tert-butyl 2-hydroxyethyl(2-(6-nitro-3,4-dihydroquinolin-1(2H)-yl)-2-oxoethyl)carbamate | 1362255-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: tert-butyl 2-hydroxyethyl(2-(6-nitro-3,4-dihydroquinolin-1(2H)-yl)-2-oxoethyl)carbamate
• 英文别名: tert-butyl N-(2-hydroxyethyl)-N-[2-(6-nitro-3,4-dihydro-2H-quinolin-1-yl)-2-oxoethyl]carbamate
• CAS: 1362255-15-9
• 化学式: C₁₈H₂₅N₃O₆
• 分子量: 379.413
• InChiKey: IOOWMFHBOZEHBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-hydroxyethyl(2-(6-nitro-3,4-dihydroquinolin-1(2H)-yl)-2-oxoethyl)carbamate 在 硼烷四氢呋喃络合物 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 21.5h， 生成 tert-butyl 2-(6-amino-3,4-dihydroquinolin-1(2H)-yl)ethyl(2-hydroxyethyl)carbamate
  参考文献：
  名称：

  1,2,3,4-Tetrahydroquinoline-Based Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: Lead Optimization Studies Resulting in the Identification of N-(1-(2-(Methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a Preclinical Development Candidate

  摘要：

  Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 (J. Med. Chem. 2011, 54, 5562-5575). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC50 = 4.7 mu M). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC50 > 30 mu M). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.

  DOI：

  10.1021/jm3000449
• 作为产物：
  描述：

  2-chloro-1-(6-nitro-3,4-dihydroquinolin-1(2H)-yl)ethanone 在 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 17.5h， 生成 tert-butyl 2-hydroxyethyl(2-(6-nitro-3,4-dihydroquinolin-1(2H)-yl)-2-oxoethyl)carbamate
  参考文献：
  名称：

  1,2,3,4-Tetrahydroquinoline-Based Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: Lead Optimization Studies Resulting in the Identification of N-(1-(2-(Methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a Preclinical Development Candidate

  摘要：

  Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 (J. Med. Chem. 2011, 54, 5562-5575). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC50 = 4.7 mu M). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC50 > 30 mu M). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.

  DOI：

  10.1021/jm3000449

文献信息

• 1,2,3,4-Tetrahydroquinoline-Based Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: Lead Optimization Studies Resulting in the Identification of <i>N</i>-(1-(2-(Methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a Preclinical Development Candidate
  作者：Jailall Ramnauth、Paul Renton、Peter Dove、Subhash C. Annedi、Joanne Speed、Sarah Silverman、Gabriela Mladenova、Shawn P. Maddaford、Salvatore Zinghini、Suman Rakhit、John Andrews、David K. H. Lee、Dongqin Zhang、Frank Porreca

  DOI：10.1021/jm3000449

  日期：2012.3.22

  Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 (J. Med. Chem. 2011, 54, 5562-5575). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC50 = 4.7 mu M). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC50 > 30 mu M). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.