四氢嘧啶 | 96702-03-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 四氢嘧啶
• 中文别名: 四氢嘧啶（依克多因）；依克多因；四氢甲基嘧啶羧酸；(S)-2-甲基-1,4,5,6-四氢甲基嘧啶-4-羧酸；依可多因
• 英文名称: ectoine
• 英文别名: ectoin；(S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid；2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid；(4S)-2-methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid
• CAS: 96702-03-3
• 化学式: C₆H₁₀N₂O₂
• 分子量: 142.158
• InChiKey: WQXNXVUDBPYKBA-YFKPBYRVSA-N

物化性质

• 熔点：
  ~280°
• 比旋光度：
  D20 +140° (c = 1.0 in methanol)
• 沸点：
  381.5±35.0 °C(Predicted)
• 密度：
  1.37
• 溶解度：
  在甲醇中可溶20 mg/mL，澄清，无色
• 稳定性/保质期：
  在常温常压下保持稳定，应避免与强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S37/39
• 危险类别码：
  R36/37/38
• WGK Germany：
  1
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  密封保存，应储存在阴凉干燥的仓库中。

SDS

Name:	Ectoine sodium salt monohydrate Material Safety Data Sheet
Synonym:	(S)-2-Methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid sodium salt monohydrat
CAS:	96702-03-3

Section 1 - Chemical Product MSDS Name:Ectoine sodium salt monohydrate Material Safety Data Sheet
Synonym:(S)-2-Methyl-1,4,5,6-tetrahydropyrimidine-4-carboxylic acid sodium salt monohydrat

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
96702-03-3	Ectoine sodium salt monohydrate	ca. 100	unlisted

Hazard Symbols: XI
Risk Phrases: 36/37/38

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Irritating to eyes, respiratory system and skin.
Potential Health Effects
Eye:
Causes eye irritation. May cause chemical conjunctivitis.
Skin:
Causes skin irritation. May be harmful if absorbed through the skin.
Ingestion:
May cause gastrointestinal irritation with nausea, vomiting and diarrhea. May be harmful if swallowed.
Inhalation:
Causes respiratory tract irritation. May be harmful if inhaled. Can produce delayed pulmonary edema.
Chronic:
Effects may be delayed.

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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.
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. Wash mouth out with 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. Do NOT use mouth-to-mouth resuscitation.
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.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical 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:
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation. Use with adequate ventilation. Wash clothing before reuse.
Storage:
Store in a cool, dry place. Store in a tightly closed container.

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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# 96702-03-3: 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
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 280 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:
Specific Gravity/Density:
Molecular Formula: C6H10N2O2
Molecular Weight: 142.2

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not currently available.
Conditions to Avoid:
Dust generation.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide.
Hazardous Polymerization: Will not occur.

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 96702-03-3 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
Ectoine sodium salt monohydrate - Not listed by ACGIH, IARC, or NTP.

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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: Not regulated.
Hazard Class:
UN Number:
Packing Group:
IMO
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing Group:
RID/ADR
Shipping Name: Not regulated.
Hazard Class:
UN Number:
Packing group:

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: XI
Risk Phrases:
R 36/37/38 Irritating to eyes, respiratory system
and skin.
Safety Phrases:
S 26 In case of contact with eyes, rinse immediately
with plenty of water and seek medical advice.
S 37/39 Wear suitable gloves and eye/face
protection.
WGK (Water Danger/Protection)
CAS# 96702-03-3: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 96702-03-3 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 96702-03-3 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

依克多因简介

依克多因又称为四氢甲基嘧啶羧酸。它使嗜盐菌免受高渗透压环境的伤害，具备两大功能：

1. 保湿：作为维持细胞内渗透压平衡的重要物质，依克多因的独特分子结构具有很强的水分子络合能力，能有效防止水分流失。它是一种出色的天然保湿剂。
2. 修复：依克多因能够对抗紫外线对皮肤造成的伤害，修复由紫外线导致的细胞DNA损伤。

依克多因来源

依克多因（Ectoine）的化学式为2-甲基-1,4,5,6,-四氢嘧啶-4-羧酸，是一种新型水溶性两性离子氨基酸衍生物。于1985年首次由Galinski在嗜盐菌中通过核磁共振法和质谱法鉴定并分离出。该物质在高盐浓度下大量累积，用作透压补偿溶质，以抵抗外部环境的高渗透压变化。

依克多因的功效与作用 保湿性

使用依克多因预处理皮肤后，可显著减少因脱水导致的损伤。一分子依克多因能络合4-5个水分子，并使细胞内的游离水分结构化。相较于甘油，依克多因对皮肤的滋润效果更为卓越。

