pyridin-3-yl carbonochloridate | 165739-74-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: pyridin-3-yl carbonochloridate
• 英文别名: pyridin-3-yl chloroformate；3-pyridyl chloroformate；pyridin-3-yl chloridocarbonate
• CAS: 165739-74-2
• 化学式: C₆H₄ClNO₂
• 分子量: 157.556
• InChiKey: UDLWVSDXEKQRKZ-UHFFFAOYSA-N

物化性质

• 沸点：
  214.0±13.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-Chloro-11-(1-Piperazinyl)-6,11-Dihydro-5H-Benzo[5,6]Cyclohepta[1,2-b]Pyridine 、 pyridin-3-yl carbonochloridate 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3-PYRIDYL 4-(8-CHLORO-6,11-DIHYDRO-5H-BENZO[5,6]-CYCLOHEPTA[1,2-b]PYRIDIN-11-YL)-1-PIPERAZINECARBOXYLATE
  参考文献：
  名称：

  Inhibitors of Farnesyl Protein Transferase. 4-Amido, 4-Carbamoyl, and 4-Carboxamido Derivatives of 1-(8-Chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-Bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine

  摘要：

  The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin -11-yl)piperazine to explore the SAR of of this series of FPT inhibitors is described. This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and 50a, respectively, both of which were orally active but were found to be rapidly metabolized in vivo. Identification of the principal metabolites led to the synthesis of a variety of new compounds that would be less readily metabolized, the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and 83a. Novel replacements for the pyridylacetyl moiety were also sought, and this resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl derivatives 135a and 160a, respectively. All of these derivatives exhibited greatly improved pharmacokinetics. The synthesis of the corresponding 3-bromo analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (+/-) and 85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (+/-), all of which exhibited potent FPT inhibition in vitro. All three showed excellent oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited excellent antitumor efficacy against a series of tumor cell lines when dosed orally in nude mice.

  DOI：

  10.1021/jm970462w
• 作为产物：
  描述：

  3-羟基吡啶 、 光气 在 吡啶 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 pyridin-3-yl carbonochloridate
  参考文献：
  名称：

  Novel lapachone compounds and methods of use thereof

  摘要：

  本发明提供了一种新型的三环螺-氧杂硫杂萘醌衍生物，一种制造该衍生物的方法，以及利用该衍生物诱导细胞死亡和/或抑制癌症或前癌细胞增殖的应用。本发明的萘醌衍生物与被称为β-拉帕醇（3,4-二氢-2,2-二甲基-2H-萘(1,2-b)吡喃-5,6-二酮）的化合物有关。

  公开号：

  US20090105166A1

文献信息

• Tricyclic carbamate compounds useful for inhibition of G-protein
  申请人：Schering Corporation

  公开号：US06075025A1

  公开（公告）日：2000-06-13

  A method of inhibiting Ras function and therefore inhibiting cellular growth is disclosed. The method comprises the administration of a compound of Formula 1.0 ##STR1## Also disclosed are novel compounds of the formulas: ##STR2## Also disclosed are processes for making 3-substituted compounds of the Formulas 1.1, 1.2 and 1.3. Further disclosed are novel compounds which are intermediates in the processes for making the 3-substituted compounds of Formulas 1.1, 1.2, and 1.3.

  揭示了一种抑制Ras功能从而抑制细胞生长的方法。该方法包括给予Formula 1.0的化合物。还揭示了以下公式的新化合物：还揭示了制备公式1.1、1.2和1.3的3-取代化合物的方法。进一步揭示了在制备公式1.1、1.2和1.3的3-取代化合物的过程中的新化合物。
• ω-Heteroarylalkylcarbamates as inhibitors of fatty acid amide hydrolase (FAAH)
  作者：Tobias Terwege、Helmut Dahlhaus、Walburga Hanekamp、Matthias Lehr

  DOI：10.1039/c4md00181h

  日期：——

  A series of heteroaryl-substituted alkylcarbamates have been synthesized and evaluated for their inhibitory potency against fatty acid amide hydrolase (FAAH).

