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硫酸长春新碱 | 2068-78-2

中文名称
硫酸长春新碱
中文别名
硫酸醛基长春碱;长春新碱硫酸盐;替莫唑胺;硫酸长春醛碱
英文名称
vincristine sulfate
英文别名
vincristine sulphate;vincristin sulphate;vincristin sulfate;Oncovin(R);methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-4-[(13S,15R,17S)-17-ethyl-17-hydroxy-13-methoxycarbonyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9-tetraen-13-yl]-8-formyl-10-hydroxy-5-methoxy-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate;sulfuric acid
硫酸长春新碱化学式
CAS
2068-78-2
化学式
C46H56N4O10*H2O4S
mdl
——
分子量
923.051
InChiKey
AQTQHPDCURKLKT-PNYVAJAMSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    300 °C
  • 沸点:
    273-281 °C
  • 比旋光度:
    D26 +8.5° (c = 0.8)
  • 溶解度:
    在甲醇中可溶20mg/mL
  • 物理描述:
    Vincristine sulfate appears as an anticancer drug. White to slightly yellow, amorphous or crystalline powder. Sensitive to light. Odorless. pH (0.1% solution) 3.5 - 4.5. (NTP, 1992)

计算性质

  • 辛醇/水分配系数(LogP):
    2.86
  • 重原子数:
    65
  • 可旋转键数:
    10
  • 环数:
    9.0
  • sp3杂化的碳原子比例:
    0.57
  • 拓扑面积:
    254
  • 氢给体数:
    5
  • 氢受体数:
    16

ADMET

毒理性
  • 致癌物分类
国际癌症研究机构致癌剂:硫酸长春新碱
IARC Carcinogenic Agent:Vincristine sulfate
来源:International Agency for Research on Cancer (IARC)
毒理性
  • 致癌物分类
国际癌症研究机构(IARC)致癌物分类:第3组:对其对人类的致癌性无法分类
IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans
来源:International Agency for Research on Cancer (IARC)
毒理性
  • 致癌物分类
国际癌症研究机构专著:第26卷:(1981年)一些抗癌和免疫抑制剂
IARC Monographs:Volume 26: (1981) Some Antineoplastic and Immunosuppressive Agents
来源:International Agency for Research on Cancer (IARC)

安全信息

  • 危险等级:
    6.1(a)
  • 危险品标志:
    T
  • 安全说明:
    S22,S24/25,S26,S36/37/39,S37/39,S45,S53
  • 危险类别码:
    R36/37/38,R61
  • WGK Germany:
    3
  • 海关编码:
    2942000000
  • 危险品运输编号:
    UN 2811 6.1/PG 2
  • 危险类别:
    6.1(a)
  • RTECS号:
    OH6340000
  • 包装等级:
    II
  • 储存条件:
    充氩气密封保存,置于4℃干燥避光环境中。

SDS

SDS:13f47c057b924b3b5c0f42bf2f98738c
查看
Name: Vincristine sulfate 95% (hplc) Material Safety Data Sheet
Synonym: Leurocristine sulfate (1:1
CAS: 2068-78-2
Section 1 - Chemical Product MSDS Name:Vincristine sulfate 95% (hplc) Material Safety Data Sheet
Synonym:Leurocristine sulfate (1:1

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS
CAS# Chemical Name content EINECS#
2068-78-2 Vincristine sulfate 95 218-190-0
Hazard Symbols: T
Risk Phrases: 23/24/25

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Toxic by inhalation, in contact with skin and if swallowed.Hygroscopic (absorbs moisture from the air).Light sensitive.
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. May cause gastrointestinal irritation with nausea, vomiting and diarrhea. May cause liver and kidney damage. May cause bone marrow depression.
Inhalation:
May cause respiratory tract irritation. May cause effects similar to those described for ingestion.
Chronic:
Chronic exposure may cause reproductive disorders and teratogenic effects.

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. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid immediately. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Get medical aid immediately. Remove from exposure and move to fresh air immediately. Do not use mouth-to-mouth resuscitation if victim ingested or inhaled the substance; induce artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device.
Notes to Physician:
Treat symptomatically and supportively.

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 carbon dioxide, dry chemical powder or water spray.

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Wash area with soap and water. 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.

