methyl 2-(3-fluorobenzyl)isonicotinate | 1251844-66-2

• 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: methyl 2-(3-fluorobenzyl)isonicotinate
• 英文别名: methyl 2-[(3-fluorophenyl)methyl]pyridine-4-carboxylate
• CAS: 1251844-66-2
• 化学式: C₁₄H₁₂FNO₂
• 分子量: 245.253
• InChiKey: IHQLVWWYAVYIIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-fluorobenzyl)isonicotinate 在 二氧化铂 甲醇 、 二氯甲烷 、 potassium carbonate 、 水 、 Brine 作用下， 以 溶剂黄146 为溶剂， 25.0 ℃ 、66.66 MPa 条件下， 反应 7.17h， 以to yield crude methyl 2-(3-fluorobenzyl)piperidine-4-carboxylate (7.6 g, 110%) as a brown oil的产率得到methyl 2-(3-fluorobenzyl)piperidine-4-carboxylate
  参考文献：
  名称：

  Isoxazol-3(2H)-one analogs as therapeutic agents

  摘要：

  或其药学上适宜的盐，其中，R1和R2独立地为氢、氘、芳基、杂环芳基、C1-C8烷基，可选地被一个或多个取代基独立地取代，所述取代基为R3，R3为芳基、杂环芳基、氟、含有一个或多个氟的C1-C6烷基、含有一个或多个氘的C1-C6烷基、含有羟基的C1-C6烷基，所述芳基和杂环芳基可选地被一个或多个卤素、氟代烷氧基、氟代烷基、磺酰基、一个或多个氘、C1-6烷基、C1-6烷氧基、腈基取代，或者R3是C1-6烷基，可选地被以下一个或多个基团中的一个或多个取代：COOR4、OCOR4、CONR5R6、NR5COR6、OR4；其中，R4为C1-10烷基，可选地被一个或多个氟、氘、烷氧基、芳基羧酸酯、烷基羧酸酯取代；R5和R6独立地选择自氢、烷基或它们可以共同形成一个4-8成员的碳环；或者R1和R2形成一个3-10成员的碳环，可选地包含O或N，并可选地被C1-10烷基或芳基、可选地被R3取代的杂环芳基取代。

  公开号：

  US08415378B2
• 作为产物：
  描述：

  2-氯异烟酸甲酯 、 3-氟苄基氯化锌 在 四(三苯基膦)钯 氮气 、 甲醇 、 乙酸乙酯 、 氯化铵 、 Sodium sulfate-III 、 ethyl acetate heptane 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以linear gradient heptane/ethyl acetate 8:2 to 5:5 over 5 CV to yield methyl 2-(3-fluorobenzyl)isonicotinate (6.766 g, 85%) as a yellow oil的产率得到methyl 2-(3-fluorobenzyl)isonicotinate
  参考文献：
  名称：

  Isoxazol-3(2H)-one analogs as therapeutic agents

  摘要：

  或其药学上适宜的盐，其中，R1和R2独立地为氢、氘、芳基、杂环芳基、C1-C8烷基，可选地被一个或多个取代基独立地取代，所述取代基为R3，R3为芳基、杂环芳基、氟、含有一个或多个氟的C1-C6烷基、含有一个或多个氘的C1-C6烷基、含有羟基的C1-C6烷基，所述芳基和杂环芳基可选地被一个或多个卤素、氟代烷氧基、氟代烷基、磺酰基、一个或多个氘、C1-6烷基、C1-6烷氧基、腈基取代，或者R3是C1-6烷基，可选地被以下一个或多个基团中的一个或多个取代：COOR4、OCOR4、CONR5R6、NR5COR6、OR4；其中，R4为C1-10烷基，可选地被一个或多个氟、氘、烷氧基、芳基羧酸酯、烷基羧酸酯取代；R5和R6独立地选择自氢、烷基或它们可以共同形成一个4-8成员的碳环；或者R1和R2形成一个3-10成员的碳环，可选地包含O或N，并可选地被C1-10烷基或芳基、可选地被R3取代的杂环芳基取代。

