(R)-piperazine-2-carboxylic acid dihydrochloride | 126330-90-3

• 物质功能分类: 医药中间体 - 杂环化合物 - 哌嗪类化合物
• 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
• 英文名称: (R)-piperazine-2-carboxylic acid dihydrochloride
• 英文别名: [2R,S]-piperazine-2-carboxylic acid dihydrochloride；(R)-Piperazine-2-carboxylic acid hydrochloride；(2R)-piperazine-2-carboxylic acid;hydrochloride
• CAS: 126330-90-3
• 化学式: C₅H₁₀N₂O₂*2ClH
• 分子量: 203.068
• InChiKey: KIUVRQJNCIUBJN-PGMHMLKASA-N

物化性质

• 熔点：
  ca 265℃
• 闪点：
  143.5℃
• 稳定性/保质期：
  如果遵照规格使用和储存，则不会分解，未有已知危险反应。请避免与氧化物接触。

计算性质

• 辛醇/水分配系数(LogP)：
  -0.95
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  61.4
• 氢给体数：
  4
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26,S36
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933599090
• 危险品运输编号：
  NONH for all modes of transport
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
(R)-Piperazine-2-carboxylic acid DiHCl
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
(R)-Piperazine-2-carboxylic acid DiHCl
Ingredient name:
CAS number: 126330-90-3

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C5H12Cl2N2O2
Molecular weight: 203.1

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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, hydrogen chloride.

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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

简介

（R）-2-哌嗪羧酸二盐酸盐属于杂环有机物，可用作医药中间体。

用途

光学活性的2-哌嗪羧酸，即（R）-哌嗪-2-羧酸二盐酸盐，是作为药物合成原料的有效化合物。

制备

已知通过使用旋光樟脑磺酸作为拆分剂，将外消旋2-哌嗪羧酸和旋光樟脑磺酸溶解在溶剂中，并用活性炭处理以去除颜色。随后，可沉淀出（R）-哌嗪-2-羧酸二盐酸盐。

反应信息

• 作为反应物：
  描述：

  (R)-piperazine-2-carboxylic acid dihydrochloride 在 aqueous NH₃ 作用下， 以 甲醇 为溶剂， 以73%的产率得到(2R)-2-哌嗪羧酰胺
  参考文献：
  名称：

  Adenosine re-uptake inhibiting derivatives of diphenyl oxazoles,

  摘要：

  一系列1-哌嗪基-N-苯乙酰胺衍生物的4,5-二苯基噁唑，噻唑和咪唑被发现是新型的腺苷转运抑制剂，可为中枢神经系统和心脏组织，尤其是神经元提供有效的抗缺血保护。一种治疗方法，用于保护中枢神经系统缺血，例如由创伤，中风或其他缺血病症引起，包括向需要此类治疗的个体投药这些新型化合物。

  公开号：

  US05382584A1
• 作为产物：
  描述：

  1,4-二苄基哌嗪-2-羧酸乙酯 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 作用下， 以 乙醇 、 水 为溶剂， 反应 10.0h， 生成 (R)-piperazine-2-carboxylic acid dihydrochloride
  参考文献：
  名称：

  4-（3-膦酰基丙基）哌嗪-2-羧酸（CPP）和不饱和类似物（E）-4-（3-膦酰基丙-2-烯基）哌嗪-2-的对映异构体的合成和NMD A拮抗性能羧酸（CPP-ene）

  摘要：

  4-（3-膦酰基丙基）哌嗪-2-羧酸的（R）和（s）-对映异构体（分别为D-和L-CPP;分别为15和16）及其不饱和类似物（制备E）-4-（3-膦酰基丙-2-烯基）哌嗪-2-羧酸（D-和L-CPP-烯，分别为13和14）。对映体的绝对构型由薄荷酯7与D-天冬酰胺的化学相关性确定。这些衍生物对NMDA受体的亲和力通过[ 3大鼠脑皮质膜中的H] CPP。在两项功能测试（青蛙半身脊髓制备和大鼠脑切片的钠流出测试）中，D-CPP-ene似乎是迄今为止已知最有效，对映体纯的竞争性NMDA拮抗剂。

  DOI：

  10.1002/hlca.19890720522

文献信息

• [EN] METHODS FOR DELAYING, PREVENTING, AND TREATING ACQUIRED RESISTANCE TO RAS INHIBITORS<br/>[FR] MÉTHODES DE RETARDEMENT, DE PRÉVENTION ET DE TRAITEMENT DE LA RÉSISTANCE ACQUISE AUX INHIBITEURS DE RAS
  申请人：REVOLUTION MEDICINES INC

  公开号：WO2021257736A1

  公开（公告）日：2021-12-23

  The present disclosure relates to compositions and methods for the treatment of diseases or disorders (e.g., cancer) with bi-steric inhibitors of mTOR in combination with RAS inhibitors. Specifically, in some embodiments this disclosure includes compositions and methods for inducing apoptosis of tumor cells and/or for delaying, preventing, or treating acquired resistance to RAS inhibitors using bi-steric mTOR inhibitors.

