(R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide | 159213-17-9

• 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: (R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide
• 英文别名: (2R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide；ethyl (3R)-2,5-dioxo-3-(phenylmethoxycarbonylamino)pyrrolidine-3-carboxylate
• CAS: 159213-17-9
• 化学式: C₁₅H₁₆N₂O₆
• 分子量: 320.302
• InChiKey: XEVSFFUCZKXTGE-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 25.0~70.0 ℃ 、101.33 kPa 条件下， 反应 33.5h， 生成 雷尼司他
  参考文献：
  名称：

  Novel, Highly Potent Aldose Reductase Inhibitors:  (R)-(−)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine- 4-spiro-3‘-pyrrolidine-1,2‘,3,5‘-tetrone (AS-3201) and Its Congeners

  摘要：

  A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors (ARIs) on the basis of their abilities to inhibit porcine lens aldose reductase (AR) in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives showed significantly potent AR inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo- [1,2-a][1,2a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (23t) (SX-3030) showed the best oral activity. The enantiomers of 23t were synthesized, and the biological activities were evaluated. It was found that AR inhibitory activity resides in the (-)-enantiomer 43 (AS-3201), which was 10 times more potent in inhibition of the AR (IC50 = 1.5 x 10(-8) M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)enantiomer 44 (SX-3202): From these results, AS-3201 was selected as the candidate for clinical development. The absolute configuration of AS-3201 was also established to be (R)-form by single-crystal X-ray analysis. In this article we report the preparation and structure-activity relationship (SAR) of tetrahydropyrrolopyrazine derivatives including a novel ARI, AS-3201.

  DOI：

  10.1021/jm9802968
• 作为产物：
  描述：

  diethyl 2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinate 在 乙醇 、 sodium ethanolate 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 乙醇 为溶剂， 反应 23.08h， 生成 (R)-2-benzyloxycarbonylamino-2-ethoxycarbonylsuccinimide
  参考文献：
  名称：

  PROCESS FOR PRODUCING OPTICALLY ACTIVE SUCCINIMIDE DERIVATIVES AND INTERMEDIATES THEREOF

  摘要：

  生产(3R)-2′-(4-溴-2-氟苯基)螺{吡咯啉-3,4′(1′H)-吡咯并[1,2-a]吡嗪}-1′,2,3′,5(2′H)-四酮的光学活性琥珀酰亚胺衍生物作为关键中间体的方法，包括以下反应步骤。

  公开号：

  US20140099681A1

文献信息

• Tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine derivatives,
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05258382A1

  公开（公告）日：1993-11-02

  Tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine derivatives of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen, halogen, trifluoromethyl, alkyl having 1 to 6 carbon atoms, alkoxy having 1 to 6 carbon atoms, or nitro, and R.sup.3 is hydrogen, halogen or alkyl having 1 to 6 carbon atoms, and pharmaceutically acceptable salts thereof, processes for preparation thereof, and pharmaceutical composition containing the same. Said compounds and their salts show excellent aldose reductase inhibitory activity and are useful for the prevention and treatment of diabetic complications.

  该文翻译如下： Tetrahydropyrrolo [1,2-a] pyrazine-4-spiro-3'-pyrrolidine 衍生物的化学式如下：##STR1## 其中 R.sup.1 和 R.sup.2 独立地表示氢、卤素、三氟甲基、具有1至6个碳原子的烷基、具有1至6个碳原子的烷氧基或硝基，而 R.sup.3 表示氢、卤素或具有1至6个碳原子的烷基，以及其制备过程和药学上可接受的盐，以及含有它们的制药组合物。这些化合物及其盐表现出出色的醛固酮还原酶抑制活性，可用于预防和治疗糖尿病并发症。
• Method for producing optically active succinimide compound
  申请人：Kudo Yoshihiro

  公开号：US20100003729A1

  公开（公告）日：2010-01-07

  There is provided a novel method for producing an optically active succinimide compound which is a useful compound utilized as an intermediate raw material for pharmaceutical products or the like. The method for producing an optically active succinimide compound of formula (2) comprises processing a racemic compound of a succinimide compound of formula (1) in the presence of a hydrolase to selectively hydrolyze one of the enantiomers, and subjecting to a post-treatment.

