辛可尼丁 | 485-71-2

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 中文名称: 辛可尼丁
• 中文别名: 辛可尼定；(9S)-6'-甲氧基辛可宁-9-醇；类金鸡纳碱；金鸡尼丁；辛可尼啶；4-喹啉基-(5-乙烯基-1-氮杂双环[2.2.2]辛烷-2-基)甲醇；(9S)-6"-甲氧基辛可宁-9-醇
• 英文名称: Cinchonidin
• 英文别名: Cinchonidine；(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-quinolin-4-ylmethanol
• CAS: 485-71-2
• 化学式: C₁₉H₂₂N₂O
• 分子量: 294.396
• InChiKey: KMPWYEUPVWOPIM-KODHJQJWSA-N

物化性质

• 熔点：
  204-206 °C(lit.)
• 比旋光度：
  -115 º (c=1, EtOH)
• 沸点：
  436.16°C (rough estimate)
• 密度：
  1.0863 (rough estimate)
• 溶解度：
  0.25克/升
• LogP：
  2.68 at 25℃
• 碰撞截面：
  168.2 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 稳定性/保质期：
  按规格使用和贮存，不会发生分解，避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• TSCA：
  Yes
• 危险等级：
  6.1(b)
• 危险品标志：
  Xn
• 安全说明：
  S36/37
• 危险类别码：
  R20/21/22
• WGK Germany：
  3
• 海关编码：
  2939200000
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 1544
• 储存条件：
  密封保存，并置于通风、干燥的地方，避免与氧化物接触。

SDS

Name:	Cinchonidine 98.5-101% (On The Dried Substance) Material Safety Data Sheet
Synonym:	Alpha-Quinidine
CAS:	485-71-2

Section 1 - Chemical Product MSDS Name:Cinchonidine 98.5-101% (On The Dried Substance) Material Safety Data Sheet
Synonym:Alpha-Quinidine

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
485-71-2	Cinchonidine	98%	207-622-3

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Light sensitive.The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
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: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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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. Runoff from fire control or dilution water may cause pollution.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Store protected from light.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. 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# 485-71-2: 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: Powder
Color: white to cream
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 200.00 - 203.00 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water: practically insoluble in water
Specific Gravity/Density:
Molecular Formula: C19H22N2O
Molecular Weight: 294.39

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, light, dust generation, excess heat, strong oxidants.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, nitrogen.
Hazardous Polymerization: Has not been reported.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 485-71-2: GD2975000 LD50/LC50:
Not available.
Carcinogenicity:
Cinchonidine - 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
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
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# 485-71-2: 2
Canada
CAS# 485-71-2 is listed on Canada's NDSL List.
CAS# 485-71-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 485-71-2 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

简介

辛可尼丁是一种喹啉型生物碱，属于金鸡纳生物碱的一种，又称金鸡尼丁，是辛可宁的立体异构体。它在醚中结晶为白色针状或棱形晶体，熔点为204～206℃，比旋光度-115°（乙醇，C＝1），折射率-107.5°（乙醇，C＝1）。辛可尼丁能溶于醇、醚、丙酮、苯和氯仿，几乎不溶于冷水。

应用

辛可尼丁作为有机合成中间体和医药中间体，在实验室有机合成过程中和化工医药研发中被广泛应用。

作用

辛可尼丁与奎宁相似，具有抗疟疾的作用。在从金鸡纳树皮提取液中分离出奎宁后，可以通过碱处理母液，并加入酒石酸使其生成难溶的酒石酸盐来分离出生物碱。

结构特点

金鸡纳碱（如奎宁、奎尼丁、辛可宁和辛可尼丁等）是一类在约两个世纪前从金鸡纳树皮中发现的重要天然产物。在过去，它们是治疗疟疾的特效药；近年来，在不对称合成中作为催化剂的优势骨架得到了广泛认可。从生物合成的角度来看，金鸡纳生物碱是由单萜吲哚生物碱衍生而来。

生物活性

Cinchonidine是一种生物碱，在有机化学中用于不对称合成。

靶点

• Ki: 330 μM (dSERT), 4.2 μM (hSERT), 36 μM (hSERT I172M), 196 μM (hSERT S438T), 15 μM (hSERT Y95F)

