N1-[4-(3-cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide | 232254-87-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N1-[4-(3-cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide
• 英文别名: N1-[4-(3-Cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide；N-[4-(3-cyanoanilino)-5-nitro-6-oxo-1H-pyrimidin-2-yl]acetamide
• CAS: 232254-87-4
• 化学式: C₁₃H₁₀N₆O₄
• 分子量: 314.26
• InChiKey: BEBOFGAISREEQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  152
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N1-[4-(3-cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide 在 stannous chloride 、 sodium borohydrid 、 四乙基氯化铵 、 三氯化铁 、 溶剂黄146 、 三氯氧磷 作用下， 以 甲醇 、 ice-water 、 乙醇 、 N,N-二甲基苯胺 、 乙腈 为溶剂， 生成 3-[2-amino-6-chloro-8-(3-fluorophenyl)-9H-9-purinyl]benzonitrile
  参考文献：
  名称：

  Purine derivatives and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes

  摘要：

  本发明提供了一种新型的糖尿病和糖尿病并发症的预防或治疗剂，基于腺苷A2受体拮抗作用。由式（I）表示的嘌呤化合物及其药理学上可接受的盐或水合物具有腺苷A2受体拮抗作用，并可用于预防或治疗糖尿病和糖尿病并发症。此外，具有与上述化合物不同结构的腺苷A2受体拮抗剂，例如KW6002等，也对预防或治疗糖尿病和糖尿病并发症有效。在该式中，W为—CH2CH2—、—CH═CH—或—C≡C—；R1为：（在该式中，X为氢原子、羟基、较低的烷基基团、较低的烷氧基团等；而R5和R6相同或不同，各自代表氢原子、较低的烷基基团、环烷基基团等）等；R2为氨基等，可能被较低的烷基基团等取代；R3为环烷基基团、可选择性取代的芳基基团等；R4为较低的烷基基团等。

  公开号：

  US06579868B1
• 作为产物：
  描述：

  间氨基苯甲腈 、 N-(6-氯-5-硝基-4-氧代-1,4-二氢嘧啶-2-基)乙酰胺 在 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以94%的产率得到N1-[4-(3-cyanoanilino)-5-nitro-6-oxo-1,6-dihydro-2-pyrimidinyl]acetamide
  参考文献：
  名称：

  2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure–activity relationships of effects on hepatic glucose production induced via agonism of the A2B adenosine receptor

  摘要：

  A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The in-primary benzamide derivative 15f was the most potent compound (IC50 = 0.017 PM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity, The IC50 values in rat hepatocyte glucose assay correlated well with the IC50 values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2) = 0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00201-2

文献信息

• Purine derivatives and adenosine A2 receptor antagonists serving as preventives/remedies for diabetes
  申请人：Eisai Co., Ltd.

  公开号：US06579868B1

  公开（公告）日：2003-06-17

  The present invention provides a preventive or therapeutic agent of a new type for diabetes mellitus and diabetic complications on the basis of an adenosine A2 receptor antagonistic action. A purine compound represented by the formula (I), its pharmacologically acceptable salt or hydrates thereof has an adenosine A2 receptor antagonistic action and is useful for prevention or therapy of diabetes mellitus and diabetic complications. In addition, adenosine A2 receptor antagonists having different structures from those of the compounds described above, for example KW6002, are also effective for prevention or therapy of diabetes mellitus and diabetic complications. In the formula, W is —CH2CH2—, —CH═CH— or —C≡C—; R1 is: (in the formula, X is hydrogen atom, hydroxyl group, a lower alkyl group, a lower alkoxy group, etc.; and R5 and R6 are the same as or different from each other and each represents hydrogen atom, a lower alkyl group, a cycloalkyl group, etc.) and the like; R2 is an amino group, etc. which maybe substituted with a lower alkyl group, etc.; R3 is a cycloalkyl group, an optionally substituted aryl group, etc.; and R4 is a lower alkyl group etc.

  本发明提供了一种新型的糖尿病和糖尿病并发症的预防或治疗剂，基于腺苷A2受体拮抗作用。由式（I）表示的嘌呤化合物及其药理学上可接受的盐或水合物具有腺苷A2受体拮抗作用，并可用于预防或治疗糖尿病和糖尿病并发症。此外，具有与上述化合物不同结构的腺苷A2受体拮抗剂，例如KW6002等，也对预防或治疗糖尿病和糖尿病并发症有效。在该式中，W为—CH2CH2—、—CH═CH—或—C≡C—；R1为：（在该式中，X为氢原子、羟基、较低的烷基基团、较低的烷氧基团等；而R5和R6相同或不同，各自代表氢原子、较低的烷基基团、环烷基基团等）等；R2为氨基等，可能被较低的烷基基团等取代；R3为环烷基基团、可选择性取代的芳基基团等；R4为较低的烷基基团等。
• USRE039112E1
  申请人：——

  公开号：——

  公开（公告）日：——
• 2-Alkynyl-8-aryladenines possessing an amide moiety: their synthesis and structure–activity relationships of effects on hepatic glucose production induced via agonism of the A2B adenosine receptor
  作者：Hitoshi Harada、Osamu Asano、Tsutomu Kawata、Takashi Inoue、Tatsuo Horizoe、Nobuyuki Yasuda、Kaya Nagata、Manabu Murakami、Junsaku Nagaoka、Seiichi Kobayashi

  DOI：10.1016/s0968-0896(01)00201-2

  日期：2001.10

  A series of 2-alkynyl-8-aryladenine derivatives bearing an amide moiety at the 9-position of adenine was synthesized. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. The in-primary benzamide derivative 15f was the most potent compound (IC50 = 0.017 PM), being 15-fold more active than the corresponding 9-methyl derivative (1). Compound 15f showed 72- and 5.2-fold selectivity for human A(2B) receptor versus human A(1) and A(2A) receptors, respectively. Structure-activity relationship (SAR) studies of the synthesized compounds indicated that a three-carbon linker, fixed in the form of a benzene ring, between the adenine core and the amide moiety is important for both A(2B) antagonistic activity and selectivity, The IC50 values in rat hepatocyte glucose assay correlated well with the IC50 values in cAMP assay using Chinese hamster ovary cells stably transfected with human A(2B) receptors (r(2) = 0.94). The A(1) and A(2A) affinities showed no correlation with the potency to inhibit NECA-induced glucose production. These results strongly support our previous conclusion that adenosine agonist-induced hepatic glucose production in rat hepatocytes is mediated through the A(2B) receptor. (C) 2001 Elsevier Science Ltd. All rights reserved.