methyl 2-isothiocyanato-4-nitrobenzoate | 67199-72-8

• 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 2-isothiocyanato-4-nitrobenzoate
• CAS: 67199-72-8
• 化学式: C₉H₆N₂O₄S
• 分子量: 238.224
• InChiKey: WDVPHMDGSSIPSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-aminobutyl)-4-(4-fluorobenzoyl)piperidine 、 methyl 2-isothiocyanato-4-nitrobenzoate 以 四氢呋喃 为溶剂， 以30 parts (62%)的产率得到3-[4-[4-(4-fluorobenzoyl)-1-piperidinyl]butyl]-2,3-dihydro-7-nitro-2-thioxo-4(1H)-quinazolinone
  参考文献：
  名称：

  Derivatives of hydroxy- or amino-substituted

  摘要：

  新颖的羟基或氨基取代的（哌啶基烷基）喹唑啉衍生物，可用作治疗患有根据发生过多血清素释放的血管床疾病的温血动物的药物。

  公开号：

  US04665075A1
• 作为产物：
  描述：

  硫光气 、 2-氨基-4-硝基苯甲酸甲酯 在 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 生成 methyl 2-isothiocyanato-4-nitrobenzoate
  参考文献：
  名称：

  Discovery of a Novel 5-HT₃ Antagonist/5-HT_1A Agonist 3-Amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3H)-one (TZB-30878) as an Orally Bioavailable Agent for Irritable Bowel Syndrome

  摘要：

  We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT1A) and subtype 3 (5-HT3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) (J. Pharmacol. Exp. Ther. 2007, 322, 1315-1323, Patent WO2005082887 (A1), 2005), a novel 5-HT1A agonist/5-HT3 antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT1A-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT1A antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT1A agonistic and 5-HT3 antagonistic activities and that 17m would be useful as a therapeutic agent for IBS.

  DOI：

  10.1021/jm1002292

文献信息

• Novel derivatives of hydroxy- or amino-substituted (piperidinylalkyl)quinazolines
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0184258A2

  公开（公告）日：1986-06-11

  Novel derivatives of hydroxy- or amino-substituted (piperidinylalkyl) quinazolines of the formula wherein Q represents 1H-indol-3-yl or a radical -X-Ar; the pharmaceutically acceptable acid addition salts and possible stereochemically isomeric forms thereof, which compounds are serotonin antagonists; pharmaceutical compositions containing such compounds as an active ingredient and methods of preparing said compounds and pharmaceutical compositions.

  式中Q代表1H-吲哚-3-基或基-X-Ar的羟基或氨基取代的（哌啶基烷基）喹唑啉类的新型衍生物；其药学上可接受的酸加成盐和可能的立体化学异构体形式，这些化合物是5-羟色胺拮抗剂；含有这些化合物作为活性成分的药物组合物以及制备所述化合物和药物组合物的方法。
• VANDENBERK, JAN;KENNIS, LUDO E. J.;MERTENS, J. C.
  作者：VANDENBERK, JAN、KENNIS, LUDO E. J.、MERTENS, J. C.

  DOI：——

  日期：——
• KABBE H.-J., J. LIEBIGS ANN. CHEM., 1978, NO 3, 398-404
  作者：KABBE H.-J.

  DOI：——

  日期：——
• US4665075A
  申请人：——

  公开号：US4665075A

  公开（公告）日：1987-05-12
• Discovery of a Novel 5-HT₃ Antagonist/5-HT_1A Agonist 3-Amino-5,6,7,8-tetrahydro-2-{4-[4-(quinolin-2-yl)piperazin-1-yl]butyl}quinazolin-4(3<i>H</i>)-one (TZB-30878) as an Orally Bioavailable Agent for Irritable Bowel Syndrome
  作者：Akira Asagarasu、Teruaki Matsui、Hiroyuki Hayashi、Satoru Tamaoki、Yukinao Yamauchi、Kouichi Minato、Michitaka Sato

  DOI：10.1021/jm1002292

  日期：2010.11.11

  We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5-HT1A) and subtype 3 (5-HT3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to improve the pharmacokinetic profile, the sulfur atom in the linker was replaced with a methylene group. Further optimization led to the discovery of compound 17m (TZB-30878) (J. Pharmacol. Exp. Ther. 2007, 322, 1315-1323, Patent WO2005082887 (A1), 2005), a novel 5-HT1A agonist/5-HT3 antagonist in the 3-aminoquinazolinone series. In in vivo functional assays, 17m dose dependently inhibited the Bezold-Jarisch reflex and induced 5-HT1A-mediated behaviors, and in an IBS animal model, 17m significantly inhibited stress-induced defecation. Pretreatment by WAY-100635 (5-HT1A antagonist) significantly attenuated but did not abolish the inhibitory effects of 17m. These results suggested that 17m exerted inhibitory effects via both 5-HT1A agonistic and 5-HT3 antagonistic activities and that 17m would be useful as a therapeutic agent for IBS.