异恶唑醋酸 | 42228-92-2

• 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: 异恶唑醋酸
• 中文别名: 阿西维辛；(α-s,5s)-α-氨基-3-氯-4,5-二氢-5-异恶唑乙酸
• 英文名称: acivicin
• 英文别名: L-(αs,5s)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid；(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125)；L-[αS,5S]-α-amino-3-chloro-4,5-dihydro-5-isoxazole acetic acid；(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid；(2S)-2-azaniumyl-2-[(5S)-3-chloro-4,5-dihydro-1,2-oxazol-5-yl]acetate
• CAS: 42228-92-2
• 化学式: C₅H₇ClN₂O₃
• mdl: MFCD00866432
• 分子量: 178.575
• InChiKey: QAWIHIJWNYOLBE-OKKQSCSOSA-N

物化性质

• 熔点：
  >200°C (dec.)
• 沸点：
  341.6±48.0 °C(Predicted)
• 密度：
  1.85±0.1 g/cm3(Predicted)
• 溶解度：
  H2O：可溶，10mg/mL（加热）
• 稳定性/保质期：

  常规情况下不会分解，没有危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R20/21/22
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 3172
• 储存条件：
  密封，在2°C至-8°C下保存

SDS

Version 1.2
Regulation (EC) No 1907/2006

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1 - Product and Company Information

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Product Name ACIVICIN

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2 - Hazards Identification

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SPECIAL INDICATION OF HAZARDS TO HUMANS AND THE ENVIRONMENT
Harmful by inhalation, in contact with skin and if swallowed.

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3 - Composition/Information on Ingredients

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Product Name CAS # EC no Annex I
Index Number
ACIVICIN 42228-92-2 None None
Formula C5H7ClN2O3
Molecular Weight 178,6000 AMU
Synonyms Acivicine *
(alpha-S,5S)-alpha-Amino-3-chloro-4,5-dihydro-5-i
soxazoleacetic acid * Antibiotic AT 125 * AT 125
*
(S-(R*,R*))-4,5-Dihydro-alpha-amino-3-chloro-5-is
oxazoleacetic acid * NSC-163501 * U 42126

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4 - First Aid Measures

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AFTER INHALATION
If inhaled, remove to fresh air. If breathing becomes difficult,
call a physician.
AFTER SKIN CONTACT
In case of skin contact, flush with copious amounts of water for
at least 15 minutes. Remove contaminated clothing and shoes.
Call a physician.
AFTER EYE CONTACT
In case of contact with eyes, flush with copious amounts of
water for at least 15 minutes. Assure adequate flushing by
separating the eyelids with fingers. Call a physician.
SIGMA www.molbase.com
AFTER INGESTION
If swallowed, wash out mouth with water provided person is
conscious. Call a physician.

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5 - Fire Fighting Measures

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EXTINGUISHING MEDIA
Suitable: Water spray. Carbon dioxide, dry chemical powder, or
appropriate foam.
SPECIAL PROTECTIVE EQUIPMENT FOR FIREFIGHTERS
Wear self-contained breathing apparatus and protective clothing
to prevent contact with skin and eyes.

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6 - Accidental Release Measures

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PROCEDURE(S) OF PERSONAL PRECAUTION(S)
Wear respirator, chemical safety goggles, rubber boots, and
heavy rubber gloves.
METHODS FOR CLEANING UP
Sweep up, place in a bag and hold for waste disposal. Avoid
raising dust. Ventilate area and wash spill site after material
pickup is complete.

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7 - Handling and Storage

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STORAGE
Store at 2-8°C

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8 - Exposure Controls / Personal Protection

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ENGINEERING CONTROLS
Mechanical exhaust required.
PERSONAL PROTECTIVE EQUIPMENT
Special Protective Measures: Wear appropriate government approved
respirator, chemical-resistant gloves, safety goggles, other
protective clothing.