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation. Do not get in eyes, on skin, or on clothing. Keep container tightly closed. Store protected from light. Use only in a chemical fume hood.
Do not breathe dust or fumes.
Storage:
Store in a tightly closed container. Keep refrigerated. (Store below 4C/39F.) Store protected from moisture. Store protected from light.
Store in a cool, dry 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# 2068-78-2: 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:
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 to pale yellow
Odor: none reported
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: > 300 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: Not available.
Solubility in water: soluble
Specific Gravity/Density: Not available.
Molecular Formula: C46H58N4O14S
Molecular Weight: 923.03

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures. Light sensitive.
Conditions to Avoid:
Incompatible materials, excess heat, exposure to moist air or water, excess light.
Incompatibilities with Other Materials:
Strong oxidizing agents, heat, moisture, heavy metal salts, direct light.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, oxides of sulfur, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Will not occur.

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 2068-78-2: OH6340000 LD50/LC50:
Not available.
Carcinogenicity:
Vincristine sulfate - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

Section 12 - ECOLOGICAL INFORMATION
Other No information available.

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

Section 14 - TRANSPORT INFORMATION

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

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 23/24/25 Toxic by inhalation, in contact with skin
and if swallowed.
Safety Phrases:
S 24/25 Avoid contact with skin and 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# 2068-78-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 2068-78-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 2068-78-2 is not listed on the TSCA inventory.
It is for research and development use only.


SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

长春新碱简介

长春新碱(Vincristine),商品名“维克思丁”、“安可平”(Oncovin),又名长春花新碱、新长春碱,医学上简称VCR。这是一种从夹竹桃科长春花属植物长春花中提取的生物碱。作为有丝分裂抑制剂,它被广泛用于化学疗法,治疗急性淋巴性白血病、急性骨髓性白血病、霍奇金氏淋巴瘤、神经母细胞瘤以及小细胞肺癌等多种癌症。

药理作用

硫酸长春新碱(vincristinesulfate,VCR)是夹竹桃科植物长春花生物碱类的细胞周期特异性抗肿瘤药物。它的抗肿瘤机制主要是通过抑制微管蛋白聚合影响纺锤体微管的形成,导致有丝分裂停滞在中期。

临床应用

硫酸长春新碱对于许多淋巴组织的恶性肿瘤,包括侵袭性非霍奇金淋巴瘤和急性淋巴细胞白血病,有着良好的治疗效果。临床上主要用于急性白血病、恶性淋巴瘤、神经母细胞瘤、慢性淋巴细胞白血病等疾病的治疗。

制备

2克硫酸长春碱溶于240毫升四氢呋喃中,加入7.5毫升冰醋酸,并在干冰冷却下将反应温度降至-65℃。搅拌下滴加配制好的重镉酸钠溶液(3克重镉酸钠溶于15毫升水中,再加入2毫升浓硫酸搅拌溶解),维持反应温度低于-50℃。滴加完毕后,在-65℃下继续搅拌反应3小时。

将反应液倒入含有35毫升浓氨水和200毫升水的混合溶液中,用600毫升二氯甲烷萃取,无水硫酸镁干燥,减压浓缩得到长春新碱粗品2.06克(HPLC检测纯度为83%)。随后,将该粗品溶解在20毫升异丙醇中,在搅拌下滴加1%的硫酸异丙醇溶液16毫升调节pH值至≤4。过滤得到固体后,真空干燥得到硫酸长春新碱粗品1.82克(HPLC检测纯度为92%)。最终将该粗品溶解在36毫升无水乙醇中,冷却至-10℃搅拌下析出固体,过滤并用无水乙醇洗涤,真空干燥后得到硫酸长春新碱1.63克(收率为81.5%,HPLC检测纯度为98.6%)。

化学性质

白色针状结晶,可溶于甲醇、乙醇、DMSO等有机溶剂,来源于长春花。

用途

这是一种天然生物碱的硫酸盐,具有抗核分裂和抗肿瘤活性。长春新碱在细胞周期S期不可逆地与微管和纺锤体蛋白结合,干扰有丝分裂纺锤体的形成,在中期抑制肿瘤细胞生长,并可能解聚微管、干扰氨基酸、环腺苷酸及谷胱甘肽代谢。

天然植物抗肿瘤药,主要用于治疗急性白血病和恶性淋巴瘤、小细胞肺癌及乳腺癌。广泛应用于癌症研究中多药物抑制与单胺氧化酶(monoamine oxidase)的抑制作用。

反应信息

  • 作为反应物:
    描述:
    硫酸长春新碱 在 sodium carbonate 作用下, 以 甲醇氯仿 为溶剂, 以98%的产率得到长春新碱
    参考文献:
    名称:
    WO2007/98091
    摘要:
    公开号:
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文献信息

