(S)-3-(tert-Butoxycarbonylamino)-N-methyl-4-phenylbutanamide | 170116-28-6

• 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: (S)-3-(tert-Butoxycarbonylamino)-N-methyl-4-phenylbutanamide
• 英文别名: Boc-(S)-β³-HPhe-NHMe；N-tert-butyloxycarbonyl-(S)-β³-homophenylalanyl-N-methylamide；Boc-β³-hPhe-NHMe；tert-butyl (S)-(4-(methylamino)-4-oxo-1-phenylbutan-2-yl)carbamate；Boc-betaPhe-NHMe；tert-butyl N-[(2S)-4-(methylamino)-4-oxo-1-phenylbutan-2-yl]carbamate
• CAS: 170116-28-6
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: DFVYVGMHDPFQFI-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-3-(tert-Butoxycarbonylamino)-N-methyl-4-phenylbutanamide 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 6.0h， 以91%的产率得到(S)-3-amino-N-methyl-4-phenylbutanamide hydrochloride
  参考文献：
  名称：

  [EN] HETEROCYCLIC SPIRO COMPOUNDS AND METHODS OF USE
  [FR] COMPOSÉS SPIRO HÉTÉROCYCLIQUES ET PROCÉDÉS D'UTILISATION

  摘要：

  本公开提供具有抑制G12C突变KRAS蛋白活性的式（I）化合物。本公开还提供包含该化合物的药物组合物，用途和治疗某些疾病的方法，例如癌症，包括但不限于肺癌、胰腺癌和结直肠癌。

  公开号：

  WO2022093856A1
• 作为产物：
  描述：

  (3S)-tert-butyl 1-benzyl-3-diazo-2-oxopropylcarbamate 、 甲胺 在 silver benzoate 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以30%的产率得到(S)-3-(tert-Butoxycarbonylamino)-N-methyl-4-phenylbutanamide
  参考文献：
  名称：

  Podlech, Joachim; Seebach, Dieter, Liebigs Annalen, 1995, # 7, p. 1217 - 1228

  摘要：

  DOI：

文献信息

• Aggregation modes in sheets formed by protected β-amino acids and β-peptides
  作者：Anindita Sengupta、Rituparna S. Roy、Varatharajan Sabareesh、Narayanaswamy Shamala、Padmanabhan Balaram

  DOI：10.1039/b516088j

  日期：——

  The crystal structures of four protected β-amino acid residues, Boc-(S)-β3-HAla-NHMe (1); Boc-(R)-β3-HVal-NHMe (2); Boc-(S)-β3-HPhe-NHMe (3); Boc-(S)-β3-HPro-OH (6) and two β-dipeptides, Boc-(R)-β3-HVal-(R)-β3-HVal-OMe (4); Boc-(R)-β3-HVal-(S)-β3-HVal-OMe (5) have been determined. Gauche conformations about the Cβ–Cα bonds (θ ∼ ±60°) are observed for the β3-HPhe residues in 3 and all four β3-HVal residues in the dipeptides 4 and 5. Trans conformations (θ ∼ 180°) are observed for β3-HAla residues in both independent molecules in 1 and for the β3-HVal and β3-HPro residues in 2 and 6, respectively. In the cases of compounds 1–5, molecules associate in the crystals via intermolecular backbone hydrogen bonds leading to the formation of sheets. The polar strands formed by β3-residues aggregate in both parallel (1, 3, 5) and antiparallel (2, 4) fashion. Sheet formation accommodates both the trans and gauche conformations about the Cβ–Cα bonds.

  四种保护的β-氨基酸残基的晶体结构被确定，包括Boc-(S)-β3-HAla-NHMe (1)；Boc-(R)-β3-HVal-NHMe (2)；Boc-(S)-β3-HPhe-NHMe (3)；Boc-(S)-β3-HPro-OH (6)，以及两个β-二肽，Boc-(R)-β3-HVal-(R)-β3-HVal-OMe (4)；Boc-(R)-β3-HVal-(S)-β3-HVal-OMe (5)。在3中观察到β3-HPhe残基及在二肽4和5中的所有四个β3-HVal残基围绕Cβ-Cα键呈现出偏斜的构象（θ ≈ ±60°）。在1中的两个独立分子及在2和6中的β3-HAla、β3-HVal和β3-HPro残基分别观察到反式构象（θ ≈ 180°）。在化合物1–5的情况下，分子通过分子间骨架氢键在晶体中结合，形成层状结构。由β3-残基形成的极性链条以平行（1、3、5）和反平行（2、4）的方式聚集。层的形成容纳了围绕Cβ-Cα键的反式和偏斜构象。
• Single-Conformation Ultraviolet and Infrared Spectroscopy of Model Synthetic Foldamers:  β-Peptides Ac-β³-hPhe-NHMe and Ac-β³-hTyr-NHMe
  作者：Esteban E. Baquero、William H. James、Soo Hyuk Choi、Samuel H. Gellman、Timothy S. Zwier

  DOI：10.1021/ja078271y

  日期：2008.4.1

  spectroscopy was used to determine that two conformations of 1 are present, with the transitions due to conformer A, with S0-S1 origin at 34431 cm(-1), being almost 20 times larger than those due to conformer B, with S0-S1 origin at 34404 cm(-1). Only one conformation of 2 was observed. Resonant ion-dip infrared spectroscopy provided single-conformation infrared spectra in the 3300-3700 cm(-1) region.

