3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino)propionic acid | 64896-99-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino)propionic acid
• 英文别名: N-(3-chloro-1,4-dioxo-1,4-dihydro-[2]naphthyl)-β-alanine；N-(3-Chlor-1,4-dioxo-1,4-dihydro-[2]naphthyl)-β-alanin；2-β-alanyl-3-chloro-1,4-naphthoquinone；3-[(3-Chloro-1,4-dioxonaphthalen-2-yl)amino]propanoic acid
• CAS: 64896-99-7
• 化学式: C₁₃H₁₀ClNO₄
• 分子量: 279.68
• InChiKey: IOKFMLQIXSIPMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino)propionic acid 、 乙酸酐 在 对甲苯磺酸 作用下， 反应 0.08h， 以87%的产率得到N-acetyl-N-(2-chloro-1,4-naphtoquinonyl)-β-alanine
  参考文献：
  名称：

  Studies on the syntheses of condensed indole-4,7-diones. II. Synthesis of pyrrolo[1,2-a]indole-5,8-dione derivatives.

  摘要：

  甲基1,2-二氢-3H-吡咯[1,2-a]苯并[f]吲哚-5,10-二酮-11-羧酸酯（9），是通过从2,3-二氯萘醌（2）出发，经过一个包含新颖环化反应的五步骤过程合成的，该过程最终得到甲基1-乙酰基-1,2,3,4-四氢-6H-萘并[2,3-b]氮杂环庚三酮-5,7,12-三酮-6-羧酸酯（13）。

  DOI：

  10.1248/cpb.28.1071
• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 β-丙氨酸 以 水 、 二甲基亚砜 为溶剂， 以89 %的产率得到3-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-ylamino)propionic acid
  参考文献：
  名称：

  一些新型萘醌-甘氨酸/β-丙氨酸苯胺衍生物作为非共价蛋白酶体抑制剂的设计、合成和生物学评价

  摘要：

  设计、合成了一系列具有 2-氯萘醌结构作为药效单元的新型非共价甘氨酸/β-丙氨酸苯胺衍生物，并评估了它们在体外对 MCF-7 细胞系的抗增殖和抗蛋白酶体活性。根据生物活性结果，所有目标化合物均在IC 50范围内表现出抗增殖活性 = 7.10 ± 0.10–41.08 ± 0.14 μM 并且它们中的大多数表现出对呈现半胱天冬酶样 (CL)、胰蛋白酶样 (TL) 和胰凝乳蛋白酶样的三个催化亚基（β1、β2 和 β5）的不同比例的抑制功效(ChT-L) 蛋白酶体的活性。抗蛋白酶体活性评估表明，与蛋白酶体的 β1 和 β2 亚基相比，化合物优先抑制 β5 亚基。在这些化合物中，化合物7和9显示出最高的抗增殖活性，IC 50值分别为 7.10 ± 0.10 和 7.43 ± 0.25 μM。此外，化合物7在 β5 抗蛋白酶体活性方面显示出与 PI-083 先导化合物相当的效力，在 10 μM 时抑制百分比为

  DOI：

  10.1111/cbdd.14212

文献信息

• Synthesis, anticancer activity, and molecular modeling of 1,4-naphthoquinones that inhibit MKK7 and Cdc25
  作者：Igor A. Schepetkin、Alexander S. Karpenko、Andrei I. Khlebnikov、Marina O. Shibinska、Igor A. Levandovskiy、Liliya N. Kirpotina、Nadezhda V. Danilenko、Mark T. Quinn

  DOI：10.1016/j.ejmech.2019.111719

  日期：2019.12

  mitogen-activated protein kinase kinase 7 (MKK7) are enzymes involved in intracellular signaling but can also contribute to tumorigenesis. We synthesized and characterized the biological activity of 1,4-naphthoquinones structurally similar to reported Cdc25 and(or) MKK7 inhibitors with anticancer activity. Compound 7 (3-[(1,4-dioxonaphthalen-2-yl)sulfanyl]propanoic acid) exhibited high binding affinity for

