(R)-2-(4-氯苄基氨基甲酰)吡咯烷-1-羧酸叔丁酯 | 1140495-84-6

• 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)-2-(4-氯苄基氨基甲酰)吡咯烷-1-羧酸叔丁酯
• 英文名称: (R)-tert-butyl 2-((4-chlorobenzyl)carbamoyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (2R)-2-[(4-chlorophenyl)methylcarbamoyl]pyrrolidine-1-carboxylate
• CAS: 1140495-84-6
• 化学式: C₁₇H₂₃ClN₂O₃
• 分子量: 338.834
• InChiKey: PLTFSYLPECZQMS-CQSZACIVSA-N

物化性质

• 沸点：
  513.0±50.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-(4-氯苄基氨基甲酰)吡咯烷-1-羧酸叔丁酯 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以88.1%的产率得到(R)-tert-butyl 2-((4-chlorobenzyl)carbamothioyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  ORTHO PYRROLIDINE, BENZYL-SUBSTITUTED HETEROCYCLE CCR1 ANTAGONISTS FOR AUTOIMMUNE DISEASES & INFLAMMATION

  摘要：

  公式为的化合物已被披露。这些化合物是CCR1拮抗剂，可用于治疗和预防炎症性和自身免疫性疾病。其他实施例也已披露。

  公开号：

  US20090093472A1
• 作为产物：
  描述：

  对氯苄胺 、 N-(tert-butoxycarbonyl)-D-proline 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以87.4%的产率得到(R)-2-(4-氯苄基氨基甲酰)吡咯烷-1-羧酸叔丁酯
  参考文献：
  名称：

  ORTHO PYRROLIDINE, BENZYL-SUBSTITUTED HETEROCYCLE CCR1 ANTAGONISTS FOR AUTOIMMUNE DISEASES & INFLAMMATION

  摘要：

  公式为的化合物已被披露。这些化合物是CCR1拮抗剂，可用于治疗和预防炎症性和自身免疫性疾病。其他实施例也已披露。

  公开号：

  US20090093472A1

文献信息

• 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.
• Novel pyrrolidine heterocycles as CCR1 antagonists
  作者：J. Robert Merritt、Ray James、Vidyadhar M. Paradkar、Chongwu Zhang、Ruiyan Liu、Jinqi Liu、Biji Jacob、Camelia Chiriac、Michael J. Ohlmeyer、Elizabeth Quadros、Pamela Wines、Jennifer Postelnek、Catherine M. Hicks、Weiqing Chen、Earl F. Kimble、Linda O’Brien、Nicole White、Hema Desai、Kenneth C. Appell、Maria L. Webb

  DOI：10.1016/j.bmcl.2010.07.082

  日期：2010.9

  A novel series of pyrrolidine heterocycles was prepared and found to show potent inhibitory activity of CCR1 binding and CCL3 mediated chemotaxis of a CCR1-expressing cell line. A potent, optimized triazole lead from this series was found to have acceptable pharmacokinetics and microsomal stability in rat and is suitable for further optimization and development. (c) 2010 Elsevier Ltd. All rights reserved.
• US8288371B2
  申请人：——

  公开号：US8288371B2

  公开（公告）日：2012-10-16
• [EN] ORTHO PYRROLIDINE, BENZYL-SUBSTITUTED HETEROCYCLE CCR1 ANTAGONISTS FOR AUTOIMMUNE DISEASES & INFLAMMATION<br/>[FR] ANTAGONISTES DE CCR1 HÉTÉROCYCLIQUES À SUBSTITUTION BENZYLIQUE D'ORTHO-PYRROLIDINE POUR LES MALADIES AUTO-IMMUNES ET L'INFLAMMATION
  申请人：PHARMACOPEIA INC

  公开号：WO2009082526A2

  公开（公告）日：2009-07-02

  Compounds of the formula (I) are disclosed. The compounds are CCR1 antagonists which are useful for the treatment and prevention of inflammatory and autoimmune diseases. Other embodiments are also disclosed.