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9 - Physical and Chemical Properties

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Appearance Physical State: Solid
Property Value At Temperature or Pressure
pH N/A
BP/BP Range N/A
MP/MP Range N/A
Flash Point N/A
Flammability N/A
Autoignition Temp N/A
Oxidizing Properties N/A
Explosive Properties N/A
Explosion Limits N/A
Vapor Pressure N/A
Partition Coefficient N/A
Viscosity N/A
Vapor Density N/A
Saturated Vapor Conc. N/A
SIGMA www.molbase.com
Evaporation Rate N/A
Bulk Density N/A
Decomposition Temp. N/A
Solvent Content N/A
Water Content N/A
Surface Tension N/A
Conductivity N/A
Miscellaneous Data N/A
Solubility N/A

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10 - Stability and Reactivity

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STABILITY
Stable: Stable.
HAZARDOUS DECOMPOSITION PRODUCTS
Hazardous Decomposition Products: Carbon monoxide, Carbon dioxide,
Nitrogen oxides, Hydrogen chloride gas.
HAZARDOUS POLYMERIZATION
Hazardous Polymerization: Will not occur

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11 - Toxicological Information

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RTECS NUMBER: NY2103000
SIGNS AND SYMPTOMS OF EXPOSURE
Exposure can cause gastrointestinal disturbances, nausea,
diarrhea, vomiting, myelosuppression, nightmares,
hallucinations, paranoia, hematopoietic toxicity, and adverse
CNS effects. In males, exposure can cause adverse effects on the
reproductive system causing cessation of sperm production and
degeneration of the testicles and of the seminiferous tubules.
ROUTE OF EXPOSURE
Multiple Routes: Harmful if swallowed, inhaled, or absorbed
through skin.
CHRONIC EXPOSURE - MUTAGEN
Mouse
250 MG/KG
Intraperitoneal
Micronucleus test
Chicken
6 UMOL/L
Cell Type: Embryo
DNA inhibition

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12 - Ecological Information

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No data available.

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13 - Disposal Considerations

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SUBSTANCE DISPOSAL
Dissolve or mix the material with a combustible solvent and burn
in a chemical incinerator equipped with an afterburner and
scrubber. Observe all federal, state, and local environmental
SIGMA www.molbase.com
regulations.

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14 - Transport Information

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RID/ADR
Non-hazardous for road transport.
IMDG
Non-hazardous for sea transport.
IATA
Non-hazardous for air transport.

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15 - Regulatory Information

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CLASSIFICATION AND LABELING ACCORDING TO EU DIRECTIVES
INDICATION OF DANGER: Xn
Harmful.
R-PHRASES: 20/21/22
Harmful by inhalation, in contact with skin and if swallowed.
S-PHRASES: 36
Wear suitable protective clothing.
Caution: Substance not yet fully tested (EU).
COUNTRY SPECIFIC INFORMATION
Germany
WGK: 3
Self-Classification

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16 - Other Information

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WARRANTY
The above information is believed to be correct but does not
purport to be all inclusive and shall be used only as a guide. The
information in this document is based on the present state of our
knowledge and is applicable to the product with regard to
appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Inc.,
shall not be held liable for any damage resulting from handling or
from contact with the above product. See reverse side of invoice
or packing slip for additional terms and conditions of sale.
Copyright 2010 Co. License granted to make
unlimitedpaper copies for internal use only.
DISCLAIMER
For R&D use only. Not for drug, household or other uses.
SIGMA www.molbase.com

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Acivicin (AT-125) 是一种由猪链霉菌产生的天然产物，是 γ-谷氨酰转肽酶（GGT）抑制剂。它能够穿透血脑屏障，并展现出抗癌和抗寄生虫的特性。

靶点

γ-glutamyl transpeptidase

体外研究

在人类HepG2细胞中，Acivicin (AT-125) 在0.1-50 μM浓度范围内（持续5天）的半数抑制浓度（IC₅₀）为0.7 μM。

体内研究

给体重在250 g至300 g之间的雄性色素长爪沙鼠皮下注射Acivicin (AT-125; 5 mg/kg，每周两次，周一和周三)，可以降低尿液中γ-GT水平70-78%。

反应信息

• 作为反应物：
  描述：

  异恶唑醋酸 在 platinum(IV) oxide 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 24.0h， 以78%的产率得到(2S,3S)-β-hydroxyornithine
  参考文献：
  名称：

  A 1,3-dipolar cycloaddition route to the 3(R)- and 3(S)-hydroxy-2(S)-arginines

  摘要：

  DOI：

  10.1021/jo00387a012
• 作为产物：
  描述：

  alpha-酮戊二酸 在 盐酸 、 lithium hydroxide 、 potassium dihydrogenphosphate 、 N-羟基丁二酰亚胺 、 草酰氯 、 aluminium amalgam 、 hog kidney acylase I 、 五氯化磷 、 碳酸氢钠 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 calcium carbonate 、 1,5-Diazabicyclo[5.4.0]undec-5-ene 作用下， 以 四氢呋喃 、 乙醚 、 硝基甲烷 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 80.0 ℃ 、2.0 kPa 条件下， 反应 42.09h， 生成 异恶唑醋酸
  参考文献：
  名称：

