二羟丙茶碱 | 479-18-5

• 物质功能分类: 原料药 - 呼吸系统用药 - 平喘药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 二羟丙茶碱
• 中文别名: 丙羟茶碱、甘油茶碱；喘定；7-(2,3-二羟基丙基)茶碱；1,3-二甲基-7-(2,3-二羟基丙基)-3,7-二氢-1H-嘌呤-2,6-二酮；喘定、甘油茶碱；7-(2,3-二羟丙基)茶碱；甘油茶碱；丙羟茶碱；新赛林
• 英文名称: diprophylline
• 英文别名: 7-(2,3-Dihydroxypropyl)-1,3-dimethylxanthine；dyphylline；7-(2,3-dihydroxypropyl)-1,3-dimethylpurine-2,6-dione
• CAS: 479-18-5
• 化学式: C₁₀H₁₄N₄O₄
• mdl: MFCD00005759
• 分子量: 254.246
• InChiKey: KSCFJBIXMNOVSH-UHFFFAOYSA-N

物化性质

• 熔点：
  161-162 °C(lit.)
• 沸点：
  397.46°C (rough estimate)
• 密度：
  1.3036 (rough estimate)
• 溶解度：
  易溶于水，微溶于乙醇（96%）。
• LogP：
  -1.100 (est)
• 物理描述：
  Solid
• 颜色/状态：
  CRYSTALS FROM ALCOHOL
• 味道：
  EXTREME BITTER TASTE
• 水溶性：
  -0.17
• 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。
• 碰撞截面：
  152.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
• 保留指数：
  2237;2266

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  98.9
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

代谢

肝脏的

Hepatic

来源:DrugBank

代谢

在体内，黄嘌呤只是部分脱甲基和氧化。它们主要以甲基尿酸或甲基黄嘌呤的形式被排出。/黄嘌呤/

IN BODY XANTHINES ARE ONLY PARTIALLY DEMETHYLATED & OXIDIZED. THEY ARE LARGELY EXCRETED AS METHYLURIC ACIDS OR AS METHYLXANTHINES. /XANTHINES/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 药物性肝损伤

化合物：茶碱

Compound:dyphylline

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

DILI 注解：无 DILI（药物性肝损伤）担忧

DILI Annotation:No-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

标签部分：没有匹配项

Label Section:No match

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 用于研究药物诱导肝损伤的FDA批准药物标签，药物发现今日，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：根据人类发生药物诱导肝损伤风险排名的最大参考药物清单。药物发现今日2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007 M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 在妊娠和哺乳期间的影响

使用期间对哺乳的影响：由于牛奶中含量相对较高，以及之前关于茶碱的报告中提到，偶尔会在哺乳婴儿中预期到兴奋作用。不期望出现严重的不良反应。通过在服用剂量后避免哺乳3到4小时，可以尽量减少牛奶中的含量。 哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Because of the relatively high levels in milk and a previous report with theophylline, occasional stimulant effects in infants should be anticipated in breastfed infants. No severe adverse reactions are expected. Amounts in milk can be minimized by avoiding breastfeeding for 3 to 4 hours after a dose. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

• 消除途径

Dyphylline 通过直接作用发挥其支气管扩张效果，并且与茶碱不同，它不被肝脏代谢，而是由肾脏原样排出。大约 88% 的单次口服剂量可以不变地从尿液中回收。

Dyphylline exerts its bronchodilatory effects directly and, unlike the­ophylline, is excreted unchanged by the kidneys without being metabolized by the liver. Approximately 88% of a single oral dose can be recovered from the urine unchanged.

