ethyl 4-bromo-2,2-diethyl-3-oxo-butanoate | 99975-19-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl 4-bromo-2,2-diethyl-3-oxo-butanoate
• 英文别名: Ethyl 4-bromo-2,2-diethyl-3-oxobutanoate
• CAS: 99975-19-6
• 化学式: C₁₀H₁₇BrO₃
• 分子量: 265.147
• InChiKey: BJFXKTGXTFNBJY-UHFFFAOYSA-N

物化性质

• 沸点：
  80 °C(Press: 1 Torr)
• 密度：
  1.278±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-bromo-2,2-diethyl-3-oxo-butanoate 在 乙醇 、 硫酸 作用下， 生成 3,3-diethyl-furan-2,4-dione
  参考文献：
  名称：

  Notes - 3,3-Disubstituted Tetronic Acids

  摘要：

  DOI：

  10.1021/jo01095a627
• 作为产物：
  描述：

  2,2-二乙基乙酰乙酸乙酯 在 溴 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 ethyl 4-bromo-2,2-diethyl-3-oxo-butanoate
  参考文献：
  名称：

  [EN] SMALL MOLECULE PROSTAGLADIN TRANSPORT INHIBITORS
  [FR] INHIBITEURS DE TRANSPORT DE PROSTAGLANDINES À PETITES MOLÉCULES

  摘要：

  该披露提供了Formula 1的化合物及其药用盐。Formula 1中的变量，例如X1-X5，A1，A2和R1-R4在此处进行描述。这些化合物可用作前列腺素转运体（PGT）抑制剂。该披露还包括含有Formula 1的化合物或其盐的药物组合物，以及使用Formula 1的化合物和其盐来治疗至少部分由前列腺素水平或环氧化酶活性介导的疾病和疾病的方法。这些疾病和疾病包括疼痛和炎症性疾病。

  公开号：

  WO2021091823A1

文献信息

• Condensed pyridazine derivatives, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06627630B1

  公开（公告）日：2003-09-30

  A condensed pyridazine derivative which is useful as a pharmaceutical composition for preventing or treating allergic skin diseases such as contact dermatitis, pruritus, dried dermatitis, acute urticaria and prurigo.

  一种浓缩的吡啶嗪衍生物，可用作预防或治疗过敏性皮肤病，如接触性皮炎、瘙痒、干性皮炎、急性荨麻疹和疥疮的药物组合物。
• NASAL DROPS CONTAINING FUSED PYRIDAZINE DERIVATIVES
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1243271A1

  公开（公告）日：2002-09-25

  A nose drop containing the compound (I) represented by the formula wherein Ar1 and Ar2 are each an aromatic group, Ar1 and Ar2 optionally form a condensed cyclic group together with the adjacent carbon atom, ring B is a nitrogen-containing heterocycle, X and Y are each a bond, an oxygen atom or S(O)p (p is 0 to 2), NR4 (R4 is H or a lower alkyl group) or a divalent linear lower hydrocarbon group optionally having substituents and containing 1 to 3 heteroatoms, A is N or CR7 (R7 is H, a halogen atom, a hydrocarbon group, an acyl group or a hydroxy group optionally having substituents), R1, R2 and R3 are each H, a halogen atom, a hydrocarbon group, an acyl group or a hydroxy group optionally having substituents, and R8 is H, a hydroxy group optionally substituted by a lower alkyl group or a carboxyl group, provided that the nitrogen-containing heterocycle represented by ring B is not a heterocycle represented by the formula wherein n is 0 - 1, or a salt thereof or a prodrug thereof, exhibits a superior prophylactic or therapeutic effect on allergic rhinitis and the like.

