(S)-2-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-2-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
• 英文别名: (S)-Atc；(2S)-2-azaniumyl-3,4-dihydro-1H-naphthalene-2-carboxylate
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: CDULPPOISZOUTK-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  替群妥英 在 盐酸 、 sodium hydroxide 、 三氟乙酸 作用下， 以 various solvent(s) 为溶剂， 反应 52.0h， 生成 (S)-2-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
  参考文献：
  名称：

  构象受限的deltorphin类似物在位置3具有2-氨基四氢-2-羧酸。

  摘要：

  设计高活性和高度选择性δ阿片类肽的两种方法被用于获得具有改变的疏水和立体电子性质的新deltorpin类似物。合成了Deltorphin I和II类似物，涉及在地址域的5和6位上用Ile代替Val取代，在信息域用2-氨基四氢-2-羧酸（Atc）代替Phe。肽在MVD分析中为亚纳摩尔范围内的激动剂，在GPI分析中为微摩尔或更高范围内的激动剂，显示出对delta受体的选择性非常高。在使用选择性tri化的阿片样物质配体的放射性受体结合试验中可以观察到非常相似的趋势。（R）-和（S）-Atc-deltoriphins在结合试验中显示出相似的Ki值，几乎完全丧失了结合的立体特异性。构象研究提供了证据，证明当Phe3被（S）-或（R）-Atc取代时，骨架构象平衡几乎没有受到干扰。Atc约束的使用提供了额外的证据，表明在与delta受体相互作用期间，残基3的侧链在chi 1处采用反式构象。

  DOI：

  10.1021/jm9602726

文献信息

• [EN] BACKBONE-CYCLIZED PEPTIDOMIMETICS<br/>[FR] PEPTIDOMIMÉTIQUES À SQUELETTE CYCLISÉ
  申请人：POLYPHOR AG

  公开号：WO2016162127A1

  公开（公告）日：2016-10-13

  Novel backbone-cyclized peptidomimetics of the general formula cyclo[-P1-P2-P3-P4-P5-P6-P7-P8-T1-T2-] (I) wherein the single elements T or P are α-amino acid residues connected in either direction which, depending on their positions in the chain, are as defined in the description and the claims, and salts thereof, have the property to modulate the GLP-1 receptor. They can be used as medicaments to treat, prevent, or delay the onset of diseases, disorders or conditions in which modulation of the human GLP-1 receptor is beneficial, such as type 2 diabetes. These backbone-cyclized peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  新型的骨架环化肽类似物的一般公式为cyclo[-P1-P2-P3-P4-P5-P6-P7-P8-T1-T2-]（I），其中单个元素T或P是α-氨基酸残基，以任一方向连接，根据它们在链中的位置，在描述和权利要求中定义，以及其盐，具有调节GLP-1受体的特性。它们可用作药物治疗、预防或延缓调节人类GLP-1受体有益的疾病、紊乱或病况，如2型糖尿病。这些骨架环化肽类似物可通过基于混合固相和溶液相合成策略的过程制造。
• Mitsunobu Approach to the Synthesis of Optically Active α,α-Disubstituted Amino Acids
  作者：Jonathan E. Green、David M. Bender、Stona Jackson、Martin J. O’Donnell、James R. McCarthy

  DOI：10.1021/ol802325h

  日期：2009.2.19

  α-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the α-carbon. Several α,α-disubstituted amino acids were synthesized in high overall chemical yield and optical purity.

  已知立体化学构型的手性叔α-羟基酯通过与​​HN 3的Mitsunobu反应转化为α-叠氮基酯。已表明，使用1,1-（偶氮二羰基）二哌啶（ADDP）和三甲基膦（PMe 3）可以在室温下以高化学收率进行该反应的优化。在α-碳处观察到构型完全反转。以高的总化学产率和光学纯度合成了几种α，α-二取代的氨基酸。
• PEPTIDES AND PEPTIDOMIMETIC COMPOUNDS, THE MANUFACTURING THEREOF AS WELL AS THEIR USE FOR PREPARING A THERAPEUTICALLY AND/OR PREVENTIVELY ACTIVE PHARMACEUTICAL COMPOSITION
  申请人：PETZELBAUER Peter

  公开号：US20100081787A1

  公开（公告）日：2010-04-01

  Peptides, peptidomimetics and derivatives thereof of the general formula I: H 2 N-GHRPX 1 - β -X 4 X 5 X 6 X 7 X 8 X 9 X 10 -X 11 (I), in which X 1 -X 10 denote one of the 20 genetically coded amino acids, wherein X 8 , X 9 and X 10 may also denote a single chemical bond; X 11 denotes OR 1 in which R 1 equals hydrogen or (C 1 -C 10 ) alkyl NR 2 R 3 with R 2 and R 3 are equal or different and denote hydrogen, (C 1 -C 10 ) alkyl, or a residue —W-PEG 5-60K , in which the PEG residue is attached via a suitable spacer W to the N-atom, or a residue NH—Y-Z-PEG 5-60K , in which Y denotes a chemical bond or a genetically coded amino acids from the group S, C, K or R and Z denotes a spacer, via which a polyethylene glycol (PEG)-residue can be attached, and their physiologically acceptable salts, and β denotes an amino acid, or a peptidomimetic element, which induces a bend or turn in the peptide backbone.

