(2S)-{[(benzyloxy)carbonyl]amino}(tetrahydro-2H-pyran-4-yl)ethanoic acid | 1098184-12-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S)-{[(benzyloxy)carbonyl]amino}(tetrahydro-2H-pyran-4-yl)ethanoic acid
• 英文别名: (S)-2-(benzyloxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid；(S)-2-(((Benzyloxy)carbonyl)amino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid；(2S)-2-(oxan-4-yl)-2-(phenylmethoxycarbonylamino)acetic acid
• CAS: 1098184-12-3
• 化学式: C₁₅H₁₉NO₅
• 分子量: 293.32
• InChiKey: VTENIAVLDXOKCR-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-{[(benzyloxy)carbonyl]amino}(tetrahydro-2H-pyran-4-yl)ethanoic acid 在 盐酸 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、202.66 kPa 条件下， 反应 39.0h， 生成 (3S,8aR)-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-2-[(2S)-2-[(N-methyl-L-alanyl)amino]-2-(tetrahydro-2H-pyran-4-yl)acetyl]octahydropyrrolo[1,2-a]pyrazine-3-carboxamide dihydrochloride
  参考文献：
  名称：

  Design and Synthesis of Potent Inhibitor of Apoptosis (IAP) Proteins Antagonists Bearing an Octahydropyrrolo[1,2-a]pyrazine Scaffold as a Novel Proline Mimetic

  摘要：

  To develop novel inhibitor of apoptosis (IAP) proteins antagonists, we designed a bicyclic octahydropyrrolo-[1,2-a]pyrazine scaffold as a novel proline bioisostere. This design was based on the X-ray co-crystal structure of four N-terminal amino acid residues (AVPI) of the second mitochondria-derived activator of caspase (Smac) with the X-chromosome-linked IAP (XIAP) protein. Lead optimization of this scaffold to improve oral absorption yielded compound 45, which showed potent cellular IAP1 (cIAP1 IC50: 1.3 nM) and XIAP (IC50: 200 nM) inhibitory activity, in addition to potent tumor growth inhibitory activity (GI(50): 1.8 nM) in MDA-MB-231 breast cancer cells. X-ray crystallographic analysis of compound 45 bound to X1AP and to cIAPI was achieved, revealing the various key interactions that contribute to the higher cIAPI affinity of compound 45 over X1AP. Because of its potent IAP inhibitory activities, compound 45 (T-3256336) caused tumor regression in a MDA-MB-231 tumor xenograft model (T/C: -53% at 30 mg/kg).

  DOI：

  10.1021/jm301674z
• 作为试剂：
  描述：

  tert-butyl (3S,8aR)-3-{[(1S,2S)-2-fluoro-2,3-dihydro-1H-inden-1-yl]carbamoyl}hexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate 、 ethyl acetate hydrochloride 、 乙酸乙酯 在 乙酸乙酯 、 N,N-二甲基甲酰胺 、 N,N-二异丙基乙胺 、 (2S)-{[(benzyloxy)carbonyl]amino}(tetrahydro-2H-pyran-4-yl)ethanoic acid 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 水 、 碳酸氢钠 、 Brine 、 magnesium sulfate 、 silica gel 、 ethyl acetate n-hexane 作用下， 反应 5.5h， 以to give the title compound (249 mg) as a white powder的产率得到benzyl [(1S)-2-[(3S,8aR)-3-{[(1S,2S)-2-fluoro-2,3-dihydro-1H-inden-1-yl]carbamoyl}hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl]-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethyl]carbamate
  参考文献：
  名称：

  Heterocyclic Compound

  摘要：

  本发明提供了一种化合物，其表示为式中的每个符号如规范中所定义，或其盐。本发明的化合物表现出强烈的IAP拮抗活性。

  公开号：

  US20110034469A1

文献信息

• [EN] SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS<br/>[FR] COMPOSÉS PYRAZOLO[1,5-A]PYRIMIDINE SUBSTITUÉS UTILISÉS COMME INHIBITEURS DE MTOR
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2011029027A1

  公开（公告）日：2011-03-10

  Compounds of Formula I: and salts thereof in which R1, R2, R2a, R3, n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.

  公式I的化合物：以及其中R1、R2、R2a、R3、n、X和环B具有说明书中给出的含义的盐，是mTOR的抑制剂，可用于治疗对mTOR抑制敏感的疾病，如癌症。
• INHIBITORS OF IAP
  申请人：Ndubaku Chudi

  公开号：US20110046066A1

  公开（公告）日：2011-02-24

  The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula (I), and G, X 1 , X 2 , R 1 , R 2 , R 3 , R 4 , R 4 ′, R 5 , R a , R b , and R c are as described herein.

  这项发明提供了新型IAP抑制剂，可作为治疗剂用于治疗恶性肿瘤，其中化合物具有一般式(I)，并且G、X1、X2、R1、R2、R3、R4、R4'、R5、Ra、Rb和Rc如本文所述。
• IMIDAZOPYRIDINE INHIBITORS OF IAP
  申请人：Koehler Michael F.T.

  公开号：US20100130539A1

  公开（公告）日：2010-05-27

  The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I: wherein Q, X 1 , X 2 , Y, Z R 1 , R 2 , R 3 , R 3 ′, R 4 , R 4 ′, R 5 , R 6 , R 6 ′ and n are as described herein.

  本发明提供了新型的IAP抑制剂，这些抑制剂可用作治疗恶性肿瘤的治疗剂，其中化合物具有以下通式I：其中Q、X1、X2、Y、Z、R1、R2、R3、R3'、R4、R4'、R5、R6、R6'和n如本文所述。
• SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS
  申请人：Andrews Steven W.

  公开号：US20120178715A1

  公开（公告）日：2012-07-12

  Compounds of Formula I: and salts thereof in which R 1 , R 2 , R 2a , R 3 , n, X and ring B have the meanings given in the specification, are inhibitors of mTOR and are useful in the treatment of diseases which are sensitive to inhibition of mTOR, such as cancers.

  式I的化合物及其盐，其中R1、R2、R2a、R3、n、X和环B具有规范中所给出的含义，是mTOR的抑制剂，可用于治疗对mTOR抑制敏感的疾病，如癌症。
• Antiviral compounds
  申请人：Cottell Jeromy J.

  公开号：US20090186869A1

  公开（公告）日：2009-07-23

  The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及抗病毒化合物、含有该化合物的组合物以及包括该化合物的治疗方法，还涉及用于制备该化合物的过程和中间体。