乙基[(2R,3S)-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)-2-哌啶基]乙酸酯 | 150618-13-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 乙基[(2R,3S)-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)-2-哌啶基]乙酸酯
• 英文名称: (2R*,3S*)-3-(tert-butoxycarbonyl)amino-2-(ethoxycarbonyl)methylpiperidine
• 英文别名: (2RS,3SR)-3-(tert-butoxycarbonyl)amino-2-(ethoxycarbonyl)methylpiperidine；ethyl trans-{3-[(tert-butoxycarbonyl)amino]piperidin-2-yl}acetate；ethyl {(2RS,3SR)-3-[(tert-butoxycarbonyl)amino]piperidin-2-yl}acetate；Ethyl (2R, 3S)-3-Boc-amino-2-piperidineacetate；ethyl 2-[(2R,3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]piperidin-2-yl]acetate
• CAS: 150618-13-6
• 化学式: C₁₄H₂₆N₂O₄
• 分子量: 286.371
• InChiKey: JWIFFLUEVLMGJF-WDEREUQCSA-N

物化性质

• 沸点：
  391.0±35.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  乙基[(2R,3S)-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)-2-哌啶基]乙酸酯 在 sodium hydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 [(S)-1-((4aS,5R)-2-Benzyl-1,3-dioxo-octahydro-pyrido[1,2-c]pyrimidin-5-ylcarbamoyl)-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  1,3-二氧杂氢吡啶并[1,2-c]嘧啶衍生物的合成及其立体化学构效关系：有效的和选择性的胆囊收缩素-A受体拮抗剂。

  摘要：

  描述了基于1,3-二氧杂氢吡啶并[1,2-c]嘧啶骨架的新型强效和选择性非肽胆囊收缩素-A（CCK-A）受体拮抗剂的合成与立体化学结构-活性的关系。这是八个非对映异构体系列中最有效的成员，（4aS，5R）-2-苄基-5- [N-[（叔丁氧羰基）-L-色氨酸]-氨基]-1,3-二氧杂氢吡啶并[1,2] -c]嘧啶显示出纳摩尔浓度的CCK-A受体亲和力，并且在CCK-A处的效力高于在CCK-B受体处的8000倍。作为CCK-A拮抗剂，该化合物以低浓度抑制胰腺腺泡细胞中CCK-8诱发的淀粉酶的释放，与典型的拮抗剂Devazepide相似。已经发现对CCK-A受体结合和选择性的高度严格的立体化学要求。L-Trp和4a

  DOI：

  10.1021/jm9703247
• 作为产物：
  描述：

  乙基(4S)-7-{[(苄氧基)羰基]氨基}-4-({[(2-甲基-2-丙基)氧基]羰基}氨基)-3-氧代庚酸酯 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 40.0 ℃ 、275.79 kPa 条件下， 反应 6.0h， 以90%的产率得到乙基[(2R,3S)-3-({[(2-甲基-2-丙基)氧基]羰基}氨基)-2-哌啶基]乙酸酯
  参考文献：
  名称：

  （2 R，3 S）-3-氨基-2-哌啶乙酸衍生物的立体定向合成，用作肽中的构象限制

  摘要：

  得自Boc-Orn（Z）-OH和硫代乙酸乙酯的β-酮酯在40°C的催化加氢反应，仅提供乙基（2 R，3 S）-3-叔丁氧基羰基氨基-2-哌啶乙酸保护的，可用于肽合成。

  DOI：

  10.1016/s0040-4039(00)73644-6

文献信息

• Adventures in Scaffold Morphing: Discovery of Fused Ring Heterocyclic Checkpoint Kinase 1 (CHK1) Inhibitors
  作者：Bin Yang、Melissa M. Vasbinder、Alexander W. Hird、Qibin Su、Haixia Wang、Yan Yu、Dorin Toader、Paul D. Lyne、Jon A. Read、Jason Breed、Stephanos Ioannidis、Chun Deng、Michael Grondine、Nancy DeGrace、David Whitston、Patrick Brassil、James W. Janetka

  DOI：10.1021/acs.jmedchem.7b01490

  日期：2018.2.8

  kinase 1 (CHK1) inhibitors are potential cancer therapeutics that can be utilized for enhancing the efficacy of DNA damaging agents. Multiple small molecule CHK1 inhibitors from different chemical scaffolds have been developed and evaluated in clinical trials in combination with chemotherapeutics and radiation treatment. Scaffold morphing of thiophene carboxamide ureas (TCUs), such as AZD7762 (1) and

