N-(4-(2-amino-5-(thiophen-2-yl)phenylcarbamoyl)benzyl)-4-ethyl-2,3-dioxopiperazine-1-carboxamide | 1364569-87-8

• 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: N-(4-(2-amino-5-(thiophen-2-yl)phenylcarbamoyl)benzyl)-4-ethyl-2,3-dioxopiperazine-1-carboxamide
• 英文别名: N-[[4-[(2-amino-5-thiophen-2-ylphenyl)carbamoyl]phenyl]methyl]-4-ethyl-2,3-dioxopiperazine-1-carboxamide
• CAS: 1364569-87-8
• 化学式: C₂₅H₂₅N₅O₄S
• 分子量: 491.571
• InChiKey: JJDCMTCOALMMMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  153
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-[(叔丁氧羰基氨基)甲基]苯甲酸 在 盐酸 、 草酰氯 、 tin(II) chloride dihdyrate 、 ammonium acetate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(4-(2-amino-5-(thiophen-2-yl)phenylcarbamoyl)benzyl)-4-ethyl-2,3-dioxopiperazine-1-carboxamide
  参考文献：
  名称：

  Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl)benzamide-series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain

  摘要：

  New orally bioavailable 5-(thiophen-2-yl)-substituted 2-aminobenzamide-series histone deacetylase inhibitors were synthesized. These compounds possess a morpholine or piperadine-derived moiety as an aqueous soluble functional group. Among them, 8b, having a 4-ethyl-2,3-dioxopiperazine-1-carboxamide group as a surface recognition domain, showed promising inhibitory activities against HCT116 cell growth and HDAC1/2. Notably, unlike MS-275, this compound did not induce apoptosis in the cell cycle tests. We therefore conducted antitumor tests of 8b and MS-275 against HCT116 cell xenografts in nude mice. Compound 8b reduced the volume of tumor mass to T/C: 60% and 47% at 45 and 80 mg/kg over 16 days, respectively. These values were comparable to the rate (T/C: 51% at 45 mg/kg) for MS-275. Furthermore, 8b, at neither 45 nor 80 mg/kg, induced the weight loss which was observed in the mice given MS-275 at 45 mg/kg. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.053

文献信息

• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
• Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl)benzamide-series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain
  作者：Yoshiyuki Hirata、Masahiko Hirata、Yasuyuki Kawaratani、Makio Shibano、Masahiko Taniguchi、Masahide Yasuda、Yoshiro Ohmomo、Yasuo Nagaoka、Kimiye Baba、Shinichi Uesato

  DOI：10.1016/j.bmcl.2012.01.053

  日期：2012.3

  New orally bioavailable 5-(thiophen-2-yl)-substituted 2-aminobenzamide-series histone deacetylase inhibitors were synthesized. These compounds possess a morpholine or piperadine-derived moiety as an aqueous soluble functional group. Among them, 8b, having a 4-ethyl-2,3-dioxopiperazine-1-carboxamide group as a surface recognition domain, showed promising inhibitory activities against HCT116 cell growth and HDAC1/2. Notably, unlike MS-275, this compound did not induce apoptosis in the cell cycle tests. We therefore conducted antitumor tests of 8b and MS-275 against HCT116 cell xenografts in nude mice. Compound 8b reduced the volume of tumor mass to T/C: 60% and 47% at 45 and 80 mg/kg over 16 days, respectively. These values were comparable to the rate (T/C: 51% at 45 mg/kg) for MS-275. Furthermore, 8b, at neither 45 nor 80 mg/kg, induced the weight loss which was observed in the mice given MS-275 at 45 mg/kg. (c) 2012 Elsevier Ltd. All rights reserved.