1-(4-(2-morpholinoethoxy)phenyl)propan-1-one | 2089-21-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(2-morpholinoethoxy)phenyl)propan-1-one
• 英文别名: 1-[4-(2-Morpholino-aethoxy)-phenyl]-propan-1-on；1-[4-(2-Morpholin-4-ylethoxy)phenyl]propan-1-one
• CAS: 2089-21-6
• 化学式: C₁₅H₂₁NO₃
• mdl: MFCD01695064
• 分子量: 263.337
• InChiKey: OYSQNUOSVOCLFK-UHFFFAOYSA-N

物化性质

• 沸点：
  411.0±35.0 °C(Predicted)
• 密度：
  1.085±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.533
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  1-(4-(2-morpholinoethoxy)phenyl)propan-1-one 、 5-chloro-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)aniline 在 三氟甲磺酸 作用下， 以 正丁醇 为溶剂， 以43%的产率得到7-chloro-3-methyl-2-[4-(2-morpholinoethoxy)phenyl]-1H-quinolin-4-one
  参考文献：
  名称：

  Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2)

  摘要：

  Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.

  DOI：

  10.1021/jm201184h
• 作为产物：
  描述：

  N-(2-氯乙基)吗啉盐酸盐 、 4-羟基苯丙酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以85%的产率得到1-(4-(2-morpholinoethoxy)phenyl)propan-1-one
  参考文献：
  名称：

  Flexible Estrogen Receptor Modulators:  Design, Synthesis, and Antagonistic Effects in Human MCF-7 Breast Cancer Cells

  摘要：

  Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds ' potential interactions with specific residues within the human estrogen receptor a ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.

  DOI：

  10.1021/jm001119l

文献信息

• Cysteine Protease inhibitors
  申请人：Nilsson Magnus

  公开号：US20080234260A1

  公开（公告）日：2008-09-25

  A compound of the formula II wherein one of R 1 and R 2 is halo and the other is H or halo; R 3 is C 1 -C 4 straight or branched chain, optionally fluorinated, alkyl; R 4 is H; or R 3 together with R 4 and the adjoining backbone carbon defines: a spiro-C 5 -C 7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl; or optionally bridged with a methylene group; or a C 4 -C 6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(═O) 2 ; where Ra is H, C 1 -C 4 alkyl or CH 3 C(═O); R 5 is independently selected from H or methyl; E is —C(═O)—, —S(═O) m —, —NR 5 S(═O) m —, —NR 5 C(═O)—, —OC(═O)—, R 6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

  化合物II的公式为其中R1和R2中的一个是卤素，另一个是氢或卤素;R3是C1-C4直链或支链，可选择氟代的烷基;R4是氢;或R3与R4和相邻的骨架碳一起定义:一个螺旋C5-C7环烷基，可选地被1至3个取代基所取代，所述取代基选自卤素、羟基、C1-C4烷基或C1-C4卤代烷基;或者可选地通过亚甲基基桥接;或者是一个C4-C6饱和杂环，其中杂原子选自O、NRa、S、S(═O)2;其中Ra是H、C1-C4烷基或CH3C(═O);R5是独立选择的H或甲基;E是—C(═O)—、—S(═O)m—、—NR5S(═O)m—、—NR5C(═O)—、—OC(═O)—;R6是稳定的、可选地取代的、单环或双环、碳环或杂环;m独立地为0、1或2;是猫hepsin K的抑制剂，用于治疗或预防骨质疏松症。
• Cysteine Protease Inhibitors
  申请人：NILSSON Magnus

  公开号：US20110112089A1

  公开（公告）日：2011-05-12

  A compound of the formula II wherein one of R 1 and R 2 is halo and the other is H or halo; R 3 is C 1 -C 4 straight or branched chain, optionally fluorinated, alkyl; R 4 is H; or R 3 together with R 4 and the adjoining backbone carbon defines: a spiro-C 5 -C 7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C 1 -C 4 alkyl or C 1 -C 4 haloalkyl; or optionally bridged with a methylene group; or a C 4 -C 6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(═O) 2 ; where Ra is H, C 1 -C 4 alkyl or CH 3 C(═O); R 5 is independently selected from H or methyl; E is —C(═O)—, —S(═O) m —, —NR 5 S(═O) m —, —NR 5 C(═O)—, —OC(═O)—, R 6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or hetorocycle; m is independently 0, 1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.

