(5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)tetrahydro-2(1H)-pyridinone | 178310-89-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)tetrahydro-2(1H)-pyridinone
• 英文别名: 5(S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)piperidin-2(1H)-one；5(S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2 (1H)-piperidone；5(S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2(1H)-piperidone；(5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)-2-piperidinone；(5S)-5-(3,4-dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)piperidin-2-one
• CAS: 178310-89-9
• 化学式: C₁₅H₁₇Cl₂NO₃
• 分子量: 330.211
• InChiKey: RKXUUBMZRYIORX-OAHLLOKOSA-N

物化性质

• 沸点：
  514.4±50.0 °C(Predicted)
• 密度：
  1.321±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5S)-5-(3,4-Dichlorophenyl)-5-(1,3-dioxolan-2-ylmethyl)tetrahydro-2(1H)-pyridinone 在 盐酸 、 氢氧化钾 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 20.0h， 生成 [(S)-1-Cyclopropylmethyl-3-(3,4-dichloro-phenyl)-6-oxo-piperidin-3-yl]-acetaldehyde
  参考文献：
  名称：

  Structure–activity relationships of 1-alkyl-5-(3,4-dichlorophenyl)-5-{2-[3-(substituted)-1-azetidinyl]-ethyl}-2-piperidones. Part 2: Improving oral absorption

  摘要：

  A series of piperidone analogues of 1b-q, seeking replacements for the polar sulfamide moiety in clinical candidate UK-224,671- 1a, possessing reduced H-bonding potential as a strategy to improve oral absorption, were prepared. These studies led to the successful identification of In, which demonstrated equivalent pharmacology and metabolic stability to la, and greatly improved oral absorption as assessed in rat PK studies. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.134

文献信息

• (Azetidin-1-ylalkyl) lactams as tachykinin antagonists
  申请人：Pfizer Inc.

  公开号：US05968923A1

  公开（公告）日：1999-10-19

  The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof, wherein R is C.sub.3 -C.sub.7 cycloalkyl, aryl or C.sub.1 -C.sub.6 alkyl, said C.sub.1 -C.sub.6 alkyl, said C.sub.1 -C.sub.6 alkyl being optionally substituted by fluoro, COOH, --COO(C.sub.1 -C.sub.4 alkyl), C.sub.3 -C.sub.7 cycloalkyl, adamantyl, aryl or het.sup.1, and said C.sub.3 -C.sub.7 cycloalkyl being optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, fluoro, fluoro (C.sub.1 -C.sub.4) alkyl and fluoro (C.sub.1 -C.sub.4) Alkoxy; R.sub.1 is phenyl, naphthyl, thienyl, benzothienyl or indolyl, each optionally substituted by 1 or 2 substituents each independently selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo and trifluormethyl; R.sup.2 is --CO.sub.2 H, --CONR.sup.3 R.sup.4, --CONR.sup.5 (C.sub.3 -C.sub.7 cycloalkyl), --NR.sup.5 (C.sub.2 -C.sub.5 alkanoyl), --NR.sup.3 R.sup.4, --NR.sup.5 CONR.sup.5 R.sup.6, (C.sub.3 -C.sub.7 cycloalkyl-C.sub.1 -C.sub.4 alkyl)R.sup.5 N--, --NR.sup.5 COCF.sub.3, --NR.sup.5 SO.sub.2 CF.sub.3, --NR.sup.5 (SO.sub.2 C.sub.1 -C.sub.4 alkyl), --NR.sup.5 SO.sub.2 NR.sup.5 R.sup.6, --NR.sup.5 (SO.sub.2 aryl), --N(aryl) (SO.sub.2 C.sub.1 -C.sub.4 alkyl), --OR.sup.5, --O(C.sub.3 -C.sub.7 cycloalkyl), --SO.sub.2 NR.sup.5 R.sup.6, het.sup.3 or a group of formulas: (a), (b), (c), (d), (e), (f), (g) or (h); X is C.sub.1 -C.sub.4 alkylene; X.sup.1 is a direct link or C.sub.1 -C.sub.6 alkylene; X.sup.2 is a direct link, CO, SO.sub.2, or NR.sup.5 CO; and m is 0, 1 or 2; together with intermediates used in the preparation of compositions containing and the use as tachykinin angatonists of such derivatives. ##STR1##