  本公开涉及使用双-立体异构体mTOR抑制剂与RAS抑制剂联合治疗疾病或病状（例如，癌症）的配方和方法。具体而言，在某些实施方式中，本公开包括用于诱导肿瘤细胞凋亡和/或用于延迟、预防或治疗对RAS抑制剂获得性耐药性的双-立体异构体mTOR抑制剂的配方和方法。
• 光学活性トリエチレンジアミン誘導体及びその製造方法
  申请人：東ソー株式会社

  公开号：JP2016147820A

  公开（公告）日：2016-08-18

  【課題】 不斉試薬として有用な光学活性トリエチレンジアミン誘導体及びその製造方法を提供する。【解決手段】 式（１ｂ）【化１】（式中、＊は不斉中心を表す。）で表される光学活性（Ｒ又はＳ）−（ヒドロキシメチル）トリエチレンジアミンを、加水分解酵素を用いた不斉アシル化反応を経て得る。【選択図】 なし

  提供一种作为手性试剂有用的光学活性三乙烯四胺衍生物及其制备方法。采用水解酶进行手性酰化反应，得到由式（1b）（化合物1）表示的光学活性（R或S）-（羟甲基）三乙烯四胺。
• Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors
  作者：Thomas Flagstad、Mette T. Pedersen、Tim H. Jakobsen、Jakob Felding、Tim Tolker-Nielsen、Michael Givskov、Katrine Qvortrup、Thomas E. Nielsen

  DOI：10.1016/j.bmcl.2021.128499

  日期：2022.2

  There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel

  全球迫切需要新的更有效的抗生素来对抗多重耐药菌。这种情况导致了针对重要细菌酶 DNA 促旋酶和拓扑异构酶 IV 的新型细菌拓扑异构酶抑制剂 (NBTI) 的大规模工业研究。然而，一些 NBTI 化合物类别与抑制 hERG 钾通道有关，hERG 钾通道是心律失常的不良原因，通过漫长的合成路线挑战药物化学工作。我们在此提出了一种固相策略，可快速促进一类有前途的新型 NBTI 的化学合成。合成了一个概念验证文库，该文库能够通过支架替代调节 hERG 亲和力和抗菌活性。
• 作为KRAS G12C突变蛋白抑制剂的腈甲基哌嗪类衍生物及其应用
  申请人：中科苏州药物研究院

  公开号：CN111205286B

  公开（公告）日：2022-12-13

  本发明公开一种作为KRAS G12C突变蛋白抑制剂的腈甲基哌嗪类衍生物及其应用，本发明化合物具有通式(I)所述结构。本发明所述的化合物相对于现有化合物对KRAS G12C突变导致的恶性肿瘤具有更高的选择性；显示了更长的半衰期，具有更好的代谢稳定性；更高的暴露量和更好的口服生物利用度以及更显著的抗肿瘤活性；
• Novel (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives: Selective inhibition of MV-4-11 biphenotypic B myelomonocytic leukemia cells’ growth is accompanied by reactive oxygen species overproduction and apoptosis
  作者：Adam Mieczkowski、Mateusz Psurski、Maciej Bagiński、Bartosz Bieszczad、Magdalena Mroczkowska、Marcin Wilczek、Joanna Czajkowska、Damian Trzybiński、Krzysztof Woźniak、Joanna Wietrzyk

  DOI：10.1016/j.bmcl.2018.01.034

  日期：2018.2

  A series of optically pure (R)- and (S)-1,3,4,12a-tetrahydropyrazino[2,1-c][1,4]benzodiazepine-6,12(2H,11H)-dione derivatives was designed and synthesized as novel anthramycin analogues in a three-step, one-pot procedure, and tested for their antiproliferative activity on nine following cell lines: MV-4-11, UMUC-3, MDA-MB-231, MCF7, LoVo, HT-29, A-549, A2780 and BALB/3T3. The key structural features

  一系列光学纯的（R）-和（S）-1,3,4,12a-四氢吡嗪并[2,1- c ] [1,4]苯并二氮杂-6,12（2 H，11 H）-二酮衍生物通过三步一锅法设计并合成了新型蒽霉素类似物，并测试了它们对以下9种细胞系的抗增殖活性：MV-4-11，UMUC-3，MDA-MB-231，MCF7，LoVo ，HT-29，A-549，A2780和BALB / 3T3。确定了负责显示细胞毒性作用的关键结构特征：手性中心的（S）-构型和侧链中存在疏水性4-联苯取代基。将溴原子引入8位（8g）或用苄基（8m）取代双内酰胺环进一步提高了所研究化合物的活性和选择性。其中，化合物8g对MV-4-11（IC 50  = 8.7μM）和HT-29（IC 50  = 17.8μM）细胞系表现出选择性的细胞毒性作用，而8m对MV-4-11（IC 50  = 10.8μM）和LoVo（IC 50  = 11.0μM）细