  公开号：

  US08415378B2

文献信息

• ISOXAZOL-3(2H)-ONE ANALOGS AS THERAPEUTIC AGENTS
  申请人：BOSTRÖM Jonas

  公开号：US20100261755A1

  公开（公告）日：2010-10-14

  or a pharmaceutically suitable salt thereof, wherein, R 1 and R 2 independently are hydrogen, deuterium, aryl, hetero aryl, C1-C8 alkyl, optionally being substituted with one or more substituents independently being R 3 , R 3 is an aryl, hetero aryl, fluorine(s), a C1-C6 alkyl containing one or more fluorine, a C1-C6 alkyl containing one or more deuterium, a C1-C6 alkyl containing hydroxy, the aryl and heteroaryl optionally being substituted with one or more halogen, a fluorinated alkoxy, a fluorinated alkyl, a sulfonyl, one or more deuterium, a C1-6 alkyl, a C1-6 alkoxy, a nitrile, or R 3 is a C1-6 alkyl optionally substituted with one or more of the following groups: COOR4, OCOR4, CONR5R6, NR5COR6, OR4; wherein, R4 is a C1-10 alkyl optionally substituted with one or more fluorine, deuterium, alkoxy, arylcarboxylate, alkyl carboxylate; R5 and R6 are independently selected from hydrogen, alkyl or they may together form a 4-8 membered carbon ring; or R1 and R2 form a 3-10 membered carbon ring optionally comprising O or N and optionally substituted with a C1-10 alkyl or aryl, hetero aryl optionally substituted with R3.

  或其药学上适用的盐，其中， R1和R2独立地是氢、氘、芳基、杂环芳基、C1-C8烷基，可选地被一个或多个取代基取代，这些取代基独立地是R3， R3是芳基、杂环芳基、氟、含有一个或多个氟的C1-C6烷基、含有一个或多个氘的C1-C6烷基、含有羟基的C1-C6烷基，芳基和杂环芳基可选地被一个或多个卤素、氟代烷氧基、氟代烷基、磺酰基、一个或多个氘、C1-6烷基、C1-6烷氧基、腈取代， 或R3是一个C1-6烷基，可选地被以下一种或多种基团取代：COOR4、OCOR4、CONR5R6、NR5COR6、OR4； 其中，R4是一个C1-10烷基，可选地被一个或多个氟、氘、烷氧基、芳基羧酸酯、烷基羧酸酯取代； R5和R6独立地选自氢、烷基，或它们可以共同形成一个4-8成员碳环； 或R1和R2形成一个3-10成员碳环，可选地包含O或N，并可选地被一个C1-10烷基或芳基、可选地被R3取代。
• US8415378B2
  申请人：——

  公开号：US8415378B2

  公开（公告）日：2013-04-09
• [EN] METHOD AND APPARATUS FOR PRODUCING HEAT ENERGY AND CARBON DIOXIDE<br/>[FR] PROCÉDÉ ET DISPOSITIF DE PRODUCTION D'ÉNERGIE THERMIQUE ET DE DIOXYDE DE CARBONE
  申请人：ASTRAZENECA AB

