1-(4-(hexyloxy)phenyl)-3-morpholinopropan-1-one | 94439-72-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(hexyloxy)phenyl)-3-morpholinopropan-1-one
• 英文别名: 3-Morpholino-1-<4-hexyloxy-phenyl>-propan-1-on；1-(4-hexyloxy-phenyl)-3-morpholin-4-yl-propan-1-one；1-(4-hexoxyphenyl)-3-morpholin-4-ylpropan-1-one
• CAS: 94439-72-2
• 化学式: C₁₉H₂₉NO₃
• 分子量: 319.444
• InChiKey: VJZCZCUEZMGVCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  吗啉 、 1-<(4-hexyloxy)phenyl>-3-chloropropan-1-one 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 以66%的产率得到1-(4-(hexyloxy)phenyl)-3-morpholinopropan-1-one
  参考文献：
  名称：

  Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors

  摘要：

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.

  DOI：

  10.1021/jm9002704

文献信息

• [EN] 1-PHENYLPROPANONE COMPOUNDS AND USE THEREOF<br/>[FR] COMPOSÉS DE 1-PHÉNYLPROPANONE ET LEUR UTILISATION
  申请人：UNIV DEGLI STUDI PADOVA

  公开号：WO2018060947A1

  公开（公告）日：2018-04-05

  The present invention relates to a 1-phenylpropanone compound of formula (I), wherein X is CH2 or an atom selected from the group consisting of O, S and Se, n is an integer from 4 to 6, A is a substituent selected from the group consisting of 4-morpholyl, 1-piperidinyl, 4-methyl-1-piperazinyl, A being optionally substituted with a (C1-C3)alkyl or (C1-C3)acyl substituent, with the proviso that when X is CH2, n is equal to 5, for use as an antitumoral agent in the treatment of breast cancer, chronic lymphatic leukemia or neuroblastoma. The invention also concerns new 1-phenylpropanone compounds, and compounds as antitumoral agents.

  本发明涉及一种化合物，其化学式为(I)，其中X为CH2或从O、S和Se组成的原子中选择的一个，n为4到6之间的整数，A为从4-吗啡基、1-哌啶基、4-甲基-1-哌嗪基中选择的取代基，A可以选择地与(C1-C3)烷基或(C1-C3)酰基取代，但当X为CH2时，n等于5，用作抗肿瘤剂治疗乳腺癌、慢性淋巴细胞白血病或神经母细胞瘤。该发明还涉及新的1-苯基丙酮化合物，以及作为抗肿瘤剂的化合物。
• 1-phenylpropanone compounds and use thereof
  申请人：UNIVERSITA' DEGLI STUDI DI PADOVA

  公开号：US11345673B2

  公开（公告）日：2022-05-31

  The present invention relates to a 1-phenylpropanone compound of formula (I), wherein X is CH2 or an atom selected from the group consisting of O, S and Se, n is an integer from 4 to 6, A is a substituent selected from the group consisting of 4-morpholyl, 1-piperidinyl, 4-methyl-1-piperazinyl, A being optionally substituted with a (C1-C3)alkyl or (C1-C3)acyl substituent, with the proviso that when X is CH2, n is equal to 5, for use as an antitumoral agent in the treatment of breast cancer, chronic lymphatic leukemia or neuroblastoma. The invention also concerns new 1-phenylpropanone compounds, and compounds as antitumoral agents.

  本发明涉及式（I）的 1-苯基丙酮化合物，其中 X 是 CH2 或选自 O、S 和 Se 组成的组的原子，n 是 4 至 6 的整数，A 是选自 4-吗啉基、1-哌啶基、4-甲基-1-哌嗪基组成的组的取代基、4-甲基-1-哌嗪基，A任选被(C1-C3)烷基或(C1-C3)酰基取代，但当X为CH2时，n等于5，用作治疗乳腺癌、慢性淋巴性白血病或神经母细胞瘤的抗肿瘤剂。本发明还涉及新的 1-苯基丙酮化合物和作为抗肿瘤剂的化合物。
• 1-PHENYLPROPANONE COMPOUNDS AND USE THEREOF
  申请人：Universita' Degli Studi Di Padova

  公开号：EP3518927B1

  公开（公告）日：2020-08-12
• Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors
  作者：Jong Yeon Hwang、Leggy A. Arnold、Fangyi Zhu、Aaron Kosinski、Thomas J. Mangano、Vincent Setola、Bryan L. Roth、R. Kiplin Guy

  DOI：10.1021/jm9002704

  日期：2009.7.9

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.