((2S)-3-((1,1-Dimethyl-2-(tetrahydrofuran-3-carbonylamino)ethyl)amino)-2-(1-methylcyclopropanecarbonyl)oxy-propyl) 4,5-dihydroxy-2-methyl-benzoate | 870809-51-1

• 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: ((2S)-3-((1,1-Dimethyl-2-(tetrahydrofuran-3-carbonylamino)ethyl)amino)-2-(1-methylcyclopropanecarbonyl)oxy-propyl) 4,5-dihydroxy-2-methyl-benzoate
• 英文别名: [(2S)-2-(1-methylcyclopropanecarbonyl)oxy-3-[[2-methyl-1-(oxolane-3-carbonylamino)propan-2-yl]amino]propyl] 4,5-dihydroxy-2-methylbenzoate
• CAS: 870809-51-1
• 化学式: C₂₅H₃₆N₂O₈
• 分子量: 492.6
• InChiKey: ANXXSWNMHQHOQC-DJNXLDHESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  143
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  [(2S)-2-(1-methylcyclopropanecarbonyl)oxy-3-[[2-methyl-1-(oxolane-3-carbonylamino)propan-2-yl]amino]propyl] 2-methyl-4,5-bis(phenylmethoxy)benzoate 生成 ((2S)-3-((1,1-Dimethyl-2-(tetrahydrofuran-3-carbonylamino)ethyl)amino)-2-(1-methylcyclopropanecarbonyl)oxy-propyl) 4,5-dihydroxy-2-methyl-benzoate
  参考文献：
  名称：

  [EN] OCULOSELECTIVE DRUGS AND PRODRUGS
  [FR] MEDICAMENTS ET PROMEDICAMENTS OCULOSELECTIFS

  摘要：

  本发明揭示了以下公式的化合物：其中R1和R2各自独立地是H，W或苯氧基保护基；R4是H或W，但至少其中一个R1，R2和R4是W；R3是氢，直链或支链C1-C10烷基，环烷基，氨基，C1-C10烷氧基，-NHC（=O）Ra或-C（=O）N（H）Ra；Ra是烷基，芳基或杂环基；Z是-0-，-O（C=O）-或NH（C=O）-，其中当Z是-0-时，R5是H，直链或支链C1-C10烷基，环烷基，环烷基上至少有一个直链或支链C1-C10烷基，Cl-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，吡啶基，四氢吡啶基，四氢吡喃基，二甲基二氧杂环己烷基，二氧杂环己烷基，吡咯基，吡咯烷基，四氢噁唑基，二氢噁唑基，苯基或苯基上取代Cl-Clo烷基，C1-C10烷氧基或卤素；W是：其中每个R6独立地是H，直链或支链C1-C10烷基或直链或支链Cl-C10烷氧基烷基；R7是烷基，环烷基，芳基或芳基烷基；当Z是-O（C=O）-时，R5是直链或支链C1-C10烷基，环烷基，环烷基上至少有一个直链或支链C1-C10烷基，Cl-CIO烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，吡啶基，四氢吡啶基，四氢吡喃基，二甲基二氧杂环己烷基，二氧杂环己烷基，吡咯基，吡咯烷基，四氢噁唑基，二氢噁唑基，苯基或苯基上取代Cl-C10烷基，C1-C10烷氧基或卤素；W是：其中每个R6独立地是H，直链或支链C1-C10烷基或直链或支链Cl-C10烷氧基烷基；R7是烷基，环烷基，芳基或芳基烷基；当Z是-NH（C=O）-时，R5是直链或支链C1-C10烷基，环烷基，环烷基上至少有一个直链或支链C1-C10烷基，Cl-CIO烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，吡啶基，四氢吡啶基，四氢吡喃基，二甲基二氧杂环己烷基，二氧杂环己烷基，吡咯基，吡咯烷基，四氢噁唑基，二氢噁唑基，苯基或苯基上取代Cl-C10烷基，C1-C10烷氧基或卤素；W是：其中每个R6独立地是H，直链或支链C1-C10烷基或直链或支链C,-Clo烷氧基烷基。本发明还揭示了制备该化合物的方法，包括该化合物的制药组合物以及通过给患者使用该制药组合物治疗的方法。

  公开号：

  WO2005115375A1

文献信息

• Prodrugs of 3,4-hydroxy benzoyloxypropanolamines
  申请人：E. I. Du Pont de Nemours & Co.

  公开号：US04897417A1

  公开（公告）日：1990-01-30

  In accordance with the present invention, disclosed herein are compounds of the formula ##STR1## wherein R is straight or branched loweralkyl, R.sub.1 is hydrogen, straight or branched loweralkyl, lowercycloalkyl, amino, loweralkoxy or acylamino, and R.sub.2 is straight or branched loweralkyl, amino, cyclohexyl, morpholino, piperidino, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolidinyl, tetrahydrooxazolyl, and dihydrooxazolyl, and pharmaceutically acceptable salts thereof. The compounds are useful in the treatment of glaucoma.

