methyl 6-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)nicotinate | 1064001-63-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 6-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)nicotinate
• 英文别名: N-(2-t-butoxycarbonylaminophenyl)-5-methoxycarbonylpyridine-2-carboxylic acid amide；methyl 6-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]carbamoyl]pyridine-3-carboxylate
• CAS: 1064001-63-3
• 化学式: C₁₉H₂₁N₃O₅
• 分子量: 371.393
• InChiKey: WEDUFVKWDGSVHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 6-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)nicotinate 在 水 、 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以81%的产率得到6-((2-((tert-butoxycarbonyl)amino)phenyl)carbamoyl)nicotinic acid
  参考文献：
  名称：

  发现新型吲哚胺2,3-双加氧酶1（IDO1）和组蛋白脱乙酰基酶（HDAC）双重抑制剂。

  摘要：

  为了同时利用免疫治疗和表观遗传抗肿瘤药，设计了第一代双吲哚胺2,3-二加氧酶1（IDO1）和组蛋白脱乙酰基酶（HDAC）抑制剂。高活性双重抑制剂10对IDO1（IC50 = 69.0 nM）和HDAC1（IC50 = 66.5 nM）均显示出优异且平衡的活性，其双重靶向机制已在癌细胞中得到验证。化合物10作为口服活性抗肿瘤药具有良好的药代动力学特征，并显着降低了血浆中的鸟尿素水平。特别地，它在鼠LLC肿瘤模型中显示出优异的体内抗肿瘤功效，且毒性低。这项概念验证研究为癌症治疗提供了一种新颖的策略。

  DOI：

  10.1021/acsmedchemlett.7b00487
• 作为产物：
  描述：

  5-(甲氧羰基)-2-吡啶羧酸 、 N-Boc-1,2-亚苯基二胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl 6-(2-(tert-butoxycarbonylamino)phenylcarbamoyl)nicotinate
  参考文献：
  名称：

  发现新型吲哚胺2,3-双加氧酶1（IDO1）和组蛋白脱乙酰基酶（HDAC）双重抑制剂。

  摘要：

  为了同时利用免疫治疗和表观遗传抗肿瘤药，设计了第一代双吲哚胺2,3-二加氧酶1（IDO1）和组蛋白脱乙酰基酶（HDAC）抑制剂。高活性双重抑制剂10对IDO1（IC50 = 69.0 nM）和HDAC1（IC50 = 66.5 nM）均显示出优异且平衡的活性，其双重靶向机制已在癌细胞中得到验证。化合物10作为口服活性抗肿瘤药具有良好的药代动力学特征，并显着降低了血浆中的鸟尿素水平。特别地，它在鼠LLC肿瘤模型中显示出优异的体内抗肿瘤功效，且毒性低。这项概念验证研究为癌症治疗提供了一种新颖的策略。

  DOI：

  10.1021/acsmedchemlett.7b00487

文献信息

• [EN] NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES<br/>[FR] NOUVEAUX COMPOSÉS BIFONCTIONNELS QUI INHIBENT LES PROTÉINES KINASES ET LES HISTONES DÉSACÉTYLASES
  申请人：4SC AG

  公开号：WO2009063054A1

  公开（公告）日：2009-05-22

  The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth.

  本发明涉及公式I的双功能化合物或其药用可接受的盐或溶剂A-L-B（I），其中A是组蛋白去乙酰化酶（HDAC）抑制基团，L是单键或连接基团，B是蛋白激酶抑制基团。根据公式（I）的双功能化合物可用于治疗恶性和非恶性肿瘤以及与异常细胞生长相关的疾病。
• INTRAOCULAR PRESSURE-LOWERING AGENT COMPRISING COMPOUND HAVING HISTONE DEACETYLASE INHIBITOR EFFECT AS ACTIVE INGREDIENT
  申请人：Yoneda Shinji

  公开号：US20100056522A1

  公开（公告）日：2010-03-04

  An object of the present invention is to find a novel pharmacological effect of a compound having an HDAC inhibitory effect. The compound having an HDAC inhibitory effect of the invention has an excellent effect of cell morphological change on trabecular meshwork cells and/or effect of intraocular pressure reduction, and is therefore useful as a preventive and/or therapeutic agent for a disease considered to be associated with aqueous humor circulation and/or intraocular pressure, particularly as a preventive and/or therapeutic agent for glaucoma or ocular hypertension.

