(R)-N-(4-氯苄基)-N-甲基吡咯烷-2-甲酰胺 | 1003959-53-2

• 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
• 中文名称: (R)-N-(4-氯苄基)-N-甲基吡咯烷-2-甲酰胺
• 英文名称: (R)-N-(4-chlorobenzyl)-N-methylpyrrolidine-2-carboxamide
• 英文别名: (2R)-N-[(4-chlorophenyl)methyl]-N-methylpyrrolidine-2-carboxamide
• CAS: 1003959-53-2
• 化学式: C₁₃H₁₇ClN₂O
• 分子量: 252.744
• InChiKey: ICRASHFCAICUPM-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-N-(4-氯苄基)-N-甲基吡咯烷-2-甲酰胺 、 4-氰基苯异氰酸酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 生成 (R)-N2-(4-chlorobenzyl)-N1-(4-cyanophenyl)-N2-methylpyrrolidine-1,2-dicarboxamide
  参考文献：
  名称：

  Novel Pyrrolidine Ureas as C−C Chemokine Receptor 1 (CCR1) Antagonists

  摘要：

  Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1 alpha (MIP-1 alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.

  DOI：

  10.1021/jm801416q
• 作为产物：
  描述：

  (R)-tert-butyl 2-[(4-chlorobenzyl)(methyl)carbamoyl]pyrrolidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (R)-N-(4-氯苄基)-N-甲基吡咯烷-2-甲酰胺
  参考文献：
  名称：

  Novel Pyrrolidine Ureas as C−C Chemokine Receptor 1 (CCR1) Antagonists

  摘要：

  Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1 alpha (MIP-1 alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.

  DOI：

  10.1021/jm801416q

文献信息

• [EN] PROLINE UREA CCR1 ANTAGONISTS FOR AUTOIMMUNE DISEASES & INFLAMMATION<br/>[FR] ANTAGONISTES CCR1 DE PROLINE URÉE UTILISÉS POUR DES MALADIES AUTO-IMMUNES ET L'INFLAMMATION
  申请人：PHARMACOPEIA INC

  公开号：WO2008011392A2

  公开（公告）日：2008-01-24

  (EN) Compounds of the formulae (I) and (II) are disclosed. The compounds are CCRl antagonists which are useful for the treatment and prevention of inflammatory and autoimmune diseases. Other embodiments are also disclosed.(FR) La présente invention concerne des composés répondant aux formules (I) et (II). Les composés sont des antagonistes des récepteurs de chémokine (CCRl) qui se révèlent utiles pour le traitement et la prévention de maladies inflammatoires et auto-immunes. L'invention concerne également d'autre modes de réalisation.
• Novel Pyrrolidine Ureas as C−C Chemokine Receptor 1 (CCR1) Antagonists
  作者：J. Robert Merritt、Jinqi Liu、Elizabeth Quadros、Michelle L. Morris、Ruiyan Liu、Rui Zhang、Biji Jacob、Jennifer Postelnek、Catherine M. Hicks、Weiqing Chen、Earl F. Kimble、W. Lynn Rogers、Linda O’Brien、Nicole White、Hema Desai、Shalini Bansal、George King、Michael J. Ohlmeyer、Kenneth C. Appell、Maria L. Webb

  DOI：10.1021/jm801416q

  日期：2009.3.12

  Monocyte infiltration is implicated in a variety of diseases including multiple myeloma, rheumatoid arthritis, and multiple sclerosis. C-C chemokine receptor 1 (CCR1) is a chemokine receptor that upon stimulation, particularly by macrophage inflammatory protein 1 alpha (MIP-1 alpha) and regulated on normal T-cell expressed and secreted (RANTES), mediates monocyte trafficking to sites of inflammation. High throughput screening of our combinatorial collection identified a novel, moderately potent CCR1 antagonist 3. The library hit 3 was optimized to the advanced lead compound 4. Compound 4 inhibited CCR1 mediated chemotaxis of monocytes with an IC50 of 20 nM. In addition, the compound was highly selective over other chemokine receptors. It had good microsomal stability when incubated with rat and human liver microsomes and showed no significant cytochrome P450 (CYP) inhibition. Pharmacokinetic evaluation of the compound in the rat showed good oral bioavailability.