  根据本发明，公开了以下式子的化合物：##STR1## 其中R是直链或支链低烷基，R.sub.1是氢、直链或支链低烷基、低环烷基、氨基、低烷氧基或酰胺基，R.sub.2是直链或支链低烷基、氨基、环己基、吗啡环基、哌啶环基、四氢呋喃基、二氢呋喃基、四氢吡喃基、二氢二氧环基、2,2-二甲基二氧环基、二氧环基、吡咯烷基、四氢噁唑基和二氢噁唑基，以及其药学上可接受的盐。这些化合物可用于治疗青光眼。
• [EN] OCULOSELECTIVE DRUGS AND PRODRUGS<br/>[FR] MEDICAMENTS ET PROMEDICAMENTS OCULOSELECTIFS
  申请人：OTHERA PHARMACEUTICALS INC

  公开号：WO2005115375A1

  公开（公告）日：2005-12-08

  Compounds of the following formula are disclosed: wherein R1 and R2 are each independently H, W, or a phenoxyl protecting group; and R4is H or W, provided that at least one of R1, R2, and R4 is W; R3 is hydrogen, straight chain or branched C1-C10 alkyl, cycloalkyl, amino, C1-C10 alkoxy, -NHC(=O)Ra, or -C(=O)N(H)Ra; Ra is alkyl, aryl, or heterocyclyl; Z is -0-, -O(C=O)-, or NH(C=O)-, wherein when Z is -0-, R5 is H, straight chain or branched C1-C10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C1-C10 alkyl, CI-Clo alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolsdinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with CI-Clo alkyl, C1-C10 alkoxy, or halo; and W is:, wherein each R6 is independently H, straight chain or branched C1-C10 alkyl, or straight chain or branched Cl-C10 alkoxyalkyl; and R7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is -O(C=O)-, R5 is straight chain or branched C1-C10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C1-C10 alkyl, CI-CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with Cl-C10 alkyl, C1-C10 alkoxy, or halo; and W is: , wherein each R6 is independently H, straight chain or branched CI-C to alkyl, or straight chain or branched C,-C to alkoxyalkyl; and R7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is-NH(C=O)-, R5 is straight chain or branched C1 -C10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C1-C10 alkyl, CI-CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, &oxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C1-C10 alkyl, C1-C10 alkoxy, or halo; and W is: ; wherein each R6 is independently H, straight chain or branched C1 -C to alkyl, or straight chain or branched C,-Clo alkoxyalkyl. Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions, are also disclosed.

  本发明揭示了以下公式的化合物：其中R1和R2各自独立地是H，W或苯氧基保护基；R4是H或W，但至少其中一个R1，R2和R4是W；R3是氢，直链或支链C1-C10烷基，环烷基，氨基，C1-C10烷氧基，-NHC（=O）Ra或-C（=O）N（H）Ra；Ra是烷基，芳基或杂环基；Z是-0-，-O（C=O）-或NH（C=O）-，其中当Z是-0-时，R5是H，直链或支链C1-C10烷基，环烷基，环烷基上至少有一个直链或支链C1-C10烷基，Cl-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，吡啶基，四氢吡啶基，四氢吡喃基，二甲基二氧杂环己烷基，二氧杂环己烷基，吡咯基，吡咯烷基，四氢噁唑基，二氢噁唑基，苯基或苯基上取代Cl-Clo烷基，C1-C10烷氧基或卤素；W是：其中每个R6独立地是H，直链或支链C1-C10烷基或直链或支链Cl-C10烷氧基烷基；R7是烷基，环烷基，芳基或芳基烷基；当Z是-O（C=O）-时，R5是直链或支链C1-C10烷基，环烷基，环烷基上至少有一个直链或支链C1-C10烷基，Cl-CIO烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，吡啶基，四氢吡啶基，四氢吡喃基，二甲基二氧杂环己烷基，二氧杂环己烷基，吡咯基，吡咯烷基，四氢噁唑基，二氢噁唑基，苯基或苯基上取代Cl-C10烷基，C1-C10烷氧基或卤素；W是：其中每个R6独立地是H，直链或支链C1-C10烷基或直链或支链Cl-C10烷氧基烷基；R7是烷基，环烷基，芳基或芳基烷基；当Z是-NH（C=O）-时，R5是直链或支链C1-C10烷基，环烷基，环烷基上至少有一个直链或支链C1-C10烷基，Cl-CIO烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，吡啶基，四氢吡啶基，四氢吡喃基，二甲基二氧杂环己烷基，二氧杂环己烷基，吡咯基，吡咯烷基，四氢噁唑基，二氢噁唑基，苯基或苯基上取代Cl-C10烷基，C1-C10烷氧基或卤素；W是：其中每个R6独立地是H，直链或支链C1-C10烷基或直链或支链C,-Clo烷氧基烷基。本发明还揭示了制备该化合物的方法，包括该化合物的制药组合物以及通过给患者使用该制药组合物治疗的方法。
• Oculoselective Drugs and Prodrugs
  申请人：Matier L. William