体外研究

• Cinchonidine（α-Quinidine）是金鸡纳树皮和甘果木中发现的生物碱，被用作有机化学中的不对称合成基块。它是一个弱的血清素转运蛋白（SERT）抑制剂，具有以下Ki值：dSERT 330 μM, hSERT 4.2 μM, hSERT I172M 36 μM, hSERT S438T 196 μM, hSERT Y95F 15 μM。

反应信息

• 作为反应物：
  描述：

  辛可尼丁 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 α-dibromocinchonidine
  参考文献：
  名称：

  对映选择性相转移催化的1-甲基-7-甲氧基-2-四氢萘酮的烷基化：脱佐辛的有效途径。

  摘要：

  为了不对称地制备（R）-（+）-1-（5-溴戊基）-1-甲基-7-甲氧基-2-四氢萘酮（3a），制备了地佐辛的关键中间体17金鸡纳生物碱衍生催化剂并用1，5-二溴戊烷筛选1-甲基-7-甲氧基-2-四氢萘酮的对映选择性烷基化反应，并确定了最佳催化剂（C7）。另外，对烷基化进行了优化，使得该方法变得实用和有效。

  DOI：

  10.3762/bjoc.14.119
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 生成 辛可尼丁
  参考文献：
  名称：

  102.将氢奎尼丁转化为氢辛可宁，将铜脲转化为辛可尼定

  摘要：

  DOI：

  10.1039/jr9460000523
• 作为试剂：
  描述：

  3-烯丙基-2-羟基苯甲酸甲酯 在 氯化亚砜 、 三乙胺 、 辛可尼丁 作用下， 以 异丙醇 、 苯 为溶剂， 反应 6.0h， 生成 (S)-4-(2-methyl-2,3-dihydro-7-benzofuroyl)amino-1-methyl-3-propyl-5-pyrazolecarboxamide
  参考文献：
  名称：

  Synthesis and Vasorelaxant Potency of Monagra. A Chiral 5-(2-Methyl-2,3-dihydro-7-benzofuryl)pyrazolopyrimidone Analog of Viagra®

  摘要：

  DOI：

  10.3987/com-01-9218

文献信息

• Synthesis of novel cinchona-amino acid hybrid organocatalysts for asymmetric catalysis
  作者：Pedro Barrulas、Maurizio Benaglia、Anthony J. Burke

  DOI：10.1016/j.tetasy.2014.05.003

  日期：2014.6

  Three novel subclasses of cinchonidine derivatives coupled to diverse amino acids were prepared in very good overall yield and tested in a benchmark organocatalytic aldol reaction, between acetone and aromatic aldehydes. These subclasses are a family of amino acid-cinchonidine (subclass A), N-formamides-cinchonidine (subclass B) and dipeptide-cinchonidine (subclass C) hybrids. Our main goal, besides

  以非常好的总收率制备了三类新的辛可尼定衍生物与不同的氨基酸偶联，并在丙酮和芳族醛之间进行了基准有机催化醛醇缩合反应，并进行了测试。这些子类是氨基酸辛可尼定（子类A），家族Ñ-formamides辛可尼定（子类B）和二肽辛可尼定（子类C）杂交。我们的主要目标，除了获得很好的收益和对映选择性，是了解氨基酸侧链残基上的不对称羟醛缩合反应的对映选择性的影响。不同的氨基酸系留辛可尼丁杂种进行了比较，它们的催化行为进行评价，从而允许在一种情况下要实现良好的对映选择性，92％ee的。用这些配体筛选了其他反应，例如Biginelli，迈克尔加成反应和酮亚胺氢化硅烷化反应，但结果不太成功。
• [EN] INDAZOLE- AND PYRROLOPYRIDINE-DERIVATIVE AND PHARMACEUTICAL USE THEREOF<br/>[FR] DÉRIVÉ D'INDAZOLE ET PYRROLOPYRIDINE ET UTILISATION PHARMACEUTIQUE DE CELUI-CI
  申请人：DAINIPPON SUMITOMO PHARMA CO