  一种含有由以下公式表示的化合物（I）的鼻滴 其中Ar1和Ar2各自是芳香基团，Ar1和Ar2可以与相邻的碳原子一起形成紧凑的环状基团，环B是含氮杂环，X和Y各自是键，氧原子或S（O）p（p为0至2），NR4（R4为H或低碳基团）或二价线性低碳氢基团，可选地具有取代基并含有1至3个杂原子，A为N或CR7（R7为H、卤素原子、碳氢基团、酰基或可选地具有取代基的羟基），R1、R2和R3各自为H、卤素原子、碳氢基团、酰基或可选地具有取代基的羟基，以及 R8为H、可选地由低碳基团或羧基取代的羟基，前提是由环B表示的含氮杂环不是由以下公式表示的杂环 其中n为0-1，或其盐或前药，对过敏性鼻炎等表现出卓越的预防或治疗作用。
• [EN] SMALL MOLECULE PROSTAGLADIN TRANSPORT INHIBITORS<br/>[FR] INHIBITEURS DE TRANSPORT DE PROSTAGLANDINES À PETITES MOLÉCULES
  申请人：ALBERT EINSTEIN COLLEGE OF MEDICINE

  公开号：WO2021091823A1

  公开（公告）日：2021-05-14

  The disclosure provides compounds of Formula 1, and the pharmaceutically acceptable salts thereof. The variables in Formula 1, e.g. X1-X5, A1, A2, and R1-R4 are described herein. Such compounds are useful as prostaglandin transport (PGT) inhibitors. The disclosure further includes pharmaceutical compositions comprising a compound of Formula 1 or salt thereof and methods of using compounds of Formula 1 and salts thereof to treat diseases and disorders mediated, at least in part, by prostaglandin levels or cyclooxygenase activity. Such diseases and disorders include painful and inflammatory conditions.

  该披露提供了Formula 1的化合物及其药用盐。Formula 1中的变量，例如X1-X5，A1，A2和R1-R4在此处进行描述。这些化合物可用作前列腺素转运体（PGT）抑制剂。该披露还包括含有Formula 1的化合物或其盐的药物组合物，以及使用Formula 1的化合物和其盐来治疗至少部分由前列腺素水平或环氧化酶活性介导的疾病和疾病的方法。这些疾病和疾病包括疼痛和炎症性疾病。
• [EN] CONDENSED PYRIDAZINE DERIVATIVES, THEIR PRODUCTION AND USE<br/>[FR] DERIVES DE PYRIDAZINE CONCENTRES, ET PRODUCTION ET UTILISATION DE CES DERIVES
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：WO1998049167A1

  公开（公告）日：1998-11-05

  (EN) The present invention provides a compound represented by formula (I) wherein Ar1 and Ar2 are independently an aromatic group which may be substituted, and Ar1 and Ar2 may form a condensed cyclic group with an adjacent carbon atom; ring B is a nitrogen-containing heterocycle which may be substituted; X and Y are the same or different and are independently a bond, an oxygen atom, S(O)p (p is an integer of 0 to 2), NR4 wherein R4 is a hydrogen atom or a lower alkyl group, or a bivalent linear lower haydrocarbon group which may contain 1 to 3 hetero atoms and the bivalent linear lower hydrocarbon group may be substituted; A is a nitrogen atom or CR7 wherein R7 is a hydrogen atom, a halogen atom, a hydrocarbon which may be substituted, an acyl group or a hydroxy group which may be substituted; R1, R2 and R3 are the same or different and are independently a hydrogen atom, a halogen atom, a hydrocarbon group which may be substituted, an acyl group or a hydroxy group which may be substituted; R8 is a hydrogen atom, a hydroxy group which may be substituted by a lower alkyl or a carboxyl group, or a salt thereof, which exhibits excellent antihistaminic or eosinophil chemotaxis-inhibiting activities and is useful in treatment or prevention of asthma, allergic conjunctivitis, allergic rhinitis, chronic urticaria or atopic dermatitis.(FR) Cette invention concerne un composé correspondant à la formule (I) où Ar1 et Ar2 représentent indépendamment un groupe aromatique pouvant être substitué, Ar1 et Ar2 pouvant former un groupe cyclique concentré possédant un atome de carbone adjacent. L'anneau B consiste en un hétérocycle contenant de l'azote et pouvant être substitué. X et Y peuvent être identiques ou différents et représentent indépendamment une liaison, un atome d'axygène, S(O)p où p est un nombre entier de 0 à 2, NR4 où R4 représente un atome d'hydrogène ou un groupe alkyle inférieur ou, encore, un groupe hydrocarbure inférieur, linéaire et bivalent pouvant comprendre de 1 à 3 atomes hétéro et pouvant être substitué. A représente un atome d'azote ou CR7 dans lequel R7 représente un atome d'hydrogène, un atome halogène, un hydrocarbure pouvant être substitué, un groupe acyle ou une groupe hydroxy pouvant être substitué. R1, R2 et R3 peuvent être identiques ou différents et représentent indépendamment un atome d'hydrogène, un atome halogène, un groupe hydrocarbure pouvant être substitué, un groupe acyle ou un groupe hydroxy pouvant être substitué. R8 représente enfin un atome d'hydrogène ou un groupe hydroxy pouvant être substitué par un alkyle inférieur ou groupe carboxyle. Cette invention concerne également un sel de ce composé, lesquels possèdent d'excellentes activités antihistaminiques ou d'inhibition de chimiotaxie éosinophile. Ce composé est utile dans le traitement ou la prévention de l'asthme, de la conjonctivite allergique, de la rhinite allergique, de l'urticaire chronique ou de la dermatite atopique.

