BOC-D-色氨酸 | 5241-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: BOC-D-色氨酸
• 中文别名: N-(叔丁氧羰基)-D-色氨酸；叔丁氧羰基-D-色氨酸；N-叔丁氧羰基-D-色氨酸；N(Alpha)-Boc-D-色氨酸；N-Boc-D-色氨酸；N-BOC-D-色氨酸
• 英文名称: Boc-D-Trp-OH
• 英文别名: (tert-butoxycarbonyl)-D-tryptophan；N-tert-butoxycarbonyl-D-tryptophan；N-Boc-D-tryptophan；Boc-D-tryptophan；N-[(tert-Butoxy)carbonyl]-D-tryptophan；(2R)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 5241-64-5
• 化学式: C₁₆H₂₀N₂O₄
• 分子量: 304.346
• InChiKey: NFVNYBJCJGKVQK-CYBMUJFWSA-N

物化性质

• 稳定性/保质期：

  常温常压下稳定，为白色晶体粉末。

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  91.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  BOC-D-色氨酸 在 potassium tert-butylate 、 水 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.33h， 生成 1-甲基-D-色氨酸
  参考文献：
  名称：

  Pentapeptides for the treatment of small cell lung cancer: Optimisation by N ind -alkyl modification of the tryptophan side chain

  摘要：

  The pentapeptide, tert-Prenyl4th-NH2 (DMePhe-DTrp-Phe-DTrp(N-tert-prenyl)-Leu-NH2), has recently been reported by our group to exhibit properties of substance P (SP) antagonist G against small cell lung cancer (SCLC). In this study, we undertook a systematic structure activity investigation to optimise this lead compound to improve its in vitro anti-tumour activity and biocompatibility. A series of D-tryptophan (D-Trp) derivatives were synthesised, with a range of aliphatic N-alkyl chains (methyl to pentyl) on the indole nitrogen (N-ind). These were incorporated into the pentapeptide sequence by substitution of the N-ind-tert-prenylated D-Trp 4th residue with the N-ind-alkylated D-Trp derivatives. These pentapeptides were significantly more potent than tert-Prenyl4th-NH2, with the N-ind-butyl modification generating the most cytotoxic peptides. Compared to tert-Prenyl4th-NH2, a single butyl modification on the 4th D-Trp residue (Butyl4th-NH2) showed a similar to 3 fold enhancement in cytotoxicity in either the chemo-naive H69 or the DMS79 (originating from a patient treated with chemotherapeutics and radiation therapy) SCLC cell lines. In addition, the di-butylated sequence on the 2nd and 4th D-Trp residues (Butyl2nd.4th-NH2) gave similar to 4.5 times higher cytotoxicity against the H69 cell line and a similar to 2 fold increase against the DMS79 cell line, compared to tert-Prenyl4th-NH2. The favoured position for butyl modification was the 4th D-Trp residue, as the Butyl2nd-NH2 peptide gave lower cytotoxicity on both cell lines. Butylated peptide sequences, when exposed to neat mouse plasma for 24 h at 37 degrees C, were found to resist degradation with >80% remaining intact compared to similar to 58% for tert-Prenyl4th-NH2. The degradation pathway in plasma occurs via de-amidation of the C-terminus, confirmed by mass spectrometry and RP-HPLC analysis. The butyl modification also conferred resistance to metabolism when tested using S9 liver fraction from mouse. The optimum analogue responsive against the DMS79 cell line was the Butyl4th-NH2 pentapeptide, which revealed a concentration dependent increase in apoptosis: the level of late apoptotic cells rose from similar to 36% at 2 mu M to similar to 96% at 6 mu M, as determined by flow cytometry, compared to the unmodified peptide that showed no such effect. Concluding, the butyl substitutions offered the best perspective for high cytotoxicity, induction of apoptosis and metabolic compatibility thereby comprising an improved broad spectrum SP antagonist candidate for treatment of SCLC. (C) 2017 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.05.053
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 D-色氨酸 在 碳酸氢钠 、 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.25h， 以96%的产率得到BOC-D-色氨酸
  参考文献：
  名称：