  公开号：WO2012169649A1

  公开（公告）日：2012-12-13

  The present invention relates to a novel indazole- or pyrrolopyridine-derivative, represented by the formula (1) below, that has an agonistic action or a partial agonistic action against serotonin-4 receptor, and a pharmaceutical composition comprising the same. Formula (1) [wherein each substituent is as defined in claim 1]

  本发明涉及一种新型吲唑基或吡咯吡啶基衍生物，由下面的式（1）表示，该衍生物对5-羟色胺-4受体具有激动作用或部分激动作用，并且包括含有该衍生物的药物组合物。式（1）[其中每个取代基如权利要求1所定义]
• FIBROSIS INHIBITOR
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1479384A1

  公开（公告）日：2004-11-24

  Medicament being useful as a fibrosis inhibitor for organs or tissues, which comprises a compound of the formula (I): wherein Ring Z is optionally substituted pyrrole ring, etc.; W2 is -CO-, -SO2-, optionally substituted C1-C4 alkylene, etc.; Ar2 is optionally substituted aryl, etc.; W1 and Ar1 mean the following (1) and (2): (1) W1 is optionally substituted C1-C4 alkylene, etc.; Ar1 is optionally substituted bicyclic heteroaryl having 1 to 4 nitrogen atoms as ring-forming atoms: (2) W1 is optionally substituted C2-C5 alkylene, optionally substituted C2-C5 alkenylene, etc.; and Ar1 is aryl or monocyclic heteroaryl, which is substituted by carboxyl, alkoxycarbonyl, etc. at the ortho- or meta-position thereof with respect to the binding position of W1, or a pharmaceutically acceptable salt thereof.

  药物作为器官或组织的纤维化抑制剂而有用，包括具有以下式（I）的化合物： 其中环Z是可选择取代的吡咯环等；W2是-CO-，-SO2-，可选择取代的C1-C4烷基等；Ar2是可选择取代的芳基等；W1和Ar1表示如下（1）和（2）： （1）W1是可选择取代的C1-C4烷基等；Ar1是可选择取代的具有1至4个氮原子作为环形成原子的双环杂芳基： （2）W1是可选择取代的C2-C5烷基，可选择取代的C2-C5烯基等；以及 Ar1是芳基或单环杂芳基，其在相对于W1的结合位置的邻位或间位处被羧基，烷氧羰基等取代， 或其药学上可接受的盐。
• SILICON BASED DRUG CONJUGATES AND METHODS OF USING SAME
  申请人：BlinkBio, Inc.

  公开号：US20170202970A1

  公开（公告）日：2017-07-20

  Described herein are silicon based conjugates capable of delivering one or more payload moieties to a target cell or tissue. Contemplated conjugates may include a silicon-heteroatom core, one or more optional catalytic moieties, a targeting moiety that permits accumulation of the conjugate within a target cell or tissue, one or more payload moieties (e.g., a therapeutic agent or imaging agent), and two or more non-interfering moieties covalently bound to the silicon-heteroatom core.

  本文描述了基于硅的共轭物，能够将一个或多个有效载荷基团传递到靶细胞或组织。考虑到的共轭物可能包括一个硅-杂原子核心，一个或多个可选的催化基团，一个定位基团，允许共轭物在靶细胞或组织内积累，一个或多个有效载荷基团（例如，治疗剂或成像剂），以及与硅-杂原子核心共价结合的两个或更多个不干扰基团。
• [EN] HETEROBICYCLIC COMPOUNDS FOR INHIBITING THE ACTIVITY OF SHP2<br/>[FR] COMPOSÉS HÉTÉROBICYCLIQUES POUR INHIBER L'ACTIVITÉ DE SHP2
  申请人：TAIHO PHARMACEUTICAL CO LTD

  公开号：WO2020022323A1

  公开（公告）日：2020-01-30

  A compound of formula (I):wherein Ring A, Q, R1,R2, R3, R4, R5, R6, R7, R8, R9, R10, R11,X, a,b, c and d are as defined in the specification.

  其中环A，Q，R1，R2，R3，R4，R5，R6，R7，R8，R9，R10，R11，X，a，b，c和d的化合物的化学式（I）：在规范中定义。

表征谱图