1-butyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one | 182365-94-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-butyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one
• 英文别名: 4-(3-butyl-2-oxo-1-benzimidazolinyl)piperidine；1-butyl-3-piperidin-4-ylbenzimidazol-2-one
• CAS: 182365-94-2
• 化学式: C₁₆H₂₃N₃O
• 分子量: 273.378
• InChiKey: YZDMPQLBUBFNGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[3-(4-chloro-3-methyl-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone 、 1-butyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one 生成 1-(1-{3-[5-Acetyl-3-(4-chloro-3-methyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-2-hydroxy-propyl}-piperidin-4-yl)-3-butyl-1,3-dihydro-benzoimidazol-2-one
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045
• 作为产物：
  描述：

  吗丁啉杂质13 在 sodium hydroxide 、 双(三甲基硅烷基)氨基钾 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成 1-butyl-3-piperidin-4-yl-1,3-dihydro-benzoimidazol-2-one
  参考文献：
  名称：

  Discovery and SAR studies of a novel series of noncovalent cathepsin S inhibitors

  摘要：

  A novel series of competitive, reversible cathepsin S (Cats) inhibitors was discovered and optimized. The 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety was found to be an effective replacement for the 4-arylpiperazin-1-yl group found in our earlier series of Cats inhibitors. This replacement imparted improved PK properties as well as decreased off-target activity. Optimization of the ketobenzimidazole moiety led to the discovery of the lead compound JNJ 10329670, which represents a novel class of selective, noncovalent, reversible, and orally bioavailable inhibitors of cathepsin S. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.045

文献信息

• Alpha 1a adrenergic receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05952351A1

  公开（公告）日：1999-09-14

  This invention relates to novel compounds, their synthesis and use as selective .alpha..sub.1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the .alpha..sub.1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

  这项发明涉及新型化合物，它们的合成以及用作选择性α1a肾上腺素受体拮抗剂的用途。这些化合物的一个应用是治疗良性前列腺增生。这些化合物在其放松富含α1a受体亚型的平滑肌组织的能力上具有选择性，同时不会引起低血压。这样的组织之一位于尿道内膜周围。因此，这些化合物的一个用途是为患有良性前列腺增生的男性提供急性缓解，从而减轻尿流受阻。这些化合物的另一个用途是与人类5α-还原酶抑制剂化合物结合，以实现对良性前列腺增生影响的急性和慢性缓解。
• ALPHA 1a ADRENERGIC RECEPTOR ANTAGONISTS
  申请人：MERCK & CO., INC.

  公开号：EP0812196A1

  公开（公告）日：1997-12-17
• EP0812196A4
  申请人：——

  公开号：EP0812196A4

  公开（公告）日：1998-05-20
• US5952351A
  申请人：——

  公开号：US5952351A

  公开（公告）日：1999-09-14
• [EN] ALPHA 1a ADRENERGIC RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR ALPHA-1a-ADRENERGIQUE
  申请人：MERCK & CO., INC.

  公开号：WO1996025934A1

  公开（公告）日：1996-08-29

  (EN) This invention relates to novel compounds, their synthesis and use as selective $g(a)1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the $g(a)1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.(FR) Cette invention se rapporte à de nouveaux composés, à leur synthèse, et à leur utilisation comme antagonistes sélectifs du récepteur $g(a)1a-adrénergique. Une première application de ces composés est le traitement de l'hyperplasie bénigne de la prostate. Ces composés sont sélectifs du point de vue de leur capacité à relâcher les tissus des muscles lisses enrichis en récepteur adrénergique de sous-type $g(a)1a, sans qu'une hypotension soit en même temps provoquée. On trouve de tels tissus autour de la membrane tapissant l'urèthre. Par conséquent, une première utilité de ces composés est d'entraîner un soulagement immédiat des sujets mâles souffrant d'hyperplasie bénigne de la prostate, en permettant un écoulement d'urine moins entravé. Une seconde utilité de ces composés est obtenue par combinaison avec un composé inhibiteur de 5-alpha-réductase humaine, pour que soit obtenu un soulagement à la fois immédiat et chronique des effets de l'hyperplasie bénigne de la prostate.