相关研究显示，在使用依克多因期间，皮肤的保湿能力持续改善；即使停用一周后，其持水能力仍高于对照组。

抗氧化

临床试验表明，依克多因能阻止随着年龄增长而减弱的细胞抗氧化功能，具有一定的抗氧化作用。实验数据显示，0.1mM Ectoine、0.5mM麦硫因和1.5mM甘露醇混合使用时，可减少400-800nm光源下人胶质细胞DNA单链断裂，降低ROS氧化反应强度，从而减轻光对皮肤的损伤。

免疫系统防护

依克多因能保护表皮中的朗格汉斯细胞（Langerhans cell）免受紫外线的压力。这些细胞在维持皮肤免疫系统的正常运作中起关键作用。因此，依克多因能够维持皮肤免疫系统的正常功能。

防光老化与防晒

皮肤衰老不仅受时间影响，还受到外部因素的影响，尤其是UVA（320-400nm）。尽管UVA的波长较长、能量较低，但其在不同纬度和季节的变化不大，会持续对皮肤造成伤害。依克多因能有效防护光老化与防晒。

用途

依克多因具有保湿修复功能，广泛应用于护肤品领域，可用于改善肤色。

制备方法

目前主要从嗜盐菌中提取依克多因。采用“细菌挤奶”工艺：在高浓度（如100g/L）的盐培养液中生长繁殖嗜盐菌；当细胞浓度达到最高时，突然将盐浓度降至低浓度（如20g/L），促使细胞释放累积于细胞内的Ectoine，以避免由于环境渗透压降低导致的细胞膨胀或破裂。最后通过过滤、结晶等技术进一步纯化。

文献显示，每天每升培养液可获得约2g Ectoise。

生物活性

依克多因是一种天然细胞保护剂，是生活在极端环境下的细菌产生的氨基酸衍生物。它作为渗透调节相容性溶质，在皮肤护理中常用，能增加皮肤表面的水合作用并稳定脂质层。依克多因具有良好的安全性，可用于研究过敏性鼻炎。

靶点

Bacterial

反应信息

• 作为反应物：
  描述：

  四氢嘧啶 在 三氟甲磺酸 作用下， 以 水 为溶剂， 生成 6-carboxy-2-methyl-1,4,5,6-tetrahydropyrimidinium trifluoromethanesulfonate
  参考文献：
  名称：

  SALTS COMPRISING A PYRIMIDINECARBOXYLIC ACID DERIVATIVE FOR COSMETIC USE

  摘要：

  这项发明涉及一种新型化合物，其包括作为阳离子或阴离子成分的嘧啶羧酸衍生物，特别是ectoin或hydroxyectoin的衍生物，以及其制备方法和作为离子液体使用或在制药、化妆品和皮肤科配方中使用的用途。

  公开号：

  US20110152292A1
• 作为产物：
  描述：

  N-乙酰-L-天门冬酰胺 在 sodium tetrahydroborate 、 potassium tert-butylate 、 sodium hydride 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 16.0h， 生成 四氢嘧啶
  参考文献：
  名称：

  一种合成小分子氨基酸衍生物依克多因的方 法

  摘要：

  本发明涉及一种小分子氨基酸衍生物(S)‑2‑甲基‑1,4,5,6‑四氢嘧啶‑4‑羧酸(依克多因)的合成方法，其特征是以廉价易得的商品化的L‑乙酰天冬酰胺为原料，先经过缩合成内酰胺、上保护、羰基还原、酰胺水解、氨基脱保护盐酸盐化再成环得到依克多因分子。该方法能够以很低的成本、较少的步骤方便的得到高纯度的(S)‑2‑甲基‑1,4,5,6‑四氢嘧啶‑4‑羧酸(依克多因)产品，反应条件温和，易于控制，环境污染很小，适合工业化生产。

  公开号：

  CN108003105B

文献信息

• SYNTHESIS OF CYCLIC AMIDINES
  申请人：Lentzen George

  公开号：US20110178292A1

  公开（公告）日：2011-07-21

  The invention relates to an innovative method for synthesis of cyclic amidines. The synthesis starts from a β-, γ- or δ-lactone which is twofold brominated. After esterification of the carboxyl function, the bromine atoms are nucleophilically substituted and the corresponding diamino compound is obtained. The ring closure to the cyclic amidine is accomplished subsequently by reaction with orthoester, imidate or thioimidate. Owing to interposing additional steps for recovery of the diamino compound in enantiomerically pure form, the enantiomers of the cyclic amidines can be stereoselectively synthesized.