来源:DrugBank

吸收、分配和排泄

快速处理速度。

...RAPID RATE OF DISPOSITION.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

它可能比茶碱和氨茶碱更一致地被胃肠道吸收，并且刺激性更小。

IT MAY BE MORE CONSISTENTLY ABSORBED FROM GI TRACT & LESS IRRITATING THAN THEOPHYLLINE & AMINOPHYLLINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

单次二氢吡啶剂量给予5名正常志愿者。19-27毫克/千克的剂量导致了19.3-23.5微克/毫升的峰值血清浓度，并且4个受试者对该剂量耐受良好。1名受试者在28毫克/千克剂量后出现了严重头痛，血清浓度为36.4微克/毫升；未代谢为茶碱。

SINGLE DYPHYLLINE DOSE WAS GIVEN TO 5 NORMAL VOLUNTEERS. DOSES OF 19-27 MG/KG RESULTED IN PEAK SERUM CONCN OF 19.3-23.5 MUG/ML & WERE TOLERATED WELL BY 4 SUBJECTS. 1 HAD SEVERE HEADACHE AFTER 28 MG/KG DOSE ASSOC WITH 36.4 MUG/ML; WAS NOT METABOLIZED TO THEOPHYLLINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在5名正常志愿者中，平均半衰期T/2为1.8小时；平均总清除率和平均肾清除率分别为333和276毫升/分钟。平均分布体积为0.8升/千克。在尿液中，83%的剂量未发生变化排出，未检测到茶碱。

IN 5 NORMAL VOLUNTEERS MEAN T/2 WAS 1.8 HR; MEAN TOTAL BODY CLEARANCE RATE & MEAN RENAL CLEARANCE RATE WERE 333 & 276 ML/MIN, RESPECTIVELY. MEAN VOL OF DISTRIBUTION WAS 0.8 L/KG. IN URINE 83% OF DOSE WAS EXCRETED UNCHANGED & THEOPHYLLINE WAS NOT DETECTED.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2939590000
• RTECS号：
  XH5100000
• 储存条件：
  密封保存，并置于通风、干燥的地方，避免与其它氧化物接触。

SDS

Name:	7-(2 3-Dihydroxypropyl)theophylline 99% Material Safety Data Sheet
Synonym:	Dyphylline; Dihydroxypropyl Theopylin
CAS:	479-18-5

Section 1 - Chemical Product MSDS Name:7-(2 3-Dihydroxypropyl)theophylline 99% Material Safety Data Sheet
Synonym:Dyphylline; Dihydroxypropyl Theopylin

---

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
479-18-5	7-(2,3-Dihydroxypropyl)theophylline	99	207-526-1

Hazard Symbols: XN
Risk Phrases: 22

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful if swallowed.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.

---

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:

---

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 agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

---

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. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

---

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# 479-18-5: 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.

---

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Powder
Color: white
Odor: None reported.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 161.00 - 162.00 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: 1g/3ml (25 c)
Specific Gravity/Density:
Molecular Formula: C10H14N4O4
Molecular Weight: 254.24

---

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, 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.
Hazardous Polymerization: Has not been reported.

---

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 479-18-5: XH5100000 LD50/LC50:
CAS# 479-18-5: Oral, mouse: LD50 = 1954 mg/kg.
Carcinogenicity:
7-(2,3-Dihydroxypropyl)theophylline - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

---

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: XN
Risk Phrases:
R 22 Harmful if swallowed.
Safety Phrases:
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# 479-18-5: 1
Canada
CAS# 479-18-5 is listed on Canada's NDSL List.
CAS# 479-18-5 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 479-18-5 is listed on the TSCA inventory.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

二羟丙茶碱是一种黄嘌呤类药物，主要用于治疗支气管哮喘、喘息性支气管炎及慢性肺气肿等。它是由茶碱和一氯丙二醇通过缩合反应制备而成的。

化学性质：

• 物理状态：白色结晶性粉末。
• 熔点：158℃（范围159-163.5℃）。
• 溶解度：易溶于水，1克本品可溶于约3毫升水中；在乙醇中的溶解度为2克/100毫升，在氯仿中为1克/100毫升。

