塞替匹仑 | 866460-33-5

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 塞替匹仑
• 中文别名: 2-(2-(1-萘甲酰基)-8-氟-1.2.3.4-四氢吡啶并[4,3-B]吲哚-5基)乙酸；2-(2-(1-萘甲酰基)-8-氟-1,2,3,4-四氢吡啶并[4,3-b]吲哚-5基)乙酸；司替匹仑
• 英文名称: setipiprant
• 英文别名: 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]-indol-5(2H)-yl)acetic acid；ACT-129968；2-[8-fluoro-2-(naphthalene-1-carbonyl)-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl]acetic acid
• CAS: 866460-33-5
• 化学式: C₂₄H₁₉FN₂O₃
• 分子量: 402.425
• InChiKey: IHAXLPDVOWLUOS-UHFFFAOYSA-N

物化性质

• 沸点：
  690.4±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO:48.67(最大浓度 mg/mL);120.94(最大浓度 mM)DMF:50.0(最大浓度 mg/mL);124.25(最大浓度 mM)DMF:PBS ( pH 7.2) (1:1):0.5(最大浓度 mg/mL);1.24(最大浓度 mM)乙醇:3.0(最大浓度 mg/mL);7.45(最大浓度 mM)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  62.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  -20℃

制备方法与用途

Setipiprant是一种口服有效的选择性CRTH2拮抗剂，而CRTH2是一种与G蛋白耦联的PGD2受体。

反应信息

• 作为反应物：
  描述：

  塞替匹仑 在 human cytochrome P₄₅₀ 、 三氟乙酸 作用下， 以 乙醇 、 正庚烷 为溶剂， 生成 2-(2-((3R,4R)-3,4-dihydroxy-3,4-dihydronaphthalene-1-carbonyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 、 2-(2-((3S,4S)-3,4-dihydroxy-3,4-dihydronaphthalene-1-carbonyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid
  参考文献：
  名称：

  Verification of the Major Metabolic Oxidation Path for the Naphthoyl Group in Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTh2) Antagonist 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968)

  摘要：

  Various racemic and enantioenriched (trans)-X,Y-dihydroxy-X,Y-dihydronaphthoyl analogues as well as X-hydroxy-naphthoyl analogues of CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido [4,3-b]indol-5(2H)-yl) acetic acid (1, Setipiprant/ACT-129968) were synthesized in order to gain insight into regio- and enantioselectivity of the metabolic oxidation of 1 and to verify the structures of four metabolites that were proposed earlier in a clinical ADME study. Analytical data of the synthetic standards were compared with data from samples of biological origin. The two major metabolites M7 and M9 were unambiguously verified as 2-(2-((trans)-3,4-dihydroxy-3,4-dihydronaphthalene-1-carbony1)- and 242-((trans)-5,6-dihydroxy-5,6-dihydronaphthalene-1-carbonyl)-8-fluoro-3,4-dihydro-1H-pyrido [4,3-b]indol-5 (2H)-yl) acetic acid, respectively, each composed of two enantiomers with 68% and 44% ee in favor of (+)-(3S,4S)-M7 and (+)-(5S,6S)-M9, respectively. Likewise, minor metabolites M3 and M13 were identified as 2-(8-fluoro-2-(5-hydroxy-1-naphthoyl) and 2-(8-fluoro-2-(4-hydroxy-1-naphthoyl)-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)acetic acid, respectively.

  DOI：

  10.1021/acs.jmedchem.5b00824
• 作为产物：
  描述：

  8-氟-2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚 在 盐酸 、 caesium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 丙酮 为溶剂， 反应 5.5h， 生成 塞替匹仑
  参考文献：
  名称：

  Identification of 2-(2-(1-Naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic Acid (Setipiprant/ACT-129968), a Potent, Selective, and Orally Bioavailable Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells (CRTH2) Antagonist

  摘要：

  Herein we describe the discovery of the novel CRTh2 antagonist 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 28 (setipiprant/ACT-129968), a clinical development candidate for the treatment of asthma and seasonal allergic rhinitis. A lead optimization program was started based on the discovery of the recently disclosed CRTh2 antagonist 2-(2-benzoyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid 5. An already favorable and druglike profile could be assessed for lead compound 5. Therefore, the lead optimization program mainly focused on the improvement in potency and oral bioavailability. Data of newly synthesized analogs were collected from in vitro pharmacological, physicochemical, in vitro ADME, and in vivo pharmacokinetic studies in the rat and the dog. The data were then analyzed using a traffic light selection tool as a visualization device in order to evaluate and prioritize candidates displaying a balanced overall profile. This data-driven process and the excellent results of the PK study in the rat (F = 44%) and the dog (F = 55%) facilitated the identification of 28 as a potent (IC50 = 6 nM), selective, and orally available CRTh2 antagonist.

  DOI：

  10.1021/jm400122f

文献信息

• 一种四氢吡啶并吲哚类化合物的制备方法
  申请人：新发药业有限公司

  公开号：CN108794468A

  公开（公告）日：2018-11-13

  本发明涉及一种四氢吡啶并吲哚类化合物的制备方法。该方法利用4‑氟‑2‑硝基甲苯与N‑(2‑氰基)乙基‑1‑萘甲酰胺在碱催化剂作用下，缩合生成中间体N‑[4‑(4‑氟‑2‑硝基苯基)‑3‑亚胺基丁基]‑1‑萘甲酰胺，产物混合液直接经催化加氢环合得到N‑(1‑萘甲酰基)‑2‑(2‑氨基)乙基‑6‑氟吲哚，后者再与甲醛环合，然后与氯乙酸在碱存在下缩合得到Setipiprant。本发明所用原料价廉易得，工艺流程短，操作简便，绿色环保，同时反应选择性好，产品收率和纯度高。
• [EN] TETRAHYDROPYRIDOINDOLE DERIVATIVES<br/>[FR] DERIVES DE TETRAHYDROPYRIDOINDOLE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2005095397A1

  公开（公告）日：2005-10-13

  The invention relates to tetrahydropyridoindole derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions comprising one or more of those compounds and methods of treatment comprising administration of said compounds.

  本发明涉及四氢吡啶并吲哚衍生物及其作为制备药物组合物的活性成分的用途。本发明还涉及相关方面，包括制备该化合物的过程、包含其中一种或多种化合物的药物组合物以及包括给予该化合物的治疗方法。
• Tetrahydropyridoindole derivatives
  申请人：Fecher Anja

  公开号：US20070191416A1

  公开（公告）日：2007-08-16

  The invention relates to tetrahydropyridoindole derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions comprising one or more of those compounds and methods of treatment comprising administration of said compounds.

  本发明涉及四氢吡啶吲哚衍生物及其作为制备药物组合物的活性成分的用途。本发明还涉及相关方面，包括制备这些化合物的过程、包含其中一种或多种化合物的药物组合物和包括给予这些化合物的治疗方法。
• Tetrhydropyridoindole Derivatives
  申请人：Fecher Anja

  公开号：US20100234396A1

  公开（公告）日：2010-09-16

  The invention relates to tetrahydropyridoindole derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions comprising one or more of those compounds and methods of treatment comprising administration of said compounds.

  本发明涉及四氢吡啶吲哚衍生物及其在制备药物组合物中作为活性成分的使用。本发明还涉及相关方面，包括制备该化合物的过程、包含其中一种或多种该化合物的药物组合物以及包括给予该化合物的治疗方法。
• J. Med. Chem. 2013, 56, 4899-4911
  作者：

  DOI：——

  日期：——