Boc-d-2-茚烷甘氨酸 | 181227-48-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 甘氨酸类衍生物
• 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
• 中文名称: Boc-d-2-茚烷甘氨酸
• 中文别名: BOC-D-2-茚满甘氨酸；Boc-D-2-茚满甘氨酸
• 英文名称: (2R)-[(t-butoxycarbonyl)amino](2,3-dihydro-1H-inden-2-yl)ethanoic acid
• 英文别名: N-tert-butoxycarbonyl-D-2-indanylglycine；(2R)-2,3-dihydro-1H-inden-2-yl({[(1,1-dimethylethyl)oxy]-carbonyl}amino)ethanoic acid；(2R)-2,3-dihydro-1H-inden-2-yl({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethanoic acid；(R)-2-((tert-Butoxycarbonyl)amino)-2-(2,3-dihydro-1H-inden-2-yl)acetic acid；(2R)-2-(2,3-dihydro-1H-inden-2-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid
• CAS: 181227-48-5
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: VCHHRDDQOOBPTC-CYBMUJFWSA-N

物化性质

• 沸点：
  470.9±28.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Boc-d-(2-inda)gly-oh
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: Boc-d-(2-inda)gly-oh
CAS number: 181227-48-5

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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.
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: C16H21NO4
Molecular weight: 291.3

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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.

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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

反应信息

• 作为反应物：
  描述：

  Boc-d-2-茚烷甘氨酸 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 (2R)-N-tert-butyl-2-[(2R,5R)-5-(2,3-dihydro-1H-inden-2-yl)-2-(2-methylpropyl)-3,6-dioxopiperazin-1-yl]-2-(3-fluoro-4-methoxyphenyl)acetamide
  参考文献：
  名称：

  2,5-二酮哌嗪作为有效的，选择性的和口服生物利用的催产素拮抗剂。3.合成，药代动力学和体内效力。

  摘要：

  描述了一系列（3R，6R，7R）-2,5-二酮哌嗪催产素拮抗剂的短而有效且高度立体选择性的合成及其在大鼠和狗中的药代动力学。使用测得的亲脂性（CHI log D）和计算的大小（cMR）来预测估计的人类口服吸收（EHOA），使我们能够对各种2,5-二酮哌嗪模板进行排名，并使我们能够将精力集中在那些模板上的机会最大。人类的生物利用度高。这迅速导致2'，4'-二氟苯基-二甲基酰胺25和苯并呋喃4在大鼠和狗中具有高水平的效力（pK（i））和良好的生物利用度。体内二甲酰胺25的效力比4强（> 20倍），并且对血管加压素受体的选择性很高，hV1a / hV1b大于10,000，hV2大约为500。

  DOI：

  10.1021/jm060073e
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 R-茚满基甘氨酸 在 水 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以96%的产率得到Boc-d-2-茚烷甘氨酸
  参考文献：
  名称：

  2,5-二酮哌嗪作为有效的，选择性的和口服生物利用的催产素拮抗剂。2.合成，手性和药代动力学。

  摘要：

  描述了一系列手性7-芳基-2,5-二酮哌嗪催产素拮抗剂的短立体选择性合成。改变7-芳基环中取代基的官能度和取代方式并改变该环外环的手性可产生有效的催产素拮抗剂（pK（i）> 8.5）。（3R，6R，7R）-2,5-二酮哌嗪系列的SAR和药代动力学分析以及在7-芳基环中引入邻位F基团以改善大鼠pK的结果在2'，4'-二氟苯基二酮哌嗪衍生物37，一种针对人催产素受体的强效催产素拮抗剂（pK（i）= 8.9），相对于所有三种加压素受体V1a，V2和V1b具有> 1000倍的选择性。

  DOI：

  10.1021/jm050557v

文献信息

• [EN] NOVEL COMPOUNDS<br/>[FR] PIPERAZINEDIONES UTILISES EN TANT QU'ANTAGONISTES DU RECEPTEUR DE L'OXYTOCINE
  申请人：GLAXO GROUP LTD

  公开号：WO2006000399A1

  公开（公告）日：2006-01-05

  Compounds of formula (I) wherein R1 is 2-indanyl, R2 is 1-methylpropyl, R3 is a group selected from 2, 6-dimethyl-3-pyridyl or 4,6-dimethyl-3-pyridyl, R4 represents methyl and R5 represents hydrogen or methyl or, R4 and R5 together with the nitrogen atom to which they are attached represent morpholino and pharmaceutically acceptable derivatives thereof are described, as are processes for their preparation, pharmaceutical compositions containing them and their use in medicine, particularly their use as oxytocin antagonists.

