3-(pentafluoro-λ⁶-sulfanyl)phenyl isocyanate | 1384879-19-9

• 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: 3-(pentafluoro-λ⁶-sulfanyl)phenyl isocyanate
• 英文别名: Pentafluoro-(3-isocyanatophenyl)-lambda6-sulfane；pentafluoro-(3-isocyanatophenyl)-λ6-sulfane
• CAS: 1384879-19-9
• 化学式: C₇H₄F₅NOS
• 分子量: 245.173
• InChiKey: MGHKJFAIRHOWBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(pentafluoro-λ⁶-sulfanyl)phenyl isocyanate 、 五氟化(3-氨苯基)硫 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以49%的产率得到1,3-bis[3-(pentafluoro-λ⁶-sulfanyl)phenyl]urea
  参考文献：
  名称：

  具有有效抗菌活性的含五氟硫烷基的三氯卡班类似物。

  摘要：

  人们对三氯卡班（一种广泛用作抗菌肥皂添加剂的多氯代二芳基脲）在环境和人类中的长期积累作用提出了关注。实际上，食品药品管理局最近已禁止将其用于个人护理产品。本文中，我们报告了新型N，N'-二芳基脲作为三氯卡班类似物的合成，抗菌活性和细胞毒性，其设计是通过还原前者的一个或多个氯原子和/或用新的五氟硫烷基（一种新的五氟硫烷基）取代它们而设计的三氟甲基，在药物开发中的重要性越来越高。有趣的是，其中一些带有五氟硫烷基的尿素显示出高效价，对革兰氏阳性细菌病原体具有广泛的抗菌活性以及高选择性指数，同时显示出比三氯卡班更低的自发突变频率。一些证据表明该化合物家族具有杀菌作用。

  DOI：

  10.3390/molecules23112853
• 作为产物：
  描述：

  三光气 、 五氟化(3-氨苯基)硫 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 3-(pentafluoro-λ⁶-sulfanyl)phenyl isocyanate
  参考文献：
  名称：

  具有有效抗菌活性的含五氟硫烷基的三氯卡班类似物。

  摘要：

  人们对三氯卡班（一种广泛用作抗菌肥皂添加剂的多氯代二芳基脲）在环境和人类中的长期积累作用提出了关注。实际上，食品药品管理局最近已禁止将其用于个人护理产品。本文中，我们报告了新型N，N'-二芳基脲作为三氯卡班类似物的合成，抗菌活性和细胞毒性，其设计是通过还原前者的一个或多个氯原子和/或用新的五氟硫烷基（一种新的五氟硫烷基）取代它们而设计的三氟甲基，在药物开发中的重要性越来越高。有趣的是，其中一些带有五氟硫烷基的尿素显示出高效价，对革兰氏阳性细菌病原体具有广泛的抗菌活性以及高选择性指数，同时显示出比三氯卡班更低的自发突变频率。一些证据表明该化合物家族具有杀菌作用。

  DOI：

  10.3390/molecules23112853

文献信息

• [EN] ANALOGS OF ADAMANTYLUREAS AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS<br/>[FR] ANALOGUES D'ADAMANTYLURÉES UTILISÉS EN TANT QU'INHIBITEURS D'HYDROLASE ÉPOXYDE SOLUBLE
  申请人：UNIV BARCELONA

  公开号：WO2017017048A1

  公开（公告）日：2017-02-02

  N-(2-oxaadamantan-1-yl)ureas of formula I, where R3 is H, C1-C3 alkyl, cyclohexyl or phenyl; R is -[CH2]n -Y; n is 0-15; in -[CH2]n - 0-n/3 of the methylene groups are optionally replaced by non adjacent oxygen atoms; and Y is a 3- or 4-substituted phenyl, a 3- or 4-substituted cyclohexyl, a N-substituted piperidin-4-yl, a N-substituted piperidin-3-yl, a di- or tri-fluorosubstituted phenyl, 4-chloro-3-trifluoromethylphenyl, 3-chloro-4-trifluoromethylphenyl, 4-fluoro-3-trifluoromethylphenyl, or 3-fluoro-4-trifluoromethylphenyl; have epoxide hydrolase (sEH) inhibitory activities similar to those of their N-(adamantan-1-yl)urea analogs. Thus, compounds I are useful as API for the treatment of sEH mediated diseases. Besides, in general, compounds (I) have higher water solubilities and lower melting points, what make them more promising from the point of view of pharmacokinetics and formulation.

  式I的N-(2-氧杂孔莫烷-1-基)脲，其中R3为H、C1-C3烷基、环己基或苯基；R为-[CH2]n-Y；n为0-15；在-[CH2]n-中，0-n/3的亚甲基基团可选择性地被非相邻的氧原子取代；Y为3-或4-取代苯基、3-或4-取代环己基、N-取代哌啶-4-基、N-取代哌啶-3-基、二氟或三氟取代苯基、4-氯-3-三氟甲基苯基、3-氯-4-三氟甲基苯基、4-氟-3-三氟甲基苯基或3-氟-4-三氟甲基苯基；具有环氧化酶（sEH）抑制活性，类似于其N-(孔莫烷-1-基)脲类似物。因此，化合物I可用作治疗sEH介导疾病的API。此外，一般而言，化合物（I）具有较高的水溶性和较低的熔点，这使它们在药代动力学和配方方面更具有前景。
• [EN] NOVEL UREAS FOR THE TREATMENT AND PREVENTION OF CANCER<br/>[FR] NOUVELLES URÉES POUR LE TRAITEMENT ET LA PRÉVENTION DU CANCER
  申请人：BETA PHARMA CANADA INC

  公开号：WO2012094451A1

  公开（公告）日：2012-07-12

  A compound of Formula (I), salts thereof, prodrugs thereof, metabolites thereof, pharmaceutical compositions containing such a compound, and use of such compound and compositions to treat diseases mediated by multiple kinases, such as raf, VEGFR, PDGFR, FLT-3, and c-Kit.

