N'-[[1-(aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide | 184005-40-1

• 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
• 英文名称: N'-[[1-(aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide
• 英文别名: (2S)-N-[(1-carbamimidoylpiperidin-4-yl)methyl]-1-(3,3-diphenylpropanoyl)pyrrolidine-2-carboxamide
• CAS: 184005-40-1
• 化学式: C₂₇H₃₅N₅O₂
• 分子量: 461.607
• InChiKey: MOPGLVWPWGBJIA-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  103
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N'-[4-piperidinylmethyl]-N-(3,3-diphenylpropionyl)-L-proline amide hydrochloride 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N'-[[1-(aminoiminomethyl)-4-piperidinyl]methyl]-N-(3,3-diphenylpropionyl)-L-proline amide
  参考文献：
  名称：

  Thrombin inhibitors

  摘要：

  本发明的化合物具有以下结构：##STR1## 例如 ##STR2## 这些化合物抑制凝血酶和相关的血栓形成。

  公开号：

  US05629324A1

文献信息

• Cyclooxygenase-2 selective inhibitors, compositions and methods of use
  申请人：NitroMed, Inc.

  公开号：US20040072883A1

  公开（公告）日：2004-04-15

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选地，至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮衍生松弛因子水平或是一氧化氮合酶底物的化合物，和/或至少一种治疗剂。本发明还提供了包含至少一种COX-2选择性抑制剂、可选地亚硝化和/或亚硝酰化，以及可选地至少一种一氧化氮给体和/或至少一种治疗剂的新型试剂盒。本发明的新型环氧合酶2选择性抑制剂可选择性地亚硝化和/或亚硝酰化。本发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠道特性；促进伤口愈合的方法；用于治疗和/或预防肾脏和/或呼吸毒性的方法；用于治疗和/或预防由于环氧合酶-2水平升高而引起的其他疾病的方法；以及用于改善COX-2选择性抑制剂的心血管特性的方法。
• CYCLOOXYGENASE-2 SELECTIVE INHIBITORS, COMPOSITIONS AND METHODS OF USE
  申请人：Bandarage Upul K.

  公开号：US20090005350A1

  公开（公告）日：2009-01-01

  The invention describes novel cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal and/or respiratory toxicity; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  本发明描述了新型环氧合酶2（COX-2）选择性抑制剂和包含至少一种环氧合酶2（COX-2）选择性抑制剂的新型组合物，以及可选择地至少包含一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物和/或至少一种治疗剂的组合物。本发明还提供了包含至少一种COX-2选择性抑制剂，可选择性地硝化和/或硝酰化，以及可选择性地至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。本发明中的新型环氧合酶2选择性抑制剂可以选择性地硝化和/或硝酰化。本发明还提供了治疗炎症、疼痛和发热的方法；用于治疗和/或改善COX-2选择性抑制剂的胃肠道性质；用于促进伤口愈合；用于治疗和/或预防肾脏和/或呼吸系统毒性；用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病；以及用于改善COX-2选择性抑制剂的心血管特征的方法。
• NITROSATED NONSTEROIDAL ANTIINFLAMMATORY COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  申请人：EARL Richard A.

  公开号：US20100093671A1

  公开（公告）日：2010-04-15

  The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

  该发明描述了新型亚硝酰化非甾体抗炎药（NSAIDs）及其药学上可接受的盐，并且描述了至少包含一种亚硝酰化NSAID和可选的至少一种化合物的新型组合物，该化合物捐赠、转移或释放一氧化氮，刺激内源性一氧化氮的合成，提高内源性内皮源性松弛因子的水平或是一氧化氮合酶的底物，并/或至少包含一种治疗剂。该发明还提供了至少包含一种亚硝酰化NSAID和至少一种化合物的新型组合物，该化合物捐赠、转移或释放一氧化氮，提高内源性内皮源性松弛因子的水平，刺激内源性一氧化氮的合成或是一氧化氮合酶的底物，并/或至少包含一种治疗剂。该发明还提供了至少包含一种亚硝酰化NSAID，可选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。该发明还提供了治疗炎症、疼痛和发热的方法；治疗胃肠道疾病的方法；促进伤口愈合的方法；治疗和/或预防使用非甾体抗炎化合物导致的胃肠道、肾脏和/或呼吸道毒性的方法；治疗炎症性疾病状态和/或疾病的方法；以及治疗和/或预防眼科疾病和/或疾病的方法。
• Cyclooxygenase-2 inhibitors, compositions and methods of use
  申请人：——

  公开号：US20020183366A1

  公开（公告）日：2002-12-05

  This invention describes novel compounds that are cyclooxygenase 2 (COX-2) selective inhibitors and novel compositions comprising at least one cyclooxygenase 2 (COX-2) selective inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or, optionally, at least one therapeutic agent. The invention also provides novel kits comprising at least one COX-2 selective inhibitor, and, optionally, at least one nitric oxide donor, and/or, optionally, at least one therapeutic agent. The novel cyclooxygenase 2 selective inhibitors of the invention can be optionally nitrosated and/or nitrosylated. The invention also provides methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 selective inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity or other toxicities; for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2; and for improving the cardiovascular profile of COX-2 selective inhibitors.