  本发明的目的是发现一种具有HDAC抑制作用的化合物的新药理作用。本发明中具有HDAC抑制作用的化合物在小梁网细胞的细胞形态改变和/或眼内压降低方面具有优异的效果，因此可作为预防和/或治疗与房水循环和/或眼内压有关的疾病的药物，特别是作为青光眼或眼压增高的预防和/或治疗药物。
• NOVEL PYRIDINECARBOXYLIC ACID (2-AMINOPHENYL) AMIDE DERIVATIVE HAVING UREA STRUCTURE
  申请人：Mogi Hiroyuki

  公开号：US20100063045A1

  公开（公告）日：2010-03-11

  Objects of the present invention are to study the synthesis of a novel pyridinecarboxylic acid (2-aminophenyl)amide derivative having a novel urea structure and to find a pharmacological effect of the derivative. The invention provides a compound represented by the formula (1) or a salt thereof. In the formula, R 1 and R 2 represent a hydrogen atom, a lower alkyl group or the like; R 3 represents a hydroxy group, a lower alkoxy group, a lower cycloalkyloxy group, an aryloxy group, a carboxy group, a lower alkoxycarbonyl group, —OCONR a R b , —NR c R d or the like; R 4 and R 5 represent a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group or the like; R a and R b represent a hydrogen atom, a lower alkyl group, a lower cycloalkyl group, an aryl group, a heterocyclic group or the like; R c and R d represent a hydrogen atom, a lower alkyl group, a lower cycloalkyl group, an aryl group or the like; X represents a lower alkylene group; Y represents a single bond, a lower alkylene group; W 1 -W 2 represents N—C or C—N; and l and m represent 0, 1, 2 or 3.

  本发明的目的是研究一种具有新型脲结构的吡啶羧酸（2-氨基苯基）酰胺衍生物的合成，并找到该衍生物的药理作用。该发明提供了由式（1）或其盐所表示的化合物。在该式中，R1和R2表示氢原子、低碳基或类似物；R3表示羟基、低烷氧基、低环烷氧基、芳氧基、羧基、低烷氧羰基、-OCONRaRb、-NRcRd或类似物；R4和R5表示卤素原子、低碳基、羟基、低烷氧基或类似物；Ra和Rb表示氢原子、低碳基、低环烷基、芳基、杂环基或类似物；Rc和Rd表示氢原子、低碳基、低环烷基、芳基或类似物；X表示低碳烷基；Y表示单键、低碳烷基；W1-W2表示N-C或C-N；l和m表示0、1、2或3。
• NOVEL BIFUNCTIONAL COMPOUNDS WHICH INHIBIT PROTEIN KINASES AND HISTONE DEACETYLASES
  申请人：Bar Thomas

  公开号：US20110065734A1

  公开（公告）日：2011-03-17

  The present invention relates to a bifunctional compound of formula I or its pharmaceutically acceptable salts or solvates A-L-B (I) wherein A is a histone deacetylase (HDAC) inhibitory moiety, L is a single bond or a linker group and B is a protein kinase inhibitory moiety. The bifunctional compound according to formula (I) is useful for the treatment of malignant and non-malignant neoplasia and diseases related to abnormal cell growth.

  本发明涉及一种式I的双功能化合物或其药学上可接受的盐或溶剂A-L-B(I)，其中A是组蛋白去乙酰化酶（HDAC）抑制基团，L是单键或连接基团，B是蛋白激酶抑制基团。根据式（I）的双功能化合物对于治疗恶性和非恶性肿瘤以及与异常细胞生长相关的疾病非常有用。
• Pyridinecarboxylic acid (2-aminophenyl) amide derivative having urea structure
  申请人：Santen Pharmaceutical Co., Ltd.

  公开号：US08012972B2

  公开（公告）日：2011-09-06

  Objects of the present invention are to study the synthesis of a novel pyridinecarboxylic acid (2-aminophenyl)amide derivative having a novel urea structure and to find a pharmacological effect of the derivative. The invention provides a compound represented by the formula (1) or a salt thereof. In the formula, R1 and R2 represent a hydrogen atom, a lower alkyl group or the like; R3 represents a hydroxy group, a lower alkoxy group, a lower cycloalkyloxy group, an aryloxy group, a carboxy group, a lower alkoxycarbonyl group, —OCONRaRb, —NRcRd or the like; R4 and R5 represent a halogen atom, a lower alkyl group, a hydroxy group, a lower alkoxy group or the like; Ra and Rb represent a hydrogen atom, a lower alkyl group, a lower cycloalkyl group, an aryl group, a heterocyclic group or the like; Rc and Rd represent a hydrogen atom, a lower alkyl group, a lower cycloalkyl group, an aryl group or the like; X represents a lower alkylene group; Y represents a single bond, a lower alkylene group; W1-W2 represents N—C or C—N; and l and m represent 0, 1, 2 or 3.

  本发明的目的是研究合成一种具有新型脲结构的吡啶羧酸（2-氨基苯基）酰胺衍生物，并找到该衍生物的药理作用。该发明提供了由式（1）或其盐所表示的化合物。在该式中，R1和R2表示氢原子、低碳基或类似物；R3表示羟基、低烷氧基、低环烷氧基、芳氧基、羧基、低烷氧羰基、-OCONRaRb、-NRcRd或类似物；R4和R5表示卤素原子、低碳基、羟基、低烷氧基或类似物；Ra和Rb表示氢原子、低碳基、低环烷基、芳基、杂环基或类似物；Rc和Rd表示氢原子、低碳基、低环烷基、芳基或类似物；X表示低碳代基；Y表示单键、低碳代基；W1-W2表示N-C或C-N；l和m表示0、1、2或3。