(8S)-1,4-二氧杂-7-氮杂螺[4.4]壬烷-8-羧酸 | 75776-51-1

• 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
• 中文名称: (8S)-1,4-二氧杂-7-氮杂螺[4.4]壬烷-8-羧酸
• 英文名称: (8S)-1,4-dioxa-7-azaspiro[4.4]nonane-8-carboxylic acid
• 英文别名: 4,4-ethylenedioxy-L-proline
• CAS: 75776-51-1
• 化学式: C₇H₁₁NO₄
• 分子量: 173.169
• InChiKey: WRHPVRWALQQWHH-YFKPBYRVSA-N

物化性质

• 熔点：
  245-247 °C
• 沸点：
  360.6±42.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  67.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (8S)-1,4-二氧杂-7-氮杂螺[4.4]壬烷-8-羧酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 (8S)-N-[(4-acetamidophenyl)methyl]-7-{2-[(4-phenoxyphenyl)formamido]acetyl}-1,4-dioxa-7-azaspiro[4.4]nonane-8-carboxamide
  参考文献：
  名称：

  [EN] PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS
  [FR] COMPOSÉS PHARMACEUTIQUES POUR LE TRAITEMENT DE TROUBLES MÉDIÉS PAR LE COMPLÉMENT

  摘要：

  这份披露提供了用于治疗医学疾病的药物化合物，例如包括补体介导的疾病在内的补体Cl-介导的疾病。

  公开号：

  WO2020198062A1
• 作为产物：
  描述：

  N-cbz-4-氧-L-脯氨酸 在 palladium on activated charcoal 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 苯 为溶剂， 反应 7.0h， 生成 (8S)-1,4-二氧杂-7-氮杂螺[4.4]壬烷-8-羧酸
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. Mercaptan, carboxyalkyl dipeptide, and phosphinic acid inhibitors incorporating 4-substituted prolines

  摘要：

  Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl, aryl, alkoxy, aryloxy, alkylthio, and arylthio substituents were prepared from derivatives of 4-hydroxy- and 4-ketoproline. In general, analogues of all three classes of inhibitors with hydrophobic substituents on proline were more potent in vitro than the corresponding unsubstituted proline compounds. 4-Substituted analogues of captopril showed greater potency and duration of action than the parent compound as inhibitors of the angiotensin I induced pressor response in normotensive rats. The S-benzoyl derivative of cis-4-(phenylthio)captopril, zofenopril, was found to be one of the most potent compounds of this class and is now being evaluated clinically as an antihypertensive agent. In the phosphinic acid series, the 4-ethylenethioketal and trans-4-cyclohexyl derivatives were found to be the most potent compounds in vitro and in vivo. A prodrug of the latter compound, fosinopril, is also being evaluated in clinical trials.

  DOI：

  10.1021/jm00401a014

文献信息

• Derivatives of mercaptoacyl prolines and pipecolic acids
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04311697A1

  公开（公告）日：1982-01-19

  This invention is directed to compounds of the formula ##STR1## and various intermediates therefore. The final products possess useful hypotensive activity.

  这项发明涉及公式##STR1##的化合物及其各种中间体。最终产品具有有用的降压活性。
• Carboxyalkanoyl and hydroxycarbamoylalkanoyl derivatives of substituted
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04311705A1

  公开（公告）日：1982-01-19

  Compounds, compositions and method of alleviating hypertension using a compound of the formula ##STR1## wherein R is hydrogen or lower alkyl; R.sub.1 is hydrogen, lower alkyl or phenyl-lower alkyl; R.sub.2 is hydrogen, lower alkyl or phenyl lower alkyl or halo substituted lower alkyl; R.sub.3 is hydroxy, --NHOH or lower alkoxy; Pr-COOR is a substituted proline of the structures ##STR2## R.sub.4 is halogen, keto, azido, cycloalkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, ##STR3## or Y--R.sub.6 ; R.sub.5 is hydrogen or lower alkyl; Y is oxygen or sulfur; R.sub.6 is lower alkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, 1- or 2-naphthyl, substituted 1- or 2- naphthyl, biphenyl, or substituted biphenyl; R.sub.7 is halogen or --Y--R.sub.8 ; R.sub.8 is lower alkyl, phenyl, phenyl-lower alkyl substituted phenyl-lower alkyl, biphenyl, napthyl, or the R.sub.8 groups join to complete an unsubstituted 5- or 6-membered ring or such ring wherein one or more carbon atoms are substituted by a lower alkyl or di(lower alkyl) group; R.sub.9 is keto, phenyl, 2- or 4-hydroxyphenyl; n is 0 or 1; and salts thereof.

  这是一段关于使用某化合物缓解高血压的方法、化合物和组合物的描述。
• Carboxyalkanoyl and hydroxycarbamoylalkanoyl derivatives of substituted prolines
  申请人：E.R. Squibb & Sons, Inc.

  公开号：EP0049589A1

  公开（公告）日：1982-04-14

  Compounds, compositions and method of alleviating hypertension using a compound of the formula wherein R is hydrogen or lower alkyl; R1 is hydrogen, lower alkyl or phenyl-lower alkyl; R2 is hydrogen, lower alkyl, phenyl lower alkyl or halo substituted lower alkyl; R3 is hydroxy, -NHOH or lower alkoxy; Pr-COOR is a substituted proline of the structures or R4 is halogen, keto, azido, cycloalkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, R5 is hydrogen or lower alkyl; Y is oxygen or sulfur; R6 is lower alkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, 1- or 2-naphthyl, substituted 1- or 2- naphthyl, biphenyl, or substituted biphenyl; R7 is halogen or -Y-R8; R8 is lower alkyl, phenyl, phenyl-lower alkyl substituted phenyl-lower alkyl, biphenyl, napthyl, or the R8 groups join to complete an unsubstituted 5- or 6- membered ring or such ring wherein one or more carbon atoms are substituted by a lower alkyl or di(lower alkyl) group; R9 is keto, phenyl, 2- or 4-hydroxyphenyl; n is 0 or 1; and salts thereof.

  使用式中化合物缓解高血压的化合物、组合物和方法 其中 R 是氢或低级烷基； R1 是氢、低级烷基或苯基低级烷基 R2 是氢、低级烷基、苯基低级烷基或卤代低级烷基； R3 是羟基、-NHOH 或低级烷氧基； Pr-COOR 是以下结构的取代脯氨酸 或 R4 是卤素、酮、叠氮、环烷基、苯基、取代苯基、苯基低级烷基、取代苯基低级烷基、 R5 是氢或低级烷基 Y 是氧或硫； R6 是低级烷基、苯基、取代苯基、苯基-低级烷基、取代苯基-低级烷基、1-或 2-萘基、取代 1-或 2-萘基、联苯或取代联苯； R7 是卤素或-Y-R8； R8 是低级烷基、苯基、苯基-低级烷基取代的苯基-低级烷基、联苯基、萘基，或 R8 基团连接成未取代的 5 或 6 成员环，或其中一个或多个碳原子被低级烷基或二(低级烷基)基团取代的环； R9 是酮、苯基、2-或 4-羟基苯基； n 为 0 或 1；及其盐类。
• KRAPCHO, J.
  作者：KRAPCHO, J.

  DOI：——

  日期：——
• ONDETTI, M. A.;CONDON, M. E.
  作者：ONDETTI, M. A.、CONDON, M. E.

  DOI：——

  日期：——