  公式（I）的化合物，其盐，前药，代谢物，含有该化合物的药物组合物，以及使用该化合物和组合物治疗由多种激酶介导的疾病，如raf，VEGFR，PDGFR，FLT-3和c-Kit。
• [EN] HRI ACTIVATORS USEFUL FOR THE TREATMENT OF CARDIOMETABOLIC DISEASES<br/>[FR] ACTIVATEURS DE HRI UTILES POUR LE TRAITEMENT DE MALADIES CARDIOMÉTABOLIQUES
  申请人：UNIV BARCELONA

  公开号：WO2018010856A1

  公开（公告）日：2018-01-18

  New compounds of formula (I) are provided,wherein: X is CH or N, preferably CH; n is 1-5, preferably 1-2; m is 0-5, preferably 1-2; and, when m is 2-5, two of the R2 radicals taken together with two adjacent carbons of the benzene ring can form a 5- or 6-membered heterocyclic ring fused with the benzene ring. Compounds (I) are heme-regulated inhibitor (HRI) activators and useful for the prevention or treatment of cardiometabolic diseases such as metabolic syndrome, obesity, insulin resistance, type 2 diabetes mellitus, non-alcoholic fatty liver disease, steatosis, non-alcoholic steatohepatitis, hypertension, dyslipidemia, atherosclerosis, and heart disease.

  提供了化合物（I）的新配方，其中：X为CH或N，优选为CH; n为1-5，优选为1-2; m为0-5，优选为1-2; 当m为2-5时，两个R2基团与苯环上相邻的两个碳原子共同形成一个与苯环融合的5-或6元杂环。化合物（I）是血红素调节酶（HRI）激活剂，可用于预防或治疗代谢综合征、肥胖症、胰岛素抵抗、2型糖尿病、非酒精性脂肪肝病、脂肪肝、非酒精性脂肪性肝炎、高血压、血脂异常、动脉粥样硬化和心脏疾病。
• 2-Oxaadamant-1-yl Ureas as Soluble Epoxide Hydrolase Inhibitors: <i>In Vivo</i> Evaluation in a Murine Model of Acute Pancreatitis
  作者：Sandra Codony、Eugènia Pujol、Javier Pizarro、Ferran Feixas、Elena Valverde、M. Isabel Loza、José M. Brea、Elena Saez、Julen Oyarzabal、Antonio Pineda-Lucena、Belén Pérez、Concepción Pérez、María Isabel Rodríguez-Franco、Rosana Leiva、Sílvia Osuna、Christophe Morisseau、Bruce D. Hammock、Manuel Vázquez-Carrera、Santiago Vázquez

  DOI：10.1021/acs.jmedchem.0c00310

  日期：2020.9.10

  In vivo pharmacological inhibition of soluble epoxide hydrolase (sEH) reduces inflammatory diseases, including acute pancreatitis (AP). Adamantyl ureas are very potent sEH inhibitors, but the lipophilicity and metabolism of the adamantane group compromise their overall usefulness. Herein, we report that the replacement of a methylene unit of the adamantane group by an oxygen atom increases the solubility, permeability, and stability of three series of urea-based sEH inhibitors. Most of these oxaanalogues are nanomolar inhibitors of both the human and murine sEH. Molecular dynamics simulations rationalize the molecular basis for their activity and suggest that the presence of the oxygen atom on the adamantane scaffold results in active site rearrangements to establish a weak hydrogen bond. The 2-oxaadamantane 22, which has a good solubility, microsomal stability, and selectivity for sEH, was selected for further in vitro and in vivo studies in models of cerulein-induced AP. Both in prophylactic and treatment studies, 22 diminished the overexpression of inflammatory and endoplasmic reticulum stress markers induced by cerulein and reduced the pancreatic damage.
• Piperidinyl Ureas Chemically Control Defective in Cullin Neddylation 1 (DCN1)-Mediated Cullin Neddylation
  作者：Jared T. Hammill、Daniel C. Scott、Jaeki Min、Michele C. Connelly、Gloria Holbrook、Fangyi Zhu、Amy Matheny、Lei Yang、Bhuvanesh Singh、Brenda A. Schulman、R. Kiplin Guy

  DOI：10.1021/acs.jmedchem.7b01277

  日期：2018.4.12

  We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit. The optimized compounds inhibit the DCN1- UBE2M protein-protein interaction in our TR-FRET binding assay and inhibit cullin neddylation in our pulse-chase NEDD8 transfer assay. The optimized compounds bind to DCN1 and selectively reduce steady-state levels of neddylated CUL1 and CUL3 in a squamous cell carcinoma cell line. Ultimately, we anticipate that these studies will identify early lead compounds for clinical development for the treatment of lung squamous cell carcinomas and other cancers.