  提供了一种新颖的方法来生产光学活性的琥珀酰亚胺化合物，该化合物是制药产品或类似产品的中间原料。生产公式（2）的光学活性琥珀酰亚胺化合物的方法包括在水解酶的存在下处理公式（1）的琥珀酰亚胺化合物的外消旋体，以选择性水解其中一种对映体，并进行后处理。
• Succinic acid diester derivative, process for production thereof, and use of the derivative in the production of pharmaceutical preparation
  申请人：Inagaki Takashi

  公开号：US20100076203A1

  公开（公告）日：2010-03-25

  The present invention provides with a process of preparing an optically active succinimide derivative, which is a key intermediate for production of ranirestat. A compound (3) is easily prepared by treating the derivative of succinic acid diester of the formula (2): wherein R 1 is an amino group protected with a group removed by hydrogenolysis or a tert-butoxycarbonylamino group and R 2 is an ethyl group optionally substituted with one or two methyl group(s) at α-position, provided that R 2 is not a tert-butyl group when R 1 is a tert-butoxycarbonylamino group; with alkali metal alkoxide and the compound (3) can be an important intermediate for production of ranirestat.

  本发明提供了一种制备光学活性琥珀酰亚胺衍生物的方法，该衍生物是生产拉尼瑞斯塔的关键中间体。通过处理公式（2）的琥珀酸二酯衍生物，可以轻松制备化合物（3）：其中R1是通过氢解去除的保护氨基或叔丁氧羰基氨基，R2是在α位上可选地取代一个或两个甲基的乙基基团，但当R1是叔丁氧羰基氨基时，R2不能是叔丁基基团。使用碱金属醇盐处理化合物（3），可以得到生产拉尼瑞斯塔的重要中间体。
• PROCESS FOR PRODUCING OPTICALLY ACTIVE SUCCINIMIDE DERIVATIVES
  申请人：Kita Shinji

  公开号：US20130196388A1

  公开（公告）日：2013-08-01

  A process for efficiently producing optically active succinimide derivatives as key intermediates of (3R)-2′-(4-bromo-2-fluorobenzyl)spiropyrrolidine-3,4′(1′H)-pyrrolo[1,2-a]pyrazine}-1′,2,3′,5(2′H)-tetraone, which comprises the following reaction steps, and the step 2 is performed by using a non-animal-derived enzyme.

  一种高效生产光学活性琥珀酰亚胺衍生物的方法，其作为(3R)-2'-(4-溴-2-氟苯基)螺吡咯烷-3,4'(1'H)-吡咯[1,2-a]吡嗪}-1',2,3',5(2'H)-四酮的关键中间体，包括以下反应步骤，其中步骤2使用非动物来源的酶进行反应。
• Process for producing optically active succinimide derivatives
  申请人：Kita Shinji

  公开号：US08900830B2

  公开（公告）日：2014-12-02

  A process for efficiently producing optically active succinimide derivatives as key intermediates of (3R)-2′-(4-bromo-2-fluorobenzyl)spiropyrrolidine-3,4′(1′H)-pyrrolo[1,2-a]pyrazine}-1′,2,3′,5(2′H)-tetraone, which comprises the following reaction steps, and the step 2 is performed by using a non-animal-derived enzyme.

  一种高效生产光学活性琥珀酰亚胺衍生物的方法，作为(3R)-2′-(4-溴-2-氟苯基)螺吡咯烷-3,4′(1′H)-吡咯并[1,2-a]吡嗪}-1′,2,3′,5(2′H)-四酮的关键中间体，包括以下反应步骤，其中步骤2使用非动物来源的酶进行。