  本发明提供了式(I)的化合物及其药学上可接受的盐，其中R为C.sub.3 -C.sub.7环烷基、芳基或C.sub.1 -C.sub.6烷基，所述的C.sub.1 -C.sub.6烷基可选择地被氟、COOH、--COO(C.sub.1 -C.sub.4烷基)、C.sub.3 -C.sub.7环烷基、亚金刚烷基、芳基或het.sup.1取代，所述的C.sub.3 -C.sub.7环烷基可选择地被1或2个取代基取代，每个取代基独立地选自C.sub.1 -C.sub.4烷基、C.sub.3 -C.sub.7环烷基、C.sub.1 -C.sub.4烷氧基、羟基、氟基、氟(C.sub.1 -C.sub.4)烷基和氟(C.sub.1 -C.sub.4)烷氧基；R.sub.1为苯基、萘基、噻吩基、苯并噻吩基或吲哚基，每个可选择地被1或2个取代基取代，每个取代基独立地选自C.sub.1 -C.sub.4烷基、C.sub.1 -C.sub.4烷氧基、卤素和三氟甲基；R.sup.2为--CO.sub.2 H、--CONR.sup.3 R.sup.4、--CONR.sup.5 (C.sub.3 -C.sub.7环烷基)、--NR.sup.5 (C.sub.2 -C.sub.5烷酰基)、--NR.sup.3 R.sup.4、--NR.sup.5 CONR.sup.5 R.sup.6、(C.sub.3 -C.sub.7环烷基-C.sub.1 -C.sub.4烷基)R.sup.5 N--、--NR.sup.5 COCF.sub.3、--NR.sup.5 SO.sub.2 CF.sub.3、--NR.sup.5 (SO.sub.2 C.sub.1 -C.sub.4烷基)、--NR.sup.5 SO.sub.2 NR.sup.5 R.sup.6、--NR.sup.5 (SO.sub.2芳基)、--N(芳基)(SO.sub.2 C.sub.1 -C.sub.4烷基)、--OR.sup.5、--O(C.sub.3 -C.sub.7环烷基)、--SO.sub.2 NR.sup.5 R.sup.6、het.sup.3或以下列式的一组：(a)、(b)、(c)、(d)、(e)、(f)、(g)或(h)；X为C.sub.1 -C.sub.4亚烷基；X.sup.1为直链或C.sub.1 -C.sub.6亚烷基；X.sup.2为直链、CO、SO.sub.2或NR.sup.5 CO；m为0、1或2；以及用于制备含有这些衍生物的组合物的中间体及其作为速激肽抗肽的用途。
• 3-Azetidinylalkylpiperidines or -pyrrolidines as tachykinin antagonists
  申请人：Pfizer Inc.

  公开号：US06242438B1

  公开（公告）日：2001-06-05

  The present invention provides compounds of formula (I) and the pharmaceutically acceptable salts thereof. Such compounds and salts are tachykinin antagonists.

  本发明提供了式(I)的化合物及其药用盐。这些化合物和盐是催吐肽拮抗剂。
• Lactams as tachkinin antagonists
  申请人：Pfizer Inc.

  公开号：US20040132710A1

  公开（公告）日：2004-07-08

  Compounds of the formula (I): 1 or a pharmaceutically acceptable salt, prodrug, solvate or polymorph thereof, wherein R, R 1 , and Z are as defined herein, are useful in treating or preventing a condition for which an NK 2 antagonist is efficacious.

  公式（I）的化合物：1或其药学上可接受的盐，前药，溶剂化合物或多晶形式，其中R，R1和Z的定义如本文所述，可用于治疗或预防NK2拮抗剂有效的疾病。
• Lactams as tachykinin antagonists
  申请人：Pfizer, Inc

  公开号：US07060836B2

  公开（公告）日：2006-06-13

  Compounds of the formula (I): or a pharmaceutically acceptable salt, prodrug, solvate or polymorph thereof, wherein R, R1, and Z are as defined herein, are useful in treating or preventing a condition for which an NK2 antagonist is efficacious.

  公式（I）的化合物： 或其药物可接受的盐、前药、溶剂或多晶体，其中R、R1和Z的定义如此处所述，可用于治疗或预防需要NK2拮抗剂有效的疾病。
• Piperidones as tachykinin antagonists
  申请人：Pfizer Limited

  公开号：EP0962457B1

  公开（公告）日：2003-08-06