替罗非班杂质 | 88940-35-6

• 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
• 中文名称: 替罗非班杂质
• 英文名称: 4-(3-pyridinyl)butyl chloride
• 英文别名: 4-(3-Pyridyl)-butylchlorid；3-(4-chloro-butyl)-pyridine；3-(4-chlorobutyl)pyridine
• CAS: 88940-35-6
• 化学式: C₉H₁₂ClN
• 分子量: 169.654
• InChiKey: QOJKBBGLSMESRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  替罗非班杂质 、 2-(1-methylethyl)-11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acid 在 potassium iodide 、 potassium carbonate 作用下， 以 N-甲基乙酰胺 为溶剂， 生成 2-(1-methylethyl)-11-oxo-11H-pyrido<2,1-b>quinazoline-8-carboxylic acid 8-<4-(3-pyridinyl)butyl ester>
  参考文献：
  名称：

  Pyrido[2,1-b]quinazoline derivatives useful as agents for treatment of

  摘要：

  该文描述了化合物的结构公式为##STR1##其中R.sub.1、R.sub.2和R.sub.3如下所述的吡啶[2,1-b]喹唑啉衍生物。公式I和II的化合物可用作治疗过敏症状的药物，也可用于治疗涉及血栓形成的血管疾病。

  公开号：

  US04551460A1
• 作为产物：
  描述：

  3-吡啶丁醇 在 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 替罗非班杂质
  参考文献：
  名称：

  Structure−Activity Relationships of (E)-3-(1,4-Benzoquinonyl)-2-[(3-pyridyl)- alkyl]-2-propenoic Acid Derivatives That Inhibit Both 5-Lipoxygenase and Thromboxane A₂ Synthetase

  摘要：

  As part of our research for the development of novel antiinflammatory drug candidates, we have designed and synthesized a series of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A(2) synthetase. In order to increase the absorption after oral administration, we introduced a carboxylic acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4-benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory activities against the production of leukotriene (LT) Bq and TXA(2) while not significantly inhibiting that of prostaglandin E(2) by glycogen-induced peritoneal cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl group influenced the inhibition of LTB(4) and TXB(2) production. An increase of lipophilicity by introducing a more lipophilic alkoxy group did not markedly increase the inhibitory activity on LTB(4) production. The position of an alkoxy group on the 1,4-benzoquinone skeleton played an important role in TXA(2) synthetase inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and proper length of methylene side chain, together with a polar substituent (carboxylic acid), showed good inhibition of both 5-LO and TXA(2) synthetase and possess a variety of pharmacologically beneficial effects.

  DOI：

  10.1021/jm950725r

文献信息

• Palladium-Catalyzed Coupling Reaction of<i>N</i>-Heteroaryl Halides with Functionalized Alkylzinc Iodides
  作者：Takao Sakamoto、Sumiko Nishimura、Yoshinori Kondo、Hiroshi Yamanaka

  DOI：10.1055/s-1988-27618

  日期：——

  The reaction of N-heteroaryl halides with ω-ethoxycarbonyl- and ω-chloroalkylzinc iodides, prepared from the corresponding alkyl iodides with zinc-copper couple, in the presence of dichlorobis(triphenylphosphine)palladium in N,N-dimethylacetamide/benzene yielded C-(ω-ethoxycarbonyl)- and C-(ω-chloroalkyl)-N-heteroarenes.

  N-杂芳基卤化物与由相应的烷基碘化物与锌铜对制备的α-乙氧基羰基-和α-氯烷基碘化锌在二氯双(三苯基膦)钯存在下在N,N-二甲基乙酰胺/苯中反应，得到C-(α-乙氧基羰基)-和C-(α-氯烷基)-N-杂芳烃。
• PROCESS FOR PRODUCTION OF HETEROARYL-TYPE BORON COMPOUNDS WITH IRIDIUM CATALYST
  申请人：Mitsubishi Rayon Co., Ltd.

  公开号：EP1481978A1

  公开（公告）日：2004-12-01

  The present invention provides an economically and industrially superior simple process that enables the selective production of an aromatic heterocyclic monoboron compound and aromatic heterocyclic diboron compound at a satisfactory yield and in a desired ratio by reacting an aromatic heterocyclic compound and a boron compound in a single step under mild conditions while changing only the charged ratios of the raw materials. The present invention provides a production process of a heteroaryl mono- or diboron compound comprising an aromatic heterocyclic compound and a boron compound in the form of bis(pinacolate)diboron or pinacolate diborane in the presence of a iridium-containing catalyst and a ligand such as a bipyridyl ligand.

