盐酸毛果芸香碱 | 54-71-7

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 中文名称: 盐酸毛果芸香碱
• 中文别名: (+)-毛果芸香碱盐酸盐；氨噻唑；(3S,4R)-4,5-二氢-3-乙基-4-(1-甲基-1H-咪唑-5-基甲基)-2(3H)-呋喃酮盐酸盐；(3S,4R)-4,5-二氢-3-乙基-4-(1-甲基-1H-咪唑-5-基甲基)-2(3H)-呋喃酮
• 英文名称: pilocarpine hydrochloride
• 英文别名: Pilocarpin-Hydrochlorid；pilocarpine; 2(3H)-furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)-methyl] monohydrochloride, (3S-cis)；(3S,4R)-3-ethyl-4-[(3-methyl-1H-imidazol-3-ium-4-yl)methyl]oxolan-2-one;chloride
• CAS: 54-71-7
• 化学式: C₁₁H₁₇N₂O₂*Cl
• 分子量: 244.721
• InChiKey: RNAICSBVACLLGM-GNAZCLTHSA-N

物化性质

• 熔点：
  202-205 °C(lit.)
• 比旋光度：
  89 º (C=5, H2O)
• 溶解度：
  H2O:100 mg/mL
• LogP：
  -0.095 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  44.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  6.1
• 危险品标志：
  T+
• 安全说明：
  S25,S45
• 危险类别码：
  R26/28
• WGK Germany：
  3
• 海关编码：
  2934999090
• 危险品运输编号：
  UN 1544 6.1/PG 3
• RTECS号：
  TK1450000
• 包装等级：
  III
• 危险类别：
  6.1
• 储存条件：
  本品应密封存放在阴凉、干燥且避光的地方。

SDS

Name:	(+)-Pilocarpine Hydrochloride Material Safety Data Sheet
Synonym:	Almocarpine; Pilocar; Pilomiotin
CAS:	54-71-7

Section 1 - Chemical Product MSDS Name:(+)-Pilocarpine Hydrochloride Material Safety Data Sheet
Synonym:Almocarpine; Pilocar; Pilomiotin

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
54-71-7	(+)-Pilocarpine Hydrochloride	99%	200-212-5

Hazard Symbols: T+
Risk Phrases: 26/28

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Very toxic by inhalation and if swallowed.Hygroscopic (absorbs moisture from the air).The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. May be harmful if swallowed.
Inhalation:
May be fatal if inhaled. May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Immediately flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid immediately.
Skin:
Get medical aid immediately. Immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes.
Ingestion:
Never give anything by mouth to an unconscious person. SPEED IS ESSENTIAL. A DOCTOR MUST BE NOTIFIED AT ONCE. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water. Wash mouth out with water.
Inhalation:
Get medical aid immediately. Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. This material in sufficient quantity and reduced particle size is capable of creating a dust explosion.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam. Use agent most appropriate to extinguish fire.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up, then place into a suitable container for disposal. Avoid generating dusty conditions. Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Minimize dust generation and accumulation. Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Keep container tightly closed. Use only in a chemical fume hood.
Storage:
Store in a cool, dry place. Store in a tightly closed container.
Store protected from moisture. Store protected from light.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 54-71-7: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystalline powder
Color: white to off-white
Odor: odorless
pH: 3.5 - 4.5 (5%aq.sol)
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 200-204 deg C
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: Freely Soluble.
Specific Gravity/Density:
Molecular Formula: C11H16N2O2.HCl
Molecular Weight: 244.72

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable.
Conditions to Avoid:
Incompatible materials, light, dust generation, excess heat, exposure to moist air or water.
Incompatibilities with Other Materials:
Moisture, oxidizing agents.
Hazardous Decomposition Products:
Hydrogen chloride, nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, oxides of chlorine.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 54-71-7: TK1450000 LD50/LC50:
CAS# 54-71-7: Oral, mouse: LD50 = 200 mg/kg.
Carcinogenicity:
(+)-Pilocarpine Hydrochloride - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.*
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
IMO
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
RID/ADR
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing group: III