  公开号：WO2010117323A1

  公开（公告）日：2010-10-14

  Formula I or a pharmaceutically suitable salt thereof, wherein, R1 and R2 independently are hydrogen, deuterium, aryl, hetero aryl, C1-C8 alkyl, optionally being substituted with one or more substituents independently being R3, R3 is an aryl, hetero aryl, fluorine(s), a C1-C6 alkyl containing one or more fluorine, a C1-C6 alkyl containing one or more deuterium, a C1-C6 alkyl containing hydroxy, the aryl and heteroaryl optionally being substituted with one or more halogen, a fluorinated alkoxy, a fluorinated alkyl, a sulfonyl, one or more deuterium, a C1-6 alkyl, a C1-6 alkoxy, a nitrile, or R3 is a C1-6 alkyl optionally substituted with one or more of the following groups: COOR4, OCOR4, CONR5R6, NR5COR6, OR4; wherein, R4 is a C1-10 alkyl optionally substituted with one or more fluorine, deuterium, alkoxy, arylcarboxylate, alkyl carboxylate; R5 and R6 are independently selected from hydrogen, alkyl or they may together form a 4-8 membered carbon ring; or R1 and R2 form a 3-10 membered carbon ring optionally comprising O or N and optionally substituted with a C1-10 alkyl or aryl, hetero aryl optionally substituted with R3.
• Discovery of the Fibrinolysis Inhibitor AZD6564, Acting via Interference of a Protein–Protein Interaction
  作者：Leifeng Cheng、Daniel Pettersen、Bengt Ohlsson、Peter Schell、Michael Karle、Emma Evertsson、Sara Pahlén、Maria Jonforsen、Alleyn T. Plowright、Jonas Boström、Tomas Fex、Anders Thelin、Constanze Hilgendorf、Yafeng Xue、Göran Wahlund、Walter Lindberg、Lars-Olof Larsson、David Gustafsson

  DOI：10.1021/ml400526d

  日期：2014.5.8

  A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 mu M, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.
• Isoxazol-3(2H)-one analogs as therapeutic agents
  申请人：Boström Jonas

  公开号：US08415378B2

  公开（公告）日：2013-04-09

  or a pharmaceutically suitable salt thereof, wherein, R1 and R2 independently are hydrogen, deuterium, aryl, hetero aryl, C1-C8 alkyl, optionally being substituted with one or more substituents independently being R3, R3 is an aryl, hetero aryl, fluorine(s), a C1-C6 alkyl containing one or more fluorine, a C1-C6 alkyl containing one or more deuterium, a C1-C6 alkyl containing hydroxy, the aryl and heteroaryl optionally being substituted with one or more halogen, a fluorinated alkoxy, a fluorinated alkyl, a sulfonyl, one or more deuterium, a C1-6 alkyl, a C1-6 alkoxy, a nitrile, or R3 is a C1-6 alkyl optionally substituted with one or more of the following groups: COOR4, OCOR4, CONR5R6, NR5COR6, OR4; wherein, R4 is a C1-10 alkyl optionally substituted with one or more fluorine, deuterium, alkoxy, arylcarboxylate, alkyl carboxylate; R5 and R6 are independently selected from hydrogen, alkyl or they may together form a 4-8 membered carbon ring; or R1 and R2 form a 3-10 membered carbon ring optionally comprising O or N and optionally substituted with a C1-10 alkyl or aryl, hetero aryl optionally substituted with R3.

  或其药学上适宜的盐，其中，R1和R2独立地为氢、氘、芳基、杂环芳基、C1-C8烷基，可选地被一个或多个取代基独立地取代，所述取代基为R3，R3为芳基、杂环芳基、氟、含有一个或多个氟的C1-C6烷基、含有一个或多个氘的C1-C6烷基、含有羟基的C1-C6烷基，所述芳基和杂环芳基可选地被一个或多个卤素、氟代烷氧基、氟代烷基、磺酰基、一个或多个氘、C1-6烷基、C1-6烷氧基、腈基取代，或者R3是C1-6烷基，可选地被以下一个或多个基团中的一个或多个取代：COOR4、OCOR4、CONR5R6、NR5COR6、OR4；其中，R4为C1-10烷基，可选地被一个或多个氟、氘、烷氧基、芳基羧酸酯、烷基羧酸酯取代；R5和R6独立地选择自氢、烷基或它们可以共同形成一个4-8成员的碳环；或者R1和R2形成一个3-10成员的碳环，可选地包含O或N，并可选地被C1-10烷基或芳基、可选地被R3取代的杂环芳基取代。