3-nitro-4-[2-(piperazine-1-yl)ethyl]aminopyridine | 1027480-43-8

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 3-nitro-4-[2-(piperazine-1-yl)ethyl]aminopyridine
• 英文别名: 3-nitro-N-(2-piperazin-1-ylethyl)pyridin-4-amine
• CAS: 1027480-43-8
• 化学式: C₁₁H₁₇N₅O₂
• mdl: MFCD12084236
• 分子量: 251.288
• InChiKey: LKBUELNQVBMSES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  86
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-nitro-4-[2-(piperazine-1-yl)ethyl]aminopyridine 在 palladium on activated charcoal 甲醇 、 氢氧化钾 、 氢气 、 sodium methylate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 139.25h， 生成 6-(4-fluorophenyl)-N,N-dimethyl-3-[4-[2-(2-methylimidazo[4,5-c]pyridin-1-yl)ethyl]piperazin-1-yl]sulfonylindole-1-carboxamide
  参考文献：
  名称：

  Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists

  摘要：

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.

  DOI：

  10.1021/jm970389+
• 作为产物：
  描述：

  N-氨乙基哌嗪 、 4-乙氧基-3-硝基吡啶 以 乙腈 为溶剂， 反应 40.0h， 以to give 3-nitro-4-[2-(piperazine-1-yl)ethyl]aminopyridine which的产率得到3-nitro-4-[2-(piperazine-1-yl)ethyl]aminopyridine
  参考文献：
  名称：

  Indole piperazine platelet activating factor antagonists

  摘要：

  本发明提供了式子##STR1##中的化合物，其中Y为> C = O或> S（O）.sub.t，其中t为1或2，以及其药学上可接受的盐，这些化合物是PAF的有效拮抗剂，可用于治疗与PAF相关的疾病，包括哮喘，鼻炎，休克，呼吸窘迫综合征，急性炎症，移植器官排斥，胃肠溃疡，过敏性皮肤病，迟发性细胞免疫，分娩，胎肺成熟和细胞分化。

  公开号：

  US05654305A1

文献信息

• Indole piperazine platelet activating factor antagonists
  申请人：Abbott Laboratories

  公开号：US05654305A1

  公开（公告）日：1997-08-05

  The present invention provides compounds of formula ##STR1## wherein Y is >C.dbd.O or >S(O).sub.t wherein t is 1 or 2 and the pharmaceutically acceptable salts thereof which are potent antagonists of PAF and are useful in the treatment of PAF-related disorders including asthma, rhinitis, shock, respiratory distress syndrome, acute inflammation, transplanted organ rejection, gastrointestinal ulceration, allergic skin diseases, delayed cellular immunity, parturition, fetal lung maturation, and cellular differentiation.

  本发明提供了化合物的结构式 ##STR1## 其中Y是>C.dbd.O或>S(O).sub.t，其中t为1或2以及其药学上可接受的盐，这些化合物是PAF的有效拮抗剂，并且在治疗包括哮喘、鼻炎、休克、呼吸窘迫综合征、急性炎症、移植器官排斥、胃肠溃疡、过敏性皮肤病、延迟细胞免疫、分娩、胎儿肺成熟和细胞分化在内的与PAF相关的疾病中有用。
• 10.1021/acs.orglett.4c01970
  作者：Zhang, Ze-Xuan、Zhang, Bing、Yuan, Meng、Zhao, Peng-Fei、Da, Chao-Shan

  DOI：10.1021/acs.orglett.4c01970

  日期：——

  With alanine as a transient directing group, Pd-catalyzed regioselective alkynylation at the indole C4-position was successfully established in a good yield. The total synthesis of the PAF antagonist demonstrated the synthetic utility of this protocol. The regioselectivity was explicitly proven by the prepared C4-selective palladacycle intermediate in the catalytic process and the DFT calculation of

  以丙氨酸作为瞬时导向基团，Pd 催化的吲哚 C4 位区域选择性炔基化反应以良好的产率成功建立。 PAF拮抗剂的全合成证明了该方案的合成效用。催化过程中制备的C4选择性环钯中间体以及吲哚C4和C2位点选择性C-H活化能垒的DFT计算明确证明了区域选择性。
• US5654305A
  申请人：——

  公开号：US5654305A

  公开（公告）日：1997-08-05
• Discovery and Evaluation of a Series of 3-Acylindole Imidazopyridine Platelet-Activating Factor Antagonists
  作者：Michael L. Curtin、Steven K. Davidsen、H. Robin Heyman、Robert B. Garland、George S. Sheppard、Alan S. Florjancic、Lianhong Xu、George M. Carrera、Douglas H. Steinman、Jeff A. Trautmann、Daniel H. Albert、Terrance J. Magoc、Paul Tapang、David A. Rhein、Richard G. Conway、Gongjin Luo、Jon F. Denissen、Kennan C. Marsh、Douglas W. Morgan、James B. Summers

  DOI：10.1021/jm970389+

  日期：1998.1.1

  Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N,N-dimethylcarbamoyl)-4-ethynyl-3-(3-fluoro-4-[(1H-2-methylimidazo[4,5-c]pyrid-1-yl)methyl] benzoyl}indole hydrochloride (ABT-491, 22m.HCl) which has been evaluated extensively and is currently in clinical development.