N-(3-chloropropyl)-N-phenylformamide | 13268-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-chloropropyl)-N-phenylformamide
• 英文别名: N-<3-Chlor-propyl>-formanilid；3-Chloropropyl(phenyl)formamide
• CAS: 13268-47-8
• 化学式: C₁₀H₁₂ClNO
• 分子量: 197.664
• InChiKey: IGYKKMODCUBDBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(3-chloropropyl)-N-phenylformamide 在 盐酸 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 11.0h， 生成 N'-(4-chlorophenyl)-N-(3-{4-[4-(morpholin-4-ylsulfonyl)benzyl]piperidin-1-yl}propyl)-N-phenylurea hydrochloride
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N′-diphenylureas

  摘要：

  We have previously reported the novel lead compound 1a as a CCR5 antagonist for treatment of HIV-1 infection. SAR studies on incorporating various acyl groups as a replacement for the 5-oxopyrrolidine-3-carbonyl group of the lead structure resulted in the discovery of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N-1-diphenylurea (4a) with significantly improved CCR5 binding affinity. Substitutions (4-Cl, 4e,f; 4-Me, 4i) on the N'-phenyl ring further increased the binding affinity. Introduction of polar substituents on the phenyl ring of the 4-benzylpiperidine moiety enhanced the inhibitory activity of the HIV-1 envelope-mediated membrane fusion (4v,w), suggesting that polar substituents at this position can interfere effectively with HIV-1 cell entry. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.004
• 作为产物：
  描述：

  1-溴-3-氯丙烷 、 N-苯基甲酰胺 在 caesium carbonate 作用下， 以 丙酮 为溶剂， 反应 8.0h， 以89%的产率得到N-(3-chloropropyl)-N-phenylformamide
  参考文献：
  名称：

  CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N′-diphenylureas

  摘要：

  We have previously reported the novel lead compound 1a as a CCR5 antagonist for treatment of HIV-1 infection. SAR studies on incorporating various acyl groups as a replacement for the 5-oxopyrrolidine-3-carbonyl group of the lead structure resulted in the discovery of N-[3-(4-benzylpiperidin-1-yl)propyl]-N,N-1-diphenylurea (4a) with significantly improved CCR5 binding affinity. Substitutions (4-Cl, 4e,f; 4-Me, 4i) on the N'-phenyl ring further increased the binding affinity. Introduction of polar substituents on the phenyl ring of the 4-benzylpiperidine moiety enhanced the inhibitory activity of the HIV-1 envelope-mediated membrane fusion (4v,w), suggesting that polar substituents at this position can interfere effectively with HIV-1 cell entry. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.004

文献信息

• [EN] CYCLIC AMINE COMPOUNDS AS CCR5 ANTAGONISTS<br/>[FR] COMPOSES D'AMINE CYCLIQUE UTILISES COMME ANTAGONISTES DE CCR5
  申请人：TAKEDA CHEMICAL INDUSTRIES LTD

  公开号：WO2001025200A1

  公开（公告）日：2001-04-12

  A compound of formula (I) (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R?1 and R2¿ may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N?+-R5 •Y-(R5¿ is a hydrocarbon group; Y- is a counter anion); R3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G1 is a bond, CO or SO¿2; G?2 is CO, SO¿2?, NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G?1¿ is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  化合物式为（I）（其中R1是氢原子，可被取代的碳氢基团，可被取代的非芳香杂环基团，R2是可被取代的碳氢基团，可被取代的非芳香杂环基团，或R1和R2可以与A一起结合形成可被取代的杂环基团；A是N或N+ -R5 • Y-（R5是碳氢基团；Y-是反离子）；R3是可被取代的环烃基团或可被取代的杂环基团；n为0或1；R4是氢原子，可被取代的碳氢基团，可被取代的杂环基团，可被取代的烷氧基，可被取代的芳氧基，或可被取代的氨基，E是可被除氧基以外的基取代的二价脂肪烃基团；G1是键，CO或SO2；G2是CO，SO2，NHCO，CONH或OCO；J是甲基或氮原子；Q和R中的每一个都是一个键或一个可被取代的二价C1-3脂肪基团；前提是当G2是OCO时，J是甲基，当另一个是键时，其中一个不是键，当G1是键时，Q和R中的每一个都没有被氧基团取代）或其盐具有强效的CCR5拮抗活性，并可用于人类各种HIV感染疾病（例如艾滋病）的治疗或预防。
• Cyclic amine compounds as CCR5 antagonists
  申请人：——

  公开号：US20030114443A1

  公开（公告）日：2003-06-19

  A compound of formula (I) (wherein R 1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R 2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R 1 and R 2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N + —R 5 .Y − (R 5 is a hydrocarbon group; Y − is a counter anion); R 3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R 4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group(s) other than oxo; G 1 is a bond, CO or SO 2 ; G 2 is CO, SO 2 , NHCO, CONH or OCO; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C 1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G 2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group(s) when G 1 is a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in human (e.g. AIDS).