  -125，（αS，5 S）-α-氨基-3-氯-4,5-二氢-5-异恶唑乙酸的抗肿瘤剂的全合成

  摘要：

  外消旋AT-125及其外消旋苏式异构体的短而有效的全合成通过受保护的α，β-脱氢谷氨酸γ-异羟肟酸酯的分子内迈克尔环化进行。分离非对映异构体并将其脱保护为外消旋AT-125，然后用猪肾酰化酶酶促拆分N-氯乙酰胺，即可提供天然αS，5 S异构体。

  DOI：

  10.1016/s0040-4020(01)96774-2

文献信息

• [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。
• Cobalamin conjugates for anti-tumor therapy
  申请人：Weinshenker M. Ned

  公开号：US20050054607A1

  公开（公告）日：2005-03-10

  The present invention provides a cobalamin-drug conjugate suitable for the treatment of tumor related diseases. Cobalamin is indirectly covalently bound to an anti-tumor drug via a cleavable linker and one or more optional spacers. Cobalamin is covalently bound to a first spacer or the cleavable linker via the 5′-OH of the cobalamin ribose ring. The drug is bound to a second spacer of the cleavable linker via an existing or added functional group on the drug. After administration, the conjugate forms a complex with transcobalamin (any of its isoforms). The complex then binds to a receptor on a cell membrane and is taken up into the cell. Once in the cell, an intracellular enzyme cleaves the conjugate thereby releasing the drug. Depending upon the structure of the conjugate, a particular class or type of intracellular enzyme affects the cleavage. Due to the high demand for cobalamin in growing cells, tumor cells typically take up a higher percentage of the conjugate than do normal non-growing cells. The conjugate of the invention advantageously provides a reduced systemic toxicity and enhanced efficacy as compared to a corresponding free drug.

  本发明提供了一种适用于治疗肿瘤相关疾病的钴胺素-药物结合物。钴胺素通过可切割的连接剂间接共价结合到抗肿瘤药物上，还可以通过一个或多个可选的间隔物。钴胺素通过其核糖环的5'-OH与第一间隔物或可切割连接剂共价结合。药物通过其现有或添加的功能基团与可切割连接剂的第二间隔物结合。在给药后，结合物与转钴胺素（其任何同工异构体）形成复合物。然后，该复合物结合到细胞膜上的受体并被细胞摄取。一旦进入细胞，细胞内酶将切割结合物，从而释放药物。根据结合物的结构，特定类别或类型的细胞内酶影响切割。由于生长细胞对钴胺素的需求量较高，肿瘤细胞通常摄取结合物的比例高于正常非生长细胞。本发明的结合物与相应的游离药物相比，具有较低的全身毒性和增强的疗效。
• [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。
• [EN] BRUTON'S TYROSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：PFIZER

  公开号：WO2014068527A1

  公开（公告）日：2014-05-08

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (BTK). Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the BTK inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions. (Formula I)

  本文披露了一种与Bruton's酪氨酸激酶（BTK）形成共价键的化合物。公开了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。公开了使用BTK抑制剂的方法，单独或与其他治疗剂联合治疗自身免疫疾病或症状、异源免疫疾病或症状、癌症，包括淋巴瘤，以及炎症性疾病或症状的方法。 (化学式I)
• [EN] PROCESSES FOR MAKING TRIAZOLO[4,5D] PYRAMIDINE DERIVATIVES AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉS DE PREPARATION DE DÉRIVÉS DE TRIAZOLO [4,5 D] PYRIMIDINE ET INTERMÉDIAIRES DE CEUX-CI
  申请人：CORVUS PHARMACEUTICALS INC

  公开号：WO2018183965A1

  公开（公告）日：2018-10-04

  Provided herein are, inter alia, methods for making triazolo[4,5]pyramidine derivatives and intermediates thereof that are useful for treating diseases.

  本文提供了制备三氮杂[4,5]吡啶衍生物及其中间体的方法，这些衍生物对治疗疾病有用。