2-acetylthiomethyl-3-phenylpropanoic acid methyl ester | 158293-54-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 2-acetylthiomethyl-3-phenylpropanoic acid methyl ester
• 英文别名: 3-acetylsulfanyl-2-benzylpropanoic acid methyl ester；Methyl 2-(acetylsulfanylmethyl)-3-phenylpropanoate；methyl 2-(acetylsulfanylmethyl)-3-phenylpropanoate
• CAS: 158293-54-0
• 化学式: C₁₃H₁₆O₃S
• 分子量: 252.334
• InChiKey: XTHHKIBLJVGRPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  363.5±35.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-acetylthiomethyl-3-phenylpropanoic acid methyl ester 在 氯化甲氧羰基硫 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.25h， 生成 isobutyric acid 1-(1-{2-[(1-ethoxycarbonyloxyethoxycarbonylmethyl)carbamoyl]-3-phenylpropyldisulfanylmethyl}-3-methylsulfanylpropylcarbamoyloxy)ethyl ester
  参考文献：
  名称：

  NOVEL AMINO ACID DERIVATIVES, METHOD FOR PREPARING SAME, AND THERAPEUTIC USE THEREOF

  摘要：

  该披露涉及到式(I)的新化合物R1NH—CH(R2)CH2—S—S—CH2—C(R3)(R4)—CONH—C(R5)(R6)—COOR7，其中R1是(酰氧基)烷基碳酸酯-C(O)—O—C(R8)(R9)—OC(O)—R10基团；R2是一个碳氢链，一个被杂环取代的亚甲基基团，R4是一个氢原子，R3是一个苯基或苄基基团，一个杂环基团，一个被杂环取代的亚甲基基团或R3和R4一起形成一个饱和环；R5和R6是氢，一个碳氢链，一个苯基或苄基基团，或R5和R6一起形成一个饱和环；R7是氢，一个苯基或苄基基团，一个式CR12(R13)C(O)OR14或OCR12(R13)OC(O)R14或OCR12(R13)OC(O)OR14的基团。该披露还涉及将这些化合物用作药物，以及含有所述化合物和药学上可接受的载体的药物组合物。该披露还涉及至少一种大麻素衍生物和/或吗啡或其衍生物和/或Gaba衍生物的联合使用，以增强式(I)的化合物的镇痛和抗抑郁效果。

  公开号：

  US20110071218A1
• 作为产物：
  描述：

  2-苄基丙烯酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 2-acetylthiomethyl-3-phenylpropanoic acid methyl ester
  参考文献：
  名称：

  用于中枢和周围疼痛治疗的新型口服活性双脑啡肽抑制剂（DENKIs）

  摘要：

  保护脑啡肽是响应伤害性刺激而释放的内源性阿片肽，是缓解急性和神经性疼痛的一种创新方法。这是通过抑制两个膜结合的锌金属肽酶，中性溶酶（NEP，EC 3.4.24.11）和氨基肽酶N（APN，EC 3.4.11.2）来抑制它们的酶促降解而实现的。已经设计出两种酶的选择性和有效抑制剂，称为脑啡肽酶，它们可以显着增加脑啡肽的细胞外浓度和半衰期，从而诱导有效的抗伤害感受作用。先前已经开发了几种双脑啡肽酶抑制剂（DENKIs）的化学家族，但缺乏口服活性。我们在这里报告新前药的设计和合成，衍生自将NEP和APN抑制剂通过具有侧链的二硫键结合的NEP和APN抑制剂共同改善口服生物利用度。在针对中枢和/或外周阿片样物质系统的各种疼痛动物模型中评估了它们的药理特性。考虑到它在急性和神经性疼痛中的功效，这些新的DENKI之一，选择19 - IIIa进行临床开发。

  DOI：

  10.1021/jm500602h

文献信息

• AMINOACID DERIVATIVES CONTAINING A DISULFANYL GROUP IN THE FORM OF MIXED DISULFANYL AND AMINOPEPTIDASE N INHIBITORS
  申请人：Roques Bernard

  公开号：US20090012153A1

  公开（公告）日：2009-01-08

  The invention relates to novel compounds of formula (I): H 2 N—CH(R 1 )—CH 2 —S—S—CH 2 —CH(R 2 )—CONH—R 5 , wherein R 1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R 2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R 5 is a CH(R 3 )—COOR 4 radical, wherein R 3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR 4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C 1 -C 6 , phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and/or morphine or the derivatives thereof are also disclosed.

  该发明涉及式(I)的新化合物：H2N—CH(R1)—CH2—S—S—CH2—CH(R2)—CONH—R5，其中R1是一个碳氢链、苯基或苯甲基基团，甲基基团被一个5或6原子杂环取代；R2是一个苯基或苯甲基基团，一个5或6原子芳香杂环，甲基基团被一个5或6原子杂环取代；R5是一个CH(R3)—COOR4基团，其中R3是氢、一个OH或OR基团、一个饱和碳氢基团、一个苯基或苯甲基基团，OR4是亲水酯基，或者由氮、硫和氧组成的几个杂原子选自的5或6元杂环，至少有两个氮原子，其中所述杂环可被一个烷基C1-C6、苯基或苯甲基基团取代。该发明化合物的用途包括作为药物、包含所述化合物的药物组合物、药用可接受的赋形剂，以及与至少一种大麻素衍生物联合使用以增强式(I)式新化合物的镇痛和抗抑郁效果和/或吗啡或其衍生物的效果。
• Aminoacid derivatives containing a disulfanyl group in the form of mixed disulfanyl and aminopeptidase N inhibitors
  申请人：Pharmaleads

  公开号：US08247608B2

  公开（公告）日：2012-08-21

  The invention relates to novel compounds of formula (I): H2N—CH(R1)—CH2—S—S—CH2—CH(R2)—CONH—R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)—COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and/or morphine or the derivatives thereof are also disclosed.

  本发明涉及一种新型化合物，其化学式为(I)：H2N—CH(R1)—CH2—S—S—CH2—CH(R2)—CONH—R5，其中R1为烃链、苯基或苄基基团，被5或6原子杂环取代的亚甲基基团；R2为苯基或苄基基团、5或6原子芳香杂环、被5或6原子杂环取代的亚甲基基团；R5为CH(R3)—COOR4基团，其中R3为氢、OH或OR基团、饱和烃基团、苯基或苄基基团，OR4为亲水性酯基团，或由氮、硫和氧组成的5或6元杂环，其中至少有两个氮原子，该杂环可被烷基C1-C6、苯基或苄基基团取代。本发明还公开了将该化合物用作药物的用途、包括该化合物的制药组合物、制药可接受的辅料、与至少一种大麻素衍生物结合使用以增强该化合物的镇痛和抗抑郁作用以及/或吗啡或其衍生物的用途。
• J. Med. Chem. 2014, 57, 5748-5763
  作者：

  DOI：——

  日期：——
• Aminoacid Derivatives Containing a Disulfanyl Group in the form of Mixed Disulfanyl and Aminopeptidase N Inhibitors
  申请人：Roques Bernard

  公开号：US20090131509A1

  公开（公告）日：2009-05-21

  The invention relates to novel compounds of formula (I): H 2 N—CH(R 1 )—CH 2 —S—S—CH 2 —CH(R 2 )—COONH—R 5 , wherein R 1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R 2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R 5 is a CH(R 3 )—COOR 4 radical, wherein R 3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR 4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C 1 -C 6 , phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and/or morphine or the derivatives thereof are also disclosed.
• US8247608B2
  申请人：——

  公开号：US8247608B2

  公开（公告）日：2012-08-21