  公开号：US20070254950A1

  公开（公告）日：2007-11-01

  Compounds of the following formula are disclosed: wherein R 1 and R 2 are each independently H, W, or a phenoxyl protecting group; and R 4 is H or W, provided that at least one of R 1 , R 2 , and R 4 is W; R 3 is hydrogen, straight chain or branched C 1 -C 10 alkyl, cycloalkyl, amino, C 1 -C 10 alkoxy, —NHC(═O)Ra, or —C(═O)N(H)R a ; R a is alkyl, aryl, or heterocyclyl; Z is -0-, —O(C═O)—, or NH(C═O)—, wherein when Z is -0-, R 5 is H, straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, CI—Clo alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolsdinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with CI—Clo alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R 6 is independently H, straight chain or branched C 1 -C 10 alkyl, or straight chain or branched C 1 -C 10 alkoxyalkyl; and R 7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is —O(C═O)—, R 5 is straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, CI—CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is:, wherein each R6 is independently H, straight chain or branched CI—C to alkyl, or straight chain or branched C,—C to alkoxyalkyl; and R7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is —NH(C═O)—, R5 is straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, CI—CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, & oxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R6 is independently H, straight chain or branched C1-C to alkyl, or straight chain or branched C,—Clo alkoxyalkyl. Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions, are also disclosed.

  公开了以下式子的化合物：其中R1和R2分别独立地为H，W或苯氧基保护基；而R4为H或W，但至少其中之一为W；R3为氢，直链或支链C1-C10烷基，环烷基，氨基，C1-C10烷氧基，—NHC（═O）Ra，或—C（═O）N（H）Ra；Ra为烷基，芳基或杂环基；Z为-0-，—O（C═O）—或NH（C═O）—，其中当Z为-0-时，R5为H，直链或支链C1-C10烷基，环烷基，至少有一个直链或支链C1-C10烷基替代的环烷基，CI-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，哌啶基，四氢吡喃基，二氢二氧杂环基，2,2-二甲基二氧杂环基，二氧杂环基，吡咯基，吡咯啉基，四氢噁唑基，二氢噁唑基，苯基，或带有CI-Clo烷基，C1-C10烷氧基或卤素替代的苯基；W为：其中每个R6独立地为H，直链或支链C1-C10烷基或直链或支链C1-C10烷氧基烷基；而R7为烷基，环烷基，芳基或芳基烷基；当Z为—O（C═O）—时，R5为直链或支链C1-C10烷基，环烷基，至少有一个直链或支链C1-C10烷基替代的环烷基，CI-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，哌啶基，四氢吡喃基，二氢二氧杂环基，2,2-二甲基二氧杂环基，二氧杂环基，吡咯基，吡咯啉基，四氢噁唑基，二氢噁唑基，苯基，或带有C1-C10烷基，C1-C10烷氧基或卤素替代的苯基；W为：其中每个R6独立地为H，直链或支链C1-C10烷基或直链或支链C1-C10烷氧基烷基；而R7为烷基，环烷基，芳基或芳基烷基；当Z为—NH（C═O）—时，R5为直链或支链C1-C10烷基，环烷基，至少有一个直链或支链C1-C10烷基替代的环烷基，CI-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，哌啶基，四氢吡喃基，二氢二氧杂环基，2,2-二甲基二氧杂环基，二氧杂环基，吡咯基，吡咯啉基，四氢噁唑基，二氢噁唑基，苯基，或带有C1-C10烷基，C1-C10烷氧基或卤素替代的苯基；W为：其中每个R6独立地为H，直链或支链C1-C10烷基或直链或支链C1-C10烷氧基烷基。还公开了制备这些化合物的方法，包括这些化合物的制药组合物以及通过给药这些制药组合物治疗患者的方法。
• OCULOSELECTIVE DRUGS AND PRODRUGS
  申请人：MATIER WILLIAM L.

  公开号：US20100179218A1

  公开（公告）日：2010-07-15

  Compounds of the following formula are disclosed: Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions are disclosed.

  以下公式的化合物已被披露：披露了制备这些化合物的方法，包括这些化合物的制药组合物和通过给患者用制药组合物治疗的方法。
• US7678829B2
  申请人：——

  公开号：US7678829B2

  公开（公告）日：2010-03-16