用途：

• 扩张支气管和冠状动脉。
• 具有利尿作用。
• 治疗支气管哮喘、喘息性支气管炎及慢性肺气肿等疾病。
• 预防支气管哮喘发作。
• 治疗心绞痛及心脏性水肿。

药理作用：

二羟丙茶碱与氨茶碱同属黄嘌呤类扩张支气管药，其毒性约为氨茶碱的1/5。它能够有效缓解呼吸系统疾病症状，并且相比茶碱具有更好的水溶性。

生产方法：

由茶碱钠盐与一氯丙二醇通过缩合反应制备而成。

注意事项及禁忌：

• 对本品或其他茶碱类药物过敏者禁用。
• 活动性消化性溃疡患者慎用。
• 未经控制的惊厥性疾病患者禁用。
• 哮喘急性严重发作的患者不宜首选使用本品。

不良反应：

可能引起多种不良反应，包括但不限于头痛、烦躁、易激动、失眠、兴奋过度等。严重情况下还可能出现心律失常甚至癫痫发作。

总之，二羟丙茶碱是一种有效的治疗支气管哮喘及其他呼吸系统疾病的药物，在临床应用中需要根据患者的具体情况合理使用，并注意监测可能的不良反应。

反应信息

• 作为反应物：
  描述：

  二羟丙茶碱 在 sodium periodate 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 theophylline-7-acetaldehyde benzoylhydrazone
  参考文献：
  名称：

  El Ashry, El Sayed H.; Rashed, Nagwa; Awad, Laila F., Journal of Chemical Research, Miniprint, 2001, # 4, p. 440 - 450

  摘要：

  DOI：
• 作为产物：
  描述：

  dyphylline 2',3'-di-p-chlorobenzoate 以 甲醇 为溶剂， 生成 二羟丙茶碱
  参考文献：
  名称：

  茶碱前药：兔血浆水解和茶碱释放

  摘要：

  茶碱[7-（2,3-二羟丙基）茶碱]的前药酯水解在人和兔血浆中均遵循一级动力学。速率常数通过初始转化率的线性回归分析估算，初始转化率是在不同的初始前药浓度下确定的。在兔血浆中，从前药中释放的茶碱比人血浆快1.3至13倍。但是，在兔子和人血浆中，药物的相对释放速率（不稳定性顺序）遵循相同的模式。静脉内给予2'，3'-双戊二酸茶碱后，兔血浆中茶碱的浓度略有增加。兔体内前药的口服给药大大维持了血浆茶碱浓度。

  DOI：

  10.1002/jps.2600770203

文献信息

• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20070093498A1

  公开（公告）日：2007-04-26

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。
• [EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013079350A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.

  式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
• [EN] INSULIN ANALOGUES WITH GLUCOSE REGULATED CONFORMATIONAL SWITCH<br/>[FR] ANALOGUES DE L'INSULINE À COMMUTATEUR DE CONFORMATION RÉGULÉ PAR LE GLUCOSE
  申请人：THERMALIN INC

  公开号：WO2021022116A1

  公开（公告）日：2021-02-04

  The present invention relates to glucose-responsive insulin analogues, compositions including the glucose-responsive insulin analogues, and methods of lowering blood sugar of a patient using the insulin analogue or compositions thereof.

  本发明涉及葡萄糖响应胰岛素类似物，包括该葡萄糖响应胰岛素类似物的组合物，以及使用该胰岛素类似物或其组合物降低患者血糖的方法。
• Novel insecticides
  申请人：Syngenta Participations AG

  公开号：EP2540718A1

  公开（公告）日：2013-01-02

  Compounds of formula I wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts and all stereoisomers and tautomeric forms of the compounds of formula I can be used as insecticides and can be prepared in a manner known per se.

  式I的化合物 其中取代基如权利要求1所定义，并且式I化合物的农药可接受盐以及所有立体异构体和互变异构形式可用作杀虫剂，并且可以按照已知的方法制备。

表征谱图