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(3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((3R,5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate sulfuric acid | 143-67-9

中文名称
——
中文别名
——
英文名称
(3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((3R,5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate sulfuric acid
英文别名
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]-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraene-10-carboxylate;sulfuric acid
(3aR,3a1R,4R,5S,5aR,10bR)-methyl 4-acetoxy-3a-ethyl-9-((3R,5S,7R,9S)-5-ethyl-5-hydroxy-9-(methoxycarbonyl)-2,4,5,6,7,8,9,10-octahydro-1H-3,7-methano[1]azacycloundecino[5,4-b]indol-9-yl)-5-hydroxy-8-methoxy-6-methyl-3a,3a1,4,5,5a,6,11,12-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate sulfuric acid化学式
CAS
143-67-9
化学式
C46H58N4O9*H2O4S
mdl
——
分子量
909.067
InChiKey
KDQAABAKXDWYSZ-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:
    267 °C (dec.)(lit.)
  • 比旋光度:
    -21.7 º (c=2, CH3OH 21 ºC)
  • 溶解度:
    在水中的溶解度10 mg/mL
  • 物理描述:
    Vinblastine sulfate appears as an anticancer drug. White to slightly yellow crystalline powder. (NTP, 1992)
  • 碰撞截面:
    278.5 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]
  • 稳定性/保质期:

    常温常压下稳定。

计算性质

  • 辛醇/水分配系数(LogP):
    3.34
  • 重原子数:
    64
  • 可旋转键数:
    10
  • 环数:
    9.0
  • sp3杂化的碳原子比例:
    0.59
  • 拓扑面积:
    237
  • 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:长春碱硫酸
IARC Carcinogenic Agent:Vinblastine 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论: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)
毒理性
  • 在妊娠和哺乳期间的影响
◉ 母乳喂养期间使用总结:大多数来源认为,在母体抗肿瘤药物治疗期间,母乳喂养是禁忌的。由于长春碱治疗药物半衰期长,可能在治疗后恢复母乳喂养是不切实际的。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可能难以哺乳她们的婴儿。 ◉ 对哺乳婴儿的影响:截至修订日期,没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响:一名在怀孕第二季度被诊断为霍奇淋巴瘤的妇女在第三季度怀孕期间接受了3轮化疗,并在产后4周恢复了化疗。在重新开始化疗后的16周内,收集了她在化疗前15至30分钟的乳汁样本。治疗方案包括多柔比星40毫克,博来霉素16单位,长春碱9.6毫克和达卡巴嗪600毫克,每2周一次,持续2小时。将她的乳汁微生物群和代谢概况与8名未接受化疗的健康妇女进行比较。患者的母乳微生物群与健康妇女明显不同,其中不动杆菌属、黄色单胞菌科和窄食单胞菌属增加,而双歧杆菌属和真杆菌属减少。在接受治疗的女性的母乳中,许多化学成分也有显著差异,尤其是DHA和肌醇含量降低。 对在同一中心怀孕第二或第三季度接受癌症化疗的74名妇女进行了电话随访研究,以确定她们产后是否成功进行母乳喂养。只有34%的妇女能够完全母乳喂养她们的婴儿,66%的妇女报告遇到母乳喂养困难。这与其他22位在怀孕期间被诊断但未接受化疗的母亲91%的母乳喂养成功率相比。其他具有统计学意义的相关性包括:1. 有哺乳困难的母亲平均接受了5.5个周期的化疗,而没有困难的母亲平均接受了3.8个周期;2. 有哺乳困难的母亲在怀孕期间平均提前3.4周接受了她们的第一个化疗周期。在接受含有长春新碱方案的6名妇女中,有5人遇到哺乳困难。
◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It is probably impractical to resume breastfeeding after vinblastine therapy because of the drug's long half-life. 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. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A woman diagnosed with Hodgkin's lymphoma during the second trimester of pregnancy received 3 rounds of chemotherapy during the third trimester of pregnancy and resumed chemotherapy 4 weeks postpartum. Milk samples were collected 15 to 30 minutes before and after chemotherapy for 16 weeks after restarting. The regimen consisted of doxorubicin 40 mg, bleomycin 16 units, vinblastine 9.6 mg and dacarbazine 600 mg, all given over a 2-hour period every 2 weeks. The microbial population and metabolic profile of her milk were compared to those of 8 healthy women who were not receiving chemotherapy. The breastmilk microbial population in the patient was markedly different from that of the healthy women, with increases in Acinetobacter sp., Xanthomonadacae and Stenotrophomonas sp. and decreases in Bifidobacterium sp. and Eubacterium sp. Marked differences were also found among numerous chemical components in the breastmilk of the treated woman, most notably DHA and inositol were decreased. A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 6 women who received a vincristine-containing regimen, 5 had breastfeeding difficulties.
来源:Drugs and Lactation Database (LactMed)

安全信息

  • 危险等级:
    6.1(a)
  • 危险品标志:
    T
  • 安全说明:
    S26,S36/37/39,S36/39,S37/39,S45,S53
  • 危险类别码:
    R22,R36/37/38,R41,R61
  • WGK Germany:
    3
  • 海关编码:
    2942000000
  • 危险品运输编号:
    1544
  • 危险类别:
    6.1(a)
  • RTECS号:
    YY8400000
  • 包装等级:
    II
  • 储存条件:
    在2-8°C的条件下保存。