  • VINBLASTINE DERIVATIVES, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
    申请人:JINAN UNIVERSITY
    公开号:US20160068552A1
    公开(公告)日:2016-03-10
    The present invention provides a new kind of vinca alkaloid derivatives, new applications thereof and preparation methods therefor. The vinca alkaloid derivatives comprise hydrazinolyzed vinca alkaloids and vinca alkaloid dipeptide derivative. The hydrazinolyzed vinca alkaloids are the compounds obtained from the reaction of vinca alkaloids or salts thereof with hydrazinolyzed hydrate; and the vinca alkaloid dipeptide derivatives are the compounds obtained from the condensation of hydrazinolyzed vinca alkaloids with N-benzyloxycarbonylglycyl proline. The present invention provides the uses of the vinca alkaloids derivatives or the pharmaceutical compositions thereof in anti-tumor, preventing or treating diabetic retinopathy, rheumatoid arthritis and serving as angiogenesis inhibitors or vascular disrupting agents.
    本发明提供了一种新型的长春碱衍生物,以及其新的应用和制备方法。长春碱衍生物包括水解长春碱和长春碱二肽衍生物。水解长春碱是通过长春碱或其盐与水解水合物反应得到的化合物;而长春碱二肽衍生物是通过水解长春碱与N-苄氧羰基甘氨酸脯氨酸的缩合反应得到的化合物。本发明提供了长春碱衍生物或其药物组合物在抗肿瘤、预防或治疗糖尿病视网膜病变、类风湿性关节炎以及作为血管生成抑制剂或血管破坏剂中的用途。
  • [EN] VINCA DERIVATIVES<br/>[FR] DERIVES DE LA PERVENCHE
    申请人:AMR TECHNOLOGY INC
    公开号:WO2005055939A3
    公开(公告)日:2005-12-29
  • Thimmaiah; Lloyd; Sethi, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1990, vol. 29, # 7, p. 678 - 680
    作者:Thimmaiah、Lloyd、Sethi
    DOI:——
    日期:——
  • WO2007/98091
    申请人:——
    公开号:——
    公开(公告)日:——
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同类化合物

长春西醇 长春西碱 长春花胺 长春花碱 长春罗定 长春素 长春磷汀 长春甘酯 长春瑞宾 长春氮芥 长春氟宁酒石酸盐 长春氟宁 长春曲醇酸 长春曲醇 长春新碱 长春匹定硫酸盐 脱水长春碱 脱乙酰基长春碱酰肼 硫酸长春碱 硫酸长春新碱 硫酸长春地辛 硫酸长春地辛 甲酰基-环氧长春碱 二(N-亚乙基长春地辛)二硫醚 O4-去乙酰基-3',4'-二去氢-4'-脱氧-C'-去甲长春花碱 N-去甲基长春碱 N-(O-4-去乙酰基-长春碱-23-酰基)-L-亮氨酸乙酯 N-(4-叠氮基-3-碘水杨酰)-N'-beta-氨基乙基长春地辛 4-去乙酰基长春花碱 3-(((2-((4-叠氮基-2-硝基苯基)氨基)乙基)氨基)羰基)-O4-去乙酰基-3-去(甲氧羰基)-长春花碱 3''-(beta-氯乙基)-2'',4''-二氧代-3,5''-螺恶唑烷-4-去乙酰氧基长春碱 2,5-哌嗪二酮,1,4-二甲基-3-亚甲基- (3'a,4'a)-4'-脱氧-3',4'-环氧-12'-羟基-长春花碱 12'-iodovinblastine 12'-thiomethylvinblastine 20',20'-difluoro-4'-deoxyvinblastine methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(cyclobutanecarbonylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[[(4-chlorobenzoyl)amino]methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-10-[[(4-methoxybenzoyl)amino]methyl]-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(3,3-dimethylbutanoylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-8-methyl-10-[[(4-nitrobenzoyl)amino]methyl]-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-8-methyl-10-[(3-methylbutanoylamino)methyl]-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-[[(4-fluorobenzoyl)amino]methyl]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(butanoylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[[(3-chlorobenzoyl)amino]methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(cyclopropanecarbonylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[[(2-chlorobenzoyl)amino]methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(2,2-dimethylpropanoylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-8-methyl-10-[(propanoylamino)methyl]-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-8-methyl-10-[(pyridine-4-carbonylamino)methyl]-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate