Ethyl 5-{2-[bis(2,2-dimethylpropoxy-carbonyl)amino]pyridin-3-yl}isoxazol-3-carboxylate | 1166997-25-6

• 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
• 英文名称: Ethyl 5-{2-[bis(2,2-dimethylpropoxy-carbonyl)amino]pyridin-3-yl}isoxazol-3-carboxylate
• 英文别名: Ethyl 5-[2-[bis(2,2-dimethylpropoxycarbonyl)amino]pyridin-3-yl]-1,2-oxazole-3-carboxylate
• CAS: 1166997-25-6
• 化学式: C₂₃H₃₁N₃O₇
• 分子量: 461.515
• InChiKey: VGTYOQHITPALJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Ethyl 5-{2-[bis(2,2-dimethylpropoxy-carbonyl)amino]pyridin-3-yl}isoxazol-3-carboxylate 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 di-tert-butyl {3-[3-(hydroxymethyl)isoxazol-5-yl]pyridin-2-yl}imidodicarbonate
  参考文献：
  名称：

  HETEROCYCLIC RING AND PHOSPHONOXYMETHYL GROUP SUBSTITUTED PYRIDINE DERIVATIVES AND ANTIFUNGAL AGENT CONTAINING SAME

  摘要：

  本发明提供了具有优异抗真菌作用的化合物，同时在水溶性和安全性等方面也表现优异。这些化合物由式（I）表示： 本发明还涉及包括该化合物的药物组合物，以该化合物作为活性成分的抗真菌剂，以及通过给予该化合物来预防或治疗真菌病的方法。

  公开号：

  US20090233883A1
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 ethyl 5-{2-[(1,1-dimethylethoxycarbonyl)amino]pyridin-3-yl}isoxazol-3-carboxylate 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 Ethyl 5-{2-[bis(2,2-dimethylpropoxy-carbonyl)amino]pyridin-3-yl}isoxazol-3-carboxylate
  参考文献：
  名称：

  HETEROCYCLIC RING AND PHOSPHONOXYMETHYL GROUP SUBSTITUTED PYRIDINE DERIVATIVES AND ANTIFUNGAL AGENT CONTAINING SAME

  摘要：

  本发明提供了具有优异抗真菌作用的化合物，同时在水溶性和安全性等方面也表现优异。这些化合物由式（I）表示： 本发明还涉及包括该化合物的药物组合物，以该化合物作为活性成分的抗真菌剂，以及通过给予该化合物来预防或治疗真菌病的方法。

  公开号：

  US20090233883A1

文献信息

• PYRIDINE DERIVATIVES SUBSTITUTED WITH HETEROCYCLIC RING AND gamma-GLUTAMYLAMINO GROUP, AND ANTIFUNGAL AGENTS CONTAINING SAME
  申请人：Tanaka Keigo

  公开号：US20100105737A1

  公开（公告）日：2010-04-29

  The present invention provides an antifungal agent which has excellent antifungal action, and which is also excellent in terms of its properties, and in particular its solubility in water and safety. The present invention discloses a compound represented by the following formula (I) or a salt thereof. (wherein R 1 represents a hydrogen atom, a halogen atom, an amino group, R 11 —NH— (wherein R 11 represents a C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a C 1-6 alkoxy C 1-6 alkyl group, or a C 1-6 alkoxycarbonyl C 1-6 alkyl group), R 12 —(CO)—NH— (wherein R 12 represents a C 1-6 alkyl group or a C 1-6 alkoxy C 1-6 alkyl group), a C 1-6 alkyl group, a hydroxy C 1-6 alkyl group, a cyano C 1-6 alkyl group, a C 1-6 alkoxy group, or a C 1-6 alkoxy C 1-6 alkyl group; R 2 represents a group represented by the formula: one of X and Y is a nitrogen atom, and the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or benzene ring which may have 1 or 2 halogen atoms or C 1 to C 6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, —CH 2 O—, —OCH 2 —, —NH—, —CH 2 NH—, —NHCH 2 —, —CH 2 S—, or —SCH 2 —; R 3 represents a hydrogen atom or a halogen atom, or represents a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a 5 - or 6 -member heteroaryl group, or a 5 - or 6 -member non-aromatic heterocyclic group, each of which may have 1 or 2 substituents selected from substituent group a; R 4 represents a hydrogen atom or a halogen atom; and R represents a hydrogen atom, or represents a C 1-6 alkyl group which may be substituted with a dimethylamino group, [substituent group α] a halogen atom, a cyano group, a C 1-6 alkyl group, a C 1-6 alkoxy group, a C 1-6 alkoxycarbonyl group, a C 3-8 cycloalkyl group, a C 2-6 alkenyl group and a C 2-6 alkynyl group).

