(8-{[(2-甲基-2-丙基)氧基]羰基}-4-氧代-1-苯基-1,3,8-三氮杂螺[4.5]癸-3-基)乙酸 | 180386-35-0

• 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: (8-{[(2-甲基-2-丙基)氧基]羰基}-4-氧代-1-苯基-1,3,8-三氮杂螺[4.5]癸-3-基)乙酸
• 中文别名: BOC-3-羧甲基-1-苯基-1-1,3,8-三氮杂螺[4.5]癸烷-4-酮
• 英文名称: 2-(8-(tert-butoxycarbonyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetic acid
• 英文别名: 2-[8-[(2-methylpropan-2-yl)oxycarbonyl]-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl]acetic acid
• CAS: 180386-35-0
• 化学式: C₂₀H₂₇N₃O₅
• 分子量: 389.451
• InChiKey: JCGYOUBJGZCPET-UHFFFAOYSA-N

物化性质

• 沸点：
  608.8±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2933990090
• 储存条件：
  2-8℃

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: Boc-3-carboxymethyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
Synonyms:

---

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

---

Section 3. Composition/information on ingredients.
Ingredient name: Boc-3-carboxymethyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
CAS number: 180386-35-0

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C20H27N3O5
Molecular weight: 389.4

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

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

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  (8-{[(2-甲基-2-丙基)氧基]羰基}-4-氧代-1-苯基-1,3,8-三氮杂螺[4.5]癸-3-基)乙酸 在 盐酸 、 硫酸 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 以100%的产率得到3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetic acid sulfuric acid sult
  参考文献：
  名称：

  From Hit to Lead. Combining Two Complementary Methods for Focused Library Design. Application to μ Opiate Ligands

  摘要：

  Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.

  DOI：

  10.1021/jm010877o
• 作为产物：
  描述：

  1-苯基-1,3,8-三氮杂螺[4.5]癸-2-烯-4-酮 在 sodium hydride 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 26.5h， 生成 (8-{[(2-甲基-2-丙基)氧基]羰基}-4-氧代-1-苯基-1,3,8-三氮杂螺[4.5]癸-3-基)乙酸
  参考文献：
  名称：

  Synthesis and Characterization of Pseudopeptide Bradykinin B2 Receptor Antagonists Containing the 1,3,8-Triazaspiro[4.5]decan-4-one Ring System

  摘要：

  A series of pseudopeptides containing alkyl-, cycloalkyl-, aryl-, and aralkyl-substituted 1,3,8-triazaspiro[4.5]decan-4-one-3-acetic acids as amino acid surrogates to replace the Pro(2)-Pro(3)-Gly(4)-Phe(5) section of the peptide bradykinin B2 receptor antagonist [Pro(3), Phe(5)]HOE 140 (D-Arg(0)-Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)-Ser(6)-D-Tic(7)-Oic(8)-Arg(9)) were prepared. These psuedopeptides were examined in vitro for their B2 receptor affinities as well as for their ability to block bradykinin mediated actions in, vivo. Two compounds in particular, NPC 18521 (I) and NPC 18688 (V) were quite potent in these latter assays, indicating that a significant portion of this prototypical second generation decapeptide antagonist can be replaced with a more compact nonpeptide molecule.

  DOI：

  10.1021/jm950676i

文献信息

• [EN] BENZOFUROPYRIMIDINONES AS PROTEIN KINASE INHIBITORS<br/>[FR] BENZOFUROPYRIMIDINONES EN TANT QU'INHIBITEURS DE PROTÉINE KINASE
  申请人：EXELIXIS INC

  公开号：WO2009086264A1

  公开（公告）日：2009-07-09

  A compound according to formula I: or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3a, R3b, R3c and R3d are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.

  根据公式I的化合物：或其药用可接受盐；其中R1、R2、R3a、R3b、R3c和R3d如规范中所定义，以及其药物组合物和使用方法。
• [EN] TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS<br/>[FR] TRIAZA-SPIRODÉCANONES UTILISÉES EN TANT QU'INHIBITEURS DE DDR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017005583A1

  公开（公告）日：2017-01-12

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.

