3-morpholino-1,2-dihydro-1-isoquinolinone | 18630-98-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-morpholino-1,2-dihydro-1-isoquinolinone
• 英文别名: 3-morpholin-4-yl-2H-isoquinolin-1-one；3-morpholin-4-yl-2H-isoquinolin-1-one；3-Morpholino-1-oxo-1,2-dihydro-isochinolin；3-Morpholino-isocarbostyril；3-(Morpholin-4-yl)-1,2-dihydroisoquinolin-1-one
• CAS: 18630-98-3
• 化学式: C₁₃H₁₄N₂O₂
• mdl: MFCD03447775
• 分子量: 230.266
• InChiKey: ZNPFINJPPZRGJT-UHFFFAOYSA-N

物化性质

• 熔点：
  211 °C(Solv: ethanol (64-17-5))
• 沸点：
  496.9±45.0 °C(Predicted)
• 密度：
  1.263±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  苯酞 以 氯苯 为溶剂， 反应 4.0h， 生成 3-morpholino-1,2-dihydro-1-isoquinolinone
  参考文献：
  名称：

  Synthesis and biological evaluation of 3-aminoisoquinolin-1(2H)-one based inhibitors of the dual-specificity phosphatase Cdc25B

  摘要：

  The cell division cycle 25B dual specificity phosphatase (Cdc25B) regulates the normal progression of the mammalian cell cycle by dephosphorylating and activating cyclin-dependent kinase (Cdk) complexes, particularly in response to DNA damage. Elevated Cdc25B levels enable a bypass of normal cell cycle checkpoints, and the overexpression of Cdc25B has been linked to a variety of human cancers. Thus, Cdc25B is an attractive target for the development of anticancer therapeutics. Herein we describe the synthesis and biological evaluation of a series of non-quinoid inhibitors of Cdc25B containing the 3-aminoisoquinolin-1(2H)-one pharmacophore. In addition to several strategies that address specific substitution patterns on isoquinolines, we have applied a regioselective Pd-catalyzed cross-coupling methodology to synthesize a new lead structure, 6-(3-aminophenyl)-3-(phenylamino) isoquinolin-1(2H)-one (13), which proved to be a reversible, competitive Cdc25B inhibitor with a K-i of 1.9 mu M. Compound 13 prevented human cancer cell growth and blocked Cdc25B-mediated mitotic checkpoint bypass. Molecular docking studies support binding near the catalytic site. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.01.043

文献信息

• Condensation of 2-Cyanomethylbenzoic Acid with Secondary Amines as a Method of Synthesis of 3-Amino-1,2-dihydro-1-isoquinolinone Derivatives
  作者：Tatyana Kucherenko、Volodimir Kysil、Volodimir Kovtunenko

  DOI：10.1081/scc-120017192

  日期：2003.1.5

  Abstract A simple one-stage method of preparation of 1,2-dihydro-1-isoquinolinone derivatives was proposed by condensation of 2-cyanomethylbenzoic acid with secondary amines.

  摘要 提出了一种通过2-氰基甲基苯甲酸与仲胺缩合制备1,2-二氢-1-异喹啉酮衍生物的简单一步法。
• Human androgen receptor DNA-binding domain (DBD) compounds as therapeutics and methods for their use
  申请人：The University of British Columbia

  公开号：US10011573B2

  公开（公告）日：2018-07-03

  A compound having the structure of Formula I, wherein A is a substituted or unsubstituted aryl or heteroaryl group, D is a substituted or unsubstituted 5- or 6-membered heteroaryl or heterocyclyl group and E is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl or heterocyclyl group. The compounds are used for the treatment of androgen modulated indications including cancer (prostate, breast, ovarian, endometrial or bladder cancer), hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age related macular degeneration. The use of the compounds for the manufacture of a medicament for modulating AR activity, a method of treatment using such compounds and a pharmaceutical composition and a commercial package comprising said compounds are also described.

  具有式 I 结构的化合物，其中 A 是取代或未取代的芳基或杂芳基，D 是取代或未取代的 5 或 6 元杂芳基或杂环基，E 是取代或未取代的芳基、杂芳基、环烷基或杂环基。这些化合物可用于治疗雄激素调节适应症，包括癌症（前列腺癌、乳腺癌、卵巢癌、子宫内膜癌或膀胱癌）、脱发、痤疮、多毛症、卵巢囊肿、多囊卵巢病、性早熟和老年性黄斑变性。此外，还描述了这些化合物在制造调节 AR 活性的药物中的用途、使用这些化合物的治疗方法以及包含上述化合物的药物组合物和商业包装。
• KIMOTO SHOSHICHIRO; OKAMOTO MASAO; NOGIMORI KATSUMI; USAMI HIROBUMI, YAKUGAKU DZASSI, YAKUGAKU ZASSNI, J. PHARM. SOS. JAR. <YKKZ-AJ>, 1976, 96+
  作者：KIMOTO SHOSHICHIRO、 OKAMOTO MASAO、 NOGIMORI KATSUMI、 USAMI HIROBUMI

  DOI：——

  日期：——
• HUMAN ANDROGEN RECEPTOR DNA-BINDING DOMAN (DBD) COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE
  申请人：The University of British Columbia

  公开号：US20170183319A1

  公开（公告）日：2017-06-29

  A compound having the structure of Formula I, wherein A is a substituted or unsubstituted aryl or heteroaryl group, D is a substituted or unsubstituted 5- or 6-membered heteroaryl or heterocyclyl group and E is a substituted or unsubstituted aryl, heteroaryl, cycloalkyl or heterocyclyl group. The compounds are used for the treatment of androgen modulated indications including cancer (prostate, breast, ovarian, endometrial or blader cancer), hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty and age related macular degeneration. The use of the compounds for the manufacture of a medicament for modulating AR activity, a method of treatment using such compounds and a pharmaceutical composition and a commercial package comprising said compounds arc also described.
• Synthesis and biological evaluation of 3-aminoisoquinolin-1(2H)-one based inhibitors of the dual-specificity phosphatase Cdc25B
  作者：Kara M. George Rosenker、William D. Paquette、Paul A. Johnston、Elizabeth R. Sharlow、Andreas Vogt、Ahmet Bakan、John S. Lazo、Peter Wipf

  DOI：10.1016/j.bmc.2015.01.043

  日期：2015.6

  The cell division cycle 25B dual specificity phosphatase (Cdc25B) regulates the normal progression of the mammalian cell cycle by dephosphorylating and activating cyclin-dependent kinase (Cdk) complexes, particularly in response to DNA damage. Elevated Cdc25B levels enable a bypass of normal cell cycle checkpoints, and the overexpression of Cdc25B has been linked to a variety of human cancers. Thus, Cdc25B is an attractive target for the development of anticancer therapeutics. Herein we describe the synthesis and biological evaluation of a series of non-quinoid inhibitors of Cdc25B containing the 3-aminoisoquinolin-1(2H)-one pharmacophore. In addition to several strategies that address specific substitution patterns on isoquinolines, we have applied a regioselective Pd-catalyzed cross-coupling methodology to synthesize a new lead structure, 6-(3-aminophenyl)-3-(phenylamino) isoquinolin-1(2H)-one (13), which proved to be a reversible, competitive Cdc25B inhibitor with a K-i of 1.9 mu M. Compound 13 prevented human cancer cell growth and blocked Cdc25B-mediated mitotic checkpoint bypass. Molecular docking studies support binding near the catalytic site. (C) 2015 Published by Elsevier Ltd.