4-(3,4-dichloro-phenyl)-4-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-pyrrolidin-2-one | 155308-38-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-(3,4-dichloro-phenyl)-4-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-pyrrolidin-2-one
• 英文别名: 4-(3,4-dichloro-phenyl)-4-[2-(tetrahydro-pyran-2-yloxy)ethyl]-pyrrolidin-2-one；4-(3,4-Dichlorophenyl)-4-(2-[tetrahydropyran-2-yloxy]ethyl)-2-(1H)pyrrolidone；4-(2-tetrahydropyranyloxyethyl)-4-(3,4-dichlorophenyl)-2-pyrrolidone；4-(3,4-dichlorophenyl)-4-[2-(oxan-2-yloxy)ethyl]pyrrolidin-2-one
• CAS: 155308-38-6
• 化学式: C₁₇H₂₁Cl₂NO₃
• 分子量: 358.265
• InChiKey: DBNVUNAABPFNEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 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：

  4-(3,4-dichloro-phenyl)-4-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-pyrrolidin-2-one 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成 4-(3,4-dichloro-phenyl)-4-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-pyrrolidine
  参考文献：
  名称：

  4-Amino-2-(aryl)-butylbenzamides and Their conformationally constrained analogues. Potent antagonists of the human neurokinin-2 (NK2) receptor

  摘要：

  A library, evaluating a range of piperazines, piperidines and acyclic amines, as replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue (2a) which was further optimised using classical single-compound synthesis to yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained analogues of (2j), generally offered no potency advantage in this particular series. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00343-3
• 作为产物：
  描述：

  α-[2-(Tetrahydropyran-2-yloxy)ethyl]-3,4-dichlorophenyl-acetonitrile 在 镍 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 4-(3,4-dichloro-phenyl)-4-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-pyrrolidin-2-one
  参考文献：
  名称：

  4-Amino-2-(aryl)-butylbenzamides and Their conformationally constrained analogues. Potent antagonists of the human neurokinin-2 (NK2) receptor

  摘要：

  A library, evaluating a range of piperazines, piperidines and acyclic amines, as replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue (2a) which was further optimised using classical single-compound synthesis to yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained analogues of (2j), generally offered no potency advantage in this particular series. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00343-3

文献信息

• Substituted pyrrolidin-3-yl-alkyl-piperidines
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05635510A1

  公开（公告）日：1997-06-03

  The present invention relates to substituted pyrrolidinyl-3-yl-alkyl-piperidines, their stereoisomers, and pharmaceutically acceptable salts thereof and processes for preparation of the same. The compounds of the present invention are useful in their pharmacological activities such as tachykinin antagonism, especially substance P and neurokinin A antagonism, and the like. Compounds having the property of tachykinin antagonism are indicated for conditions associated with neurogenic inflammation and other diseases described herein.

  本发明涉及取代吡咯啉基-3-基-烷基-哌啶、其立体异构体和药学上可接受的盐以及其制备方法。本发明的化合物在药理活性方面具有用途，如快速激肽拮抗作用，特别是物质P和神经激肽A的拮抗作用等。具有快速激肽拮抗性质的化合物适用于与神经源性炎症和本文所述的其他疾病相关的情况。
• Heterocyclic compounds, method of preparing them and pharmaceutical
  申请人：Sanofi

  公开号：US05656639A1

  公开（公告）日：1997-08-12

  The invention relates to compounds of the formula ##STR1## in which: m is 2 or 3; n is 0, 1 or 2; Am is ##STR2## R.sub.1 is a (C.sub.1 -C.sub.4)-alkyl or a benzyl; R.sub.2 is a substituted or unsubstituted phenyl; x is zero or one; Ar is a substituted or unsubstituted phenyl, a naphthyl or an indolyl; Z is a substituted or unsubstituted phenyl; and A.sup..crclbar. is an anion; the salts thereof, where appropriate, with mineral or organic acids and the solvates thereof, where appropriate. These compounds have a strong affinity for the NK.sub.1 receptor and are useful for preparing drugs for the treatment of substance P-dependent pathological conditions.