  本发明提供一种化合物，其表示为式（I），其中Ar1和Ar2分别为芳香基团，可以被取代，且Ar1和Ar2可以与相邻的碳原子形成紧缩环；环B为含氮杂环，可以被取代；X和Y相同或不同，且分别为键，氧原子，S（O）p（p为0到2的整数），NR4（其中R4为氢原子或较低的烷基基团），或者是一个双价线性较低的碳氢基团，可以含1到3个杂原子，且该双价线性较低的碳氢基团可以被取代；A为氮原子或CR7（其中R7为氢原子、卤素原子、可被取代的烃基、酰基或可被取代的羟基）；R1、R2和R3相同或不同，且分别为氢原子、卤素原子、可被取代的烃基、酰基或可被取代的羟基；R8为氢原子、可被较低的烷基或羧基取代的羟基，或其盐。该化合物具有优异的抗组胺和抑制嗜酸性粒细胞趋化活性，可用于治疗或预防哮喘、过敏性结膜炎、过敏性鼻炎、慢性荨麻疹或特应性皮炎。
• FUSED PYRIDAZINE DERIVATIVES, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1123936A1

  公开（公告）日：2001-08-16

  A compound (I) represented by the formula: wherein Ar1 and Ar2 are Independently an aromatic group optionally having a substituent, and Ar1 and Ar2 may form a condensed cyclic group with an adjacent carbon atom; ring B is a nitrogen-containing heterocycle optionally having a substituent; X and Y are the same or different and are independently a band, an oxygen atom, S(O)p (p is an integer of 0 to 2), NR4 wherein R4 is a hydrogen atom or a lower alkyl group, or a bivalent linear lower hydrocarbon group which may contain 1 to 3 hetero atoms and the bivalent linear lower hydrocarbon group may be substituted; A is a nitrogen atom or CR7 wherein R7 is a hydrogen atom, a halogen atom, a hydrocarbon optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R1, R2 and R3 are the same or different and are independently a hydrogen atom, ahalogen atom, ahydrocarbon group optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R8 is a hydrogen atom, a hydroxy group which may be substituted by lower alkyl or a carboxyl group, provided that the nitrogen-containing heterocycle represented by ring B is not a heterocycle represented by the formula: wherein n is 0 or 1, or a salt thereof, exhibits excellent anti-allergic, anti-histaminic, anti-inflammatory and eosinophil chemotaxis inhibiting activity and is useful as a pharmaceutical composition for preventing or treating allergic skin diseases such as contact dermatitis, pruritus, dried dermatitis, acute urticaria and prurigo. According to the method for producing of the present invention, the compound (I') represented by the formula: wherein Ar1' and Ar2' are independently an aromatic group optionally having a substituent, and Ar1' and Ar2' may form a condensed cyclic group with an adjacent carbon atom; ring B' is a nitrogen-containing heterocycle optionally having a substituent; X and Y are the same or different and are independently a bond, an oxygen atom, S(O)p (p is an integer of 0 to 2), NR4 wherein R4 is a hydrogen atom or a lower alkyl group, or a bivalent linear lower hydrocarbon group which may contain 1 to 3 hetero atoms and the bivalent linear lower hydrocarbon group may be substituted; A is a nitrogen atom or CR7 wherein R7 is a hydrogen atom, a halogen atom, a hydrocarbon optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R1 is a hydrocarbon group substituted with an optionally esterified carboxyl group, R2 and R3 are the same or different and are independently a hydrogen atom, a halogen atom, a hydrocarbon group optionally having a substituent, an acyl group or a hydroxy group optionally having a substituent; R8 is a hydrogen atom, a hydroxy group which may be substituted by lower alkyl or a carboxyl group, or a salt thereof, exhibiting excellent anti-allergic, anti-histaminic, anti-inflammatory and eosinophil chemotaxis inhibiting activity and is useful as a pharmaceutical composition for preventing or treating adthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, chronic urticaria, can be produced in good efficiency and in a high yield. The hydrate of a compound represented by the formula; wherein R is a hydrogen atom or an ethyl group, or a succinate or citrate of the compound (I") exhibits excellent anti-allergic, anti-histaminic, anti-inflammatory and eosinophil chemotaxis inhibiting activity and is useful as a pharmaceutical composition for preventing or treating adthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, chronic urticaria, and has excellent stability.

