2-oxo-N-(2, 2, 2-trifluoroethyl)oxazolidine-3-sulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2-oxo-N-(2, 2, 2-trifluoroethyl)oxazolidine-3-sulfonamide
• 英文别名: 2-oxo-N-(2,2,2-trifluoroethyl)-1,3-oxazolidine-3-sulfonamide
• 化学式: C₅H₇F₃N₂O₄S
• 分子量: 248.183
• InChiKey: ATJQESDQCXNYLN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  84.1
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  dimethylcarbamic acid 3-(3-aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-chromen-7-yl ester 、 2-oxo-N-(2, 2, 2-trifluoroethyl)oxazolidine-3-sulfonamide 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以87%的产率得到dimethylcarbamic acid 3-(3-(N-2,2,2-trifluoroethyl-sulfamoyl)aminobenzyl)-6-chloro-4-methyl-2-oxo-2H-1-benzopyran-7-yl ester
  参考文献：
  名称：

  The sulfamide moiety affords higher inhibitory activity and oral bioavailability to a series of coumarin dual selective RAF/MEK inhibitors

  摘要：

  Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.001
• 作为产物：
  描述：

  2,2,2-三氟乙基胺 、 2-氧代噁唑烷-3-磺酰氯 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 以1.97 g的产率得到2-oxo-N-(2, 2, 2-trifluoroethyl)oxazolidine-3-sulfonamide
  参考文献：
  名称：

  The sulfamide moiety affords higher inhibitory activity and oral bioavailability to a series of coumarin dual selective RAF/MEK inhibitors

  摘要：

  Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.10.001

文献信息

• Discovery of 3-benzyl-1,3-benzoxazine-2,4-dione analogues as allosteric mitogen-activated kinase kinase (MEK) inhibitors and anti-enterovirus 71 (EV71) agents
  作者：Jing Sun、Yan Niu、Chao Wang、Hao Zhang、Bingyu Xie、Fengrong Xu、Hongwei Jin、Yihong Peng、Lei Liang、Ping Xu

  DOI：10.1016/j.bmc.2016.05.055

  日期：2016.8

  Enterovirus 71 (EV71) is a kind of RNA virus and one of the two causes of Hand, foot and mouth disease (HFMD). Inhibitors that target key components of Ras/Raf/MEK/ERK pathway in host cells could impair replication of EV71. A series of 3-benzyl-1,3-benzoxazine-2,4-diones were designed from a specific MEK inhibitor G8935, by replacing the double bond between C3 and C4 within the coumarin scaffold with

  肠病毒71（EV71）是一种RNA病毒，是手足口病（HFMD）的两种原因之一。靶向宿主细胞中Ras / Raf / MEK / ERK途径关键成分的抑制剂可能会破坏EV71的复制。由特定的MEK抑制剂G8935设计了一系列3-苄基-1,3-苯并恶嗪-2,4-二酮，方法是用酰胺键取代香豆素骨架中C3和C4之间的双键。在12种衍生物中，一种化合物（9f）表现出亚微摩尔抑制活性。对9f的进一步优化导致产生了两种活性化合物（9k和9m），具有纳摩尔生物活性（55 nM和60 nM）。酶促测定的结果还表明，该系列化合物是未磷酸化MEK1的变构抑制剂。通过分子动力学模拟预测化合物9k的结合方式，其关键相互作用与已发表的MEK1 / 2变构抑制剂相同。在基于细胞的测定中，化合物9k和9m可有效抑制横纹肌肉瘤（RD）细胞中的ERK1 / 2途径，EV71 VP1的表达和EV71诱导的细胞病变效应（CPE）。
• Hybrids of MEK inhibitor and NO donor as multitarget antitumor drugs
  作者：Chao Wang、Dandan Xi、Han Wang、Yan Niu、Lei Liang、Fengrong Xu、Yihong Peng、Ping Xu

  DOI：10.1016/j.ejmech.2020.112271

  日期：2020.6

  A series of hybrids of MEK inhibitor and nitric oxide donor have been designed and synthesized. Compound 18h [4-(3-((3-(2-fluoro-3-((N-methylsulfamoyl)amino)benzyl)-4-methyl-2-oxo-2H-chromen-7-yl)oxy) propoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide] was proven to be more potent than the clinical compound R05126766 in MDA-MB-231 cells. Compound 18h can significantly reduce the levels of pMEK and pERK, induce cell apoptosis in MDA-MB-231 cells, and release NO in cells efficiently, suggesting that these hybrids, while displaying the properties of both MEK inhibitors and NO donors have a mechanism of action different from that of MEK inhibitors and NO donors. Thus, we are able to report a series of multitarget hybrids with better antitumor potency than a known MEK inhibitor and NO donor. (C) 2020 Elsevier Masson SAS. All rights reserved.
• The sulfamide moiety affords higher inhibitory activity and oral bioavailability to a series of coumarin dual selective RAF/MEK inhibitors
  作者：Toshihiro Aoki、Ikumi Hyohdoh、Noriyuki Furuichi、Sawako Ozawa、Fumio Watanabe、Masayuki Matsushita、Masahiro Sakaitani、Kazutomo Ori、Kenji Takanashi、Naoki Harada、Yasushi Tomii、Mitsuyasu Tabo、Kiyoshi Yoshinari、Yuko Aoki、Nobuo Shimma、Hitoshi Iikura

  DOI：10.1016/j.bmcl.2013.10.001

  日期：2013.12

  Introducing a sulfamide moiety to our coumarin derivatives afforded enhanced Raf/MEK inhibitory activity concomitantly with an acceptable PK profile. Novel sulfamide 17 showed potent HCT116 cell growth inhibition (IC50 = 8 nM) and good PK profile (bioavailability of 51% in mouse), resulting in high in vivo antitumor efficacy in the HCT116 xenograft (ED50 = 4.8 mg/kg). We confirmed the sulfamide moiety showed no negative impact on tests run on the compound to evaluate DMPK (PK profiles in three animal species, CYP inhibition and CYP induction) and the safety profile (hERG and AMES tests). Sulfamide 17 had favorable properties that warranted further preclinical assessment (C) 2013 Elsevier Ltd. All rights reserved.