  本发明涉及以下式子的化合物：##STR1## 其中：m为2或3；n为0、1或2；Am为##STR2## R1为(C1-C4)-烷基或苄基；R2为取代或未取代的苯基；x为零或一；Ar为取代或未取代的苯基、萘基或吲哚基；Z为取代或未取代的苯基；A.sup..crclbar.为阴离子；以及相应的矿物酸或有机酸盐和溶剂化物。这些化合物具有对NK.sub.1受体的强亲和力，并且可用于制备用于治疗物质P依赖性病理状况的药物。
• 1-azoniabicyclo\x9b2.2.1!heptanes, method of preparing them and
  申请人：Sanofi

  公开号：US05679693A1

  公开（公告）日：1997-10-21

  The invention relates to quaternary basic amides of the formula ##STR1## in which Ar is an optionally substituted mono-, di- or tricyclic aromatic or heteroaromatic group; T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C.sub.1 -C.sub.4, or a C.sub.1 -C.sub.5 -alkylene group; Ar' is an unsubstituted or mono- or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C.sub.1 -C.sub.4 -alkyl, or a C.sub.1 -C.sub.4 -.omega.-alkoxy(C.sub.2 -C.sub.4)alkyl, or a C.sub.2 -C.sub.4 -.omega.-alkanoyloxy (C.sub.1 -C.sub.4)alkyl;. Q is hydrogen; or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group; Am.sup..sym. is the radical ##STR2## in which X.sub.1, X.sub.2 and X.sub.3, together with the nitrogen atom to which they are bonded, form a 1-AZONIABICYCLO\x9b2.2.1!HEPTANE optionally substituted by a phenyl or benzyl group; and A.sup..crclbar. is a pharmaceutically acceptable anion. These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.

  本发明涉及公式##STR1##中的季铵基酰胺，其中Ar是可选的取代的单环、双环或三环芳香或杂芳基；T是直接键，羟甲基烷基，其中烷氧基为C.sub.1-C.sub.4，或C.sub.1-C.sub.5-烷基烷基；Ar'是未取代或单取代或多取代的苯基，噻吩基，苯并噻吩基，萘基或吲哚基；R是氢或C.sub.1-C.sub.4-烷基，或C.sub.1-C.sub.4-.omega.-烷氧基（C.sub.2-C.sub.4）烷基，或C.sub.2-C.sub.4-.omega.-烷酰氧（C.sub.1-C.sub.4）烷基；Q是氢；或者Q和R一起形成1,2-乙烯，1,3-丙烯或1,4-丁烷基；Am.sup..sym.是基团##STR2##其中X.sub.1、X.sub.2和X.sub.3与它们结合的氮原子一起形成一个1-AZONIABICYCLO\x9b2.2.1!HEPTANE，该1-AZONIABICYCLO\x9b2.2.1!HEPTANE 可以选择性地被苯基或苄基取代；A.sup..crclbar.是药学上可接受的阴离子。这些化合物有助于制备用于治疗涉及Tachykinin系统的病理状况的药物。
• 1-azoniabicyclo[2.2.1] heptanes and pharmaceutical compositions in which
  申请人：Sanofi

  公开号：US05554763A1

  公开（公告）日：1996-09-10

  The invention relates to quaternary basic amides of the formula ##STR1## in which Ar is an optionally substituted mono-, di- or tri-cyclic aromatic or heteroaromatic group; T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C.sub.1 -C.sub.4, or a C.sub.1 -C.sub.5 -alkylene group; Ar' is an unsubstituted or mono- or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C.sub.1 -C.sub.4 -alkyl, or a .omega.-C.sub.1 -C.sub.4 -alkoxy(C.sub.2 -C.sub.4)alkyl, or a .omega.-C.sub.2 -C.sub.4 -alkanoyloxy (C.sub.1 -C.sub.4)alkyl;. Q is hydrogen; or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group; Am.sup..sym. is the radical ##STR2## in which X.sub.1, X.sub.2 and X.sub.3, together with the nitrogen atom to which they are bonded, form an azabicyclic or azatricyclic system optionally substituted by a phenyl or benzyl group; and A.sup..crclbar. is a pharmaceutically acceptable anion. These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.

