174635-69-9
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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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
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Synonyms : (S)-3-Methyl-2-phenyl-N-(1-phenylpropyl)-4-quinolinecarboxamide
Formula : C26H24N2O
Molecular Weight : 380,48 g/mol

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Section 4. FIRST AID MEASURES
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
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.
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

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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

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Avoid dust formation. Avoid breathing vapors, mist or gas.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Sweep up and shovel. Keep in suitable, closed containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Provide appropriate exhaust ventilation at places where dust is formed.Normal measures for preventive fire
protection.
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

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
General industrial hygiene practice.
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).

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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) Evaporation 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) Autoignition 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

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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
Other decomposition products - no data available

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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 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
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause 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

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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
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

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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

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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
no data available

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Section 16. OTHER INFORMATION
Further information
Copyright 2012 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

SB-222200 是一种有效、选择性且具有血脑屏障渗透性的 NK-3 受体拮抗剂，适用于中枢神经系统疾病的研宄。

靶点

NK3

体外研究

SB-222200 能抑制放射标记的 [MePhe7]神经激肽 B (NKB) 结合到稳定表达人 NK-3 受体的人 CHO 细胞膜上，其 Ki 值为 4.4 nM。此外，它还能拮抗 NKB 引起的 HEK293 稳定表达 hNK-3 受体细胞中的 Ca2+ 活化，IC50 值为 18.4 nM。

与 hNK-1 和 hNK-2 受体相比，SB-222200 对 hNK-3 受体的选择性较高 (Ki > 100,000 nM) 和 Ki = 250 nM)。在 HEK293-hNK-3R 细胞中，SB-222200（浓度为 10 nM 至 1 μM）可产生剂量依赖性的、可克服的 NKB 引起的 Ca2+ 活化抑制。

体内研究

SB-222200 (5 mg/kg，30 分钟前给予) 能抑制由选择性 NK-3 受体激动剂 senktide（HY-P0187）诱导的行为反应。此外，其终端消除半衰期为约 2 小时，在大鼠中的系统血浆清除率为 56 mL/min/kg，并具有中等大的分布容积 (3-5 L/kg)。

实验结果

• 动物模型： 雄性 BALB/c 小鼠（19-21 g）

• 剂量： 5 mg/kg

• 给药方式： 口服

• 结果： 能产生 senktide 引起的行为反应抑制达 57%。

• 动物模型： 雄性 Sprague-Dawley 大鼠（300-400 g）

• 剂量： i.v. 2.5 mg/kg；p.o. 10 mg/kg

• 给药方式： 静脉注射和口服灌胃

• 结果： 口服生物利用度为 46%，T1/2 分别为静脉注射 2.4 小时和口服给药 2.1 小时，最大血药浓度 Cmax 为 427 ng/mL。

反应信息

• 作为反应物：
  描述：

  SB 222200; 3-甲基-2-苯基-N-((1S)-1-苯基丙基)喹啉-4-甲酰胺 、 N-溴代丁二酰亚胺(NBS) 在 氮 、 四氯化碳 、 二氯甲烷 、 碳酸氢钠 、 disodium;dioxido-oxo-sulfanylidene-λ6-sulfane 、 Sodium sulfate-III 作用下， 以 四氯化碳 为溶剂， 反应 1.0h， 以to give 2.9 g of desired product (24%) as a yellow-white solid的产率得到3-(bromomethyl)-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide
  参考文献：
  名称：

  Alkyl sulfoxide quinolines as NK-3 receptor ligands

  摘要：

  本发明涉及化合物I的制备方法，其中化合物I的化学式中的R1，A，R2，R3，R4，R5，n，m和q如规范中所述，所述化合物的药学上可接受的盐，制备方法，含有该化合物的制药组合物，以及使用该化合物的方法。

  公开号：

  US07964733B2
• 作为产物：
  描述：

  (S)-N-(1-phenylpropyl)-3-bromo-2-phenylquinoline-4-carboxamide 在 四(三苯基膦)钯 正丁基锂 、 四甲基乙二胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 为溶剂， 反应 102.0h， 生成 SB 222200; 3-甲基-2-苯基-N-((1S)-1-苯基丙基)喹啉-4-甲酰胺
  参考文献：
  名称：

  Functionalization through Lithiation of (S)-N-(1-Phenylpropyl)-2-phenylquinoline-4-carboxamide. Application to the Labeling with Carbon-11 of NK-3 Receptor Antagonist SB 222200

  摘要：

  Lithiation of (S)-N-(1-phenylpropyl)-2-phenylquinoline-4-carboxamide with the complex n-BuLi/TMEDA (1/1 molar ratio) in THF at -60 degrees C for 5 h occurred selectively at the position 3 of the quinoline ring. This selectivity was shown by the absence of racemization of the stereogenic center and the formation of the corresponding functionalized quinolines in 59-74% yield by subsequent reaction with an electrophile at -60 degrees C for 1 h. The 3-trimethylstannyl derivative was subjected to a Stille reaction using methyl, phenyl, or thienyliodide to afford the alkyl or aryl quinolines in moderate to good yields. This methodology was successfully applied to the radiosynthesis of [C-11] SB 222200 using methyl iodide labeled with carbon-11 (beta(+) emitter, t(1/2) = 20.4 min) for the in vivo study of NK-3 receptor by positron emission tomography (48-58% radiochemical yields from [C-11] CH3I, decay corrected, 45 min total synthesis time).

  DOI：

  10.1021/jo062285p

文献信息

• [EN] A QUINOLINE AMIDE DERIVATIVE AS AGENT AGAINST DISORDERS OF THE CNS<br/>[FR] DERIVES D'AMIDE QUINOLEIQUE UTILISES COMME AGENTS CONTRE DES TROUBLES DU SNC
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004050627A1

  公开（公告）日：2004-06-17

  A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, is provided (Formula I) as is a process for its preparation and methods for its use in therapy, particularly in treating CNS or CNS-mediated disorders.

  提供一种化合物，其化学式为（I），或其药用可接受的盐或溶剂化合物，同时提供其制备方法以及在治疗中的应用方法，特别是用于治疗中枢神经系统或中枢神经系统介导的疾病。
• Use of NK-1 receptor antagonists against benign prostatic hyperplasia
  申请人：——

  公开号：US20030004157A1

  公开（公告）日：2003-01-02

  The invention relates to the use of an NK-1 receptor antagonist for the treatment or prevention of benign prostatic hyperplasia (BPH). The preferred NK-1 receptor antagonists are compounds of the general formula 1 wherein the meanings of R, R 1 , R 2 , R 2′ , R 3 , R 4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof Preferred compounds are 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1&lgr; 6 -thiomorpholin-4-yl)-4-o-tolyl-pyridin-3-yl]-N-methyl-isobutyramide and 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1&lgr; 6 -thiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists and a pharmaceutically acceptable excipient for the treatment and/or prevention of benign prostatic hyperplasia.

  本发明涉及使用NK-1受体拮抗剂治疗或预防良性前列腺增生（BPH）。首选的NK-1受体拮抗剂是一般式1中R，R1，R2，R2'，R3，R4的含义在规范中解释的化合物，以及其药学上可接受的酸盐和前药。首选化合物是2-(3,5-双三氟甲基苯基)-N-甲基-N-(6-吗啉-4-基-4-o-甲苯基-吡啶-3-基)-异丁酰胺，2-(3,5-双三氟甲基苯基)-N-甲基-N-[6-(4-甲基哌嗪-1-基)-4-o-甲苯基-吡啶-3-基]-异丁酰胺，2-(3,5-双三氟甲基苯基)-N-[6-(1,1-二氧-1&lgr;6-硫代吗啉-4-基)-4-o-甲苯基-吡啶-3-基]-N-甲基异丁酰胺和2-(3,5-双三氟甲基苯基)-N-[6-(1,1-二氧-1&lgr;6-硫代吗啉-4-基)-4-(4-氟-2-甲基苯基)-吡啶-3-基]-N-甲基异丁酰胺。本发明还涉及包含一种或多种此类NK-1受体拮抗剂和药学上可接受的载体的制药组合物，用于治疗和/或预防良性前列腺增生。
• [EN] A QUINOLINE AMIDE DERIVATIVE AS AGENT AGAINST DISORDERS OF THE CNS<br/>[FR] DERIVE D'AMIDE QUINOLEIQUE UTILISE COMME AGENT CONTRE DES TROUBLES DU SNC
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004050626A1

  公开（公告）日：2004-06-17

  A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, is provided, as is a process for its preparation and methods for its use in therapy, particularly in treating CNS or CNS-mediated disorders.

  提供一种化合物(I)的公式，或其药学上可接受的盐或溶剂，以及其制备方法和在治疗中使用的方法，特别是在治疗中枢神经系统或中枢神经系统介导的疾病方面。
• [EN] QUINOLINE DERIVATIVES AS TACHYKININ NK3 RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE QUINOLINE UTILISES COMME ANTAGONISTES DU RECEPTEUR NK3 DE LA TACHYKININE
  申请人：SMITHKLINE BEECHAM FARMACEUTICI S.P.A.

  公开号：WO1995032948A1

  公开（公告）日：1995-12-07

  (EN) NK3 receptor antagonists of formula (I) are useful in treating $i(inter alia) pulmonary disorders, CNS disorders and neurodegenerative disorders.(FR) L'invention se rapporte à des antagonistes du récepteur NK3 de la formule (I) qui sont utiles dans le traitement, entre autres, des maladies pulmonaires, des troubles du SNC et des troubles neurodégénératifs.

  NK3受体拮抗剂(I)的公式在治疗肺部疾病、中枢神经系统疾病和神经退行性疾病等方面非常有用。
• Quinoline derivatives(2)
  申请人：——

  公开号：US20030236281A1

  公开（公告）日：2003-12-25

  NK 3 receptor antagonists of formula (I): 1 are useful in treating inter alia pulmonary disorders, CNS disorders and neurodegenerative disorders.

  公式（I）的NK3受体拮抗剂1在治疗肺部疾病、中枢神经系统疾病和神经退行性疾病等方面是有用的。