  本发明提供了一种具有优异的抗真菌作用，并且在其性质，特别是在水溶性和安全性方面也具有优异性的抗真菌剂。本发明揭示了下式（I）所表示的化合物或其盐。（其中R1表示氢原子，卤素原子，氨基团，R11—NH—（其中R11表示C1-6烷基，羟基C1-6烷基，C1-6烷氧基C1-6烷基或C1-6烷氧羰基C1-6烷基），R12—（CO）—NH—（其中R12表示C1-6烷基或C1-6烷氧基C1-6烷基），C1-6烷基，羟基C1-6烷基，氰基C1-6烷基，C1-6烷氧基或C1-6烷氧基C1-6烷基; R2表示由公式表示的基团：其中X和Y中的一个是氮原子，另一个是氮原子或氧原子；环A表示一个5-或6-成员的杂环或苯环，可以有1或2个卤素原子或C1到C6烷基；Z表示单键，亚甲基基团，乙烯基团，氧原子，硫原子，-CH2O-，-OCH2-，-NH-，-CH2NH-，-NHCH2-，-CH2S-或-SCH2-; R3表示氢原子或卤素原子，或表示C1-6烷基，C3-8环烷基，C6-10芳基，5-或6-成员杂芳基或5-或6-成员非芳杂环基，每个基团可以有1或2个从取代基团a中选择的取代基团; R4表示氢原子或卤素原子; R表示氢原子，或表示可用二甲基氨基团取代的C1-6烷基，[取代基团α]卤素原子，氰基，C1-6烷基，C1-6烷氧基，C1-6烷氧羰基，C3-8环烷基，C2-6烯基和C2-6炔基）。
• METHOD FOR MANUFACTURING HETEROCYCLE SUBSTITUTED PYRIDINE DERIVATIVES
  申请人：Niijima Jun

  公开号：US20110263845A1

  公开（公告）日：2011-10-27

  It is an object of the present invention to provide an efficient method for manufacturing heterocycle-substituted pyridine derivatives. The present invention provides a method for manufacturing a compound represented by the following formula (I): the method including reacting a compound represented by the following formula (III): and a compound represented by the following formula (II): in a solvent and in the presence of a palladium catalyst and a base, wherein R 1 represents a hydrogen atom, etc.; R 2 represents a hydrogen atom, a C 1-6 alkyl group, an amino group that may be protected with a protective group, etc.; one of X and Y represents a nitrogen atom and the other represents a nitrogen atom or an oxygen atom; Q represents a leaving group; the ring A represents a 5- or 6-member heteroaryl ring or a benzene ring, which may have one or two halogen atoms or C 1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, etc.; R represents a hydrogen atom or a C 1-6 alkyl group, etc.; R 3 represents a hydrogen atom or a halogen atom, etc.; and R 4 represents a hydrogen atom or a halogen atom; provided that when Z represents a single bond, or when R 3 represents a hydrogen atom, then R 1 , R 2 , and R 4 cannot all be a hydrogen atom at the same time.

  本发明的目的是提供一种制造杂环取代吡啶衍生物的高效方法。本发明提供了一种制造以下式（I）化合物的方法：在溶剂和钯催化剂和碱存在下，将以下式（III）化合物和以下式（II）化合物反应，其中R1代表氢原子等；R2代表氢原子，C1-6烷基，可能被保护基保护的氨基等；X和Y中的一个代表氮原子，另一个代表氮原子或氧原子；Q代表离去基团；环A代表5-或6-成员杂芳基环或苯环，可以有一或两个卤素原子或C1-6烷基；Z代表单键，亚甲基基，乙烯基，氧原子等；R代表氢原子或C1-6烷基等；R3代表氢原子或卤素原子等；R4代表氢原子或卤素原子；但当Z代表单键或当R3代表氢原子时，R1、R2和R4不能同时为氢原子。
• PYRIDINE DERIVATIVES SUBSTITUTED WITH HETEROCYCLIC RING AND y-GLUTAMYLAMINO GROUP, AND ANTIFUNGAL AGENTS CONTAINING SAME
  申请人：TANAKA Keigo

  公开号：US20120277439A1

  公开（公告）日：2012-11-01

  The present invention provides an antifungal agent which has excellent antifungal action, and which is also excellent in terms of its properties, and in particular its solubility in water and safety. The present invention discloses a compound represented by the following formula (I) or a salt thereof: wherein R 1 , R 2 , R 3 and R 4 are defined in the specification; one of X and Y is a nitrogen atom, and the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or benzene ring which may have 1 or 2 halogen atoms or C 1 to C 6 alkyl groups; and Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, —CH 2 O—, —OCH 2 —, —NH—, —CH 2 NH—, —NHCH 2 —, —CH 2 S—, or —SCH 2 —.

  本发明提供了一种具有优异的抗真菌作用的抗真菌剂，其性质也非常优异，特别是其在水中的溶解性和安全性。本发明公开了以下式（I）或其盐所表示的化合物：其中R1、R2、R3和R4在规范中定义；X和Y中的一个是氮原子，另一个是氮原子或氧原子；环A表示一个具有1或2个卤素原子或C1到C6烷基的5-或6成员杂环芳烃环或苯环；Z表示单键、亚甲基、乙烯基、氧原子、硫原子、-CH2O-、-OCH2-、-NH-、-CH2NH-、-NHCH2-、-CH2S-或-SCH2-。
• PYRIDINE DERIVATIVE SUBSTITUTED WITH HETEROCYCLE AND PHOSPHONOXYMETHYL GROUP AND ANTIFUNGAL AGENT CONTAINING THE SAME
  申请人：Eisai R&D Management Co., Ltd.

  公开号：EP2223926A1

  公开（公告）日：2010-09-01

  The present invention provides antifungal agents that have excellent antifungal action, and is also excellent in terms of its properties, particularly its solubility in water and its safety. According to the present invention, disclosed are compounds represented by the following formula (I): (wherein R1 represents a hydrogen atom, a halogen atom, an amino group, R11-NH-(wherein R11 represents a C1-6 alkyl group, a hydroxy C1-6 alkyl group, a C1-6 alkoxy C1-6 alkyl group, or a C1-6 alkoxycarbonyl C1-6 alkyl group), R12-(CO)-NH- (wherein R12 represents a C1-6 alkyl group or a C1-6 alkoxy C1-6 alkyl group), a C1-6 alkyl group, a hydroxy C1-6 alkyl group, a cyano C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6 alkoxy C1-6 alkyl group; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group, or a di-C1-6 alkylamino group; one of X and Y represents a nitrogen atom, and the other represents a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring, which may have one or two halogen atoms or C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, -CH2O- -OCH2-, -NH-, -CH2NH-, -NHCH2-, -CH2S-, or -SCH2-; R3 represents a hydrogen atom or a halogen atom, or a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-member heteroaryl group, or a 5- or 6-member non-aromatic heterocyclic group, wherein these groups may have one or two substituents selected from a substituent group α; and R4 represents a hydrogen atom or a halogen atom; [substituent Group α] a halogen atom, a cyano group, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkoxycarbonyl group, a C3-8 cycloalkyl group, a C2-6 alkenyl group, and a C2-6 alkynyl group).