  已合成一系列杂环基取代的烷基氨基甲酸酯，并对其在抑制脂肪酸酰胺水解酶（FAAH）方面的抑制效力进行了评估。
• ω-Imidazolyl- and ω-Tetrazolylalkylcarbamates as Inhibitors of Fatty Acid Amide Hydrolase: Biological Activity and in vitro Metabolic Stability
  作者：Tobias Terwege、Walburga Hanekamp、David Garzinsky、Simone König、Oliver Koch、Matthias Lehr

  DOI：10.1002/cmdc.201500445

  日期：2016.2

  Fatty acid amide hydrolase (FAAH) is a serine hydrolase that terminates the analgesic and anti‐inflammatory effects of endocannabinoids such as anandamide. Herein, structure–activity relationship studies on a new series of aryl N‐(ω‐imidazolyl‐ and ω‐tetrazolylalkyl)carbamate inhibitors of FAAH were investigated. As one result, a pronounced increase in inhibitory potency was observed if a phenyl residue

  脂肪酸酰胺水解酶（FAAH）是一种丝氨酸水解酶，可终止内源性大麻素（如anandamide）的镇痛和抗炎作用。在此，研究了一系列新的FAAH芳基N-（ω-咪唑基和ω-四唑基烷基）氨基甲酸酯抑制剂的结构活性关系。结果是，如果连接到氨基甲酸酯氧原子上的苯基残基被吡啶3-3-基部分取代，则抑制效力会显着提高。活性最高的化合物的IC 50值在低纳摩尔范围内。另外，对这些抑制剂的代谢特性进行了研究。在大鼠肝脏匀浆和猪血浆中，其降解程度显示出强烈依赖于与氨基甲酸酯键合的芳基残基的种类以及与氨基甲酸酯基团与杂环系统连接的烷基间隔基的长度和类型。在酯酶抑制剂的帮助下，已表明在猪血浆中，类似羧酸酯酶和对氧磷酶参与了氨基甲酸酯的裂解。此外，还发现高活性的吡啶基-3-基氨基甲酸酯与白蛋白发生反应，从而导致共价白蛋白加合物。
• Pyridyl Non-Aromatic Nitrogen-Containing Heterocyclic-1-Carboxylate Compound
  申请人：Ishii Takahiro

  公开号：US20100009971A1

  公开（公告）日：2010-01-14

  A novel pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate compound or its pharmaceutically acceptable salt has a potent FAAH-inhibitory activity. Further, the pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate compound of the present disclosure is also useful in the treatment of urinary frequency and urinary incontinence, overactive bladder and/or pain.

  一种新型的吡啶基非芳香性含氮杂环-1-羧酸酯化合物或其药学上可接受的盐具有强效的FAAH抑制活性。此外，本公开的吡啶基非芳香性含氮杂环-1-羧酸酯化合物也可用于治疗尿频、尿失禁、过度活跃的膀胱和/或疼痛。
• Tricyclic carbamate compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
  申请人：Schering Corporation

  公开号：US06300338B1

  公开（公告）日：2001-10-09

  A method of inhibiting Ras function and therefore inhibiting cellular growth is disclosed. The method comprises the administration of a compound of Formula 1.0 Also disclosed are novel compounds of the formulas: Also disclosed are processes for making 3-substituted compounds of the Formulas 1.1, 1.2 and 1.3. Further disclosed are novel compounds which are intermediates in the processes for making the 3-substituted compounds of Formulas 1.1, 1.2, and 1.3.

  本发明公开了一种抑制Ras功能从而抑制细胞生长的方法。该方法包括给予式1.0的化合物。本发明还公开了式1.1、1.2和1.3的新化合物。本发明还公开了制备式1.1、1.2和1.3的3-取代化合物的方法。此外，本发明还公开了制备式1.1、1.2和1.3的3-取代化合物的中间体新化合物。