(±)-trans-2-((tert-butoxycarbonyl)amino)cyclopentanecarboxylic acid | 136315-71-4

• 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: (±)-trans-2-((tert-butoxycarbonyl)amino)cyclopentanecarboxylic acid
• 英文别名: trans-2-[[(1,1-dimethylethoxy)carbonyl]amino]cyclopentanecarboxylic acid；N-(tert-butyloxycarbonyl)-trans-2-aminocyclopentanecarboxylic acid；trans-2-((tert-butoxycarbonyl)amino)cyclopentane-1-carboxylic acid；trans-2-aminocyclopentanecarboxylic acid；trans-2-((tert-Butoxycarbonyl)amino)cyclopentanecarboxylic acid；(1R,2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acid
• CAS: 136315-71-4
• 化学式: C₁₁H₁₉NO₄
• 分子量: 229.276
• InChiKey: BUEPEVBYNBQNED-HTQZYQBOSA-N

物化性质

• 熔点：
  137-138 °C
• 沸点：
  382.5±31.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924299090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (±)-trans-2-((tert-butoxycarbonyl)amino)cyclopentanecarboxylic acid 在 N-甲基吗啉 、 盐酸 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 反应 15.17h， 生成 (1R,2R)-(-)-2-氨基-1-环戊烷羧酸
  参考文献：
  名称：

  Probing a molecular model of taste utilizing peptidomimetic stereoisomers of 2-aminocyclopentanecarboxylic acid methyl ester

  摘要：

  On the basis of the preferred conformations of L-aspartyl dipeptide derivatives containing alpha-amino acids at the second position and their retro-inverso analogues deduced by a combination of X-ray crystallography, H-1 NMR spectroscopy, and molecular mechanics calculations, we have proposed a model describing the molecular array required for the sweet taste. The conformation of a sweet molecule is described as possessing an "L shape", with the AH (proton donor) and B (proton acceptor) zwitterionic ring of the aspartyl moiety forming the stem, and the hydrophobic group X forming the base of the "L". Planarity of the molecule in the x and y dimensions is critical for sweet taste. Substantial deviation from this plane into negative z dimension is correlated with bitter taste while other deviations lead to tasteless molecules. To examine the model, the preferred conformations for a series of L-aspartyl dipeptides containing a 2-aminocyclopentanecarboxylic acid (2-Ac5c) residue at the second position were calculated using molecular mechanics. The peptidomimetic 2-Ac5c residue is a beta-amino acid with two chiral centers, resulting in four isomers [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c, cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c]. Two stereoisomers, L-aspartyl-trans-(1R,2R)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-trans-(1R,2R)-2-Ac5c-OMe] and L-aspartyl-cis-(1S,2R)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-cis-(1S,2R)-2-Ac5c-OMe], prefer the L-shape conformations and are thus predicted to be sweet. For L-aspartyl-trans-(1S,2S)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-trans-(1S,2S)-2-Ac5c-OMe], the methyl ester group projects behind the stem of the L shape, producing a large negative z component and is predicted to exhibit a bitter taste. The calculations predict that L-aspartyl-cis-(1R,2S)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-cis-(1R,2S)-2-Ac5c-OMe] will be tasteless. In this investigation, in addition to the calculations, we report the synthesis and experimental conformational analysis of the four stereoisomers of Asp-2-Ac5c-OMe. The absolute configurations of the 2-Ac5c residues were assigned by X-ray diffraction studies and by correlating optical rotation and enantiomeric excess values. These studies fully confirm our configurational assignments of the stereoisomers of Asp-2-Ac5c-OMe. Thus, the structure-taste relationships observed for the new class of L-aspartyl taste ligands containing the 2-Ac5c beta-amino acid methyl esters in the second position agree with and strengthen our model for the sweet and bitter taste responses.

  DOI：

  10.1021/jo00023a033
• 作为产物：
  描述：

  2-氧代环戊羧酸乙酯 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 (±)-trans-2-((tert-butoxycarbonyl)amino)cyclopentanecarboxylic acid
  参考文献：
  名称：

  (S,S)-trans-Cyclopentane-Constrained Peptide Nucleic Acids. A General Backbone Modification that Improves Binding Affinity and Sequence Specificity

  摘要：

  Replacing the ethylenediamine portion of aminoethylglycine peptide nucleic acids (aegPNAs) with one or more (S,S)-trans-cyclopentane diamine units significantly increases binding affinity and sequence specificity to complementary DNA, making these modified PNAs ideal for use as nucleic acid probes in genomic analysis. The synthesis and study of this new class of PNAs (tcypPNAs) is described in which trans-cyclopentane diamine has been incorporated into several positions, and in varying number, within PNA backbones of mixed-base sequences.