  该发明涉及一种合成环氨基甲酸盐的创新方法。合成从β-、γ-或δ-内酯开始，该内酯经过双溴化。在羧基酯化后，溴原子被亲核取代，得到相应的二氨基化合物。随后通过与正酯、亚胺酯或硫代亚胺的反应实现环氨基甲酸盐的环闭合。由于插入额外步骤以以对映纯形式回收二氨基化合物，因此可以立体选择性地合成环氨基甲酸盐的对映体。
• [EN] CONTROLLED-RELEASE TYROSINE KINASE INHIBITOR COMPOUNDS WITH LOCALIZED PK PROPERTIES<br/>[FR] COMPOSÉS INHIBITEURS DE TYROSINE KINASE À LIBÉRATION CONTRÔLÉE PRÉSENTANT DES PROPRIÉTÉS PHARMACOCINÉTIQUES LOCALISÉES
  申请人：ASCENDIS PHARMA ONCOLOGY DIV A/S

  公开号：WO2020254613A1

  公开（公告）日：2020-12-24

  The present invention relates to a water-insoluble controlled-release tyrosine kinase inhibitor ("TKI") compound for use in the treatment of a cell-proliferation disorder, wherein said water-insoluble controlled-release TKI compound releases one or more TKI drug, wherein the water-insoluble controlled-release TKI compound is administered by intra-tissue administration and wherein the total amount of TKI moieties and TKI drug molecules remaining locally in such tissue 3 days after said intra-tissue administration is at least 25% of the amount of TKI moieties or TKI drug molecules administered by said intra-tissue administration; and to related aspects.

  本发明涉及一种水不溶性控释酪氨酸激酶抑制剂（“TKI”）化合物，用于治疗细胞增殖紊乱，其中所述水不溶性控释TKI化合物释放一种或多种TKI药物，所述水不溶性控释TKI化合物通过组织内给药给予，并且在所述组织内给药后的第3天，所述组织中残留的TKI基团和TKI药物分子的总量至少为所述组织内给药给予的TKI基团或TKI药物分子总量的25％；以及相关方面。
• Flavonoid derivative
  申请人：Buchholz Herwig

  公开号：US20070134172A1

  公开（公告）日：2007-06-14

  The invention relates to a novel flavonoid derivative, to an extract comprising the flavonoid derivative, to the cosmetic and pharmaceutical use thereof, to preparations comprising the flavonoid derivative or extract, and to a process for the preparation of the flavonoid derivative or extract.

  这项发明涉及一种新型黄酮衍生物，一种包含该黄酮衍生物的提取物，以及其在化妆品和药用方面的使用，包括含有该黄酮衍生物或提取物的制剂，以及一种制备该黄酮衍生物或提取物的方法。
• Extracts of Isochrysis sp.
  申请人：Herrmann Martina

  公开号：US20100080761A1

  公开（公告）日：2010-04-01

  The present invention relates to extracts of Isochrysis sp., preferably Tahitian Isochrysis, its cosmetic, dermatological and/or therapeutic uses and compositions and cosmetic, dermatological or therapeutic products comprising such an extract of Isochrysis sp., preferably Tahitian Isochrysis.

  本发明涉及Isochrysissp.的提取物，优选为塔希提Isochrysis，及其在化妆品、皮肤病学和/或治疗学上的用途以及包含该Isochrysissp.提取物的化妆品、皮肤病学或治疗学产品，优选为塔希提Isochrysis。
• [EN] TREATMENT OF INFECTIONS<br/>[FR] TRAITEMENT D'INFECTIONS
  申请人：ASCENDIS PHARMA AS

  公开号：WO2020064844A1

  公开（公告）日：2020-04-02

  The present invention relates among other aspects to a conjugate or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising said conjugate or its pharmaceutically acceptable salt for use in a method of preventing or treating an infection, wherein said conjugate is water-insoluble and comprises a polymeric moiety -Z to which a plurality of moieties -L2-X0D-L1-D are covalently conjugated, wherein each -D is independently an antibiotic moiety; each -L1- is independently a linker moiety to which -D is covalently and reversibly conjugated; each -X0D- is independently absent or a linkage and each -L2- is independently either a chemical bond or a spacer moiety.

  本发明涉及一种共轭物或其药用可接受的盐，或包含所述共轭物或其药用可接受的盐的药物组合物，用于预防或治疗感染的方法，其中所述共轭物不溶于水，包括一个聚合物基团-Z，其中多个基团-L2-X0D-L1-D以共价结合方式共轭，其中每个-D独立地是抗生素基团；每个-L1-独立地是连接基团，与-D以共价和可逆方式结合；每个-X0D-独立地不存在或是一个连接，每个-L2-独立地是化学键或间隔基团。