  本发明提供了一种经济上和工业上优越的简单工艺，通过在温和条件下使芳香杂环化合物和硼化合物进行单步反应，同时仅改变原料的带电比例，就能以满意的产率和所需的比例选择性地生产芳香杂环单硼化合物和芳香杂环二硼化合物。 本发明提供了一种杂芳基单硼或二硼化合物的生产工艺，该工艺由芳香杂环化合物和双(频哪醇)二硼或频哪醇二硼烷形式的硼化合物在含铱催化剂和配体如双吡啶配体的存在下组成。
• Process for production of heteroaryl-type boron compounds with iridium catalyst
  申请人：Miyaura Norio

  公开号：US20050148775A1

  公开（公告）日：2005-07-07

  The present invention provides an economically and industrially superior simple process that enables the selective production of an aromatic heterocyclic monoboron compound and aromatic heterocyclic diboron compound at a satisfactory yield and in a desired ratio by reacting an aromatic heterocyclic compound and a boron compound in a single step under mild conditions while changing only the charged ratios of the raw materials. The present invention provides a production process of a heteroaryl mono- or diboron compound comprising an aromatic heterocyclic compound and a boron compound in the form of bis(pinacolate)diboron or pinacolate diborane in the presence of a iridium-containing catalyst and a ligand such as a bipyridyl ligand.

  本发明提供了一种经济上和工业上优越的简单工艺，通过在温和条件下使芳香杂环化合物和硼化合物进行单步反应，同时仅改变原料的带电比例，就能以满意的产率和所需的比例选择性地生产芳香杂环单硼化合物和芳香杂环二硼化合物。本发明提供了一种杂芳基单硼或二硼化合物的生产工艺，该工艺由芳香杂环化合物和双(频哪醇)二硼或频哪醇二硼烷形式的硼化合物在含铱催化剂和配体如双吡啶配体的存在下组成。
• Pyrido[2,1-b]quinazolinecarboxamide derivatives as platelet activating factor antagonists
  作者：Jefferson W. Tilley、Barbara Burghardt、Charles Burghardt、Thomas F. Mowles、Franz Josef Leinweber、Larry Klevans、Richard Young、Gerry Hirkaler、Kenneth Fahrenholtz

  DOI：10.1021/jm00397a034

  日期：1988.2

  A series of N-[(heteroaryl)alkyl]pyrido[2,1-b]quinazolines were evaluated for their ability to inhibit the binding of radiolabeled platelet activating factor (PAF) to its receptor on dog platelets. The most potent compounds in this series were found to be pyrido[2,1-b]quinazoline-8-carboxamides possessing a four- or six-carbon chain between the carboxamide nitrogen atom and a 3-pyridinyl or 5-pyrimidinyl moiety. Since earlier metabolism studies with pyridoquinazolinecarboxamides suggest that the carboxamide moiety is labile to hydrolysis in vivo, attempts were made to find isosteric replacements for this group. The substitutions examined led to a loss of activity; however, insertion of a methyl group on the carbon atom alpha to the carboxamide nitrogen led to an enantioselective enhancement of potency. (R)-2-(1-Methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (34) was more potent than the corresponding S enantiomer in the PAF binding assay and was also shown to be more resistant to degradation by amidases present in whole liver homogenates obtained from guinea pig, dog, and squirrel monkey. The corresponding rac-2-(1-methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (33) was found to inhibit transient PAF-induced thrombocytopenia and decreases in blood pressure in guinea pigs after intravenous or oral administration and to have a duration of action of greater than 5 h after an oral dose of 200 mg/kg. Compound 33 thus represents the prototype of a new class of orally active PAF antagonists.
• TILLEY, JEFFERSON W.;BURGHARD, BARBARA;BURGHARDT, CHARLES;MOWLES, THOMAS +, J. MED. CHEM., 31,(1988) N 2, 466-472
  作者：TILLEY, JEFFERSON W.、BURGHARD, BARBARA、BURGHARDT, CHARLES、MOWLES, THOMAS +

  DOI：——

  日期：——