  本发明涉及公式##STR1##中的季铵基酰胺，其中Ar是可选取代的单、双或三环芳香或杂芳基团；T是直接键，羟甲基烷基，其中烷氧基为C.sub.1-C.sub.4，或C.sub.1-C.sub.5-烷基烷基；Ar'是未取代或单或多取代的苯基，噻吩基，苯并噻吩基，萘基或吲哚基；R是氢或C.sub.1-C.sub.4-烷基，或.omega.-C.sub.1-C.sub.4-烷氧基(C.sub.2-C.sub.4)烷基，或.omega.-C.sub.2-C.sub.4-烷酰氧(C.sub.1-C.sub.4)烷基；Q是氢；或者Q和R一起形成1,2-乙烯基，1,3-丙烯基或1,4-丁烷基；Am.sup..sym.是基团##STR2##其中X.sub.1、X.sub.2和X.sub.3与它们结合的氮原子一起形成一个可选取代的苯基或苄基的氮杂双环或氮杂三环系统；A.sup..crclbar.是一种药学上可接受的负离子。这些化合物对于制备用于治疗涉及Tachykinin系统的病理条件的药物是有用的。
• Quaternary basic amides, method of preparing them and pharmaceutical
  申请人：Sanofi

  公开号：US05712288A1

  公开（公告）日：1998-01-27

  The invention relates to quaternary basic amides of the formula ##STR1## in which Ar is an optionally substituted mono-, di- or tri-cyclic aromatic or heteroaromatic group; T is a direct bond, a hydroxymethylene group, an alkoxymethylene group in which the alkoxy group is C.sub.1 -C.sub.4, or a C.sub.1 -C.sub.5 -alkylene group; Ar' is an unsubstituted or mono- or poly-substituted phenyl, a thienyl, a benzothienyl, a naphthyl or an indolyl; R is hydrogen or a C.sub.1 -C.sub.4 -alkyl, or a C.sub.1 -C.sub.4 -.omega.-alkoxy(C.sub.2 -C.sub.4)alkyl, or a C.sub.2 -C.sub.4 -.omega.-alkanoyloxy (C.sub.1 -C.sub.4)alkyl; Q is hydrogen; or else Q and R together form a 1,2-ethylene, 1,3-propylene or 1,4-butylene group; Am.sup..sym. is the radical ##STR2## in which X.sub.1, X.sub.2 and X.sub.3, together with the nitrogen atom to which they are bonded, form a 1-azoniabicyclo\x9b2.2.2!octane optionally substituted by a phenyl or benzyl group; and A.sup..crclbar. is a pharmaceutically acceptable anion. These compounds are useful for the preparation of drugs intended for the treatment of pathological conditions involving the tachykinin system.

  本发明涉及公式##STR1##中的季铵基酰胺，其中Ar是一个可选的取代的单环、双环或三环芳香或杂芳基团；T是直接键，羟甲基烷基，其中烷氧基是C.sub.1-C.sub.4，或C.sub.1-C.sub.5-烷基烷基；Ar'是未取代或单取代或多取代的苯基、噻吩基、苯并噻吩基、萘基或吲哚基；R是氢或C.sub.1-C.sub.4-烷基，或C.sub.1-C.sub.4-ω-烷氧基(C.sub.2-C.sub.4)烷基，或C.sub.2-C.sub.4-ω-酰氧基(C.sub.1-C.sub.4)烷基；Q是氢；或者Q和R一起形成1,2-乙烯基、1,3-丙烯基或1,4-丁烷基；Am.sup..sym.是基团##STR2##其中X.sub.1、X.sub.2和X.sub.3与它们连接的氮原子一起形成一个可选取代的苯基或苄基的1-氮杂双环[2.2.2]辛烷；A.sup..crclbar.是一种药学上可接受的阴离子。这些化合物可用于制备用于治疗涉及Tachykinin系统的病理状况的药物。