SDS

SDS:eb39a74deffd858fad41c23ae76c6252
查看
Name: Vinblastine sulfate 96.0-102.0% (hplc) Material Safety Data Sheet
Synonym:
CAS: 143-67-9
Section 1 - Chemical Product MSDS Name:Vinblastine sulfate 96.0-102.0% (hplc) Material Safety Data Sheet
Synonym:

Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS
CAS# Chemical Name content EINECS#
143-67-9 Vinblastine sulfate 96-102% 205-606-0
Hazard Symbols: T
Risk Phrases: 22 37/38 41 61

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Harmful if swallowed. Irritating to respiratory system and skin.
Risk of serious damage to eyes. May cause harm to the unborn child.Harmful.Hygroscopic (absorbs moisture from the air).
Potential Health Effects
Eye:
May cause irreversible eye injury.
Skin:
Causes skin irritation.
Ingestion:
Harmful if swallowed.
Inhalation:
Causes respiratory tract irritation.
Chronic:
May cause digestive tract disturbances.

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:
Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Get medical aid if irritation develops or persists.
Ingestion:
Get medical aid immediately. 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.
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.
Extinguishing Media:
Use water spray, dry chemical, or carbon dioxide.

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.

Section 7 - HANDLING and STORAGE
Handling:
Do not breathe dust, vapor, mist, or gas. Do not get in eyes, on skin, or on clothing. Use only in a chemical fume hood.
Storage:
Store in a tightly closed container. Store in a dry area. Keep refrigerated. (Store below 4C/39F.)

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 143-67-9: Personal Protective Equipment Eyes: Not available.
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.

Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystalline powder
Color: white - slightly yellow
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 267 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: negligible in water
Specific Gravity/Density:
Molecular Formula:
Molecular Weight: 909.05

Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Not available.
Conditions to Avoid:
Incompatible materials, light, exposure to moist air or water.
Incompatibilities with Other Materials:
Strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported

Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 143-67-9: YY8400000 LD50/LC50:
CAS# 143-67-9: Oral, mouse: LD50 = 423 mg/kg; Oral, rat: LD50 = 305 mg/kg.
Carcinogenicity:
Vinblastine sulfate - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

Section 12 - ECOLOGICAL INFORMATION


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

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.

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 61 May cause harm to the unborn child.
R 22 Harmful if swallowed.
R 37/38 Irritating to respiratory system and skin.
R 41 Risk of serious damage to eyes.
Safety Phrases:
S 53 Avoid exposure - obtain special instructions
before use.
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.
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# 143-67-9: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 143-67-9 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 143-67-9 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

性质

硫酸长春碱为白色或类白色的疏松状或无定形固体,具有引湿性,遇光或热易变黄。它在中极易溶解,在甲醇或三氯甲烷中可溶解,在乙醇中的溶解度极微。

用途

硫酸长春碱(Vinblastine Sulfate)是一种国家基本药物,主要用于治疗霍奇淋巴瘤及恶性淋巴瘤,也适用于绒毛膜上皮癌和乳腺癌的治疗。此外,它还用于支气管肺癌、软组织肉瘤、睾丸肿瘤、卵巢癌、消化道癌以及恶性黑色素瘤和神经母细胞瘤等疾病的治疗。它是目前国际上应用最广泛的天然植物抗癌药物之一。

药理作用

硫酸长春碱是一种从夹竹桃科植物长春花中提取的生物碱,属于细胞周期特异性抗肿瘤药,主要作用于G1、S及M期,并对M期有延缓作用。它可以干扰增殖细胞纺锤体的形成,使有丝分裂停滞在中期。在高剂量下,它能直接破坏染色体并使微管蛋白质结晶化,阻止微管蛋白质的装配。此外,它还具有一定的免疫抑制作用。

化学性质

硫酸长春碱是一种白色结晶粉末,可溶于甲醇乙醇DMSO等有机溶剂,来源于长春花。

用途

从植物长春花中分离出的一种天然生物碱,能与微管蛋白结合并抑制微管的形成,导致有丝分裂纺锤体的断裂和细胞周期M期肿瘤细胞的停滞。主要用于治疗霍奇淋巴瘤、绒毛膜上皮癌,并对淋巴肉瘤、急性白血病和乳腺癌等有一定的疗效。

