[4S-(4α,7α,12β)]-7-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido[2,1-a][2]-benzazepine-4-carboxylic acid | 142589-81-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: [4S-(4α,7α,12β)]-7-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido[2,1-a][2]-benzazepine-4-carboxylic acid
• 英文别名: (4S,7S,12bR)-7-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido[2,1-a][2]benzazepine-4-carboxylic acid；(4S,7S,12bR)-7-(1,3-dioxoisoindol-2-yl)-6-oxo-2,3,4,7,8,12b-hexahydro-1H-pyrido[2,1-a][2]benzazepine-4-carboxylic acid
• CAS: 142589-81-9
• 化学式: C₂₃H₂₀N₂O₅
• 分子量: 404.422
• InChiKey: LLRVWEHGZKXEOH-QYZOEREBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  [S(R*,R*)]-1-[2-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)-1-oxo-3-phenylpropyl]-1,2,3,4-tetrahydro-2-pyridinecarboxylicacid, methyl ester 在 三氟甲磺酸 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 以65.4%的产率得到[4S-(4α,7α,12β)]-7-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-1,2,3,4,6,7,8,12b-octahydro-6-oxopyrido[2,1-a][2]-benzazepine-4-carboxylic acid
  参考文献：
  名称：

  Process Development in the Synthesis of the ACE Intermediate MDL 28,726

  摘要：

  MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240, An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed resolution of the lithium salt of the N-trifluoroacetamide of (R,S)-6-hydroxynorleucine. All of the steps were optimized and completed in reactor equipment using environmentally acceptable processes. Process development of this route is described.

  DOI：

  10.1021/op970125x

文献信息

• Novel amino and nitro containing tricyclic compounds useful as inhibitors of ace
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0492369A1

  公开（公告）日：1992-07-01

  The present invention relates to compounds of the formula wherein    A is methylene, oxygen, sulfur or N-B wherein B is R₁ or COR₂ wherein R₁ is hydrogen, a C₁-C₄ alkyl or an Ar-Z-group wherein Ar is aryl and Z is a C₀-C₄ alkyl and R₂ is a -CF₃, a C₁-C₁₀ alkyl or an Ar-Z group;    R is hydrogen or a C₁-C₄ alkyl; and    X and Y are each independently hydrogen, nitro or amino, with the proviso that when X is nitro or amino, Y must be hydrogen, and when Y is nitro or amino, X must be hydrogen; and pharmaceutically acceptable salts thereof, which are inhibitors of Angiotensin Converting Enzyme.

  本发明涉及式如下的化合物 其中 A 是亚甲基、氧、硫或 N-B，其中 B 是 R₁ 或 COR₂ ，其中 R₁ 是氢、C₁-C₄ 烷基或 Ar-Z 基团，其中 Ar 是芳基，Z 是 C₀-C₄ 烷基，R₂ 是 -CF₃、C₁-C₁₀ 烷基或 Ar-Z 基团； R 是氢或 C₁-C₄ 烷基；以及 X和Y各自独立地是氢、硝基或氨基，但条件是当X是硝基或氨基时，Y必须是氢，当Y是硝基或氨基时，X必须是氢；以及 其药学上可接受的盐、 是血管紧张素转换酶的抑制剂。
• AMINO ACID DERIVATIVE
  申请人：Eisai Co., Ltd.

  公开号：EP0671172A1

  公开（公告）日：1995-09-13

  An amino acid derivative having an angiotensin I-converting enzyme inhibitor activity, a vasopressin antagonism and an atrial natriuretic peptide hydrolase inhibitor activity, and represented by general formula (I) wherein R¹ represents hydrogen or acyl; R² represents hydrogen, lower alkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; m and n represent each independently an integer of 0.1 or 2; and J represents a cyclic group having an angiotensin I-converting enzyme inhibitor activity.

  一种具有血管紧张素Ⅰ转换酶抑制剂活性、血管加压素拮抗剂活性和心房钠尿肽水解酶抑制剂活性的氨基酸衍生物，由通式(I)表示 其中R¹代表氢或酰基；R²代表氢、低级烷基、环烷基、任选取代的芳基、任选取代的杂芳基、任选取代的芳烷基或任选取代的杂芳基烷基；m和n各自独立地代表0.1或2的整数；J代表具有血管紧张素I-转化酶抑制剂活性的环状基团。
• Novel antihypertensive agent
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0249223B1

  公开（公告）日：1992-10-14
• Novel sulfhydryl containing tricyclic lactams and their pharmacological methods of use
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0322914B1

  公开（公告）日：1994-01-19
• US4824832A
  申请人：——

  公开号：US4824832A

  公开（公告）日：1989-04-25