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T+
Risk Phrases:
R 26/28 Very toxic by inhalation and if swallowed.
Safety Phrases:
S 25 Avoid contact with eyes.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 54-71-7: 3
Canada
CAS# 54-71-7 is listed on Canada's NDSL List.
CAS# 54-71-7 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 54-71-7 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Pilocarpine HCl (NSC 5746) 是一种非选择性的毒蕈碱型乙酰胆碱受体激动剂，常被用作产生癫痫实验模型。

靶点

Target	Value
mAChR

体外研究

Pilocarpine是一种从美国热带灌木的毛果芸香碱类植物叶子中提取的拟副交感神经生物碱。它是一种非选择性的毒蕈碱型受体激动剂，能有效作用于副交感神经系统中的M3毒蕈碱型乙酰胆碱受体，用于治疗青光眼和口干症。Pilocarpine作用于虹膜括约肌中的M3亚型毒蕈碱受体，引起肌肉收缩，导致瞳孔缩小，并促使睫状肌收缩。当睫状肌收缩时，它会增加巩膜突的张力并打开小梁网，促进房水流出以降低眼内压。在眼科中，Pilocarpine也可用于减少人工晶状体移植后患者夜晚对灯光的眩光症状，最常用浓度为1%。此外，Pilocarpine还常用于治疗化疗引起的口腔干燥症，并刺激大量唾液和汗液分泌。

体内研究

实验观察了Pilocarpine诱导的对照大鼠(CN)与运动大鼠(EX)的唾液分泌情况。结果显示，Pilocarpine在EX大鼠中诱导的唾液分泌量显著高于CN大鼠(P<0.01)，而EX大鼠唾液中的钠离子浓度则明显低于CN大鼠(P<0.05)。

用途

非选择性毒蕈碱型乙酰胆碱受体激动剂；用于建立癫痫实验模型。

反应信息

• 作为反应物：
  描述：

  盐酸毛果芸香碱 在 劳森试剂 作用下， 以 xylene 为溶剂， 反应 7.0h， 以4.63 g的产率得到3-ethyl-4,5-dihydro-4-<(1-methyl-1H-imidazol-5-yl)methyl>-2(3H)-thiophenethione
  参考文献：
  名称：

  Muscarinic activity of the thiolactone, lactam, lactol, and thiolactol analogs of pilocarpine and a hypothetical model for the binding of agonists to the M1 receptor

  摘要：

  Pilocarpine isosteres have been synthesized and characterized with regard to their in vitro muscarinic properties. The results indicate that the carbonyl oxygen of the lactone function of pilocarpine is of primary importance for agonist activity with the ether oxygen being of lesser or secondary importance. An X-ray structure determination for the hydrogen O,O'-ditoluoyltartrate salt of thiolactone pilocarpine isostere 2a has been performed. This compound has an unusual pharmacological profile exhibiting M1-agonist selectivity as well as presynaptic antagonism. As a result this compound is also viewed as having therapeutic potential for Alzheimer's disease. A model for the binding of pilocarpine and other muscarinic agonists to the third transmembrane helix of the human m1 muscarinic receptor has been developed.

  DOI：

  10.1021/jm00079a002
• 作为产物：
  描述：

  (3S,4RS,5RS)-3-ethyl-4-(methoxycarbonyl)-5-(1-methyl-1H-imidazol-5-yl)dihydro-2(3H)-furanone 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 氢气 作用下， 以 甲醇 为溶剂， -5.0~25.0 ℃ 、413.69 kPa 条件下， 反应 84.0h， 生成 盐酸毛果芸香碱
  参考文献：
  名称：

  An effective chirospecific synthesis of (+)-pilocarpine from L-aspartic acid

  摘要：

  A short and efficient synthesis of (+)-pilocarpine (1) has been accomplished in 10 steps and 51 % overall yield from L-aspartic acid. The synthesis features a diastereoselective alkylation of a protected aspartic acid diester derivative and a selective hydrolysis of the alpha-methyl ester to give the corresponding amino acid. Subsequent replacement of the amino group with bromo, esterification, and a modified Reformatsky reaction with 1-methylimidazole-5-carboxaldehyde (8) afforded imidazole-substituted lactone 28. Details concerning this novel lactone synthesis are also described. Finally, hydrogenolysis of the lactone carbon-oxygen bond and selective reduction of the resulting monoester afforded pure (+)-pilocarpine (1).

