3-[4-（2-氯-5-氟苯氧基）-1-哌啶基]-6-（5-甲基-1,3,4-恶二唑-2-基）哒嗪 | 944808-88-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 3-[4-（2-氯-5-氟苯氧基）-1-哌啶基]-6-（5-甲基-1,3,4-恶二唑-2-基）哒嗪
• 中文别名: 2-(6-(4-(2-氯-5-氟苯氧基)哌啶-1-基)哒嗪-3-基)-5-甲基-1,3,4-噁二唑
• 英文名称: (3-[4-(2-chloro-5-fluorophenoxy)-1-piperidinyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)-pyridazine)
• 英文别名: 3-[4-(2-chloro-5-fluorophenoxy)-1-piperidinyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)-pyridazine；3-[4-(2-chloro-5-fluorophenoxy)-1-piperidinyl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyridazine；CAY 10566；CAY10566；2-(6-(4-(2-Chloro-5-fluorophenoxy)piperidin-1-yl)pyridazin-3-yl)-5-methyl-1,3,4-oxadiazole；2-[6-[4-(2-chloro-5-fluorophenoxy)piperidin-1-yl]pyridazin-3-yl]-5-methyl-1,3,4-oxadiazole
• CAS: 944808-88-2
• 化学式: C₁₈H₁₇ClFN₅O₂
• 分子量: 389.817
• InChiKey: WFOFPVXMPTVOTJ-UHFFFAOYSA-N

物化性质

• 熔点：
  160 - 170°C
• 沸点：
  600.2±65.0 °C(Predicted)
• 密度：
  1.369±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  77.2
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-[4-（2-氯-5-氟苯氧基）-1-哌啶基]-6-（5-甲基-1,3,4-恶二唑-2-基）哒嗪 在 氨 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以35%的产率得到3-[4-(2-chloro-5-fluorophenoxy)piperidin-1-yl]-6-(5-methyl-1H-1,2,4-triazol-3-yl)pyridazine
  参考文献：
  名称：

  Discovery of Potent, Selective, Orally Bioavailable Stearoyl-CoA Desaturase 1 Inhibitors

  摘要：

  Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.

  DOI：

  10.1021/jm070219p
• 作为产物：
  描述：

  2-氯-5-氟苯酚 在 [1,1'-bis(diphenylphosphino)ferrocene]PdCl₂(II)*CH₂Cl₂ sodium hydroxide 、 偶氮二甲酸二叔丁酯 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 三苯基膦 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0~100.0 ℃ 、1.38 MPa 条件下， 反应 15.0h， 生成 3-[4-（2-氯-5-氟苯氧基）-1-哌啶基]-6-（5-甲基-1,3,4-恶二唑-2-基）哒嗪
  参考文献：
  名称：

  Discovery of Potent, Selective, Orally Bioavailable Stearoyl-CoA Desaturase 1 Inhibitors

  摘要：

  Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.

  DOI：

  10.1021/jm070219p

文献信息

• Treatment of viral infections by modulation of host cell metabolic pathways
  申请人：Munger Josh

  公开号：US20090239830A1

  公开（公告）日：2009-09-24

  Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in “suicide” of viral-infected cells (but not uninfected cells) in order to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, as well as in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. The antiviral activity of enzyme inhibitors is demonstrated.

  描述了在病毒感染时发生的某些代谢物浓度和通量的改变。选择涉及代谢途径的宿主细胞酶作为干预靶点；即恢复代谢通量以不利于病毒复制，或进一步扰乱代谢通量导致病毒感染细胞的“自杀”（但不包括未感染的细胞），以限制病毒传播。虽然可以选择相关代谢途径中的任何酶，但是在这些代谢途径中关键控制点的关键酶更适合作为候选抗病毒药物靶点。使用这些酶的抑制剂来逆转或重定向病毒感染的影响。使用体外筛选分析和宿主细胞以及动物模型测试药物候选物的抗病毒活性。然后使用动物模型测试候选化合物在预防和治疗病毒感染方面的功效。证明了酶抑制剂的抗病毒活性。
• TREATMENT OF VIRAL INFECTIONS BY MODULATION OF HOST CELL METABOLIC PATHWAYS
  申请人：MUNGER Josh

  公开号：US20130065850A1

  公开（公告）日：2013-03-14

  Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in “suicide” of viral-infected cells (but not uninfected cells) in order to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, as well as in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. The antiviral activity of enzyme inhibitors is demonstrated.

  描述了某些代谢物浓度和通量的改变，这些改变是对病毒感染的反应。选择参与代谢途径的宿主细胞酶作为干预的目标，即恢复代谢通量以削弱病毒复制，或进一步扰乱代谢通量导致病毒感染细胞的“自杀”（但不包括未感染的细胞），以限制病毒传播。虽然可以选择相关代谢途径中的任何酶，但是在这些代谢途径的关键控制点上的关键酶被优先选择作为候选抗病毒药物靶点。使用这些酶的抑制剂来扭转或重定向病毒感染的影响。通过体外和宿主细胞的筛选试验以及动物模型来测试药物候选物的抗病毒活性。然后使用动物模型来测试候选化合物在预防和治疗病毒感染方面的功效。证明了酶抑制剂的抗病毒活性。
• SELECTIVE INHIBITORS OF UNDIFFERENTIATED CELLS
  申请人：Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

  公开号：EP2852387A2

  公开（公告）日：2015-04-01
• METHODS OF USING SCD1 ANTAGONISTS
  申请人：Genentech, Inc.

  公开号：US20130096181A1

  公开（公告）日：2013-04-18

  Provided herein are therapies for the treatment of pathological conditions, such as cancer, and method of using SCD1 antagonists.
• METHODS FOR TREATING CANCER
  申请人：CHILDREN'S HOSPITAL MEDICAL CENTER

  公开号：US20180042925A1

  公开（公告）日：2018-02-15

  Some embodiments of the invention include methods to treat cancer in animals by administering an SCD inhibitor. Other embodiments include treating cancer in animals where the SCD gene inhibitor is absent in one or both chromatids by administering an SCD inhibitor. Still other embodiments include treating cancer in animals by administering an SCD inhibitor where the SCD gene is absent in one or both chromatids and the animal has a daily intake of one or more of (a) a specified amount of total fat, (b) a specified amount of total fatty acid, (c) a specified amount of total monounsaturated fatty acid, or (d) a specified amount of total oleic acid. Additional embodiments of the invention are also discussed herein.