  (+)-诺卡二嗪 B 及其类似物的仿生全合成

  摘要：

  Nocardioazines A 和 B 是异戊二烯化的、具有生物活性的吡咯并吲哚啉天然产物，从诺卡氏菌中分离出来，具有不对称的环- d -Trp- d -Trp DKP 核心。基于我们更深入的生物合成理解，(+)-诺卡二嗪 B 的仿生全合成仅需 7 个步骤即可完成，总产率为 23.2%。该途径使用相同数量的步骤并以相似的效率访问 (+)-nocardioazine B 的区域选择性和立体选择性 C3-异戊二烯化类似物。成功的策略要求尽早执行仿生 C3-异戊二烯化步骤。使用未经保护的色氨酸羧酸导致形成关键中间体exo - 12a的高非对映选择性、exo - 12b和exo - 12c (>19:1)。有证据表明，N 1-甲基化导致异戊二烯化反应分叉，产生 C2-正异戊二烯化异构体。Nocardioazine A 具有异戊二烯-环氧化物桥，在多重耐药的哺乳动物结肠癌细胞中抑制 P-糖蛋白 (P-gp)

  DOI：

  10.1021/acs.joc.2c01120
• 作为试剂：
  描述：

  C,C,C-Trifluoro-N-[3-(6-hydroxy-2-methyl-4-oxo-4H-chromen-3-yl-methyl)phenyl]methanesulfonamide 在 4-二甲氨基吡啶 、 lithium hydroxide 、 sodium tetrahydroborate 、 cerium(III) chloride 、 TEA 、 L-Selectride 、 BOC-D-色氨酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 C,C,C-Trifluoro-N-{3-[(2S,3R,4S)-6-(6-fluoro-benzothiazol-2-ylmethoxy)-4-hydroxy-2-methyl-chroman-3-ylmethyl]-phenyl}-methanesulfonamide
  参考文献：
  名称：

  Development of new chromanol antagonists of leukotriene D4

  摘要：

  By addressing the issues of potency and metabolism in 3, a new series of LTD, antagonists represented by (+)-26 was developed which is equipotent to clinical LTD, antagonists Zafirlukast (1) and Pranlukast (2). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00273-x

文献信息

• SUBSTITUTED CYCLOHEXYLDIAMINES
  申请人：Zemolka Saskia

  公开号：US20090247591A1

  公开（公告）日：2009-10-01

  The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain or other conditions.

  这项发明涉及具有亲和力与μ-阿片受体和ORL 1-受体的化合物，其生产方法，含有这些化合物的药物以及利用这些化合物治疗疼痛或其他疾病的用途。
• Identification of Potent Non-Peptide Somatostatin Antagonists with sst₃ Selectivity
  作者：Lydie Poitout、Pierre Roubert、Marie-Odile Contour-Galcéra、Christophe Moinet、Jacques Lannoy、Jacques Pommier、Pascale Plas、Dennis Bigg、Christophe Thurieau

  DOI：10.1021/jm0108449

  日期：2001.8.1

  Using a solution-phase parallel synthesis strategy, a series of non-peptide somatostatin analogues were prepared, and their binding affinities to the five human somatostatin receptor subtypes (sst(1-5)) were determined. Imidazolyl derivatives 2 were found to bind with moderate affinity but with high selectivity to the sst(3) receptor subtype. Further modifications of these structures led to a more

  使用溶液相平行合成策略，制备了一系列非肽生长抑素类似物，并确定了它们与五种人类生长抑素受体亚型（sst（1-5））的结合亲和力。发现咪唑基衍生物2具有中等亲和力，但对sst（3）受体亚型具有高选择性。这些结构的进一步修饰导致了更有效的配体类别，即四氢-β-咔啉衍生物4。其中，化合物4k（BN81644）和4n（BN81674）选择性结合且与sst（3）受体亚型具有高亲和力（K（i）分别为0.64和0.92 nM）。此外，4k和4n逆转了1 nM生长抑素通过sst（3）受体诱导的对环AMP积累的抑制，IC（50）分别为2.7和0.84 nM。最有效的化合物4n通过增加SRIF-14介导的cAMP积累抑制的EC（50）和2.8 nM的K（B）而显示为人类sst（3）受体的竞争性拮抗剂（其中K（B ）是将激动剂剂量反应改变2倍的拮抗剂浓度。就我们所知，这些新的衍生物是已知的第一个有效且高度选择性
• [EN] NOVEL AGENTS TARGETING CYP51<br/>[FR] NOUVEAUX AGENTS CIBLANT CYP51
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015048306A1

