N-[N-[(1,1-二甲基乙氧基)羰基]-2-甲基丙氨酰]-D-色氨酸 | 159634-94-3

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 色氨酸类衍生物
• 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
• 中文名称: N-[N-[(1,1-二甲基乙氧基)羰基]-2-甲基丙氨酰]-D-色氨酸
• 中文别名: N-[N-[(1,1-二甲基乙氧基)羰基]- 2-甲基丙氨酰]-D-色氨酸
• 英文名称: (R)-2-(2-tert-Butoxycarbonylamino-2-methyl-propionylamino)-3-(1H-indol-3-yl)-propionic acid
• 英文别名: N-Boc-Aib-(D)-Trp-OH；(2R)-2-{2-[(tert-butoxy)carbonylamino]-2-methylpropanoylamino}-3-indol-3-ylpropanoic acid；(R)-α-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]-1H-indole-3-propanoic acid；α(R)-[[2-[[(1,1-dimethylethoxy)-carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid；(2R)-2-{2-[(tert-butoxy)carbonylamino]-2-methyl propanoylamino}-3-indole-3-ylpropanoic acid；(R)-2-(2-(tert-butoxycarbonylamino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acid；(R)-2-(2-((tert-Butoxycarbonyl)amino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acid；(2R)-3-(1H-indol-3-yl)-2-[[2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]propanoic acid
• CAS: 159634-94-3
• 化学式: C₂₀H₂₇N₃O₅
• 分子量: 389.451
• InChiKey: DSCBSBPYDCIRPP-OAHLLOKOSA-N

物化性质

• 沸点：
  664.2±55.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  N-[N-[(1,1-二甲基乙氧基)羰基]-2-甲基丙氨酰]-D-色氨酸 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 阿拉莫林
  参考文献：
  名称：

  A Practical Synthesis of the Pseudotripeptide RC-1291

  摘要：

  The rapid process development of a scaleable synthesis of the pseudotripeptide RC-1291 for preclinical and clinical evaluation is described. By employing a nontraditional N-to-C coupling strategy, the peptide chain of RC-1291 was assembled in high yield, with minimal racemization and in an economical manner by introducing the most expensive component last. A one-pot deprotection/crystallization procedure was developed for the isolation of RC-1291 free base, which afforded the target compound in excellent yield and with a purity of > 99.5% without chromatographic purification.

  DOI：

  10.1021/op0502506
• 作为产物：
  描述：

  D-色氨酸 在 N-甲基吗啉 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 生成 N-[N-[(1,1-二甲基乙氧基)羰基]-2-甲基丙氨酰]-D-色氨酸
  参考文献：
  名称：

  Treatment of insulin resistance with growth hormone secretagogues

  摘要：

  这项发明涉及治疗哺乳动物的胰岛素抵抗方法，包括向该哺乳动物施用化合物I的有效量，其中变量在规范中定义，或其立体异构混合物、对映异构体富集物、对映异构体纯物、对映体富集物或对映体纯异构体，或其药学上可接受的盐和前药。化合物I是生长激素分泌素，因此对于增加内源生长激素水平是有用的。在另一个方面，这项发明提供了一些在合成上述化合物中有用的中间体，以及对合成所述中间体和化合物I有用的某些过程。这项发明进一步涉及方法，包括向人类或其他动物施用功能性生长抑素拮抗剂，如α-2肾上腺素受体激动剂和化合物I的组合。

  公开号：

  US06448263B1

文献信息

• Spiro piperidines and homologs promote release of growth hormone
  申请人：Merck & Co., Inc.

  公开号：US05578593A1

  公开（公告）日：1996-11-26

  There are disclosed certain novel compounds identified as spiro piperidines and homologs which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such spiro compounds as the active ingredient thereof are also disclosed.

  已披露某些新型化合物，被确定为螺环哌啶和同系物，可以促进人类和动物体内生长激素的释放。这种特性可以用于促进食用动物的生长，使可食用肉制品的生产更加高效，在人类中，可用于治疗生长激素分泌不足所导致的生理或医学状况，如生长激素缺乏儿童的矮小身材，并用于治疗通过生长激素的合成效应得到改善的医学状况。还披露了含有这种螺环化合物作为活性成分的促生长激素组合物。
• Spiro piperidines and homologs which promote release of growth hormone
  申请人：Merck & Co., Inc.

  公开号：US05536716A1

  公开（公告）日：1996-07-16

  There are disclosed certain novel compounds identified as spiro piperidines and homologs which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such spiro compounds as the active ingredient thereof are also disclosed.

  已披露了某些新颖的化合物，被识别为螺环哌啶和同系物，可以促进人类和动物体内生长激素的释放。这种特性可用于促进食用动物的生长，使可食肉制品的生产更加高效，在人类中，可用于治疗生长激素分泌不足所导致的生理或医学状况，如生长激素缺乏儿童的矮小身材，并用于治疗通过生长激素的合成效应改善的医学状况。还披露了含有这些螺环化合物作为活性成分的促生长激素释放组合物。
• Growth hormone secretagogues
  申请人：Eli Lilly and Company

  公开号：US06828331B1

  公开（公告）日：2004-12-07

  What is disclosed are growth hormone secretagogues, and their uses, of the formula wherein R1 is C6H5CH2OCH2—, C6H5 (CH2)3— or indol-3-ylmethyl; Y is pyrrolidin-1-yl, 4-C1-C6 alkylpiperidin-1-yl or NR2R2; R2 are each independently a C1 to C6 alkyl; R3 is 2-napthyl or phenyl para-substituted by W; W is H, F, CF3, C1-C6 alkoxy or phenyl; and R4 is H or CH3, or a pharmaceutically acceptable salt or solvate thereof.

  揭示的是生长激素促分泌素及其用途的公式，其中R1为 O —，C6H5(CH2)3—或吲哚-3-基甲基；Y为吡咯烷-1-基，4-C1-C6烷基哌啶-1-基或NR2R2；R2各自独立为C1到C6烷基；R3为2-萘基或对位由W取代的苯基；W为H，F，CF3，C1-C6烷氧基或苯基；R4为H或CH3，或其药用可接受的盐或溶剂。
• Synthesis and biological activities of phenyl piperazine- based peptidomimetic growth hormone secretagogues
  作者：Khaled J. Barakat、Kang Cheng、Wanda W.-S. Chan、Bridget S. Butler、Thomas M. Jacks、Klaus D. Schleim、Donald F. Hora、Gerard J. Hickey、Roy G. Smith、Arthur A. Patchett、Ravi P. Nargund

  DOI：10.1016/s0960-894x(98)00238-8

  日期：1998.6

  A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.

  通过尝试模仿分别为4和1的螺二氢茚基哌啶和螺二氢吲哚磺酰胺特权结构中的苯基取代基排列，发现了一种新型的，基于口服活性的苯基哌嗪基的GH促分泌剂。这些化合物中最好的18种（EC50 = 2.8 nM）几乎可以与MK-0677一样有效地从大鼠垂体细胞释放GH。
• 3-SPIROCYCLIC PIPERIDINE DERIVATIVES AS GHRELIN RECEPTOR AGONISTS
  申请人：Ambarkhane Ameet Vijay

  公开号：US20120302540A1

  公开（公告）日：2012-11-29

  The invention relates to derivatives of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a disorder or a disease mediated by the ghrelin receptor.

  该发明涉及公式（I）的衍生物，其中取代基如规范中定义；制备这种衍生物的过程；包含这种衍生物的药物组合物；将这种衍生物作为药物；将这种衍生物用于治疗由胃泌素受体介导的疾病或障碍。