  已经在喷射冷却的分离分子条件下探索了两种模型 β-肽 Ac-beta3-hPhe-NHMe (1) 和 Ac-beta3-hTyr-NHMe (2) 的构象偏好和红外和紫外光谱特征。两个分子的质量分辨共振双光子电离光谱分别记录在苯基或苯酚环取代基的 S0-S1 起源区域。UV-UV 烧孔光谱用于确定存在 1 的两种构象，由构象 A 引起的跃迁，S0-S1 原点位于 34431 cm(-1)，几乎比构象引起的跃迁大 20 倍B，S0-S1 原点位于 34404 cm(-1)。仅观察到 2 的一种构象。共振离子浸入红外光谱在 3300-3700 cm(-1) 区域提供单构象红外光谱。两种分子的构象异构体 A 的光谱分别在 3400 和 3488 cm(-1) 处具有 H 键合和游离酰胺 NH 拉伸红外跃迁，而 1 的构象异构体 B 在 3417 和 3454 cm(-1) 处具有波段。为了与实验进行比较，在
• Single-Conformation Ultraviolet and Infrared Spectroscopy of Model Synthetic Foldamers:  β-Peptides Ac-β³-hPhe-β³-hAla-NHMe and Ac-β³-hAla-β³-hPhe-NHMe
  作者：Esteban E. Baquero、William H. James、Soo Hyuk Choi、Samuel H. Gellman、Timothy S. Zwier

  DOI：10.1021/ja078272q

  日期：2008.4.1

  The conformational preferences and infrared and ultraviolet spectral signatures of two model P-peptides, Ac-beta(3)-hPhe-beta(3)-hAla-NHMe (1) and Ac-beta(3)-hAla-beta(3)-hPhe-NHMe (2), have been explored under jet-cooled, isolated-molecule conditions. The mass-resolved, resonant two-photon ionization spectra of the two molecules were recorded in the region of the S-0-S-1 origin of the phenyl substituents (37200-37800 cm(-1)). UV-UV hole-burning spectroscopy was used to determine the ultraviolet spectral signatures of five conformational isomers of both 1 and 2. Transitions due to two conformers (labeled A and B) dominate the R2PI spectra of each molecule, while the other three are minor conformers (C-E) with transitions a factor of 3-5 smaller. Resonant ion-dip infrared spectroscopy was used to obtain single-conformation infrared spectra in the 3300-3700 cm(-1) region. The infrared spectra showed patterns of NH stretch transitions c aracter stic of the number and type of intramolecular H-bonds present in the -peptide backbone. For comparison with experiment, full optimizations of low-lying minima of both molecules were carried out at DFT B3LYP/6-31+G*, followed by single point MP2/6-31+G* and selected MP2/aug-cc-pVDZ calculations at the DFT optimized geometries. Calculated harmonic vibrational frequencies and infrared intensities for the amide NH stretch vibrations were used to determine the beta-peptide backbone structures for nine of the ten observed conformers. Conformers 1B, 1D, and 2A were assigned to double ring structures containing two C6 H-boncled rings (C6a/C6a), conformers 1A and 2B are C10 single H-bonded rings, conformers 1C and 2D are double ring structures composed of two C8 H-bonded rings (C8/C8), and conformers 1E and 2E are double ring/double acceptor structures in which two NH groups H-bond to the same C=O group, thereby weakening both H-bonds. Both 1E and 2E are tentatively assigned to C6/C8 double ring/double acceptor structures, although C8/C12 structures cannot be ruled out unequivocally. Finally, no firm conformational assignment has been made for conformer 2C whose unusual infrared spectrum contains one very strong H-bond with NH stretch frequency at 3309 cm(-1), a second H-bonded NH stretch fundamental of more typical value (3399 cm(-1)), and a third fundamental at 3440 cm(-1), below that typical of a branched-chain free NH. The single conformation spectra provide characteristic wavenumber ranges for the amide NH stretch fundamentals ascribed to C6 (3378-3415 cm(-1)), C8 (3339-3369 cm(-1)), and C10 (3381-3390 cm(-1)) H-boncled rings.
• Podlech, Joachim; Seebach, Dieter, Liebigs Annalen, 1995, # 7, p. 1217 - 1228
  作者：Podlech, Joachim、Seebach, Dieter

  DOI：——

  日期：——
• [EN] HETEROCYCLIC SPIRO COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS SPIRO HÉTÉROCYCLIQUES ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2022093856A1

  公开（公告）日：2022-05-05

  The present disclosure provides compounds of Formula (I) having activity as inhibitors of G12C mutantKRASprotein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses and methods of treating certain disorders, such as cancer, including but not limited to lung, pancreatic and colorectal cancers.

  本公开提供具有抑制G12C突变KRAS蛋白活性的式（I）化合物。本公开还提供包含该化合物的药物组合物，用途和治疗某些疾病的方法，例如癌症，包括但不限于肺癌、胰腺癌和结直肠癌。