氨曲南主环 | 80082-65-1

• 物质功能分类: 有机原料 - 氨基化合物 - 磺酸类氨基化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: 氨曲南主环
• 中文别名: 氨曲南小环；(3S-反式)-3-氨基-4-甲基-2-氧代-1-氮杂环丁烷磺酸；氨曲南母核；单环母核；氨曲南中间体；3-氨基-2-甲基-4-氧化代-1-磺酸基氮杂环丁烷；3-氨基-2-甲基-4-氧代-1-磺酸基氮杂环丁烷；(2S-反式)-3-氨基-4-甲基-2-氧代-1-氮杂环丁烷磺酸；AMOAA
• 英文名称: (2S,3S)-3-amino-2-methyl-4-oxoazetidine-1-sulfonic acid
• 英文别名: (3S,4S)-3-amino-4-methyl-2-oxoazetidine-1-sulfonic acid；(3S)-trans-3-amino-4-methyl-2-oxoazetidine-1-sulfonic acid；(2S,3S)-3-amino-2-methyl-4-oxo-1-azetidinesulfonic acid；(3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid；(2S,3S)-3-azaniumyl-2-methyl-4-oxoazetidine-1-sulfonate
• CAS: 80082-65-1
• 化学式: C₄H₈N₂O₄S
• mdl: MFCD08061571
• 分子量: 180.185
• InChiKey: ISUIVWNWEDIHJD-HRFVKAFMSA-N

物化性质

• 熔点：
  206-211°C
• 密度：
  1.75±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933790090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  -20°C freezer

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: (2S,3S)-3-Amino-2-methyl-4-oxoazetidine-1-sulfonic acid
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: (2S,3S)-3-Amino-2-methyl-4-oxoazetidine-1-sulfonic acid
CAS number: 80082-65-1

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C4H8N2O4S
Molecular weight: 180.2

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, sulfur oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

氨曲南

氨曲南（aztreonam），简称AZT，是第一个应用于临床的单环β-内酰胺类抗生素。它对需氧革兰阴性菌具有强大的抗菌活性，包括大肠杆菌、克雷伯氏肺炎杆菌和奥克西托菌等。其通过与敏感需氧革兰阴性菌细胞膜上的青霉素结合蛋白高度亲合而抑制细胞壁的合成。

与大多数β-内酰胺类抗生素不同，氨曲南不诱导细菌产生β-内酰胺酶，并且对细菌产生的大多数β-内酰胺酶具有高度稳定性。因此，在微生物对青霉素类、头孢菌素类和氨基糖苷等药物耐药时，应用氨曲南仍然有效。此外，与青霉素和头孢菌素相比，氨曲南的不良反应较少，尤其是过敏反应的发生率更低，特别适于免疫低下、老年人及青霉素过敏患者。

氨曲南对肾功能正常的患者无明显肾毒性作用，并且在治疗严重泌尿道和胆道感染方面安全有效。根据其药理机制，临床上主要用于以下几类感染：

1. 尿路感染：可以单独应用治疗敏感菌引起的尿路感染（包括肾盂肾炎和膀胱炎）。
2. 呼吸道感染：适用于上呼吸道感染、重症支气管炎以及囊性纤维化患者急性重症气管、肺部绿脓杆菌感染，对β-内酰胺类药物过敏的囊性纤维化患者的慢性肺部绿脓杆菌感染。
3. 腹腔感染：可用于治疗腹膜炎。
4. 淋病：氨曲南对革兰阴性需氧杆菌有较强的杀菌效果，并且对β-内酰胺酶高度稳定，不易被水解破坏，也不诱导细菌产生β-内酰胺酶。因此，它特别适用于耐药的顽固性淋菌性尿道炎及产β-内酰胺酶的淋球菌感染。

氨曲南中间体还可用于制造其他β-内酰胺类药物。

反应信息

• 作为反应物：
  描述：

  (Z)-2-[[[1-(2-amino-4-thiazolyl)-2-(3-oxido-1H-benzotriazol-1-yl)-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid methanesulfonate (1:1) salt 、 氨曲南主环 在 三乙胺 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以81%的产率得到氨曲南
  参考文献：
  名称：

  氨基噻唑（亚胺氧乙酸）乙酸的区域选择性活化：单环内酰胺氨曲南的高效合成

  摘要：

  单环内酰胺氨曲南的有效合成[[2S-[2α,3β(Z)]]-3[[(2-氨基-4-噻唑基)[(1-羧基-1-甲基乙氧基)亚氨基]乙酰基]氨基]- 2-甲基-4-氧代-1-氮杂环丁烷磺酸] (1) 描述了用区域选择性活化的氨基噻唑亚胺氧基乙酸二酸 15 或 18 酰化 α-氨基氮杂环丁酮 22。二苯甲基酯 10 与 N-羟基苯并三唑和二环己基碳二亚胺反应，然后酯脱保护形成一元酸酰胺 15。或者，二酸 9 的化学选择性瞬时甲硅烷基化，然后用 N-羟基琥珀酰亚胺活化形成活性酯 18。α-氨基氮杂环丁酮 22 用酰胺酰化15 或酯 18 以 75-85% 的产率产生氨曲南 (1)。

  DOI：

  10.1021/op025572d
• 作为产物：
  描述：

  (2S,3S)-3-{[(苄氧基)羰基]氨基}-2-甲基-4-氧代吖丁啶-1-磺酸四丁基铵盐 在 钯 氢气 、 甲酸 、 title compound 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 氨曲南主环
  参考文献：
  名称：

