4-Piperidinamine, N-methyl-N-(3-(2-methylpropyl)-2-pyridinyl)-1-((5-((methylsulfonyl)amino)-1H-indol-2-yl)carbonyl)- | 179556-43-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-Piperidinamine, N-methyl-N-(3-(2-methylpropyl)-2-pyridinyl)-1-((5-((methylsulfonyl)amino)-1H-indol-2-yl)carbonyl)-
• 英文别名: N-[2-[4-[methyl-[3-(2-methylpropyl)pyridin-2-yl]amino]piperidine-1-carbonyl]-1H-indol-5-yl]methanesulfonamide
• CAS: 179556-43-5
• 化学式: C₂₅H₃₃N₅O₃S
• 分子量: 483.635
• InChiKey: JKPIHCSBJFLPKX-UHFFFAOYSA-N

物化性质

• 沸点：
  705.5±70.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-溴-3-吡啶甲醛 在 palladium on activated charcoal 盐酸 、 正丁基锂 、 氢气 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 100.0 ℃ 、137.9 kPa 条件下， 反应 50.5h， 生成 4-Piperidinamine, N-methyl-N-(3-(2-methylpropyl)-2-pyridinyl)-1-((5-((methylsulfonyl)amino)-1H-indol-2-yl)carbonyl)-
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of the (Alkylamino)piperidine-Containing BHAP Class of Non-Nucleoside Reverse Transcriptase Inhibitors:  Effect of 3-Alkylpyridine Ring Substitution

  摘要：

  Development of resistance to currently approved HIV therapies has continued to fuel research efforts to improve the metabolic stability and spectrum of activity of the (alkyl amino)piperidine containing bis(heteroaryl)piperazine (AAP-BHAP) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners. Testing of representative analogues in an in vitro liver microsome assay indicated that the alkyl substituent would not appreciably improve the metabolic stability of the AAP-BHAP template. In vivo pharmacokinetic evaluation of three compounds confirmed these results in that high systemic clearances were observed. Nevertheless, one compound (13), PNU-103657, possessed oral bioavailability in rats approaching that of the structurally related NNRTI drug delavirdine which is currently on the market for the treatment of HIV infection.

  DOI：

  10.1021/jm990051a

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS WITH IMPROVED DISSOLUTION<br/>[FR] COMPOSITIONS PHARMACEUTIQUES A DISSOLUTION AMELIOREE
  申请人：TRANSFORM PHARMACEUTICALS INC

  公开号：WO2004000284A1

  公开（公告）日：2003-12-31

  The invention relates to methods of screening mixtures containing a pharmaceutical compound an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a recrystallization/precipitation retardant and an optional enhancer.

  本发明涉及筛选包含药物化合物和赋形剂的混合物的方法，以识别延缓固态成核的药物化合物/赋形剂组合的特性。该发明还涉及通过将药物与再结晶/沉淀抑制剂和可选增效剂结合，来增加低溶解度药物在胃液条件下的溶解度、溶出性和生物利用度。
• Pharmaceutical compositions with improved dissolution
  申请人：Tawa Mark

  公开号：US20060134198A1

  公开（公告）日：2006-06-22

  The invention relates to methods of screening mixtures containing a pharmaceutical compound and an excipient to identify properties of the pharmaceutical compound/excipient combination that retard solid-state nucleation. The invention further relates to increasing the solubility, dissolution and bioavailability of a drug with low solubility in gastric fluids conditions by combining the drug with a precipitation retardant and an optional enhancer.

  本发明涉及筛选混合物的方法，该混合物含有药物化合物和赋形剂，以识别药物化合物/赋形剂组合的性质，以延缓固态成核。本发明还涉及通过将药物与沉淀抑制剂和可选增效剂结合，在胃液条件下增加低溶解度药物的溶解度、溶出度和生物利用度的方法。
• Stabilized oral pharmaceutical composition
  申请人：——

  公开号：US20030105144A1

  公开（公告）日：2003-06-05

  An orally deliverable pharmaceutical composition is provided comprising an aminosulfonyl-comprising drug, for example a selective cyclooxygenase-2 inhibitory drug such as celecoxib, and a solvent liquid comprising a polyethylene glycol and one or more free radical-scavenging antioxidants. At least a substantial part of the drug is in dissolved form in the solvent liquid. The composition has rapid-onset properties and is useful in treatment of cyclooxygenase-2 mediated conditions and disorders.

  一种可口服给药的药物组合物由含氨磺酰的药物（例如塞来昔布等选择性环氧化酶-2抑制剂）和含聚乙二醇及一种或多种自由基清除抗氧化剂的溶剂液组成。至少有相当一部分药物以溶解形式存在于溶剂液中。该组合物具有快速起效的特性，可用于治疗环氧化酶-2 介导的病症和紊乱。
• Oral dosage form of a sulfonamide prodrug
  申请人：——

  公开号：US20030100595A1

  公开（公告）日：2003-05-29

  A pharmaceutical composition that is substantially free of water comprises at least one orally deliverable dosage unit comprising a therapeutically effective amount of a sulfonamide prodrug and, where the prodrug is readily degradable ex vivo, has means to inhibit such degradation prior to oral administration. Illustratively the prodrug is parecoxib or a water-soluble salt thereof, and the composition has means to inhibit conversion of the parecoxib to valdecoxib. A method of treating or preventing a COX-2 mediated disorder in a subject comprises (a) dissolving at least one dosage unit of such a composition in a pharmaceutically acceptable aqueous vehicle to form a solution, and (b) orally administering the solution to the subject before substantial precipitation of insoluble matter occurs in the solution.

  一种基本上不含水的药物组合物包含至少一个口服给药剂量单位，其中含有治疗有效量的磺胺原药，如果原药在体内外容易降解，则在口服给药前具有抑制这种降解的方法。举例来说，原药是帕瑞昔布或其水溶性盐，组合物具有抑制帕瑞昔布转化为缬癸昔布的方法。一种治疗或预防受试者 COX-2 介导的疾病的方法包括：(a)将至少一个剂量单位的这种组合物溶解在药学上可接受的水性载体中以形成溶液，和(b)在溶液中出现大量不溶物沉淀之前将溶液口服给受试者。
• ORAL DOSAGE FORM OF A SULFONAMIDE PRODRUG SUCH AS PARECOXIB
  申请人：Pharmacia Corporation

  公开号：EP1446118A1

  公开（公告）日：2004-08-18