  一种由式表示的化合物(I)： 其中 Ar1 和 Ar2 独立地为可选具有取代基的芳香基团，且 Ar1 和 Ar2 可与相邻碳原子形成缩合环基；环 B 为可选具有取代基的含氮杂环；X和Y相同或不同，且独立地为带、氧原子、S(O)p（p为0至2的整数）、NR4（其中R4为氢原子或低级烷基）或可含有1至3个杂原子的二价线性低级烃基，且该二价线性低级烃基可被取代；A是氮原子或CR7，其中R7是氢原子、卤素原子、可选具有取代基的烃、酰基或可选具有取代基的羟基；R1、R2和R3相同或不同，且独立地是氢原子、卤素原子、可选具有取代基的烃、酰基或可选具有取代基的羟基；R8 是氢原子、可被低级烷基取代的羟基或羧基，条件是环 B 所代表的含氮杂环不是式中所代表的杂环： 其中 n 为 0 或 1 的杂环，或其盐，具有优异的抗过敏、抗组胺、抗炎和抑制嗜酸性粒细胞趋化的活性，可用作预防或治疗过敏性皮肤病如接触性皮炎、瘙痒症、干燥性皮炎、急性荨麻疹和瘙痒症的药物组合物。 根据本发明的生产方法，由式表示的化合物（I'）： 其中 Ar1'和 Ar2'独立地是任选具有取代基的芳香基团，Ar1'和 Ar2'可与相邻碳原子形成缩合环基；环 B'是任选具有取代基的含氮杂环；X和Y相同或不同，且独立地为键、氧原子、S(O)p（p为0至2的整数）、NR4（其中R4为氢原子或低级烷基）或二价线性低级烃基，该二价线性低级烃基可含有1至3个杂原子，且该二价线性低级烃基可被取代；A为氮原子或CR7（其中R7为氢原子、卤素原子、可选择具有取代基的烃、酰基或可选择具有取代基的羟基）；R1 是被任选酯化羧基取代的烃基，R2 和 R3 相同或不同，且独立地为氢原子、卤素原子、任选具有取代基的烃、酰基或任选具有取代基的羟基；R8 是氢原子、可被低级烷基或羧基取代的羟基或其盐，具有优异的抗过敏、抗组胺、抗炎和抑制嗜酸性粒细胞趋化的活性，可用作预防或治疗哮喘、过敏性鼻炎、特应性皮炎、过敏性结膜炎、慢性荨麻疹的药物组合物，生产效率高，产量大。 由式表示的化合物的水合物； 式中 R 为氢原子或乙基的化合物的水合物，或化合物（I"）的琥珀酸盐或柠檬酸盐，具有优异的抗过敏、抗组胺、抗炎和抑制嗜酸性粒细胞趋化的活性，可用作预防或治疗哮喘、过敏性鼻炎、特应性皮炎、过敏性结膜炎、慢性荨麻疹的药物组合物，并具有优异的稳定性。