  Process for preparing (s)-3-amino-2-oxo-1-azetidinesulfonic acid salts

  摘要：

  这项发明的过程提供了将具有以下公式的氨基酸酰胺转化为具有以下公式的3-氨基-2-氧代-1-氮杂环戊烷磺酸盐的方法： 其中R.sub.2和R.sub.3中的一个是氢，另一个是氢、烷基、环烷基、苯基或取代苯基，M.sup..sym.是氢或阳离子。

  公开号：

  US04625022A1

文献信息

• [EN] BICYCLIC ARYL MONOBACTAM COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS D'ARYLMONOBACTAME BICYCLIQUES ET LEURS MÉTHODES D'UTILISATION POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES
  申请人：MERCK SHARP & DOHME

  公开号：WO2017155765A1

  公开（公告）日：2017-09-14

  The present invention relates to bicyclic aryl monobactam compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A1, L, M, W, X, Y, Z, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a bicyclic aryl monobactam compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of one or more beta-lactamase inhibitor compounds.

  本发明涉及公式（I）的双环芳基单β内酰胺化合物及其药学上可接受的盐，其中A1、L、M、W、X、Y、Z、RX和Rz如本文所定义。本发明还涉及包含本发明的双环芳基单β内酰胺化合物或其药学上可接受的盐以及药学上可接受的载体的组合物。该发明还涉及治疗细菌感染的方法，包括向患者施用本发明化合物的治疗有效量，单独或与一种或多种β-内酰胺酶抑制剂化合物的治疗有效量结合使用。
• [EN] BIARYL MONOBACTAM COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS DE BIARYLMONOBACTAME ET PROCÉDÉS D'UTILISATION CORRESPONDANTS POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：MERCK SHARP & DOHME

  公开号：WO2017106064A1

  公开（公告）日：2017-06-22

  The present invention relates to biaryl monobactam compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein X, Y, Z, A1, Q, A2, M, W, RX and Rz are as defined herein. The present invention also relates to compositions which comprise a biaryl monobactam compound of the invention or a pharmaceutically acceptable salt therof, and a pharmaceutically acceptable carrier. The invention further relates to methods for treating a bacterial infection comprising administering to the patient a therapeutically effective amount of a compound of the invention, either alone or in combination with a therapeutically effective amount of a second beta-lactam antibiotic.

  本发明涉及公式I的联苯单环内酰胺化合物及其药学上可接受的盐，其中X、Y、Z、A1、Q、A2、M、W、RX和Rz如本文所定义。本发明还涉及包含本发明的联苯单环内酰胺化合物或其药学上可接受的盐以及药学上可接受的载体的组合物。该发明还涉及治疗细菌感染的方法，包括向患者施用本发明化合物的治疗有效量，单独或与第二种β-内酰胺类抗生素的治疗有效量结合。
• AZTREONAM DERIVATIVES AND USES THEREOF
  申请人：ARIXA PHARMACEUTICALS, INC.

  公开号：US20190100516A1

  公开（公告）日：2019-04-04

  Disclosed herein are aztreonam derivatives, therapeutic methods of using the aztreonam derivatives, particularly in combination with β-lactamase inhibitors, and pharmaceutical compositions thereof. The aztreonam derivatives can be administered orally to provide orally bioavailable aztreonam.

  本文披露了阿特雷纳姆衍生物，使用阿特雷纳姆衍生物的治疗方法，特别是与β-内酰胺酶抑制剂结合使用的方法，以及它们的药物组成物。这些阿特雷纳姆衍生物可以口服给药，从而提供口服可利用的阿特雷纳姆。
• Toward Orally Absorbed Prodrugs of the Antibiotic Aztreonam. Design of Novel Prodrugs of Sulfate Containing Drugs. Part 2
  作者：Eric M. Gordon、Matthew A. J. Duncton、Brian J. Wang、Longwu Qi、Dazhong Fan、Xianfeng Li、Zhi-Jie Ni、Pingyu Ding、Ruslan Grygorash、Eddy Low、Guijun Yu、Jiawei Sun

  DOI：10.1021/acsmedchemlett.9b00534

  日期：2020.2.13

  antibiotic. Aztreonam is active against Gram-negative bacteria and is still used today. The oral bioavailability of aztreonam in humans is less than 1%. Herein we describe the design and synthesis of potential oral prodrugs of aztreonam.

  Aztreonam于1980年首次发现，是FDA批准的静脉内单环β-内酰胺类抗生素。Aztreonam对革兰氏阴性细菌具有活性，至今仍在使用。氨曲南在人类中的口服生物利用度小于1％。在本文中，我们描述了氨曲南潜在的口服前药的设计和合成。
• 3-(Heteroaryl acetamido)-2-oxo-azetidine-1-sulfonic acids derivatives as antibacterial agents
  申请人：——

  公开号：US20040019203A1

  公开（公告）日：2004-01-29

  The present invention relates to novel Syn isomers of racemates and optical isomers of 3-(heteroaryl acetamido)-2-oxo-azetidine-1-sulfonic acids of formula (I) and its use in treating the infections caused by gram-negative pathogenic bacteria.

  本发明涉及式(I)的新型Syn异构体和3-(杂环基乙酰胺基)-2-氧代-氮杂环丙氧基-1-磺酸的光学异构体的立体异构体，以及其在治疗由革兰氏阴性病原细菌引起的感染中的用途。