反应信息

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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 heteroaryl residue; (d) Ar 4 is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue; (e) R 5 is hydrogen, hydroxy, alkyl or substituted alkyl; (f) - - - - - represents a bond present or absent; and (g) W, X, Y and Z are independently or together C(O)—, C(S), S, O, or NH; or a pharmaceutically acceptable salt thereof.
    该发明涉及某些对治疗癌症和其他疾病有用的杂环化合物,其具有以下式(I): 1 其中: (a) m是整数0或1; (b) R12是烷基,取代烷基,环烷基,取代环烷基,杂环基,取代杂环基,杂芳基,取代杂芳基,芳基或取代芳基残基; (c) Ar3是芳基,取代芳基,杂芳基或取代杂芳基残基; (d) Ar4是芳基,取代芳基,杂芳基或取代杂芳基残基; (e) R5是氢,羟基,烷基或取代烷基; (f) - - - - - 代表存在或不存在的键;以及 (g) W、X、Y和Z独立或一起是C(O)、C(S)、S、O或NH;或其药学上可接受的盐。
  • [EN] COMPOUNDS AND COMPOSITIONS COMPRISING CDK INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS ET COMPOSITIONS COMPRENANT DES INHIBITEURS DES CDK ET MÉTHODES DE TRAITEMENT DU CANCER
    申请人:UNIV GEORGIA STATE RES FOUND
    公开号:WO2010129858A1
    公开(公告)日:2010-11-11
    Disclosed herein are compounds suitable for use as antitumor agents, methods for treating cancer wherein the disclosed compounds are used in making a medicament for the treatment of cancer, methods for treating a tumor comprising, administering to a subject a composition comprising one or more of the disclosed cytotoxic agents, and methods for preparing the disclosed antitumor agents.
    本文披露了适用作抗肿瘤药剂的化合物,用于治疗癌症的方法,其中所披露的化合物用于制备治疗癌症的药物,治疗肿瘤的方法包括向受试者施用包含一种或多种所披露的细胞毒性药剂的组合物,以及制备所披露的抗肿瘤药剂的方法。
  • [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE TYROSINE KINASE DE BRUTON
    申请人:BIOCAD JOINT STOCK CO
    公开号:WO2018092047A1
    公开(公告)日:2018-05-24
    The present invention relates to a new compound of formula I: or pharmaceutically acceptable salt, solvate or stereoisomer thereof, wherein: V1 is C or N, V2 is C(R2) or N, whereby if V1 is C then V2 is N, if V1 is C then V2 is C(R2), or if V1 is N then V2 is C(R2); each n, k is independently 0, 1; each R2, R11 is independently H, D, Hal, CN, NR'R", C(O)NR'R", C1-C6 alkoxy; R3 is H, D, hydroxy, C(O)C1-C6 alkyl, C(O)C2-C6 alkenyl, C(O)C2-C6 alkynyl, C1-C6 alkyl; R4 is H, Hal, CN, CONR'R", hydroxy, C1-C6 alkyl, C1-C6 alkoxy; L is CH2, NH, O or chemical bond; R1 is selected from the group of the fragments, comprising: Fragment 1, Fragment 2, Fragment 3 each A1, A2, A3, A4 is independently CH, N, CHal; each A5, A6, A7, A8, A9 is independently C, CH or N; R5 is H, CN, Hal, CONR'R", C1-C6 alkyl, non-substituted or substituted by one or more halogens; each R' and R" is independently selected from the group, comprising H, C1-C6 alkyl, C1-C6 cycloalkyl, aryl; R6 is selected from the group: [formula II] each R7, R8, R9, R10 is independently vinyl, methylacetylenyl; Hal is CI, Br, I, F, which have properties of inhibitor of Bruton's tyrosine kinase (Btk), to pharmaceutical compositions containing such compounds, and their use as pharmaceuticals for treatment of diseases and disorder.
    本发明涉及一种新的化合物,其化学式为I:或其药学上可接受的盐、溶剂化合物或立体异构体,其中:V1为C或N,V2为C(R2)或N,如果V1为C,则V2为N,如果V1为C,则V2为C(R2),或者如果V1为N,则V2为C(R2);每个n,k独立地为0或1;每个R2,R11独立地为H,D,Hal,CN,NR'R",C(O)NR'R",C1-C6烷氧基;R3为H,D,羟基,C(O)C1-C6烷基,C(O)C2-C6烯基,C(O)C2-C6炔基,C1-C6烷基;R4为H,Hal,CN,CONR'R",羟基,C1-C6烷基,C1-C6烷氧基;L为CH2,NH,O或化学键;R1从包括的片段组中选择:片段1,片段2,片段3,每个A1,A2,A3,A4独立地为CH,N,CHal;每个A5,A6,A7,A8,A9独立地为C,CH或N;R5为H,CN,Hal,CONR'R",C1-C6烷基,未取代或被一个或多个卤素取代;每个R'和R"独立地从包括H,C1-C6烷基,C1-C6环烷基,芳基的组中选择;R6从组中选择:[化学式II]每个R7,R8,R9,R10独立地为乙烯基,甲基乙炔基;Hal为CI,Br,I,F,具有布鲁顿酪氨酸激酶(Btk)抑制剂的性质,以及含有这种化合物的药物组合物,以及它们作为治疗疾病和紊乱的药物的用途。
  • Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
    申请人:Xu Feng
    公开号:US20100120727A1
    公开(公告)日:2010-05-13
    In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.
    在一个方面,本发明提供了一种硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面,本发明提供了一种硝西汀前药的组合物。在另一个方面,本发明提供了一种硝西汀或其衍生物水杨酸盐的组合物。在另一个方面,本发明提供了使用硝西汀类似物或硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
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