  化合物的式子 (I) (其中R1是氢原子、可以被取代的碳氢基团、可以被取代的非芳香族杂环基团，R2是可以被取代的碳氢基团、可以被取代的非芳香族杂环基团，或R1和R2可以与A结合形成可以被取代的杂环基团；A是N或N+—R5.Y−(R5是碳氢基团；Y−是反离子)；R3是可以被取代的环烃基团或可以被取代的杂环基团；n为0或1；R4是氢原子、可以被取代的碳氢基团、可以被取代的杂环基团、可以被取代的烷氧基、可以被取代的芳氧基，或可以被取代的氨基团；E是可以被取代的二价脂肪烃基团，该基团可以被除氧基团外的其他基团取代；G1是键、CO或SO2；G2是CO、SO2、NHCO、CONH或OCO；J是甲基或氮原子；Q和R中的每一个都是键或可以被取代的二价C1-3脂肪基团；但是当G2是OCO时，J是甲基；当Q和R中的一个是键时，另一个不是键；当G1是键时，Q和R中的每一个都没有被氧基团取代)或其盐具有强效的CCR5拮抗活性，可以用于治疗或预防人类各种HIV感染性疾病（例如艾滋病）。
• Cyclic Amine Compounds as CCR5 Antagonists
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1886994A1

  公开（公告）日：2008-02-13

  A compound of the formula: (wherein R1 is a hydrogen atom, a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, R2 is a hydrocarbon group which may be substituted, a non-aromatic heterocyclic group which may be substituted, or R1 and R2 may combine to each other together with A to form a heterocyclic group which may be substituted; A is N or N+-R5 . Y- (R5 is a hydrocarbon group; Y- is a counter anion) ; R3 is a cyclic hydrocarbon group which may be substituted or a heterocyclic group which may be substituted; n is 0 or 1; R4 is a hydrogen atom, a hydrocarbon group which may be substituted, a heterocyclic group which may be substituted, an alkoxy group which may be substituted, an aryloxy group which may be substituted, or an amino group which may be substituted, E is a divalent aliphatic hydrocarbon group which may be substituted by group (s) other than oxo;G1 is a bond, CO or SO2 ; G2 is CO,S02, NHCO, CONH or OCO ; J is methine or a nitrogen atom; and each of Q and R is a bond or a divalent C1-3 aliphatic hydrocarbon which may be substituted; provided that J is methine when G2 is OCO, that one of Q and R is not a bond when the other is a bond and that each of Q and R is not substituted by oxo group (s) whenGo ils a bond) or a salt thereof has a potent CCR5 antagonistic activity and can be advantageously used for the treatment or prevention of infectious disease of various HIV in humans (e.g. AIDS).

  式中的化合物： (其中 R1 是氢原子、可被取代的烃基、可被取代的非芳香杂环基团，R2 是可被取代的烃基、可被取代的非芳香杂环基团，或 R1 和 R2 可与 A 相互结合形成可被取代的杂环基团；A 是 N 或 N+-R5 .Y-（R5 是烃基；Y- 是反阴离子）；R3 是可被取代的环烃基或可被取代的杂环基；n 是 0 或 1；R4 是氢原子、可被取代的烃基、可被取代的杂环基、可被取代的烷氧基、可被取代的芳氧基或可被取代的氨基；E 是可被除氧代以外的基团（s）取代的二价脂肪族烃基；G1 是键、CO 或 SO2；G2 是 CO、S02、NHCO、CONH 或 OCO；J 是甲烷或氮原子；Q 和 R 各自是键或可被取代的二价 C1-3 脂肪族烃；条件是：当 G2 为 OCO 时，J 为甲烷；当另一个为键时，Q 和 R 中的一个不是键；当 Go ils 为键时，Q 和 R 中的每一个没有被氧化基团（s）取代）或其盐具有强效的 CCR5 拮抗活性，可有利地用于治疗或预防人类各种 HIV 感染性疾病（如艾滋病）。例如艾滋病）。
• CYCLIC AMINE COMPOUNDS AS CCR5 ANTAGONISTS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1220842A1

  公开（公告）日：2002-07-10
• US6562978B1
  申请人：——

  公开号：US6562978B1

  公开（公告）日：2003-05-13