  本发明涉及式(I)的化合物或其药用盐，其中L和R1至R5如本文所述，以及它们的制备方法、包含它们的药物组合物，以及它们作为药物的用途。
• Novel Autotaxin Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis: A Clinical Candidate Discovered Using DNA-Encoded Chemistry
  作者：John W. Cuozzo、Matthew A. Clark、Anthony D. Keefe、Anna Kohlmann、Mark Mulvihill、Haihong Ni、Louis M. Renzetti、Daniel I. Resnicow、Frank Ruebsam、Eric A. Sigel、Heather A. Thomson、Ce Wang、Zhifeng Xie、Ying Zhang

  DOI：10.1021/acs.jmedchem.0c00688

  日期：2020.7.23

  with a number of human diseases including idiopathic pulmonary fibrosis (IPF). We screened a single DNA-encoded chemical library (DECL) of 225 million compounds and identified a series of potent inhibitors. Optimization of this series led to the discovery of compound 1 (X-165), a highly potent, selective, and bioavailable small molecule. Cocrystallization of compound 1 with human autotaxin demonstrated

  分泌的磷酸二酯酶自分泌生物素的活性产生炎症信号分子LPA，并与许多人类疾病有关，包括特发性肺纤维化（IPF）。我们筛选了一个含有2.25亿种化合物的单一DNA编码化学文库（DECL），并确定了一系列有效的抑制剂。该系列产品的优化导致发现化合物1（X-165），这是一种高效，选择性和生物利用度高的小分子。化合物1与人自分泌紫杉醇的共结晶表明，它具有一种新颖的结合模式，既占据了疏水口袋，又占据了自分泌紫杉醇活性位点附近的通道。化合物1在纳摩尔水平上抑制人和小鼠血浆中LPA的产生，并在人肺纤维化的小鼠模型中显示出功效。成功完成IND启用研究后，化合物1被FDA批准用于I期临床试验。这些结果表明DECL命中可以很容易地优化为临床候选。
• Activity-Based DNA-Encoded Library Screening
  作者：Wesley G. Cochrane、Marie L. Malone、Vuong Q. Dang、Valerie Cavett、Alexander L. Satz、Brian M. Paegel

  DOI：10.1021/acscombsci.9b00037

  日期：2019.5.13

  Robotic high-throughput compound screening (HTS) and, increasingly, DNA-encoded library (DEL) screening are driving bioactive chemical matter discovery in the postgenomic era. HTS enables activity-based investigation of highly complex targets using static compound libraries. Conversely, DEL grants efficient access to novel chemical diversity, although screening is limited to affinity-based selections

  机器人高通量化合物筛选（HTS）以及越来越多的DNA编码文库（DEL）筛选正在推动后基因组时代的生物活性化学物质发现。HTS可以使用静态化合物库对高度复杂的目标进行基于活动的调查。相反，尽管筛选仅限于基于亲和力的选择，但DEL可以有效地获得新型化学多样性。在这里，我们描述了一种基于液滴的集成微流控电路，该电路可直接筛选固相DEL的活性。磷酸二酯酶自分泌生物素抑制剂的67 100个成员库的示例筛选产生了35个用于纳米级规模的合成和验证（20种有活性）的高优先级结构，指导了大规模规模的合成候选物的选择（5/5化合物的IC50值为4-10μM）。我们进一步将基于活动的命中与基于相似性的DEL选择的命中进行了比较。这个小型的筛选平台为将DELs应用到更复杂的目标（信号通路，细胞反应）铺平了道路，并代表了一种可分布的小分子发现方法。
• Bradykinin antagonist pseudopeptide derivatives of substituted
  申请人：Scios Inc.

  公开号：US05610142A1

  公开（公告）日：1997-03-11

  Novel compounds with as few as three natural amino acids that incorporate a substituted 4-keto-1,3,8-triazaspiro[4.5]decan-3-alkanoyl bridge in place of selected fragments of peptidic bradykinin receptor antagonists are pseudopeptides with potent bradykinin receptor antagonist actions. These pseudopeptides and their pharmaceutical compositions are of benefit in treating conditions and diseases of mammals, including humans, in which an excess of bradykinin or a related kinin is produced endogenously or is received exogenously, for example via insect bite.

  这些小说化合物仅包含三种天然氨基酸，它们将肽类布雷金受体拮抗剂的部分片段替换为取代的4-酮基-1,3,8-三氮杂螺[4.5]癸烷-3-脂肪酰桥，是具有强效布雷金受体拮抗剂作用的伪肽。这些伪肽及其制药组合物对于治疗哺乳动物（包括人类）中自身产生过多布雷金或相关的激肽，或通过昆虫叮咬等外源性途径接收到过多激肽的情况和疾病具有益处。