  通用公式I：H2N-GHRPX1-β-X4X5X6X7X8X9X10-X11(I)中的肽、肽类似物和衍生物，其中X1-X10表示20种遗传编码的氨基酸之一，其中X8、X9和X10也可以表示单一化学键；X11表示OR1，其中R1等于氢或(C1-C10)烷基NR2R3，其中R2和R3相同或不同，表示氢、(C1-C10)烷基，或者残基—W-PEG5-60K，其中PEG残基通过适当的间隔物W连接到N-原子，或者残基NH—Y-Z-PEG5-60K，其中Y表示化学键或来自S、C、K或R组的遗传编码氨基酸，Z表示间隔物，通过该间隔物可以连接聚乙二醇（PEG）残基，并且它们的生理上可接受的盐，β表示氨基酸或诱导肽骨架中弯曲或转弯的肽类或肽类似元素。
• TEMPLATE-FIXED PEPTIDOMIMETICS WITH CCR10 ANTAGONISTIC ACTIVITY
  申请人：Jung Francoise

  公开号：US20120283168A1

  公开（公告）日：2012-11-08

  Novel template-fixed β-hairpin peptidomimetics of the general formula (I) wherein the single elements T or P are α-amino acid residues connected in either direction which, depending on their positions in the chain, are as defined in the description and the claims, and salts thereof, have the property to antagonize the receptor CCR10. They can be used as medicaments to treat or prevent diseases or conditions in the area of dermatological and cutaneous disorders, inflammation, allergic disorders, respiratory diseases, diseases of the gastro-intestinal tract, ophthalmic diseases, haematology and cancer. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  具有以下一般式(I)的小说模板固定β-发夹仿生肽，其中单个元素T或P是α-氨基酸残基，可以连接在任何方向上，具体取决于它们在链中的位置，如描述和索赔中所定义，及其盐，具有拮抗受体CCR10的特性。它们可用作药物，用于治疗或预防皮肤病和皮肤疾病、炎症、过敏性疾病、呼吸道疾病、胃肠道疾病、眼科疾病、血液学和癌症等领域。这些β-发夹仿生肽可以通过基于混合固相和溶液相合成策略的过程制备。
• Peptidylaminodiols
  申请人：ABBOTT LABORATORIES

  公开号：EP0189203A2

  公开（公告）日：1986-07-30

  The invention relates to renin inhibiting compounds of the formula: wherein R10 is A is hydrogen or an N-protecting group; w is 0 or 1; B is hydrogen, hydroxy, NH, N-alkyl, loweralkyl or arylalkyl; with the proviso that when w is 1, B is NH and when w is 0, B is hydrogen, hydroxy, loweralkyl or arylalkyl; R1is loweralkyl or lipophilic or aromatic or hydrophilic amino acid side chains; m is 1-3; n is 1-3; p is 1-3; q is 1-3; s is 1-3; t is 0-2; R2 is hydrogen or loweralkyl; R3 and R4 are independently selected from loweralkyl, lipophilic or aromatic amino acid side chains; R5 and R7 are independently selected from hydrogen or loweralkyl; and R6 is hydrogen, loweralkyl, vinyl, arylalkyl or wherein R8 is hydrogen or loweralkyl, X is O, NH or S and R9 is hydrogen, loweralkyl or alkanoyl or XR9 together can be loweralkylsulfonyl, N3 or Cl.

  本发明涉及式中的肾素抑制化合物： 其中 R10 是 A是氢或N-保护基；w是0或1；B是氢、羟基、NH、N-烷基、低级烷基或芳基烷基；但当w是1时，B是NH，当w是0时，B是氢、羟基、低级烷基或芳基烷基；R1是低级烷基或亲油性或芳香性或亲水性氨基酸侧链；m是1-3；n是1-3；p是1-3；q是1-3；s是1-3；t是0-2；R2是氢或低级烷基；R3 和 R4 独立选自低烷基、亲油或芳香族氨基酸侧链；R5 和 R7 独立选自氢或低烷基；R6 是氢、低烷基、乙烯基、芳烷基或其中 R8 是氢或低烷基，X 是 O、NH 或 S，R9 是氢、低烷基或烷酰基或 XR9 合在一起可以是低烷基磺酰基、N3 或 Cl。