  该化合物的公式为II，其中R1和R2中的一个是卤素，另一个是氢或卤素；R3是直链或支链的C1-C4烷基，可以是氟代的；R4是氢；或者R3与R4和相邻的骨架碳共同定义了一个螺旋状的C5-C7环烷基，可以选择性地用1至3个取代基中的卤素、羟基、C1-C4烷基或C1-C4卤代烷基进行取代；或者选择性地用亚甲基桥接；或者是一个具有O、NRa、S、S(═O)2等杂原子的C4-C6饱和杂环，其中Ra是H、C1-C4烷基或CH3C(═O)；R5是独立选择的H或甲基；E是—C(═O)—、—S(═O)m—、—NR5S(═O)m—、—NR5C(═O)—、—OC(═O)—；R6是一个稳定的、可以选择性地取代的单环或双环的碳环或杂环；m是独立选择的0、1或2。这些化合物是猫hepsin K的抑制剂，并且在治疗或预防骨质疏松症方面有用。
• Flexible Estrogen Receptor Modulators:  Design, Synthesis, and Antagonistic Effects in Human MCF-7 Breast Cancer Cells
  作者：Mary J. Meegan、Rosario B. Hughes、David G. Lloyd、D. Clive Williams、Daniela M. Zisterer

  DOI：10.1021/jm001119l

  日期：2001.3.1

  Although many series of estrogen receptor antagonists continue to be produced, the majority are direct structural analogues of existing modulators. To examine the tolerance of the estrogen receptor toward flexible ligands, a series of novel flexible estrogen receptor antagonists were prepared and their antiproliferative effects on human MCF-7 breast tumor cells investigated. Each of these compounds deviated from the traditional triphenylethylene backbone associated with common tamoxifen analogues through the introduction of a flexible methylene (benzylic) spacing group between one of the aryl rings and the ethylene group and through variations in the basic side chain moiety. The compounds prepared, when assayed in conjunction with a tamoxifen standard, demonstrated high potency in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity and high binding affinity. A computational study was undertaken to investigate the compounds ' potential interactions with specific residues within the human estrogen receptor a ligand-binding domain (ER-LBD), predicting these compounds bind in an antiestrogenic fashion within the ER-LBD and interact with those important residues previously identified in the structures of ER-LBD agonist/antagonist cocrystals. These compounds further illustrate the eclectic nature of the estrogen receptor in terms of ligand flexibility tolerance.
• US7915300B2
  申请人：——

  公开号：US7915300B2

  公开（公告）日：2011-03-29
• Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting <i>Plasmodium falciparum</i> Type II NADH:Quinone Oxidoreductase (PfNDH2)
  作者：Suet C. Leung、Peter Gibbons、Richard Amewu、Gemma L. Nixon、Chandrakala Pidathala、W. David Hong、Bénédicte Pacorel、Neil G. Berry、Raman Sharma、Paul A. Stocks、Abhishek Srivastava、Alison E. Shone、Sitthivut Charoensutthivarakul、Lee Taylor、Olivier Berger、Alison Mbekeani、Alasdair Hill、Nicholas E. Fisher、Ashley J. Warman、Giancarlo A. Biagini、Stephen A. Ward、Paul M. O’Neill

  DOI：10.1021/jm201184h

  日期：2012.3.8

  Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a molecule suitable for further development. In order to reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (8b). 8b has IC(50)s in the nanomolar range versus both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg versus Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogues in this series also demonstrate nanomolar activity against the bc(1) complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies.