氨甲蝶呤 | 60388-53-6

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 中文名称: 氨甲蝶呤
• 中文别名: (+/-)氨甲喋呤
• 英文名称: methotrexate
• 英文别名: 4-amino-N10-methylpteroylglutamic acid；N-[4-[[(2,4-Diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid；(+/-)-methotrexate；(R,S)-amethopterin；amethopterin (R,S)；d,l-methotrexate；DL-Amethopterin；2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid
• CAS: 60388-53-6
• 化学式: C₂₀H₂₂N₈O₅
• 分子量: 454.445
• InChiKey: FBOZXECLQNJBKD-UHFFFAOYSA-N

物化性质

• 熔点：
  195 °C (dec.)(lit.)
• 密度：
  1.536±0.06 g/cm3(Predicted)
• 溶解度：
  H2O：加入最少量的 0.1 L NaOH 进行溶解，然后用中性缓冲液或盐水稀释。稀释后的原液冷藏可稳定 1 周，20°C 冷冻可稳定 1 个月。
• 稳定性/保质期：
  1. 遵照规定使用和储存则不会分解。
  2. 有毒，能引起遗传基因的损伤，可能危害胎儿，使用时应穿戴适当的防护服以避免暴露。

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  211
• 氢给体数：
  5
• 氢受体数：
  12

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的总结：大多数来源认为，在高剂量抗癌药物甲氨蝶呤治疗期间，母乳喂养是被禁忌的。建议在甲氨蝶呤化疗剂量后至少有1周的禁欲期。化疗可能会不利地影响母乳的正常微生物组和化学成分。在怀孕期间接受化疗的妇女更有可能在哺乳婴儿时遇到困难。 母体剂量的甲氨蝶呤达到92毫克（1.12毫克/公斤）时，在乳汁中产生低水平，导致一些作者认为，低单一剂量或每周剂量，例如用于宫外孕或类风湿性关节炎的剂量，对哺乳婴儿的风险较低，尽管一些专家意见警告不要使用。在每周低剂量甲氨蝶呤后停止哺乳24小时，可能会使婴儿的剂量减少40%。如果在长期低剂量甲氨蝶呤使用期间进行母乳喂养，可以考虑监测婴儿的完整血细胞计数和分类。 ◉ 对哺乳婴儿的影响：在分娩后第151天，一位哺乳的母亲开始每周皮下注射甲氨蝶呤25毫克。在那时，估计婴儿在给药后24小时内的摄入量为3.4微克/公斤。这位母亲在继续接受每周皮下注射甲氨蝶呤25毫克的同时，又额外哺乳了9个月（具体程度未说明）。婴儿未出现不良反应。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关已发布信息。

◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal high-dose antineoplastic drug therapy with methotrexate. An abstinence period of at least 1 week after chemotherapy doses of methotrexate has been suggested. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk. Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant. Maternal doses of methotrexate up to 92 mg (1.12 mg/kg) produce low levels in milk, leading some authors to state that low single or weekly doses, such as those used for ectopic pregnancy or rheumatoid arthritis, are of low risk to the breastfed infant, although some expert opinion warns against this use. Withholding breastfeeding for 24 hours after a weekly low dose of methotrexate may decrease the infant's dose by 40%. If breastfeeding during long-term, low-dose methotrexate use is undertaken, monitoring of the infant's complete blood count and differential could be considered. ◉ Effects in Breastfed Infants:On day 151 postpartum, weekly methotrexate 25 mg subcutaneously begun a nursing mother. The estimated intake of the infant at that time was 3.4 mcg/kg in the first 24 hours after administration. The mother continued to breastfeed (extent not stated) for an additional 9 months while receiving subcutaneous methotrexate 25 mg weekly. No adverse effects were noted in the infant. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

安全信息

• 安全说明：
  S45,S53
• 危险类别码：
  R46,R61
• 危险品运输编号：
  UN 1544 6.1/PG 2
• 储存条件：
  存放在-20°C的阴凉干燥处，并充入氩气密封。

SDS

Name:	DL-Amethopterin hydrate Material Safety Data Sheet
Synonym:	DL-Amethopterin
CAS:	60388-53-6

Section 1 - Chemical Product MSDS Name:DL-Amethopterin hydrate Material Safety Data Sheet
Synonym:DL-Amethopterin

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
60388-53-6	DL-Amethopterin hydrate	ca 100	262-213-7

Hazard Symbols: T
Risk Phrases: 46 61

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
May cause heritable genetic damage. May cause harm to the unborn child.Hygroscopic (absorbs moisture from the air).Light sensitive.The toxicological properties of this material have not been fully investigated.Mutagen.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation. May be absorbed through the skin in harmful amounts.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Exposure may cause anemia and other blood abnormalities.
Inhalation:
May cause respiratory tract irritation. May cause effects similar to those described for ingestion. The toxicological properties of this substance have not been fully investigated.
Chronic:
May alter genetic material. Possible risk of harm to the unborn child.

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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.
Extinguishing Media:
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. 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. Deep freeze (below -20C).
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# 60388-53-6: 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:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Powder
Color: orange - yellow crystalline powder
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 195 deg C dec
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: > 195 deg C
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C20H22N8O5.xH2O
Molecular Weight: 454.44

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, light, dust generation, excess heat, exposure to moist air or water.
Incompatibilities with Other Materials:
Strong acids, strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 60388-53-6: MA1224100 LD50/LC50:
Not available.
Carcinogenicity:
DL-Amethopterin hydrate - 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 46 May cause heritable genetic damage.
R 61 May cause harm to the unborn child.
Safety Phrases:
S 53 Avoid exposure - obtain special instructions
before use.
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# 60388-53-6: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 60388-53-6 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 60388-53-6 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

应用

甲氨蝶呤是一种抗叶酸类抗肿瘤药物，主要通过抑制二氢叶酸还原酶来阻碍肿瘤细胞的合成，从而抑制其生长和繁殖。

反应信息

• 作为反应物：
  描述：

  氨甲蝶呤 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 methotrexate disodium salt
  参考文献：
  名称：

  Methotrexate compositions

  摘要：

  一种含有甲氨蝶呤液晶形态颗粒的粉末，适用于吸入。

  公开号：

  US20060039985A1
• 作为产物：
  描述：

  dicyanomethyl N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamate 以89的产率得到氨甲蝶呤
  参考文献：
  名称：

  [EN] A NEW METHOD FOR PRODUCING ANTIFOLATE AGENTS HAVING GLUTAMIC ACID PART IN THEIR STRUCTURE
  [FR] NOUVEAU PROCÉDÉ DE FABRICATION D'AGENTS ANTIFOLIQUES AYANT UNE PARTIE ACIDE GLUTAMIQUE DANS LEUR STRUCTURE

  摘要：

  一种新的制备具有谷氨酸结构部分的抗叶酸剂的方法被开发出来，该方法通过保护谷氨酸或其N-取代衍生物的羧基，以形成式（II）的化合物的氰甲酯，然后在非常温和的条件下水解，以高收率和高分析和光学纯度获得抗叶酸剂。

  公开号：

  WO2012074496A1

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• Heterocyclic derivatives for the treatment of cancer and other proliferative diseases
  申请人：——

  公开号：US20020143182A1

  公开（公告）日：2002-10-03

  The invention relates to certain heterocyclic compounds useful for the treatment of cancer and other diseases, having the Formula (I): 1 wherein: (a) m is an integer 0 or 1; (b) R 12 is an alkyl, a substituted alkyl, a cycloalkyl, a substituted cycloalkyl, a heterocyclic, a substituted heterocyclic, a heteroaryl, a substituted heteroaryl, an aryl or a substituted aryl residue; (c) Ar 3 is an aryl, a substituted aryl, a heteroaryl or a substituted