4-isobutyl-3-methylthiophene-2-carboxylic acid | 944326-68-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 4-isobutyl-3-methylthiophene-2-carboxylic acid
• 英文别名: 3-methyl-4-(2-methylpropyl)thiophene-2-carboxylic acid
• CAS: 944326-68-5
• 化学式: C₁₀H₁₄O₂S
• 分子量: 198.286
• InChiKey: SREGAMSQFXAQCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  319.8±30.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-isobutyl-3-methylthiophene-2-carboxylic acid 在 氨 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 56.17h， 生成 rac-1-amino-3-{4-[5-(4-isobutyl-3-methylthiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethylphenoxy}propan-2-ol
  参考文献：
  名称：

  Novel S1P₁ Receptor Agonists - Part 2: From Bicyclo[3.1.0]hexane-Fused Thiophenes to Isobutyl Substituted Thiophenes

  摘要：

  Previously, we reported on the discovery of a novel series of bicyclo[3.1.0]hexane fused thiophene derivatives that serve as potent and selective S1P(1), receptor agonists. Here, we discuss our efforts to simplify the bicyclohexane fused thiophene head. In a first step the bicyclohexane moiety could be replaced by a simpler, less rigid cyclohexane ring without compromising the SIP receptor affinity profile of these novel compounds. In a second step, the thiophene head was simplified even further by replacing the cyclohexane ring with an isobutyl group attached either to position 4 or position S of the thiophene. These structurally much simpler headgroups again furnished potent and selective S1P(1) agonists (e.g., 87), which efficiently and dose dependently reduced the number of circulating lymphocytes upon oral administration to male Wistar rats. For several compounds discussed in this report lymphatic transport is an important route of absorption that may offer opportunities for a tissue targeted approach with minimal plasma exposure.

  DOI：

  10.1021/jm401456d
• 作为产物：
  描述：

  5-甲基-2-己酮 在 草酰氯 、 potassium tert-butylate 、 水 、 sodium ethanolate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 为溶剂， 反应 82.33h， 生成 4-isobutyl-3-methylthiophene-2-carboxylic acid
  参考文献：
  名称：

  Novel S1P₁ Receptor Agonists - Part 2: From Bicyclo[3.1.0]hexane-Fused Thiophenes to Isobutyl Substituted Thiophenes

  摘要：

  Previously, we reported on the discovery of a novel series of bicyclo[3.1.0]hexane fused thiophene derivatives that serve as potent and selective S1P(1), receptor agonists. Here, we discuss our efforts to simplify the bicyclohexane fused thiophene head. In a first step the bicyclohexane moiety could be replaced by a simpler, less rigid cyclohexane ring without compromising the SIP receptor affinity profile of these novel compounds. In a second step, the thiophene head was simplified even further by replacing the cyclohexane ring with an isobutyl group attached either to position 4 or position S of the thiophene. These structurally much simpler headgroups again furnished potent and selective S1P(1) agonists (e.g., 87), which efficiently and dose dependently reduced the number of circulating lymphocytes upon oral administration to male Wistar rats. For several compounds discussed in this report lymphatic transport is an important route of absorption that may offer opportunities for a tissue targeted approach with minimal plasma exposure.

  DOI：

  10.1021/jm401456d

文献信息

• NOVEL THIOPHENE DERIVATIVES AS S1P1/EDG1 RECEPTOR AGONISTS
  申请人：Boli Martin

  公开号：US20100240717A1

  公开（公告）日：2010-09-23

  The invention relates to thiophene derivatives of formula (I)/their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents wherein: A represents *—CO—CH═CH—, *—CO—CH 2 CH 2 —, *—CO—CH 2 —NH—, wherein the sterisks indicate the bond that is linked to the thiophene group of Formula (I), and R1-R3 are as defined in the claims.

  本发明涉及公式（I）的噻吩衍生物/它们的制备及其作为药物活性化合物的用途。所述化合物特别作为免疫抑制剂，其中：A代表*—CO—CH═CH—、*—CO—CH2CH2—、*—CO—CH2—NH—，其中星号表示与公式（I）的噻吩基团相连的键，R1-R3如权利要求所定义。
• Thiophene derivatives as S1P1/EDG1 receptor agonists
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：US08003800B2

  公开（公告）日：2011-08-23

  The invention relates to thiophene derivatives of formula (I)/their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents wherein: A represents *—CO—CH═CH—, *—CO—CH2CH2—, *—CO—CH2—NH—, wherein the asterisks indicate the bond that is linked to the thiophene group of Formula (I), and R1-R3 are as defined in the claims.

  本发明涉及公式(I)的噻吩衍生物/它们的制备以及它们作为药物活性化合物的用途。所述化合物特别作为免疫抑制剂，其中：A代表*—CO—CH═CH—、*—CO—CH2CH2—、*—CO—CH2—NH—，其中星号表示与公式(I)的噻吩基团连接的键，而R1-R3如权利要求所定义。
• WO2007/80542
  申请人：——

  公开号：——

  公开（公告）日：——
• US8003800B2
  申请人：——

  公开号：US8003800B2

  公开（公告）日：2011-08-23
• [EN] NOVEL THIOPHENE DERIVATIVES AS S1P1/EDG1 RECEPTOR AGONISTS<br/>[FR] NOUVEAUX DERIVES DE THIOPHENE UTILISES EN TANT QU'AGONISTES DES RECEPTEURS S1P1/EDG1
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2007080542A1

  公开（公告）日：2007-07-19

  [EN] The invention relates to thiophene derivatives of formula (I) / their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents wherein: A represents *-CO-CH=CH-, *-CO-CH₂CH₂-, *-CO-CH₂-NH-, wherein the sterisks indicate the bond that is linked to the thiophene group of Formula (I) , and R1-R3 are as defined in the claims.
  [FR] La présente invention concerne des dérivés de thiophène de formule (I, ainsi que leur préparation et leur utilisation en tant que composés pharmaceutiquement actifs. Lesdits composés agissent plus particulièrement comme des agents immunosuppresseurs, A représentant *-CO-CH=CH-, *-CO-CH₂CH₂-, *-CO-CH₂-NH-, les astérisques indiquant la liaison avec le groupe thiophène de formule (I) et R1-R3 étant tels que définis dans les revendications.