  化合物的公式(I)，其中R1是2-茚基，R2是1-甲基丙基，R3是从2,6-二甲基-3-吡啶基或4,6-二甲基-3-吡啶基中选择的基团，R4代表甲基，R5代表氢或甲基或者，R4和R5与它们连接的氮原子一起代表吗啡啉基团及其药用可接受的衍生物，描述了它们的制备过程，含有它们的药物组合物以及它们在医学中的用途，特别是作为催产素拮抗剂的用途。
• [EN] SUBSTITUTED DIKETOPIPERAZINES AS OXYTOCIN ANTAGONISTS<br/>[FR] DICETOPIPERAZINES SUBSTITUEES UTILISEES COMME ANTAGONISTES DES OXYTOCINES
  申请人：GLAXO GROUP LTD

  公开号：WO2006000400A1

  公开（公告）日：2006-01-05

  Compounds of formula (IA) wherein R1 is 2-indanyl, R2 is 1-methylpropyl, R3 is 1-methyl-indazol-5-yl, R4 represents methyl and R5 represents hydrogen or methyl, and pharmaceutically acceptable derivatives thereof are described, as are processes for their preparation, pharmaceutical compositions containing them and their use in medicine, particularly their use as oxytocin antagonists.

  描述了式（IA）的化合物，其中R1是2-吲哚基，R2是1-甲基丙基，R3是1-甲基吲唑-5-基，R4代表甲基，R5代表氢或甲基，以及它们的药学上可接受的衍生物，以及它们的制备方法、含有它们的药物组合物和在医学上的用途，特别是它们作为催产素拮抗剂的用途。
• Pyridyl-2,5-Diketopiperazines as Potent, Selective, and Orally Bioavailable Oxytocin Antagonists: Synthesis, Pharmacokinetics, and In Vivo Potency
  作者：Alan D. Borthwick、John Liddle、Dave E. Davies、Anne M. Exall、Christopher Hamlett、Deirdre M. Hickey、Andrew M. Mason、Ian E. D. Smith、Fabrizio Nerozzi、Simon Peace、Derek Pollard、Steve L. Sollis、Michael J. Allen、Patrick M. Woollard、Mark A. Pullen、Timothy D. Westfall、Dinesh J. Stanislaus

  DOI：10.1021/jm201287w

  日期：2012.1.26

  A six-stage stereoselective synthesis of indanyl-7-(3′-pyridyl)-(3R,6R,7R)-2,5-diketopiperazines oxytocin antagonists from indene is described. SAR studies involving mono- and disubstitution in the 3′-pyridyl ring and variation of the 3-isobutyl group gave potent compounds (pKi > 9.0) with good aqueous solubility. Evaluation of the pharmacokinetic profile in the rat, dog, and cynomolgus monkey of those

  茚满基-7-（3'-吡啶基）的6级立体选择性合成- （3 - [R，6 - [R，7 - [R）-2,5-二酮哌嗪类催产素从茚拮抗剂进行说明。SAR研究涉及3'-吡啶基环中的单-和解离以及3-异丁基的变化，给出了具有良好水溶性的强效化合物（p K i > 9.0）。在大鼠中，与低食蟹猴和人固有清除率的那些衍生物的狗，和食蟹猴，得到2'，6'-二甲基-3'-吡啶基的药代动力学分布的评价- [R -仲-丁基吗啉酰胺Epelsiban（69），高效催产素拮抗剂（p K i= 9.9），在所有三种人血管加压素受体hV1aR，hV2R和hV1bR上具有> 31000倍的选择性，而没有明显的P450抑制作用。Epelsiban对四种物种的微粒体的内在清除率较低，具有良好的生物利用度（55％），与大鼠的阿托西班效价相当，但在体外的效价比阿托西班高100倍，并且在遗传毒性筛选中呈阴性。雌性大鼠令人满意的口服安全性。
• 2,5-Diketopiperazines as potent and selective oxytocin antagonists 1: identification, stereochemistry and initial SAR
  作者：Paul G. Wyatt、Michael J. Allen、Alan D. Borthwick、Dave E. Davies、Anne M. Exall、Richard J.D. Hatley、Wendy R. Irving、David G. Livermore、Neil D. Miller、Fabrizio Nerozzi、Steve L. Sollis、Anna Katrin Szardenings

  DOI：10.1016/j.bmcl.2005.03.045

  日期：2005.5

  This paper covers efforts to discover orally active potent and selective oxytocin antagonists. Screening pooled libraries identified a novel series of 2,5-diketopiperazine derivatives with antagonist activity at the human oxytocin receptor. We report the initial structure-activity relationship investigations and the determination of the stereochemistry of the most potent compounds.

  本文涵盖了发现口服活性强效和选择性催产素拮抗剂的努力。筛选合并的文库鉴定了一系列对人催产素受体具有拮抗活性的2,5-二酮哌嗪衍生物。我们报告了最初的结构-活性关系调查和最有效的化合物的立体化学的确定。
• [EN] SUBSTITUTED DIKETOPIPERAZINES FOR THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA<br/>[FR] DICETOPIPERAZINES POUR LE TRAITEMENT DE L'HYPERPLASIE BENIGNE DE LA PROSTATE
  申请人：GLAXO GROUP LTD

  公开号：WO2005000311A1

  公开（公告）日：2005-01-06

  A method of treating or preventing benign prostatic hyperplasia which comprises administering to a mammal in need thereof of an effective amount of a compound of Formula (I) where R1, R2, R3 and R4 are defined as provided in claim 1.

  一种治疗或预防良性前列腺增生的方法，包括向需要治疗的哺乳动物施用化合物(I)的有效量，其中R1、R2、R3和R4的定义如权利要求书1所述。