N2-[N-acetyl-3-(2-naphthyl)-D-alanyl]-L-arginyl-3-(2-naphthyl)-D-alaninamide | 475498-27-2

• 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: N2-[N-acetyl-3-(2-naphthyl)-D-alanyl]-L-arginyl-3-(2-naphthyl)-D-alaninamide
• 英文别名: Ac-D-2Nal-Arg-D-2Nal-NH2；(2S)-2-[[(2R)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-N-[(2R)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]-5-(diaminomethylideneamino)pentanamide
• CAS: 475498-27-2
• 化学式: C₃₄H₃₉N₇O₄
• 分子量: 609.728
• InChiKey: FJFLYSMWSRRMRO-FRXPANAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  195
• 氢给体数：
  6
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  Ac-D-2-Nal-Arg(Z)2-D-2-Nal-NH2 在 palladium dihydroxide 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 15.0h， 生成 N2-[N-acetyl-3-(2-naphthyl)-D-alanyl]-L-arginyl-3-(2-naphthyl)-D-alaninamide
  参考文献：
  名称：

  Identification of Arginine Analogues as Antagonists and Agonists for the Melanocortin-4 Receptor

  摘要：

  在本研究中，为了探索有效的小分子黑皮质素-4 (MC4) 受体配体，我们发现三肽 3a，含有 D-Phe-Arg-2-Nal（Nal；萘丙氨酸）序列，对 MC4 受体表现出中等亲和力。结构优化导致鉴定出对 MC4 受体具有高亲和力的化合物，即三肽 3e，其对 MC4 受体的亲和力比先导化合物 3a 高 70 倍。此外，为了进一步降低三肽3e的肽特性，我们发现二肽3g对MC4受体表现出相对较高的亲和力。此外，在这些类似物中，发现第 7 位 Nal 残基萘基环的取代位置（1' 与 2'）对于区分激动剂和拮抗剂活性很重要。本文描述了作为 MC4 受体配体的精氨酸类似物的合成及其构效关系。

  DOI：

  10.1248/cpb.55.1232

文献信息

• ARGININE DERIVATIVES
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：EP1388537A1

  公开（公告）日：2004-02-11

  An arginine derivative represented by the formula: [wherein Ar1 and Ar2 may be the same or different, and are each a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group or a heteroaromatic ring group containing one or more of nitrogen, oxygen and sulfur atoms; Y1 is a C1-5 alkylene group, a C2-5 alkenylene group or a single bond; and the C1-5 alkylene group optionally contains a carbon atom substituted with a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group or a C1-10 acylamino group; Q is a carbonyl group or a sulfonyl group; Y2 is a C1-5 alkylene group; the C1-5 alkylene group optionally contains a carbon atom substituted with a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group, a hydroxyl group, a carbamoyl group, a mono-C1-5 alkylamide group or a di-C1-5 alkylamide group], or a pharmaceutically acceptable salt thereof. There are provided peptidergic ligands which have the affinity and specificity to MC4 receptor.

  一种以以下式表示的精氨酸衍生物：[其中Ar1和Ar2可以相同或不同，分别为苯基，取代苯基，萘基，取代萘基或含有一个或多个氮，氧和硫原子的杂环芳基环；Y1为C1-5烷基，C2-5烯基烷基或单键；C1-5烷基可以选用含有苯基，取代苯基，萘基，取代萘基或C1-10酰胺基的碳原子进行取代；Q为羰基或磺酰基；Y2为C1-5烷基；C1-5烷基可以选用含有苯基，取代苯基，萘基，取代萘基，羟基，氨基甲酰基，单C1-5烷基酰胺基或双C1-5烷基酰胺基的碳原子进行取代]，或其药学上可接受的盐。提供了具有MC4受体亲和力和特异性的肽类配体。
• Arginine derivatives
  申请人：——

  公开号：US20040147567A1

  公开（公告）日：2004-07-29

  An arginine derivative represented by the formula: 1 [wherein Ar 1 and Ar 2 may be the same or different, and are each a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group or a heteroaromatic ring group containing one or more of nitrogen, oxygen and sulfur atoms; Y 1 is a C 1-5 alkylene group, a C 2-5 alkenylene group or a single bond; and the C 1-5 alkylene group optionally contains a carbon atom substituted with a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group or a C 1-10 acylamino group; Q is a carbonyl group or a sulfonyl group; Y 2 is a C 1-5 alkylene group; the C 1-5 alkylene group optionally contains a carbon atom substituted with a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group, a hydroxyl group, a carbamoyl group, a mono-C 1-5 alkylamide group or a di-C 1-5 alkylamide group], or a pharmaceutically acceptable salt thereof. There are provided peptidergic ligands which have the affinity and specificity to MC 4 receptor.

  一种精氨酸衍生物，其分子式为 1 其中 Ar 1 和 Ar 2 可以相同或不同，且各自为苯基、取代苯基、萘基、取代萘基或含有一个或多个氮、氧和硫原子的杂芳环基团；Y 1 是一个 C 1-5 烯基、C 2-5 烯基或单键；而 C 1-5 烯基可选择包含一个被苯基、取代苯基、萘基、取代萘基或 C 1-10 酰氨基； Q 是羰基或磺酰基； Y 2 是一个 C 1-5 烯基；C 1-5 烯基可选择包含一个被苯基、取代苯基、萘基、取代萘基、羟基、氨基甲酰基、单-C 1-5 烷基酰胺基团或二-C 1-5 烷基酰胺基团或二-C 1-5 烷基酰胺基团或其药学上可接受的盐。 提供的肽配体对 MC 4 受体的亲和性和特异性。
• Identification of Arginine Analogues as Antagonists and Agonists for the Melanocortin-4 Receptor
  作者：Dai Nozawa、Taketoshi Okubo、Shigeyuki Chaki、Shigeru Okuyama、Atsuro Nakazato

  DOI：10.1248/cpb.55.1232

  日期：——

  In the present study, conducted to explore potent and small molecular melanocortin-4 (MC4) receptor ligands, we found that tripeptide 3a, containing a D-Phe-Arg-2-Nal (Nal; naphthylalanine) sequence, exhibited a moderate affinity for the MC4 receptor. Structural optimization led to the identification of a compound with a high affinity for the MC4 receptor, namely, tripeptide 3e, which showed a 70-fold higher affinity for the MC4 receptor than the lead compound 3a. Moreover, in an effort to further reduce the peptidic characters of tripeptide 3e, we found that dipeptide 3g exhibited a relatively high affinity for the MC4 receptor. Furthermore, in these analogues, the substituted position (1′ vs. 2′) of the naphthyl ring of Nal residue at position 7 was found to be important for the differentiation of agonist and antagonist activity. The synthesis and structure–activity relationships of the arginine analogues as MC4 receptor ligands were described in this paper.

  在本研究中，为了探索有效的小分子黑皮质素-4 (MC4) 受体配体，我们发现三肽 3a，含有 D-Phe-Arg-2-Nal（Nal；萘丙氨酸）序列，对 MC4 受体表现出中等亲和力。结构优化导致鉴定出对 MC4 受体具有高亲和力的化合物，即三肽 3e，其对 MC4 受体的亲和力比先导化合物 3a 高 70 倍。此外，为了进一步降低三肽3e的肽特性，我们发现二肽3g对MC4受体表现出相对较高的亲和力。此外，在这些类似物中，发现第 7 位 Nal 残基萘基环的取代位置（1' 与 2'）对于区分激动剂和拮抗剂活性很重要。本文描述了作为 MC4 受体配体的精氨酸类似物的合成及其构效关系。