8-chloro-2-[2-(dimethylamino)ethyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one | 1108169-75-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 8-chloro-2-[2-(dimethylamino)ethyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one
• 英文别名: Benzothienopyrimidinone deriv., 6j；8-chloro-2-[2-(dimethylamino)ethyl]-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one
• CAS: 1108169-75-0
• 化学式: C₁₄H₁₄ClN₃OS
• 分子量: 307.804
• InChiKey: RKJBOGXNNPWZEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  72.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  8-chloro-2-(chloromethyl)-3H-[1]benzothiolo[3,2-d]pyrimidin-4-one 、 三甲胺 以 N,N-二甲基甲酰胺 为溶剂， 生成 8-chloro-2-[2-(dimethylamino)ethyl][1]benzothieno[3,2-d]pyrimidin-4(3H)-one
  参考文献：
  名称：

  Discovery of 3H-Benzo[4,5]thieno[3,2-d]pyrimidin-4-ones as Potent, Highly Selective, and Orally Bioavailable Inhibitors of the Human Protooncogene Proviral Insertion Site in Moloney Murine Leukemia Virus (PIM) Kinases

  摘要：

  Pim-1, Pim-2, and Pim-3 are a family of serine/threonine kinases which have been Found to be overexpressed in a variety of hematopoietic malignancies and solid tumors. Benzothienopyrimidinones were discovered as a novel class of Pim inhibitors that potently inhibit all three Pim kinases with subnanomolar to low single-digit nanomolar K-i values and exhibit excellent selectivity against a panel of diverse kinases. Protein crystal structures of the bound Pim-1 complexes of benzothienopyrimidinones 3b (PDB code 3JYA), 6e (PDB code 3JYO), and 12b (PDB code 3JXW) were determined and used to guide SAR studies. Multiple compounds exhibited potent antiproliferative activity in K562 and MV4-11 cells with submicromolar EC50 values. For example, compound 14j inhibited the growth of K562 cells with an EC50 value of 1.7 mu M and showed K-i values of 2, 3, and 0.5 nM against Pim-1, Pim-2, and Pim-3, respectively. These novel Pim kinase inhibitors efficiently interrupted the phosphorylation of Bad in both K562 and LnCaP-Bad cell lines, indicating that their potent biological activities are mechanism-based. The pharmacokinetics of 14j was studied in CD-1 mice and shown to exhibit bioavailability of 76% after oral dosing. ADME profiling of 14j suggested a long half-life in both human and mouse liver microsomes, good permeability, modest protein bin-ling, and no CYP inhibition below 20 mu M concentration.

  DOI：

  10.1021/jm900943h

文献信息

• PIM KINASE INHIBITORS AS CANCER CHEMOTHERAPEUTICS
  申请人：Wang Le

  公开号：US20090030196A1

  公开（公告）日：2009-01-29

  Inhibitors of Pim kinases, ways to make them and methods of treating patients using them are disclosed.

  本发明揭示了抑制Pim激酶的抑制剂、制备方法以及使用它们治疗患者的方法。
• Non-ionic surfactants for solubilizing poorly solubule molecules
  申请人：von Corswant Christian

  公开号：US20060287542A1

  公开（公告）日：2006-12-21

  New non-ionic surfactants in the form of polyoxyalkylene glycol hydroxy fatty acid derivatives or monoalkylated polyoxyalkylene glycol hydroxy fatty acid derivatives having a polyoxyalkylene / alkyl polyoxyalkylene chain with a chain-length of 25-455 repeating units and a specified substituent on the hydroxy position of the specified hydroxy fatty acid, according to the general formula (I) CH 3 —(CH 2 ) x —CH—(CH 2 ) y —CO—[—O—R 3 —] z —O—R 1 R 2 —O (I); wherein for example R 1 is methyl, R 2 is optionally substituted C 14 —C 22 acyl, alkyl, or alkenyl, R 3 is ethylene, x is 2-12, y is 7-17, (x+y) is 3-19 and z is 25-57; advantageously prepared by involving an enzymatic process, formulations comprising them, their use as solubilizers and a process involving a hydrolytic enzyme for preparing them.

  新的非离子表面活性剂采用聚氧烷基乙二醇羟基脂肪酸衍生物或单烷基化聚氧烷基乙二醇羟基脂肪酸衍生物形式，具有聚氧烷基/烷基聚氧烷基链，链长为25-455个重复单元，并且在指定羟基脂肪酸的羟基位置上具有指定的取代基，按照通式(I) CH3—(CH2)x—CH—(CH2)y—CO—[—O—R3—]z—O—R1R2—O (I)；其中，例如R1为甲基，R2为可选取代的C14-C22酰基，烷基或烯基，R3为乙烯，x为2-12，y为7-17，(x+y)为3-19，z为25-57；通过涉及酶法的方法优选制备，包含它们的配方，它们作为溶解剂的用途以及涉及水解酶制备它们的方法。
• NEW NON-IONIC SURFACTANTS FOR SOLUBILIZING POORLY SOLUBLE MOLECULES
  申请人：AstraZeneca AB

  公开号：EP1615874B1

  公开（公告）日：2013-12-25
• US7491836B2
  申请人：——

  公开号：US7491836B2

  公开（公告）日：2009-02-17
• Discovery of 3<i>H</i>-Benzo[4,5]thieno[3,2-<i>d</i>]pyrimidin-4-ones as Potent, Highly Selective, and Orally Bioavailable Inhibitors of the Human Protooncogene Proviral Insertion Site in Moloney Murine Leukemia Virus (PIM) Kinases
  作者：Zhi-Fu Tao、Lisa A. Hasvold、Joel D. Leverson、Edward K. Han、Ran Guan、Eric F. Johnson、Vincent S. Stoll、Kent D. Stewart、Geoff Stamper、Nirupama Soni、Jennifer J. Bouska、Yan Luo、Thomas J. Sowin、Nan-Horng Lin、Vincent S. Giranda、Saul H. Rosenberg、Thomas D. Penning

  DOI：10.1021/jm900943h

  日期：2009.11.12

  Pim-1, Pim-2, and Pim-3 are a family of serine/threonine kinases which have been Found to be overexpressed in a variety of hematopoietic malignancies and solid tumors. Benzothienopyrimidinones were discovered as a novel class of Pim inhibitors that potently inhibit all three Pim kinases with subnanomolar to low single-digit nanomolar K-i values and exhibit excellent selectivity against a panel of diverse kinases. Protein crystal structures of the bound Pim-1 complexes of benzothienopyrimidinones 3b (PDB code 3JYA), 6e (PDB code 3JYO), and 12b (PDB code 3JXW) were determined and used to guide SAR studies. Multiple compounds exhibited potent antiproliferative activity in K562 and MV4-11 cells with submicromolar EC50 values. For example, compound 14j inhibited the growth of K562 cells with an EC50 value of 1.7 mu M and showed K-i values of 2, 3, and 0.5 nM against Pim-1, Pim-2, and Pim-3, respectively. These novel Pim kinase inhibitors efficiently interrupted the phosphorylation of Bad in both K562 and LnCaP-Bad cell lines, indicating that their potent biological activities are mechanism-based. The pharmacokinetics of 14j was studied in CD-1 mice and shown to exhibit bioavailability of 76% after oral dosing. ADME profiling of 14j suggested a long half-life in both human and mouse liver microsomes, good permeability, modest protein bin-ling, and no CYP inhibition below 20 mu M concentration.