布南色林 | 132810-10-7

• 物质功能分类: 生物化工 - 抑制剂 - 神经信号通路(Neuronal Signaling)
• 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: 布南色林
• 中文别名: 2-(4-乙基-1-哌嗪基)-4-(4-氟苯基)-5,6,7,8,9,10-六氢环辛[b]吡啶；布兰色林；布南瑟林
• 英文名称: blonanserin
• 英文别名: 2-(4-ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydro-cycloocta[b]pyridine；2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine；bionanserin
• CAS: 132810-10-7
• 化学式: C₂₃H₃₀FN₃
• 分子量: 367.51
• InChiKey: XVGOZDAJGBALKS-UHFFFAOYSA-N

物化性质

• 熔点：
  117-119°C
• 沸点：
  540.8±50.0 °C(Predicted)
• 密度：
  1.095±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：≥10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  19.4
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

布洛南色林主要通过CYP3A4代谢。它会经历环辛烷环的羟基化以及哌嗪环的N-氧化和N-去乙基化。N-去乙基化和羟基化的代谢物具有活性，但活性程度低于母药。

Blonanserin is mainly metabolized by CYP3A4. It undergoes hydoxylation of the cyclooctane ring as well as N-oxidation and N-deethylation of the piperazine ring. The N-deethylated and hydroxylated metabolites are active but to a lesser degree than the parent drug.

来源:DrugBank

毒理性

• 蛋白质结合

布洛纳森是超过99.7%与血浆蛋白结合的。血清白蛋白是主要的结合蛋白。

Blonanserin is over 99.7% bound to plasma proteins . Serum albumin is the primary binder.

来源:DrugBank

吸收、分配和排泄

• 吸收

布洛纳森的达峰时间（Tmax）为1.5小时，生物利用度为55%。当与食物一起服用时，观察到达峰时间延长，相对生物利用度增加。

Blonanserin has a Tmax of 1.5 h and a bioavailablity of 55%. Tmax has been observed to be prolonged and relative bioavailability increased when administered with food.

来源:DrugBank

吸收、分配和排泄

• 消除途径

57%的布洛纳塞林通过尿液排出，30%通过粪便排出。粪便中只有5%是原药，没有原药通过尿液排出。

57% of blonanserin is excreted in the urine and 30% in the feces. Only 5% of the drug in the feces is the parent drug with no parent drug excreted through the urine.

来源:DrugBank

吸收、分配和排泄

• 分布容积

布洛纳森的Vc为9500升，Vt为8560升，总Vd为18060升。

Blonanserin has a Vc of 9500 L and a Vt of 8560 L for a total Vd of 18060 L.

来源:DrugBank

吸收、分配和排泄

• 清除

布洛纳森的清除率为1230升/小时。

Blonanserin has a clearance of 1230 L/h.

来源:DrugBank

安全信息

• 危险品标志：
  Xn
• 危险类别码：
  R22
• WGK Germany：
  1
• 海关编码：
  29339900
• 危险品运输编号：
  NONH for all modes of transport
• 储存条件：
  | 冰箱 |

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : BLONANSERIN
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. : 132810-10-7

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SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
Chronic aquatic toxicity (Category 4), H413
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)
Harmful if swallowed.
May cause long lasting harmful effects to aquatic life.
Precautionary statement(s) none
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Synonyms : AD-5423
Lonasen
2-(4-Ethyl-1-piperazinyl)-4-(fluorophenyl)-5,6,7,8,9, 10-
hexahydrocycloocta[b]pyridine
Formula : C23H30FN3
Molecular Weight : 367,50 g/mol
CAS-No. : 132810-10-7
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Blonanserin
Acute Tox. 4; Aquatic Chronic -
4; H302, H413
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Blonanserin
Xn, R22 -
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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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

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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), Hydrogen fluoride
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
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
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the
environment must be avoided.
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.

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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.Normal measures for preventive fire
protection.
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.
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

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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
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into
the environment must be avoided.

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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) 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- log Pow: 5,266
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

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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

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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 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.

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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
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
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. Contact a licensed
professional waste disposal service to dispose of this material. 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.

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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
Further information
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

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

布南色林是一种非典型抗精神病药物,用于治疗精神分裂症等疾病。其特点包括:

1. 有效剂量较小,安全性较高。

2. 对精神分裂症阳性症状和阴性症状均有较好的疗效,尤其对阴性症状效果更明显。

3. 副作用较少,尤其是锥体外系反应的发生率较低。

4. 口干、便秘等不良反应发生率也低于一些传统药物如氟哌啶醇。

5. 对催乳素的影响较小。

6. 恶性综合征等严重副作用的风险较低。

7. 与其他非典型抗精神病药相比,布南色林在某些方面具有优势,但仍需长期临床观察和研究验证其疗效和安全性。

总之,布南色林作为一种新型的非典型抗精神病药物,为精神分裂症的治疗提供了一种新的选择。但具体使用时仍需根据患者个体情况制定合理用药方案。

反应信息

• 作为反应物：
  描述：

  布南色林 在 盐酸 作用下， 以 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 0.33h， 以0.37 g的产率得到blonanserin hydrochloride
  参考文献：
  名称：

  高純度ブロナンセリンの製造方法

  摘要：

  建立一种以更高收率获得更高纯度的布洛南色林的方法。制备布洛南色林的方法包括：（a）获得布洛南色林；（b）将获得的布洛南色林与酸接触，分离出沉淀的布洛南色林酸盐并纯化；（c）精制获得的布洛南色林酸盐；（d）将经过（c）处理的布洛南色林酸盐与碱接触以回收布洛南色林的方法。【选择图】无

  公开号：

  JP2018127406A
• 作为产物：
  描述：

  1-(4-氟苯基)-2-甲氧基乙酮 在 苯膦酰二氯 、 sodium hydride 、 1-ethyl-3-methylimidazolium tetrafluoroborate 、 potassium iodide 作用下， 以 甲苯 为溶剂， 反应 17.0h， 生成 布南色林
  参考文献：
  名称：

  一种布南色林的合成方法

  摘要：

  本发明公开了一种布南色林的合成方法，包括以下步骤：1)以氟苯甲酸甲酯为原料，与乙腈缩合得到化合物3；2)将多聚磷酸升温后，加入化合物3、环辛酮环和离子液体，一步反应得到化合物4；3)化合物4经苯膦酰二氯化物氯化后得到化合物5；4)将化合物5与碘化钾、N‑乙基哌嗪混合后，再加入离子液体，升温发生亲和取代反应得布南色林。其中，步骤2)和步骤3)中所述的离子液体为1‑乙基‑3‑甲基咪唑四氟硼酸盐，步骤2)中离子液体的加入量为化合物3的质量的30％；步骤3)中离子液体的加入量与化合物5的质量的30％；相对于现有的布南色林的合成方法，反应时间大大缩短，产率增大，降低生产成本低，适用于工业生产。

  公开号：

  CN106045909A

文献信息

• MACROCYCLES AS PDE1 INHIBITORS
  申请人：H. Lundbeck A/S

  公开号：US20190185489A1

  公开（公告）日：2019-06-20

  The present invention provides macrocycles of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

  本发明提供了式(I)的大环化合物作为PDE1抑制剂，并将其用作药物，特别用于治疗神经退行性疾病和精神疾病。
• 1H-PYRAZOLO[4,3-B]PYRIDINES AS PDE1 INHIBITORS
  申请人：H. Lundbeck A/S

  公开号：US20190194189A1

  公开（公告）日：2019-06-27

  The present invention provides 1H-pyrazolo[4,3-b]pyridines of formula (I) as PDE1 inhibitors and their use as a medicament, in particular for the treatment of neurodegenerative disorders and psychiatric disorders.

  本发明提供了式(I)的1H-吡唑并[4,3-b]吡啶类化合物作为PDE1抑制剂，并将其用作药物，特别用于治疗神经退行性疾病和精神疾病。
• [EN] COMT INHIBITING METHODS AND COMPOSITIONS<br/>[FR] PROCÉDÉS D'INHIBITION DE LA COMT ET COMPOSITIONS ASSOCIÉES
  申请人：LIEBER INST FOR BRAIN DEV

  公开号：WO2016123576A1

  公开（公告）日：2016-08-04

  The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.

  这些发明包括一种抑制受试者中COMT酶的方法，以及式I的化合物或其药用可接受盐，这些化合物在治疗由COMT介导的各种疾病中有用，包括帕金森病和/或精神分裂症。
• Chemical Compounds
  申请人：Brown Alan Daniel

  公开号：US20120010182A1

  公开（公告）日：2012-01-12

  The invention relates to sulfonamide derivatives, to their use in medicine, to compositions containing them, to processes for their preparation and to intermediates used in such processes. More particularly the invention relates to new sulfonamide Nav1.7 inhibitors of formula (I): or pharmaceutically acceptable salts thereof, wherein Z 1 , R a , R b , R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description. Nav 1.7 inhibitors are potentially useful in the treatment of a wide range of disorders, particularly pain.

  该发明涉及磺胺衍生物，其在医学上的应用，含有它们的组合物，其制备方法以及用于这些方法的中间体。 更具体地，该发明涉及公式（I）的新磺胺基Nav1.7抑制剂： 或其药学上可接受的盐，其中Z 1 ，R a ，R b ，R 1 ，R 2 ，R 3 ，R 4 和R 5 如描述中所定义。 Nav 1.7抑制剂在治疗各种疾病，特别是疼痛方面具有潜在用途。
• [EN] TREATMENT OF AUTISM SPECTRUM DISORDERS, OBSESSIVE-COMPULSIVE DISORDER AND ANXIETY DISORDERS<br/>[FR] TRAITEMENT DE TROUBLES DU SPECTRE AUTISTIQUE, DE TROUBLES OBSESSIVO-COMPULSIFS ET DE TROUBLES DE L'ANXIÉTÉ
  申请人：RUGEN HOLDINGS CAYMAN LTD

  公开号：WO2018098128A1

  公开（公告）日：2018-05-31

  Disclosed are methods for treating NMDA receptor-mediated disorders by administering certain NR2B subunit-selective NMDA (N methyl-D aspartate) antagonists. NMDA receptor-mediated disorders include autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders.

  揭示了通过给予特定NR2B亚单位选择性NMDA（N-甲基-D-天冬氨酸）拮抗剂来治疗NMDA受体介导的疾病的方法。NMDA受体介导的疾病包括自闭症谱系障碍、强迫症和焦虑症。