6-<1S-(3S,4-dihydro-8-hydroxy-1H-2-benzopyran-1-one-3-yl)-3-methylbutylamino>-4S,5S-dihydroxy-6-oxo-3S-ammoniohexanoate, γ-lactone-N-ethyl derivative | 77700-96-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-<1S-(3S,4-dihydro-8-hydroxy-1H-2-benzopyran-1-one-3-yl)-3-methylbutylamino>-4S,5S-dihydroxy-6-oxo-3S-ammoniohexanoate, γ-lactone-N-ethyl derivative
• 英文别名: 4-<1-hydroxy-2-<<1-(3,4-dihydro-8-hydroxy-1-oxo-1H-2-benzopyran-3-yl)-3-methylbutyl>amino>-2-oxoethyl>-3-(ethylamino)butan-4-olide；(2S)-2-[(2S,3S)-3-(ethylamino)-5-oxooxolan-2-yl]-2-hydroxy-N-[(1S)-1-[(3S)-8-hydroxy-1-oxo-3,4-dihydroisochromen-3-yl]-3-methylbutyl]acetamide
• CAS: 77700-96-0
• 化学式: C₂₂H₃₀N₂O₇
• 分子量: 434.489
• InChiKey: IMPKHMMWFQRYCH-OLOWNEEMSA-N

物化性质

• 沸点：
  763.0±60.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  134
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-<1S-(3S,4-dihydro-8-hydroxy-1H-2-benzopyran-1-one-3-yl)-3-methylbutylamino>-4S,5S-dihydroxy-6-oxo-3S-ammoniohexanoate, γ-lactone-N-ethyl derivative 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (3S,4S,5S)-3-Ethylamino-4,5-dihydroxy-5-[(S)-1-((S)-8-hydroxy-1-oxo-isochroman-3-yl)-3-methyl-butylcarbamoyl]-pentanoic acid
  参考文献：
  名称：

  1H-2-Benzopyran-1-one derivatives, microbial products with pharmacological activity. Conversion into orally active derivatives with antiinflammatory and antiulcer activities

  摘要：

  A novel gastroprotective substance, 6-[[1(S)-[3(S),4-dihydro-8-hydroxy-1-oxo-1H-2-benzopyran-3-yl] -3-methylbutyl]amino]-4(S),5(S)-dihydroxy-6-oxo-3(S)-ammoniohexanoate (AI-77-B, 1), isolated from a culture broth of Bacillus pumilus AI-77, was chemically modified to prodrugs that are active by oral dosing. Compound 1 was lactonized and then monoalkylated at the primary amine position. Six N-alkylated gamma-lactone derivatives of 1 (with alkyl chains being methyl 5a, ethyl 5b, n-propyl 5c, n-butyl 5d, n-pentyl 5e, or n-hexyl 5f) were synthesized and eight compounds including 1 and gamma-lactone derivative 2 were compared for their gastroprotective activities and blood levels after oral administration in rats. Further, chloroform-water partition coefficients of 5a-f were also compared as a measure of lipid solubility. The protective effects of these compounds on stress ulcers were mutually related to blood levels of dealkylated compounds (1 and 2). Parent compound 1 was detected in blood at 1 h after each of 5a-d was administered. When 5b or 5c was administered, high activity and high blood levels of 1 were observed in comparison with those levels obtained with 5a or 5d. Neither 5e nor 5f were detected in any amount in blood by oral administration without special formulation due to extremely low solubilities and agglutinative properties in intestinal fluid. Interestingly, 5b and 5c were found to have antiinflammatory activities in addition to potent antiulcerogenicity action.

  DOI：

  10.1021/jm00379a002
• 作为产物：
  描述：

  在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 0.5h， 生成 6-<1S-(3S,4-dihydro-8-hydroxy-1H-2-benzopyran-1-one-3-yl)-3-methylbutylamino>-4S,5S-dihydroxy-6-oxo-3S-ammoniohexanoate, γ-lactone-N-ethyl derivative
  参考文献：
  名称：

  1H-2-Benzopyran-1-one derivatives, microbial products with pharmacological activity. Conversion into orally active derivatives with antiinflammatory and antiulcer activities

  摘要：

  A novel gastroprotective substance, 6-[[1(S)-[3(S),4-dihydro-8-hydroxy-1-oxo-1H-2-benzopyran-3-yl] -3-methylbutyl]amino]-4(S),5(S)-dihydroxy-6-oxo-3(S)-ammoniohexanoate (AI-77-B, 1), isolated from a culture broth of Bacillus pumilus AI-77, was chemically modified to prodrugs that are active by oral dosing. Compound 1 was lactonized and then monoalkylated at the primary amine position. Six N-alkylated gamma-lactone derivatives of 1 (with alkyl chains being methyl 5a, ethyl 5b, n-propyl 5c, n-butyl 5d, n-pentyl 5e, or n-hexyl 5f) were synthesized and eight compounds including 1 and gamma-lactone derivative 2 were compared for their gastroprotective activities and blood levels after oral administration in rats. Further, chloroform-water partition coefficients of 5a-f were also compared as a measure of lipid solubility. The protective effects of these compounds on stress ulcers were mutually related to blood levels of dealkylated compounds (1 and 2). Parent compound 1 was detected in blood at 1 h after each of 5a-d was administered. When 5b or 5c was administered, high activity and high blood levels of 1 were observed in comparison with those levels obtained with 5a or 5d. Neither 5e nor 5f were detected in any amount in blood by oral administration without special formulation due to extremely low solubilities and agglutinative properties in intestinal fluid. Interestingly, 5b and 5c were found to have antiinflammatory activities in addition to potent antiulcerogenicity action.

  DOI：

  10.1021/jm00379a002

文献信息

• 1H-2-Benzopyran-1-one derivatives, microbial products with pharmacological activity. Conversion into orally active derivatives with antiinflammatory and antiulcer activities
  作者：Yukiji Shimojima、Takashi Shirai、Tsuneo Baba、Hiroshi Hayashi

  DOI：10.1021/jm00379a002

  日期：1985.1

  A novel gastroprotective substance, 6-[[1(S)-[3(S),4-dihydro-8-hydroxy-1-oxo-1H-2-benzopyran-3-yl] -3-methylbutyl]amino]-4(S),5(S)-dihydroxy-6-oxo-3(S)-ammoniohexanoate (AI-77-B, 1), isolated from a culture broth of Bacillus pumilus AI-77, was chemically modified to prodrugs that are active by oral dosing. Compound 1 was lactonized and then monoalkylated at the primary amine position. Six N-alkylated gamma-lactone derivatives of 1 (with alkyl chains being methyl 5a, ethyl 5b, n-propyl 5c, n-butyl 5d, n-pentyl 5e, or n-hexyl 5f) were synthesized and eight compounds including 1 and gamma-lactone derivative 2 were compared for their gastroprotective activities and blood levels after oral administration in rats. Further, chloroform-water partition coefficients of 5a-f were also compared as a measure of lipid solubility. The protective effects of these compounds on stress ulcers were mutually related to blood levels of dealkylated compounds (1 and 2). Parent compound 1 was detected in blood at 1 h after each of 5a-d was administered. When 5b or 5c was administered, high activity and high blood levels of 1 were observed in comparison with those levels obtained with 5a or 5d. Neither 5e nor 5f were detected in any amount in blood by oral administration without special formulation due to extremely low solubilities and agglutinative properties in intestinal fluid. Interestingly, 5b and 5c were found to have antiinflammatory activities in addition to potent antiulcerogenicity action.