viloxazine | 46346-82-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: viloxazine
• 英文别名: 2-[phenoxymethyl]-morpholine；2-(Phenoxymethyl)morpholin；2(RS)-(phenoxymethyl)morpholine；2-(Phenoxymethyl)morpholine
• CAS: 46346-82-1
• 化学式: C₁₁H₁₅NO₂
• mdl: MFCD06738824
• 分子量: 193.246
• InChiKey: OFBLNBCFCXAZGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  viloxazine 、 2-氯甲基苯并咪唑 在 potassium carbonate 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 以66%的产率得到2-(2-phenoxymethylmorpholin-4-ylmethyl)benzimidazole
  参考文献：
  名称：

  Morpholine derivatives as dopamine receptor subtype ligands

  摘要：

  一类代替基吗啡啶衍生物，其化学式为##STR1## 其中Y代表一个含有一个或两个氮原子的可选取代的双环杂芳香环系统，该环系统包括一个与五或六元杂芳香环融合的六元芳香或杂芳香环; Z代表一个可选取代的芳基烷基，芳基氧甲基或芳基烷氧甲基基团，是体内多巴胺受体亚型的配体，因此在多巴胺系统疾病的治疗和/或预防中特别是精神分裂症方面有用。

  公开号：

  US05614518A1
• 作为产物：
  描述：

  4-苄基-2-(氯甲基)吗啉 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~120.0 ℃ 、101.33 kPa 条件下， 反应 0.33h， 生成 viloxazine
  参考文献：
  名称：

  Development of the First Generation of Disulfide-Based Subtype-Selective and Potent Covalent Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors

  摘要：

  Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, on the basis of the scaffold of 16, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analogue, 3a, effectively inhibits PDK1 both at the molecular (k(mact)/K-i = 4.17 x 10(3) M-1 s(-1)) and the cellular level (down to 0.1 mu M). In contrast to 16, 3a is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2-4. 3a also significantly alters glucose metabolic pathways in A549 cells by decreasing ECAR and increasing ROS. Moreover, in the xenograft models, 3a shows significant antitumor activity with no negative effect to the mice weight. Collectively, these data demonstrate that 3a may be an excellent lead compound for the treatment of cancer as a first-generation subtype-selective and covalent PDK1 inhibitor.

  DOI：

  10.1021/acs.jmedchem.6b01245

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC AMINE DERIVATIVES AS MULTIKINASE INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS D'AMINE HÉTÉROCYCLIQUES SUBSTITUÉS COMME INHIBITEURS DE MULTIKINASE POUR LE TRAITEMENT DU CANCER
  申请人：PIRAMAL ENTPR LTD

  公开号：WO2015128698A1

  公开（公告）日：2015-09-03

  The present invention relates to compounds of formula (I), their isotopic forms, stereoisomeric forms, tautomeric forms, pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs or N-oxides thereof. The present invention also relates to processes for the preparation of compounds of formula (I) and pharmaceutical compositions comprising the compounds of formula (I). The compounds and their pharmaceutical compositions are multikinase inhibitors and are useful in the treatment of proliferative disorders, such as cancers.

  本发明涉及式(I)的化合物，其同位素形式，立体异构体形式，互变异构体形式，药学上可接受的盐，药学上可接受的溶剂化合物，前药，多晶形或其N-氧化物。本发明还涉及制备式(I)化合物的方法和包括式(I)化合物的药物组合物。这些化合物及其药物组合物是多激酶抑制剂，可用于治疗增殖性疾病，如癌症。
• Heterocyclic cyclopentyl tetrahydroisoquinoline and tetrahydropyridopyridine modulators of chemokine receptor activity
  申请人：Butora Gabor

  公开号：US20080081803A1

  公开（公告）日：2008-04-03

  The present invention is directed to compounds of the formula I: Wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X, n and the broken lines are as defined herein which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptor CCR-2.

  本发明涉及以下式I的化合物： 其中R1、R2、R3、R4、R5、R6、R7、R8、R9、X、n和虚线如本文所定义，这些化合物可用作趋化因子受体活性的调节剂。特别地，这些化合物可用作趋化因子受体CCR-2的调节剂。
• Combination therapy
  申请人：——

  公开号：US20040102360A1

  公开（公告）日：2004-05-27

  The present invention relates to methods of treating cancer using a combination of at least two Akt inhibitors or a compound which is an inhibitor of Akt and an inhibitor of a protein kinase, which methods comprise administering to a mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound(s) which are inhibitors of Akt and compound(s) which are inhibitors of protein kinases. The invention also relates to methods of preparing such compositions.

  本发明涉及使用至少两种Akt抑制剂的组合或一种同时是Akt抑制剂和蛋白激酶抑制剂的化合物来治疗癌症的方法，该方法包括向哺乳动物施用来自以下组合中选择的至少两种治疗剂的量，该组合包括Akt抑制剂和蛋白激酶抑制剂。该发明还涉及制备这种组合物的方法。
• LONG-CHAIN FATTY ACYL ELONGASE INHIBITOR COMPRISING ARYLSULFONYL DERIVATIVE AS ACTIVE INGREDIENT
  申请人：Jitsuoka Makoto

  公开号：US20110009622A1

  公开（公告）日：2011-01-13

  [Problem] To provide compounds useful as preventives or remedies for circular system disorders, nervous system disorders, metabolic disorders, reproduction system disorders, digestive system disorders, neoplasm, infectious diseases, etc., or as herbicides. [Means for Solution] A long-chain fatty acyl elongase inhibitor comprising, as the active ingredient thereof, a compound or a pharmaceutically-active salt thereof of a formula (I): [wherein W represents a hydrogen atom, a C 1-6 alkyl, etc.; X represents an aryl, a heteroaryl, etc.; n indicates 0 or 1; Z represents a hydrogen atom, a C 1-6 alkyl, etc.; A 1 , A 2 , A 3 and A 4 each independently represent CH or N].

  提供化合物，可用作循环系统紊乱、神经系统紊乱、代谢紊乱、生殖系统紊乱、消化系统紊乱、肿瘤、传染病等的预防或治疗，或用作除草剂的方法。一种长链脂肪酰基延长酶抑制剂，其作为活性成分包括下述公式（I）的化合物或其药用活性盐：[其中，W代表氢原子、C1-6烷基等；X代表芳基、杂环芳基等；n表示0或1；Z代表氢原子、C1-6烷基等；A1，A2，A3和A4分别独立地代表CH或N]。
• [EN] A PROCESS FOR THE PREPARATION OF MORPHOLINO SULFONYL INDOLE DERIVATIVES<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE DÉRIVÉS DE MORPHOLINOSULFONYLINDOLE
  申请人：PIRAMAL HEALTHCARE LTD

  公开号：WO2012143874A1

  公开（公告）日：2012-10-26

  The present invention relates to a process for the preparation of the compounds of formula (I) which are morpholino sulphonyl indole derivatives. The compounds of formula (I) are capable of inhibiting, modulating or regulating Insulin-Like-Growth Factor I Receptors or Insulin Receptors. The present invention also relates to the processes for preparation of the pharmaceutically acceptable salts of the compounds of formula (I).

  本发明涉及一种制备式(I)化合物的方法，这些化合物是吗啡啶磺酰基吲哚衍生物。式(I)化合物能够抑制、调节或调控胰岛素样生长因子I受体或胰岛素受体。本发明还涉及制备式(I)化合物的药用可接受盐的方法。