  公开（公告）日：2015-04-02

  The invention provides inhibitors of a sterol C14-demethylase, a new series of 4- aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) developed using structure-based drug design as well as structure -property relationship (SPR) analyses. The screening hit starting point, LP 10 (KD < 42 nM; EC50 of 0.65 μΜ), has been optimized to give the potential leads that have low nanomolar binding affinity to TcCYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts. Many of the optimized compounds have improved microsome stability, and most are selective against the T. cruzi CYP51 relative to human CYPs 1A2, 2D6 and 3A4 (<50% inhibition at 1 μΜ). A rationale for the improvement of microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of several compounds of the invention with the T. brucei CYP51 (TbCYP51) ortholog has been characterized by x-ray structure analysis. Orally active compounds and their cyclodextrin complexes have been shown to be effective against Chagas-infected mice.

  该发明提供了一种甾醇C14-去甲基酶的抑制剂，这是一种新系列基于4-氨基吡啶的首选抑制剂，通过基于结构的药物设计以及结构-性质关系（SPR）分析来瞄准Trypanosoma cruzi CYP51（TcCYP51）而开发的。筛选起始点LP 10（KD < 42 nM；EC50为0.65 μΜ）已经经过优化，产生了具有低纳摩尔级别结合亲和力和对在人类肌细胞培养的T. cruzi游离体的显著活性的潜在首选抑制剂。许多经过优化的化合物具有改善的微粒体稳定性，大多数相对于人类CYPs 1A2、2D6和3A4对T. cruzi CYP51具有选择性（在1 μΜ下<50%的抑制）。提出了改善微粒体稳定性和抑制剂对人类代谢CYP酶的选择性的理由。此外，通过X射线结构分析表征了该发明的几种化合物与T. brucei CYP51（TbCYP51）同源物的结合方式。口服活性化合物及其环糊精复合物已被证明对克氏病感染的小鼠有效。
• PHARMACEUTICAL COMPOUNDS AS INHIBITORS OF CELL PROLIFERATION AND THE USE THEREOF
  申请人：ANDERSON MARK B.

  公开号：US20100068197A1

  公开（公告）日：2010-03-18

  Disclosed are compounds of Formula I effective as cytotoxic agents. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  揭示的是作为细胞毒性剂有效的I式化合物。本发明的化合物在治疗多种临床病况中是有用的，这些病况中发生异常细胞的不受控制的生长和扩散。
• Effective enmein-type mimics of clinical candidate HAO472: Design, synthesis and biological evaluation
  作者：Xu Hu、Ziyi Bai、Jian Qiao、Haonan Li、Shengtao Xu、Xianhua Wang、Yongnan Xu、Jinyi Xu、Huiming Hua、Dahong Li

  DOI：10.1016/j.ejmech.2019.03.046

  日期：2019.6

  A series of enmein-type diterpenoid amino acid ester derivatives (14–22) were designed and synthesized according to l-alanine-(14-oridonin) ester trifluoroacetate (clinical candidate HAO472). Their antiproliferative activities were tested against SGC-7901, Bel-7402, HL-60, PC-3, A549 and K562 cancer cell lines and L-02 normal liver cells. The results showed that compound 19 possessed the most potent

  一系列enmein型的二萜类氨基酸酯衍生物（14 - 22）是根据设计并合成升-alanine-（14-冬凌草甲素）酯三氟乙酸盐（临床候选HAO472）。测试了它们对SGC-7901，Bel-7402，HL-60，PC-3，A549和K562癌细胞系和L-02正常肝细胞的抗增殖活性。结果表明，化合物19具有与IC的最有效的细胞毒性50个 s的抗人肝癌Bel-7402和慢性骨髓性白血病K562细胞和比更有效的亚微摩尔级升-alanine-（14-冬凌草甲素）酯（23）。更重要的是19 对L-02细胞显示出比母体3（IC 50 = 25.47μM）低70倍的细胞毒性，后者表现出一定的选择性。在Bel-7402细胞中进一步的机制研究表明，19可以诱导细胞凋亡，G 1期细胞周期停滞和线粒体功能障碍。caspase-3，Bax和细胞色素c上调以及pro-caspase-3，Bcl-2和Bcl-xL下

表征谱图