公开(公告)号：US20070208181A1

公开(公告)日：2007-09-06

申请号：US11683534

申请日：2007-03-08

申请人： Ronald Lauener ,  David Burgoyne ,  Patrick Rebstein ,  Lloyd Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

发明人： Ronald Lauener ,  David Burgoyne ,  Patrick Rebstein ,  Lloyd Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

IPC分类号： C07D207/24

CPC分类号： C07D207/26 ,  C07C255/46 ,  C07C271/60 ,  C07D213/75 ,  C07D233/32 ,  C07D239/10 ,  C07D473/04 ,  C07D473/06

摘要： The present invention is directed to a method for reducing the emetogenic effects of PDE inhibitors, and more particularly is directed to compounds having PDE4 inhibition activity with little or no emetogenic side-effects, and chemical methods including benzylation for preparing such compounds. A benzyl group may be attached to either a carbon or nitrogen atom of a PDE4 inhibitor. Suitable benzylation chemistry is to extract a hydrogen from a PDE4 inhibitor, preferably with a base, and then react the resulting nucleophilic PDE4 inhibitor with a benzylating agent, e.g., benzyl bromide or a derivative thereof.

摘要翻译： 本发明涉及一种减少PDE抑制剂的致吐作用的方法，更具体地涉及具有很少或不具有致吐性副作用的具有PDE4抑制活性的化合物，以及包括用于制备这些化合物的苄基化的化学方法。 苄基可以连接到PDE4抑制剂的碳原子或氮原子上。 合适的苄基化学方法是从PDE4抑制剂，优选用碱提取氢，然后使得到的亲核PDE4抑制剂与苄化试剂如苄基溴或其衍生物反应。