1-benzyloxycarbonylamino-2-butanone | 224441-65-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-benzyloxycarbonylamino-2-butanone
• 英文别名: 1-[(benzyloxycarbonyl)amino]-2-butanone；1-benzyloxycarbonylamino2-butanone；Benzyl (2-oxobutyl)carbamate；benzyl N-(2-oxobutyl)carbamate
• CAS: 224441-65-0
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: GQXXEURLDOMPBM-UHFFFAOYSA-N

物化性质

• 沸点：
  371.4±35.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzyloxycarbonylamino-2-butanone 在 10percent Pd/C 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 以100%的产率得到1-氨基-2-丁酮盐酸盐
  参考文献：
  名称：

  Discovery of Aminothiazole Inhibitors of Cyclin-Dependent Kinase 2:  Synthesis, X-ray Crystallographic Analysis, and Biological Activities

  摘要：

  High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC50 values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.

  DOI：

  10.1021/jm0201520
• 作为产物：
  描述：

  1-[(benzyloxycarbonyl)amino]-2-butanol 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以82%的产率得到1-benzyloxycarbonylamino-2-butanone
  参考文献：
  名称：

  Discovery of Aminothiazole Inhibitors of Cyclin-Dependent Kinase 2:  Synthesis, X-ray Crystallographic Analysis, and Biological Activities

  摘要：

  High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC50 values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.

  DOI：

  10.1021/jm0201520

文献信息

• Aminothiazole inhibitors of cyclin dependent kinases
  申请人：Bristol-Myers Squibb Company

  公开号：US06040321A1

  公开（公告）日：2000-03-21

  Compounds of the formula ##STR1## and pharmaceuticaly acceptable salts thereof. As used in formula I, and throughout the specification, the symbols have the following meanings: R.sub.1 and R.sub.2 are independently hydrogen, fluorine or alkyl; R.sub.3 is aryl or heteroaryl R.sub.4 is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylalkyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl; or CO-alkyl, CONH-alkyl, COO-alkyl, SO.sub.2 -alkyl, C(NCN)NH-alkyl, C(NNO.sub.2)NH-alkyl, C(NH)NH-alkyl, C(NH)NHCO-alkyl, C(NOR.sub.6)NH-alkyl, R.sub.5 is hydrogen or alkyl; R.sub.6 is hydrogen, alkyl, cycloalkyl, aryl, cycloalkylakyl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; m is an integer of 0 to 2; and n is an integer of 1 to 3. The compounds of formula I are protein kinase inhibitors and are useful in the treatment and prevention of proliferative diseases, for example, cancer, inflammation and arthritis. They may also be useful in the treatment of neurodegenerative diseases such as Alzheimer's disease, cardiovascular diseases, viral diseases and fungal diseases.

  公式##STR1##的化合物及其药用盐。在公式I中使用时，以及在说明书中，符号具有以下含义：R.sub.1和R.sub.2独立地是氢、氟或烷基；R.sub.3是芳基或杂环芳基；R.sub.4是氢、烷基、环烷基、芳基、环烷基烷基、芳基烷基、杂环芳基、杂环芳基烷基、杂环烷基、杂环烷基烷基；或CO-烷基、CONH-烷基、COO-烷基、SO.sub.2-烷基、C(NCN)NH-烷基、C(NNO.sub.2)NH-烷基、C(NH)NH-烷基、C(NH)NHCO-烷基、C(NOR.sub.6)NH-烷基；R.sub.5是氢或烷基；R.sub.6是氢、烷基、环烷基、芳基、环烷基烷基、芳基烷基、杂环芳基、杂环芳基烷基、杂环烷基或杂环烷基烷基；m是0到2的整数；n是1到3的整数。公式I的化合物是蛋白激酶抑制剂，可用于治疗和预防增殖性疾病，例如癌症、炎症和关节炎。它们也可能对治疗神经退行性疾病如阿尔茨海默病、心血管疾病、病毒性疾病和真菌性疾病有益。
• HETERO RING DERIVATIVE
  申请人：Takahashi Fumie

  公开号：US20120165309A1

  公开（公告）日：2012-06-28

  [Object] A novel and excellent method for preventing or treating rejection in the transplantation of various organs, allergy diseases, autoimmune diseases, hematologic tumor, or the like, based on a PI3Kδ-selective inhibitory action and/or an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action (including an activation inhibitory action), is provided [Means for Solution] It was found that a 3-substituted triazine or 3-substituted pyrimidine derivative exhibits a PI3Kδ-selective inhibitory action, and/or an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action (including an activation inhibitory action), and can be an agent for preventing or treating rejection in the transplantation of various organs, allergy diseases (asthma, atopic dermatitis, etc.), autoimmune diseases (rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, etc.), hematologic tumor (leukemia etc.), or the like, thereby completing the present invention.

  [目标]提供一种基于PI3Kδ选择性抑制作用和/或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括激活抑制作用）的新颖优良方法，用于预防或治疗各种器官移植、过敏性疾病、自身免疫性疾病、血液肿瘤等的排斥反应。 [解决方案]发现3-取代-1,3,5-三嗪或3-取代嘧啶衍生物表现出PI3Kδ选择性抑制作用和/或IL-2产生抑制作用和/或B细胞增殖抑制作用（包括激活抑制作用），可以作为预防或治疗各种器官移植、过敏性疾病（哮喘、特应性皮炎等）、自身免疫性疾病（类风湿性关节炎、银屑病、溃疡性结肠炎、克罗恩病、系统性红斑狼疮等）、血液肿瘤（白血病等）等排斥反应的药物，从而完成了本发明。
• SOLUBLE GUANYLATE CYCLASE ACTIVATORS
  申请人：BOSANAC Todd

  公开号：US20130203729A1

  公开（公告）日：2013-08-08

  The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 -R 5 and n are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  本发明涉及式（I）的化合物及其药学上可接受的盐，其中R1-R5和n的定义如本文所述。本发明还涉及包括这些化合物的制药组合物，在治疗各种疾病和障碍中使用这些化合物的方法，制备这些化合物的过程以及这些过程中有用的中间体。
• AMINOTHIAZOLE INHIBITORS OF CYCLIN DEPENDENT KINASES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1042307A1

  公开（公告）日：2000-10-11
• EP1042307A4
  申请人：——

  公开号：EP1042307A4

  公开（公告）日：2003-01-29