  DOI：

  10.1021/jo00057a031
• 作为试剂：
  描述：

  乙酸2-甲基-4,6-二硝基苯基酯 在 盐酸毛果芸香碱 buffer solution 作用下， 以 水 、 乙腈 为溶剂， 生成 二硝酚 、 溶剂黄146
  参考文献：
  名称：

  Beyrich; Neubauer, Pharmazie, 1987, vol. 42, # 12, p. 824 - 826

  摘要：

  DOI：

文献信息

• [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：UNIV GEORGIA STATE RES FOUND

  公开号：WO2010129858A1

  公开（公告）日：2010-11-11

  Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.

  本文披露了适用作抗肿瘤药剂的化合物，用于治疗癌症的方法，其中所披露的化合物用于制备治疗癌症的药物，治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物，以及制备所披露的抗肿瘤药剂的方法。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
  申请人：BIOCAD JOINT STOCK CO

  公开号：WO2018092047A1

  公开（公告）日：2018-05-24

  The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.

  本发明涉及一种新的化合物，其化学式为I：或其药学上可接受的盐、溶剂化合物或立体异构体，其中：V1为C或N，V2为C(R2)或N，如果V1为C，则V2为N，如果V1为C，则V2为C(R2)，或者如果V1为N，则V2为C(R2)；每个n，k独立地为0或1；每个R2，R11独立地为H，D，Hal，CN，NR'R"，C(O)NR'R"，C1-C6烷氧基；R3为H，D，羟基，C(O)C1-C6烷基，C(O)C2-C6烯基，C(O)C2-C6炔基，C1-C6烷基；R4为H，Hal，CN，CONR'R"，羟基，C1-C6烷基，C1-C6烷氧基；L为CH2，NH，O或化学键；R1从包括的片段组中选择：片段1，片段2，片段3，每个A1，A2，A3，A4独立地为CH，N，CHal；每个A5，A6，A7，A8，A9独立地为C，CH或N；R5为H，CN，Hal，CONR'R"，C1-C6烷基，未取代或被一个或多个卤素取代；每个R'和R"独立地从包括H，C1-C6烷基，C1-C6环烷基，芳基的组中选择；R6从组中选择：[化学式II]每个R7，R8，R9，R10独立地为乙烯基，甲基乙炔基；Hal为CI，Br，I，F，具有布鲁顿酪氨酸激酶（Btk）抑制剂的性质，以及含有这种化合物的药物组合物，以及它们作为治疗疾病和紊乱的药物的用途。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• [EN] PROCESSES FOR MAKING TRIAZOLO[4,5D] PYRAMIDINE DERIVATIVES AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉS DE PREPARATION DE DÉRIVÉS DE TRIAZOLO [4,5 D] PYRIMIDINE ET INTERMÉDIAIRES DE CEUX-CI
  申请人：CORVUS PHARMACEUTICALS INC

  公开号：WO2018183965A1

  公开（公告）日：2018-10-04

  Provided herein are, inter alia, methods for making triazolo[4,5]pyramidine derivatives and intermediates thereof that are useful for treating diseases.

  本文提供了制备三氮杂[4,5]吡啶衍生物及其中间体的方法，这些衍生物对治疗疾病有用。
• [EN] AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION<br/>[FR] DÉGRONIMÈRES DE C3-GLUTARIMIDE LIÉS À UNE AMINE POUR LA DÉGRADATION DE PROTÉINES CIBLES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2017197051A1

  公开（公告）日：2017-11-16

  This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

  这项发明提供了胺连接的C3-戊二酰亚胺Degronimers和Degrons，用于治疗应用，如本文进一步描述的，以及它们的使用方法、组合物以及它们的制备方法。