2,3-二氟-5-甲基苯腈 | 1003712-18-2

• 物质功能分类: 有机原料 - 有机氟化合物 - 氟苯腈系列
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2,3-二氟-5-甲基苯腈
• 中文别名: 2,3-二氟-5-甲苯甲腈
• 英文名称: 2,3-difluoro-5-methylbenzonitrile
• CAS: 1003712-18-2
• 化学式: C₈H₅F₂N
• mdl: MFCD09996953
• 分子量: 153.131
• InChiKey: YHCHCXBCEMMYSF-UHFFFAOYSA-N

物化性质

• 沸点：
  214.8±35.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2926909090

反应信息

• 作为反应物：
  描述：

  2,3-二氟-5-甲基苯腈 在 N-溴代丁二酰亚胺(NBS) 、 1-羟基苯并三唑 、 silver nitrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 四氯化碳 、 N,N-二甲基乙酰胺 、 水 、 乙腈 为溶剂， 反应 69.5h， 生成 4-(3-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)-4,5-difluorobenzyl)phthalazin-1(2H)-one
  参考文献：
  名称：

  Discovery, mechanism and metabolism studies of 2,3-difluorophenyl-linker-containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy

  摘要：

  Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially breast and ovarian cancers, and tumor cell lines deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, with the help of molecular docking, we identified a novel series of 2,3-difluorophenyl-linker analogues (15-54) derived from olaparib (1) as PARPI inhibitors. Lead optimization led to the identification of 47, which showed high selectivity and high potency against PARP1 enzyme (IC50 = 13 nM), V-C8 cells (IC50 = 0.003 nM), Capan-1 cells (IC50 = 7.1 nM) and MDA-MB-436 cells (IC50 = 0.2 nM). Compound 47 had more potent PARPI-DNA trapping and double-strand breaks (DSBs)-induction activities than 1 and induced G2/M arrest and caspase-dependent apoptosis. Compound 47 (50 mg/kg, 94.2%) had a more beneficial effect on tumor growth inhibition than 1 (100 mg/kg, 65.0%) in a BRCA1-mutated xenograft model and significantly inhibited tumor growth (40 mg/kg, 48.1%) in a BRCA2-mutated xenograft model, with no negative influence on the body weight of the mice. Collectively, these data demonstrated that 47 might be an excellent drug candidate for the treatment of cancer, especially for BRCA-deficient tumors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.053
• 作为产物：
  描述：

  3,4-二氟甲苯 在 正丁基锂 、 copper(l) cyanide 作用下， 以 四氢呋喃 、 甲基叔丁基醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 2,3-二氟-5-甲基苯腈
  参考文献：
  名称：

  Discovery, mechanism and metabolism studies of 2,3-difluorophenyl-linker-containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy

  摘要：

  Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially breast and ovarian cancers, and tumor cell lines deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, with the help of molecular docking, we identified a novel series of 2,3-difluorophenyl-linker analogues (15-54) derived from olaparib (1) as PARPI inhibitors. Lead optimization led to the identification of 47, which showed high selectivity and high potency against PARP1 enzyme (IC50 = 13 nM), V-C8 cells (IC50 = 0.003 nM), Capan-1 cells (IC50 = 7.1 nM) and MDA-MB-436 cells (IC50 = 0.2 nM). Compound 47 had more potent PARPI-DNA trapping and double-strand breaks (DSBs)-induction activities than 1 and induced G2/M arrest and caspase-dependent apoptosis. Compound 47 (50 mg/kg, 94.2%) had a more beneficial effect on tumor growth inhibition than 1 (100 mg/kg, 65.0%) in a BRCA1-mutated xenograft model and significantly inhibited tumor growth (40 mg/kg, 48.1%) in a BRCA2-mutated xenograft model, with no negative influence on the body weight of the mice. Collectively, these data demonstrated that 47 might be an excellent drug candidate for the treatment of cancer, especially for BRCA-deficient tumors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.053

文献信息

• OXADIAZOLE DERIVATIVES
  申请人：Quattropani Anna

  公开号：US20120022109A1

  公开（公告）日：2012-01-26

  The invention relates to oxadiazole compounds of formula I. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.

  该发明涉及式I的噁唑烷化合物。该化合物在治疗自身免疫性疾病，如多发性硬化症等方面是有用的。
• US8815919B2
  申请人：——

  公开号：US8815919B2

  公开（公告）日：2014-08-26
• [EN] OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE
  申请人：MERCK SERONO SA

  公开号：WO2010115751A2

  公开（公告）日：2010-10-14

  The invention relates to compounds of formula I: wherein R1, R2, Ra, Rb, W, Q and S have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.
• [EN] GPR52 MODULATORS AND METHODS OF USE<br/>[FR] MODULATEURS DE GPR52 ET PROCÉDÉS D'UTILISATION
  申请人：[en]NEUROCRINE BIOSCIENCES, INC.

  公开号：WO2022232017A1

  公开（公告）日：2022-11-03

  The present disclosure relates to compounds of Formula (I) that modulate the activity of G-protein coupled receptor 52 (GPR52), pharmaceutically acceptable salts of compounds of Formula (I), and pharmaceutical compositions thereof. Compounds, pharmaceutical salts of compounds, and pharmaceutical compositions of the present disclosure are directed to methods useful in the treatment or prophylaxis of a neurological disease or disorder and conditions related thereto.