(R,S)-2-amino-4-[2-(diisopropoxyphosphorylmethoxy)ethylsulfanyl]butyrate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R,S)-2-amino-4-[2-(diisopropoxyphosphorylmethoxy)ethylsulfanyl]butyrate
• 英文别名: 2-Amino-4-[2-[di(propan-2-yloxy)phosphorylmethoxy]ethylsulfanyl]butanoic acid
• 化学式: C₁₃H₂₈NO₆PS
• 分子量: 357.408
• InChiKey: UQMZBTNCGSFWLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  22
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R,S)-2-amino-4-[2-(diisopropoxyphosphorylmethoxy)ethylsulfanyl]butyrate 在 三甲基溴硅烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以31%的产率得到2-Amino-4-(2-phosphonomethoxy-ethylsulfanyl)-butyric acid
  参考文献：
  名称：

  S-Alkylated Homocysteine Derivatives:  New Inhibitors of Human Betaine-Homocysteine S-Methyltransferase

  摘要：

  A series of S-alkylated derivatives of homocysteine were synthesized and characterized as inhibitors of human recombinant betaine-homocysteine S-methyltransferase ( BHMT). Some of these compounds inhibit BHMT with IC50 values in the nanomolar range. BHMT is very sensitive to the structure of substituents on the sulfur atom of homocysteine. The S-carboxybutyl and S-carboxypentyl derivatives make the most potent inhibitors, and an additional sulfur atom in the alkyl chain is well tolerated. The respective ( R, S)-5-( 3-amino-3-carboxy-propylsulfanyl)-pentanoic, ( R, S)-6-( 3-amino-3-carboxy-propylsulfanyl)-hexanoic, and ( R, S)2-amino-4-(2-carboxymethylsulfanyl- ethylsulfanyl)-butyric acids are very potent inhibitors and are the strongest ever reported. We determined that ( R, S)-5-( 3-amino-3-carboxy-propylsulfanyl)-pentanoic acid displays competitive inhibition with respect to betaine binding with a K-i(app) of 12 nM. Some of these compounds are currently being tested in mice to study the influence of BHMT on the metabolism of sulfur amino acids in vivo.

  DOI：

  10.1021/jm050885v
• 作为产物：
  描述：

  DL-高半胱氨酸 、 diisopropyl 2-(chloroethoxy)methylphosphonate 在 sodium carbonate 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 49.0h， 以8%的产率得到(R,S)-2-amino-4-[2-(diisopropoxyphosphorylmethoxy)ethylsulfanyl]butyrate
  参考文献：
  名称：

  S-Alkylated Homocysteine Derivatives:  New Inhibitors of Human Betaine-Homocysteine S-Methyltransferase

  摘要：

  A series of S-alkylated derivatives of homocysteine were synthesized and characterized as inhibitors of human recombinant betaine-homocysteine S-methyltransferase ( BHMT). Some of these compounds inhibit BHMT with IC50 values in the nanomolar range. BHMT is very sensitive to the structure of substituents on the sulfur atom of homocysteine. The S-carboxybutyl and S-carboxypentyl derivatives make the most potent inhibitors, and an additional sulfur atom in the alkyl chain is well tolerated. The respective ( R, S)-5-( 3-amino-3-carboxy-propylsulfanyl)-pentanoic, ( R, S)-6-( 3-amino-3-carboxy-propylsulfanyl)-hexanoic, and ( R, S)2-amino-4-(2-carboxymethylsulfanyl- ethylsulfanyl)-butyric acids are very potent inhibitors and are the strongest ever reported. We determined that ( R, S)-5-( 3-amino-3-carboxy-propylsulfanyl)-pentanoic acid displays competitive inhibition with respect to betaine binding with a K-i(app) of 12 nM. Some of these compounds are currently being tested in mice to study the influence of BHMT on the metabolism of sulfur amino acids in vivo.

  DOI：

  10.1021/jm050885v

文献信息

• <b><i>S</i></b>-Alkylated Homocysteine Derivatives:  New Inhibitors of Human Betaine-Homocysteine <i>S</i>-Methyltransferase
  作者：Jiri Jiracek、Michaela Collinsova、Ivan Rosenberg、Milos Budesinsky、Eva Protivinska、Hana Netusilova、Timothy A. Garrow

  DOI：10.1021/jm050885v

  日期：2006.6.1

  A series of S-alkylated derivatives of homocysteine were synthesized and characterized as inhibitors of human recombinant betaine-homocysteine S-methyltransferase ( BHMT). Some of these compounds inhibit BHMT with IC50 values in the nanomolar range. BHMT is very sensitive to the structure of substituents on the sulfur atom of homocysteine. The S-carboxybutyl and S-carboxypentyl derivatives make the most potent inhibitors, and an additional sulfur atom in the alkyl chain is well tolerated. The respective ( R, S)-5-( 3-amino-3-carboxy-propylsulfanyl)-pentanoic, ( R, S)-6-( 3-amino-3-carboxy-propylsulfanyl)-hexanoic, and ( R, S)2-amino-4-(2-carboxymethylsulfanyl- ethylsulfanyl)-butyric acids are very potent inhibitors and are the strongest ever reported. We determined that ( R, S)-5-( 3-amino-3-carboxy-propylsulfanyl)-pentanoic acid displays competitive inhibition with respect to betaine binding with a K-i(app) of 12 nM. Some of these compounds are currently being tested in mice to study the influence of BHMT on the metabolism of sulfur amino acids in vivo.