  Checkpoint激酶1（CHK1）抑制剂是潜在的癌症治疗剂，可用于增强DNA损伤剂的功效。已经开发了多种来自不同化学支架的小分子CHK1抑制剂，并在临床试验中结合化学疗法和放射治疗进行了评估。噻吩羧酰胺脲（TCU）的支架变形，例如AZD7762（1）和相关系列的三唑并喹啉（TZQs），导致鉴定了稠环双环CHK1抑制剂，7-羧酰胺噻吩并吡啶（7-CTP）和7-羧酰胺吲哚。X射线晶体结构揭示了以共面方式将铰链结合羧酰胺基团与噻吩并吡啶核对齐的关键分子内非共价硫-氧相互作用。与吲哚NH的分子内氢键也可有效地将羧酰胺锁定在与CHK1的优选结合构象中。对7-CTP系列进行优化后，鉴定出了铅化合物44，该化合物表现出可观的类药物特性以及良好的体外和体内药效。
• 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-<i>c</i>]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structure−Activity Relationship Studies on the Substituent at N2-Position
  作者：José M. Bartolomé-Nebreda、Rosario Patiño-Molina、Mercedes Martín-Martínez、Isabel Gómez-Monterrey、M. Teresa García-López、Rosario González-Muñiz、Edurne Cenarruzabeitia、Miriam Latorre、Joaquín Del Río、Rosario Herranz

  DOI：10.1021/jm010813d

  日期：2001.6.1

  To establish structure-activity relationships a new series of analogues of the highly potent and selective CCK1 receptor antagonist (4aS,5R)-2-benzyl-5-(N-Boc-tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]-pyrimidine (1a) modified at N2-position of the central scaffold has been prepared and evaluated as CCK receptor ligands. With this aim the N2-benzyl group has been replaced by methyl, cyclohexyl, aromatic groups, 1-phenylethyl, and 1-carboxy-2-phenylethyl group. Then, substituents with different electronic and steric properties were introduced into different positions of the phenyl group of analogues 19a and 19b. The results of the CCK receptor binding and in vitro functional activity evaluation suggest the importance of the lipophilic character and an appropriate spatial orientation of the moiety linked at the N2-position of the 1,3-dioxoperhydropyrido[1,2-c]pyrimidine template for potent and selective binding and antagonist activity at CCK1 receptor subtype. The 2-cyclohexyl and (2S)-1-naphthyl derivatives 18a and (2S)-20a have emerged as more potent and selective CCK1 receptor antagonists than the lead compound 1a. Additionally, the results confirm the (4aS,5R)stereochemistry at the central bicyclic skeleton as an essential structural requirement for potent binding to this receptor subtype.
• 5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-<i>c</i>]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-<i>c</i>]pyrimidine Scaffold
  作者：José M. Bartolomé-Nebreda、M. Teresa García-López、Rosario González-Muñiz、Edurne Cenarruzabeitia、Miriam Latorre、Joaquín Del Río、Rosario Herranz

  DOI：10.1021/jm010898i

  日期：2001.11.1

  To further define the pharmacophore of the potent and selective 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 receptor antagonists the electronic and topographic properties of the central 1, 3-dioxoperhydro-pyrido[1,2-c]pyrimidine scaffold have been modified. With this aim, the 1- and 3-oxo groups have been replaced by the thioxo- and deoxi-analogues, and the fused piperidine ring has been contracted to the corresponding pyrrolidine moiety. The results of the evaluation of the new analogues as CCK receptor ligands, in rat pancreas and cerebral cortex preparations, showed that, whereas replacement of oxygen with sulfur is allowed, reduction of the 1- or 3-oxo groups or the contraction of the fused piperidine ring lead to the complete loss of binding affinity at CCK1 receptors. The thioxo-analogues 5a, 8a, 12a, and 12b showed functional CCK1 antagonist activity, inhibiting the CCK-8-stimulated amylase release from pancreatic acinar cells. The 1-thioxo analogue 5a, with subnanomolar affinity (IC50 = 0.09 x 10(-9) M), was found to be the most potent and selective compound within the family of 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 antagonists.
• EP1852432
  申请人：——

  公开号：——

  公开（公告）日：——