ethyl 3-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate | 391249-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate
• 英文别名: Ethyl 3-{6-Amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl}benzoate；Ethyl 3-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)ethynyl]purin-9-yl]benzoate
• CAS: 391249-24-4
• 化学式: C₂₈H₂₆FN₅O₃
• 分子量: 499.545
• InChiKey: ZGUXYJQWQIYWBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 3-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 5.0h， 以86%的产率得到3-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoic acid
  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
• 作为产物：
  描述：

  3-氨基苯甲酸乙酯 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium tetrahydroborate 、 copper(l) iodide 、 二碘甲烷 、 四乙基氯化铵 、 氨 、 溶剂黄146 、 N,N-二甲基苯胺 、 三乙胺 、 tin(ll) chloride 、 三氯氧磷 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 ethyl 3-[6-amino-8-(3-fluorophenyl)-2-[2-(1-hydroxycyclohexyl)-1-ethynyl]-9H-9-purinyl]benzoate
  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：EP1054012A1

  公开（公告）日：2000-11-22

  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 may be 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.

  本发明提供了一种基于腺苷 A2 受体拮抗作用的新型糖尿病和糖尿病并发症预防或治疗剂。 由式（I）代表的嘌呤化合物、其药理上可接受的盐或其水合物具有腺苷 A2 受体拮抗作用，可用于预防或治疗糖尿病和糖尿病并发症。此外，与上述化合物结构不同的腺苷 A2 受体拮抗剂，例如 KW6002，也可有效预防或治疗糖尿病和糖尿病并发症。 式中，W为-CH2CH2-、-CH=CH-或-C≡C-；R1为： (式中，X 是氢原子、羟基、低级烷基、低级烷氧基等；R5 和 R6 彼此相同或不同，各自代表氢原子、低级烷基、环烷基等）等；R2 是可被低级烷基等取代的氨基等；R3 是环烷基、任选取代的芳基等；R4 是低级烷基等。
• US6579868B1
  申请人：——

  公开号：US6579868B1

  公开（公告）日：2003-06-17
• USRE39112E1
  申请人：——

  公开号：USRE39112E1

  公开（公告）日：2006-05-30