  DOI：

  10.1021/ja046280q

文献信息

• Radical cyclization in heterocycle synthesis. Part 13: Sulfanyl radical addition–cyclization of oxime ethers and hydrazones connected with alkenes for synthesis of cyclic β-amino acids
  作者：Okiko Miyata、Kanami Muroya、Tomoko Kobayashi、Rina Yamanaka、Seiko Kajisa、Junko Koide、Takeaki Naito

  DOI：10.1016/s0040-4020(02)00412-x

  日期：2002.5

  combination of sulfanyl radical addition–cyclization of the oxime ethers and hydrazones connected with alkenes and subsequent conversion of a phenylsulfanylmethyl group to a carboxyl group provides a novel method for the construction of the cyclic β-amino acids. Upon treatment with thiophenol in the presence of AIBN, the oxime ethers and hydrazones smoothly underwent sulfanyl radical addition-cyclization

  硫醚基自由基加成－肟醚和与烯烃连接的的环化反应以及随后苯硫烷基甲基到羧基的转化提供了一种构造环状β-氨基酸的新方法。在AIBN存在下用苯硫酚处理后，使肟醚和平稳地进行硫烷基自由基加成-环化反应，得到2-（苯基硫烷基甲基）环烷基胺。该方法已成功应用于2-氨基环戊烷羧酸和4-氨基-3-吡咯烷羧酸的实际合成。
• [EN] TRICYCLIC INHIBITORS OF HEPATITIS B VIRUS<br/>[FR] INHIBITEURS TRICYCLIQUES DU VIRUS DE L'HÉPATITE B
  申请人：OSPEDALE SAN RAFFAELE SRL

  公开号：WO2020030781A1

  公开（公告）日：2020-02-13

  The present invention relates to compounds that are inhibitors of hepatitis B virus (HBV). Compounds of this invention are useful alone or in combination with other agents for treating, ameliorating, preventing or curing HBV infection and related conditions. The present invention also relates to pharmaceutical compositions containing said compounds.

  本发明涉及抑制乙型肝炎病毒（HBV）的化合物。本发明的化合物可单独使用或与其他药剂结合用于治疗、改善、预防或治愈HBV感染及相关疾病。本发明还涉及含有上述化合物的药物组合物。
• [EN] IMIDAZOLE DERIVATIVES AS ANTIVIRAL AGENTS<br/>[FR] NOUVEAUX DÉRIVÉS DE QUERCÉTINE UTILES COMME AGENTS ANTIVIRAUX
  申请人：LUPIN LTD

  公开号：WO2013021344A1

  公开（公告）日：2013-02-14

  Compounds of the general formula (I) their tautomeric forms, their stereoisomers, their analogs, their prodrugs, their isotopes, their N-oxides, their metabolites, their pharmaceutically acceptable salts, polymorphs, solvates, optical isomers, clathrates, co-crystals, combinations with suitable medicament, pharmaceutical compositions containing them, methods of making of the above compounds, and their use as antiviral candidate, more specifically as anti-HCV are disclosed.

  通式（I）的化合物，它们的互变异构体，立体异构体，类似物，前药，同位素，N-氧化物，代谢物，药学上可接受的盐，多型体，溶剂合物，光学异构体，包合物，共晶体，与合适药物的组合，含有它们的药物组合物，上述化合物的制备方法，以及它们作为抗病毒候选药物的用途，更具体地作为抗HCV药物的用途被披露。
• PENTACYCLIC HETEROCYCLES
  申请人：Eisai R&D Management Co., Ltd.

  公开号：US20200283452A1

  公开（公告）日：2020-09-10

  The present invention provides compounds represented by formulas (I) to (XVII) or pharmaceutically acceptable salts thereof:

  本发明提供了由式(I)至(XVII)表示的化合物或其药学上可接受的盐：
• Design and Synthesis of Conformationally Constrained RORγt Inverse Agonists
  作者：Ayumu Sato、Yoshiyuki Fukase、Mitsunori Kono、Atsuko Ochida、Tsuneo Oda、Yusuke Sasaki、Naoki Ishii、Yoshihide Tomata、Shoji Fukumoto、Yumi N. Imai、Keiko Uga、Akira Shibata、Masashi Yamasaki、Hideyuki Nakagawa、Mikio Shirasaki、Robert Skene、Isaac Hoffman、Bi‐Ching Sang、Gyorgy Snell、Junya Shirai、Satoshi Yamamoto

  DOI：10.1002/cmdc.201900416

  日期：2019.11.20

  novel RORγt inverse agonist. A U-shaped conformation in the complex structure of 1 a with RORγt protein was confirmed. Further improvement of the pharmacokinetic (PK) profiles was required because of the low drug exposure in mice upon oral administration (mouse AUC of 1 a: 27 ng ⋅ h ⋅ mL-1 at 1 mg ⋅ kg-1 , p.o.). To improve the PK profiles, conformationally constrained U-shaped scaffolds were investigated

  维甲酸相关的孤儿受体γt（RORγt）反向激动剂可用于治疗自身免疫性疾病。以前，我们报道了一种具有柔性线性接头的新型喹唑啉二酮1a作为新型RORγt反向激动剂。证实了1a与RORγt蛋白的复合结构中的U形构象。由于口服后小鼠体内的药物暴露量低（1 a的小鼠AUC：27 ng⋅h mL-1，1 mg⋅kg-1，po），因此需要进一步改善药代动力学（PK）曲线。为了改善PK谱，研究了构象受限的U形支架。结果，成功鉴定了具有改善的PK谱和高效力的吗啉类似物。喹唑啉部分的N1位上的取代基也被修饰，导致报道分子活性的增强。因此，化合物43（N 2-（3-氯-4-氰基苯基）-N 4-（3-（环丙基甲基）-1-异丙基-2,4-二氧-1,2,3,4-四氢喹唑啉-6-基）吗啉-2,4-二甲酰胺）显示出改善的药物暴露（小鼠AUC：1 mg⋅kg-1，po时为1289 ng⋅h⋅mL-1）。另外，在小鼠药效学模