(S)-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazoline-1-carboxylic acid | 380223-09-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: (S)-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazoline-1-carboxylic acid
• 英文别名: (S)-2,3-Dihydro-1H-9-oxo-pyrrolo[2,1-b]quinazolin-1-carboxylic acid；(1S)-9-oxo-2,3-dihydro-1H-pyrrolo[2,1-b]quinazoline-1-carboxylic acid
• CAS: 380223-09-6
• 化学式: C₁₂H₁₀N₂O₃
• 分子量: 230.223
• InChiKey: YJEPYYUKWZTLJR-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazoline-1-carboxylic acid 在 四(三苯基膦)钯 、 1,3-二甲基巴比妥酸 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 生成 (1S)-N-[(3S)-2-hydroxy-5-oxooxolan-3-yl]-9-oxo-2,3-dihydro-1H-pyrrolo[2,1-b]quinazoline-1-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of tricyclic pyrrolopyrimidinones as dipeptide mimetics: Inhibition of interleukin-1β-converting enzyme

  摘要：

  The application of a tricyclic pyrrolopyrimidinone scaffold for the synthesis of peptidomimetic inhibitors of interleukin-1 beta-converting enzyme (ICE) is reported. The synthesis of the tricyclic scaffold and conversion of it to a variety of target ICE inhibitors were accomplished in 4-5 steps. In vitro biological evaluation of the tricyclic pyrrolopyrimidinones revealed fair to good ICE inhibitors, with the most active compound exhibiting an IC50 of 14 nM in a caspase-1 enzyme binding assay. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.046
• 作为产物：
  描述：

  ethyl (1S)-9-oxo-2,3-dihydro-1H-pyrrolo[2,1-b]quinazoline-1-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 (S)-9-oxo-1,2,3,9-tetrahydro-pyrrolo[2,1-b]quinazoline-1-carboxylic acid
  参考文献：
  名称：

  Synthesis and evaluation of tricyclic pyrrolopyrimidinones as dipeptide mimetics: Inhibition of interleukin-1β-converting enzyme

  摘要：

  The application of a tricyclic pyrrolopyrimidinone scaffold for the synthesis of peptidomimetic inhibitors of interleukin-1 beta-converting enzyme (ICE) is reported. The synthesis of the tricyclic scaffold and conversion of it to a variety of target ICE inhibitors were accomplished in 4-5 steps. In vitro biological evaluation of the tricyclic pyrrolopyrimidinones revealed fair to good ICE inhibitors, with the most active compound exhibiting an IC50 of 14 nM in a caspase-1 enzyme binding assay. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.046

文献信息

• Caspase inhibitors and uses thereof
  申请人：——

  公开号：US20020045623A1

  公开（公告）日：2002-04-18

  This invention provides novel caspase inhibitors of formula I: 1 wherein R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; X 2 —X 1 is N(R 3 )—C(R 3 ), C(R 3 ) 2 —C(R 3 ), C(R 3 ) 2 —N, N═C, C(R 3 )═C, C(═O)—N, or C(═O)—C(R 3 ); each R 3 is independently selected from hydrogen or C 16 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by ═O, or one or more halogen, C 1-4 alkyl, or C 1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.

  本发明提供了新型的caspase抑制剂，其化学式为I：1，其中R1为氢、CHN2、R或—CH2Y；R为脂肪基、芳基、芳基烷基、杂环基或杂环基烷基；Y为电负性离去基；R2为CO2H、CH2CO2H或其酯、酰胺或同分异构体；X2—X1为N(R3)—C(R3)、C(R3)2—C(R3)、C(R3)2—N、N═C、C(R3)═C、C(═O)—N或C(═O)—C(R3)；每个R3独立选择自氢或C16脂肪基；环C为融合的芳基环；n为0、1或2；环A中的每个亚甲基碳原子可以选择性地且独立地被═O或一个或多个卤素、C1-4烷基或C1-4烷氧基取代。这些化合物对于治疗caspase介导的疾病是有用的。
• CAPASE INHIBITORS AND USES THEREOF
  申请人：Charrier Jean-Damien

  公开号：US20090023739A1

  公开（公告）日：2009-01-22

  This invention provides novel caspase inhibitors of formula I: wherein R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; X 2 —X 1 is N(R 3 )—C(R 3 ), C(R 3 ) 2 —C(R 3 ), C(R 3 ) 2 —N, N═C, C(R 3 )═C, C(═O)—N, or C(═O)—C(R 3 ); each R 3 is independently selected from hydrogen or C 1-6 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by ═O, or one or more halogen, C 1-4 alkyl, or C 1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.

  本发明提供了一种新颖的caspase抑制剂，其化学式为I：其中R1为氢、CHN2、R或—CH2Y；R为脂肪基、芳基、芳基烷基、杂环基或杂环基烷基；Y为电负性离去基团；R2为CO2H、CH2CO2H或其酯、酰胺或同分异构体；X2—X1为N(R3)—C(R3)、C(R3)2—C(R3)、C(R3)2—N、N═C、C(R3)═C、C(═O)—N或C(═O)—C(R3)；每个R3独立地选择自氢或C1-6脂肪基；环C为融合的芳基环；n为0、1或2；环A中的每个亚甲基碳原子可选且独立地被═O、一个或多个卤素、C1-4烷基或C1-4烷氧基取代。这些化合物可用于治疗caspase介导的疾病。
• Caspase Inhibitors and Uses Thereof
  申请人：Charrier Jean-Damien

  公开号：US20110003824A1

  公开（公告）日：2011-01-06

  This invention provides novel caspase inhibitors of formula I: wherein R 1 is hydrogen, CHN 2 , R, or —CH 2 Y; R is an aliphatic group, an aryl group, an aralkyl group, a heterocyclyl group, or a heterocyclylalkyl group; Y is an electronegative leaving group; R 2 is CO 2 H, CH 2 CO 2 H, or esters, amides or isosteres thereof; X 2 -X 1 is N(R 3 )—C(R 3 ), C(R 3 ) 2 —C(R 3 ), C(R 3 ) 2 —N, N═C, C(R 3 )═C, C(═O)—N, or C(═O)—C(R 3 ); each R 3 is independently selected from hydrogen or C 1-6 aliphatic; Ring C is a fused aryl ring; n is 0, 1 or 2; and each methylene carbon in Ring A is optionally and independently substituted by ═O, or one or more halogen, C 1-4 alkyl, or C 1-4 alkoxy. The compounds are useful for treating caspase-mediated diseases.

  本发明提供了式I的新型caspase抑制剂： 其中，R1是氢，CHN2，R或—CH2Y; R是脂肪基团，芳基团，芳基烷基团，杂环基团或杂环基烷基团; Y是电负性离去基团; R2是CO2H，CH2CO2H或其酯，酰胺或异构体; X2-X1是N（R3）—C（R3），C（R3）2—C（R3），C（R3）2—N，N═C，C（R3）═C，C（═O）—N或C（═O）—C（R3）; 每个R3独立地选择自氢或C1-6脂肪基; 环C是螺合芳基环; n为0、1或2; 环A中的每个亚甲基碳原子可以选择性地且独立地被═O或一个或多个卤素、C1-4烷基或C1-4烷氧基取代。这些化合物可用于治疗caspase介导的疾病。
• CASPASE INHIBITORS AND USES THEREOF
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1289993B1

  公开（公告）日：2007-10-31
• US7407964B2
  申请人：——

  公开号：US7407964B2

  公开（公告）日：2008-08-05