  本发明提供的抗真菌剂具有极佳的抗真菌作用，而且在性能，特别是在水中的溶解性和安全性方面也非常出色。根据本发明，公开了由下式（I）代表的化合物： (其中 R1 代表氢原子、卤素原子、氨基、R11-NH-（其中 R11 代表 C1-6 烷基、羟基 C1-6 烷基、C1-6 烷氧基 C1-6 烷基或 C1-6 烷氧羰基 C1-6 烷基）、R12-(CO)-NH-（其中 R12 代表 C1-6 烷基或 C1-6 烷氧基 C1-6 烷基）、C1-6 烷基、羟基 C1-6 烷基、氰基 C1-6 烷基、C1-6 烷氧基或 C1-6 烷氧基 C1-6 烷基； R2 代表氢原子、C1-6 烷基、氨基或二-C1-6 烷基氨基； X 和 Y 中的一个代表氮原子，另一个代表氮原子或氧原子； 环 A 代表 5 或 6 个成员的杂芳基环或苯环，其中可以有一个或两个卤素原子或 C1-6 烷基； Z 代表单键、亚甲基、亚乙基、氧原子、硫原子、-CH2O- -OCH2-、-NH-、-CH2NH-、-NHCH2-、-CH2S- 或 -SCH2-； R3 代表氢原子或卤素原子，或 C1-6 烷基、C3-8 环烷基、C6-10 芳基、5 或 6 元杂芳基或 5 或 6 元非芳香杂环基，其中这些基团可具有一个或两个选自取代基 α 的取代基；以及 R4 代表氢原子或卤素原子； [取代基团 α］ 卤素原子、氰基、C1-6 烷基、C1-6 烷氧基、C1-6 烷氧羰基、C3-8 环烷基、C2-6 烯基和 C2-6 烷炔基）。
• PROCESS FOR PRODUCTION OF HETEROCYCLE-SUBSTITUTED PYRIDINE DERIVATIVE
  申请人：Eisai R&D Management Co., Ltd.

  公开号：EP2226320A1

  公开（公告）日：2010-09-08

  It is an object of the present invention to provide an efficient method for manufacturing heterocycle-substituted pyridine derivatives. The present invention provides a method for manufacturing a compound represented by the following formula (I): the method including reacting a compound represented by the following formula (III): and a compound represented by the following formula (II): in a solvent and in the presence of a palladium catalyst and a base, wherein R1 represents a hydrogen atom, etc.; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group that may be protected with a protective group, etc.; one of X and Y represents a nitrogen atom and the other represents a nitrogen atom or an oxygen atom; Q represents a leaving group; the ring A represents a 5- or 6-member heteroaryl ring or a benzene ring, which may have one or two halogen atoms or C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, etc.; R represents a hydrogen atom or a C1-6 alkyl group, etc.; R3 represents a hydrogen atom or a halogen atom, etc.; and R4 represents a hydrogen atom or a halogen atom; provided that when Z represents a single bond, or when R3 represents a hydrogen atom, then R1, R2, and R4 cannot all be a hydrogen atom at the same time.

  本发明的目的是提供一种制造杂环取代的吡啶衍生物的有效方法。本发明提供了一种制造下式（I）所代表的化合物的方法： 该方法包括使下式(III)代表的化合物反应： 和下式（II）代表的化合物进行反应： 在溶剂中并在钯催化剂和碱存在下进行反应、 其中 R1 代表氢原子等；R2 代表氢原子、C1-6 烷基、可被保护基保护的氨基等；X 和 Y 中的一个代表氮原子，另一个代表氮原子或氧原子；Q 代表离去基团；环 A 代表 5 或 6 元杂芳基环或苯环，其中可有一个或两个卤素原子或 C1-6 烷基；Z 代表单键、亚甲基、亚乙基、氧原子等。R代表氢原子或C1-6烷基等；R3代表氢原子或卤素原子等；R4代表氢原子或卤素原子； 但当 Z 代表单键或 R3 代表氢原子时，R1、R2 和 R4 不能同时都是氢原子。