  本发明描述了新型化合物，它们是环氧合酶2（COX-2）选择性抑制剂，以及包括至少一种COX-2选择性抑制剂的新型组合物，以及可选地，至少一种捐赠、转移或释放一氧化氮的化合物，刺激内源性一氧化氮合成，提高内源性内皮源性松弛因子水平或是一氧化氮合酶底物，和/或，可选地，至少一种治疗剂。本发明还提供了包括至少一种COX-2选择性抑制剂的新型试剂盒，以及可选地，至少一种一氧化氮供体，和/或，可选地，至少一种治疗剂。本发明的新型环氧合酶2选择性抑制剂可以选择性地硝化和/或亚硝化。本发明还提供了治疗炎症、疼痛和发热的方法；治疗和/或改善COX-2选择性抑制剂的胃肠道特性；促进伤口愈合；治疗和/或预防肾毒性或其他毒性；治疗和/或预防由于升高的COX-2水平引起的其他疾病；和改善COX-2选择性抑制剂的心血管特性。
• トロンビン阻害剤の投与による炎症疾患の処置法
  申请人：——

  公开号：JP2002525298A

  公开（公告）日：2002-08-13

  \n (57)【要約】\n本発明は、患者を、トロンビン阻害剤を含む組成物で処置することを含む、患者の炎症疾患の処置法である。かかる疾患は、腎炎、全身性エリテマトーデス、慢性関節リウマチ、糸球体腎炎、および類肉腫症を含むがこれに限定されない。１つのクラスの方法で、トロンビン阻害剤は、３−（２−フェニルエチルアミノ）−６−メチル−１−（２−アミノ−６−メチル−５−メチレン−カルボキシアミドメチルピリジニル）−２−ピラジノン、Ｎ’−［［１−（アミノイミノメチル）−４−ピペリジニル］メチル］−Ｎ−（３，３−ジフェニルプロピオニル）−Ｌ−プロリンアミド、および３−（２−フェネチルアミノ）−６−メチル−１−（２−アミノ−６−メチル−５−メチレンカルボキシアミドメチルピリジニル）−２−ピリジノンまたは医薬的に許容されるその塩からなる群から選択する。本発明はまた、患者を、トロンビン阻害剤およびＮＳＡＩＤ、例えばＣＯＸ−２阻害剤を含む組成物で処置することを含む、患者の炎症疾患を処置する方法である。かかる疾患は、腎炎、全身性エリテマトーデス、慢性関節リウマチ、糸球体腎炎、および類肉種症を含むがこれに限定されない。１つのクラスの方法で、トロンビン阻害剤は、３−（２−フェニルエチルアミノ）−６−メチル−１−（２−アミノ−６−メチル−５−メチレン−カルボキシアミドメチルピリジニル）−２−ピラジノン、Ｎ’−［［１−（アミノイミノメチル）−４−ピペリジニル］メチル］−Ｎ−（３，３−ジフェニルプロピオニル）−Ｌ−プロリンアミド、および３−（２−フェネチルアミノ）−６−メチル−１−（２−アミノ−６−メチル−５−メチレンカルボキシアミドメチルピリジニル）−２−ピリジノンまたは医薬的に許容されるその塩からなる群から選択し、ＣＯＸ−２阻害剤は、３−フェニル−４−（４−（メチルスルホニル）フェニル）−２−（５Ｈ）−フラノンまたは医薬的に許容されるその塩である。\n

  \(57) [Abstract] The invention is a method of treating inflammatory diseases in patients, comprising treating patients with a composition containing a thrombin inhibitor.这类疾病包括但不限于肾炎、系统性红斑狼疮、类风湿性关节炎、肾小球肾炎和肉样瘤病。-6-methyl-1-(2-amino-6-methyl-5-2-吡嗪酮、N'-[[1-(2-吡嗪酮、N'-[[1-( 氨基亚氨基甲基-4-哌啶基]甲基]-N-(3,3-二苯基丙酰基)-L脯氨酰胺，以及 3-(2-苯乙胺基)-6-甲基-1-(2-氨基-6-甲基-6-脯氨酰胺)-氨基-6-甲基-6-甲基-5-亚甲基羧酰胺甲基吡啶基）-2-吡啶酮，或选自由其药学上可接受的盐组成的组。本发明还包括一种治疗患者炎症性疾病的方法，该方法包括用包含凝血酶抑制剂和非甾体抗炎药（如 COX-2 抑制剂）的组合物治疗患者。这类疾病包括但不限于肾炎、系统性红斑狼疮、类风湿性关节炎、肾小球肾炎和肉瘤病。在一类方法中，凝血酶抑制剂是 3-(2-苯基乙基氨基)-6-methyl-1-(2-amino-6-methyl-5-2-吡嗪酮，N'-[[1-(2-吡嗪酮、N'-[[1-( 氨基亚氨基甲基-4-哌啶基]甲基]-N-(3,3-二苯基丙酰基)-L脯氨酰胺，以及 3-(2-苯乙胺基)-6-甲基-1-(2-氨基-6-甲基-6-脯氨酰胺)-氨基-6-甲基-6-甲基-5-亚甲基羧酰胺甲基吡啶基）-2-吡啶酮，或选自由其药学上可接受的盐组成的组，其中 COX-2 抑制剂是 3-苯基-4-(4-(甲磺酰基)苯基)-2-(5H)-呋喃酮或其药学上可接受的盐。\n