  细胞分裂周期25（Cdc25）和有丝分裂原激活的蛋白激酶激酶7（MKK7）是参与细胞内信号传导的酶，但也可能有助于肿瘤发生。我们合成并表征了与报道的具有抗癌活性的Cdc25和/或MKK7抑制剂在结构上相似的1,4-萘醌的生物活性。化合物7（3-[（（1,4-二氧萘并萘-2-基）硫烷基]丙酸）对MKK7的结合亲和力高（Kd = 230 nM），大于NSC 95397的亲和力（Kd = 1.1μM） 。尽管铅皮蛋黄素对MKK7的结合亲和力较低，但该化合物和含硫衍生物4和6-8是Cdc25A和Cdc25B的有效抑制剂。相对于MKK4和Cdc25 A / B，含有苯氨基侧链的衍生物22e具有选择性，而其异构体22f是Cdc25 A / B的选择性抑制剂。对几种萘醌的对接研究突出了有关分子取向和氢键相互作用的有趣方面，这可能有助于解释该化合物对MKK7和Cdc25B的活性。还筛选了最有效的基于萘醌的MKK7和/或Cdc25
• Long-acting gonadotropin-releasing hormone analogs and methods of use thereof
  申请人：Koch Yitzhak

  公开号：US20060100154A1

  公开（公告）日：2006-05-11

  The present invention relates to the design, synthesis and biological evaluation of potent long-acting gonadotropin-releasing hormone (GnRH) analogs including agonists and antagonists comprising a GnRH peptide conjugated to emodic acid or an emodic acid derivative. These long acting analogs bind to GnRH receptors with high affinity and are devoid of any toxicity or antiproliferative effects. The present invention further relates to therapeutic uses of these GnRII analogs as contraceptives, in controlling fertility and in treating and/or preventing sex-hormone dependent diseases or conditions.

  本发明涉及设计、合成和生物评价强效长效性促性腺激素释放激素（GnRH）类似物，包括激动剂和拮抗剂，其包括将GnRH肽与大黄酸或大黄酸衍生物结合的类似物。这些长效类似物与GnRH受体结合亲和力高，没有任何毒性或抗增殖作用。本发明还涉及这些GnRII类似物作为避孕药、控制生育和治疗和/或预防性激素依赖性疾病或症状的治疗用途。
• Design, Synthesis, and Evaluation of a Long-Acting, Potent Analogue of Gonadotropin-Releasing Hormone
  作者：Shai Rahimipour、Nurit Ben-Aroya、Mati Fridkin、Yitzhak Koch

  DOI：10.1021/jm010112g

  日期：2001.10.1

  The design, synthesis, and biological evaluation of a gonadotropin-releasing hormone (GnRH) agonist, [D-Lys(6)(1,3,8-trihydroxy-6-carboxyanthraquinone)]GnRH ([D-Lys(6)(Emo)]GnRH), is described. Synthesis of this analogue was carried out in a homogeneous solution as well as on a polymer support. [D-Lys(6)(Emo)]GnRH was found to bind to rat pituitary GnRH receptors (IC50 = 0.25 nM), to induce luteinizing hormone (LH) release (ED50 = 27 pM), and to be devoid of any toxicity. This analogue also proved to be a very potent agonist in vivo and exhibited a prolonged bioactivity. Six hours after its administration to rats, LH levels were substantially higher than those of rats treated with a 10-fold higher dose of the parent peptide. Moreover, chronic treatment of adult male rats with [D-Lys(6)(Emo)]GnRH (0.1 nmol/rat) for one week resulted in a further decrease of the weight of the testes and prostate as compared to those of rats that were treated with a higher dose of [D-Lys] GnRH (1 nmol/rat). The prolonged activity of [D-Lys(6)(Emo)]GnRH may be attributed to its emodic acid moiety, which enhances the binding affinity of the analogue to human serum albumin. Indeed, we found that emodic. acid binds to human serum albumin almost completely at the examined range of concentrations.
• DREGERIS YA. YA.; LIEPINYA I. YA.; FREJMANIS YA. F., LATV. PSR ZINATNU AKAD. VESTIS. KIM.
  作者：DREGERIS YA. YA.、 LIEPINYA I. YA.、 FREJMANIS YA. F.

  DOI：——

  日期：——
• NAPHTHOQUINONE DERIVATIVES USEFUL FOR PREVENTION OF AMYLOID DEPOSITS AND TREATMENT OF DISEASES INVOLVING AMYLOIDOGENESIS
  申请人：Scherzer Roni

  公开号：US20110224184A1

  公开（公告）日：2011-09-15

  The present invention provides pharmaceutical compositions comprising substituted 1,4 naphthoquinones that are effective in preventing oligomerization of beta amyloid and subsequent pathologies associated with amyloid fibrils. These compositions are useful for the treatment of disease involving amyloidogenesis including neurodegenerative diseases such as Alzheimer's Disease or senile dementia. Particularly effective compositions comprise 1,4 naphthoquinones substituted with an amino acid residue selected from a heterocyclic or aromatic amino acid.