公开(公告)号：US07459479B2

公开(公告)日：2008-12-02

申请号：US11683534

申请日：2007-03-08

申请人： Ronald W. Lauener ,  David L. Burgoyne ,  Patrick J. Rebstein ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

发明人： Ronald W. Lauener ,  David L. Burgoyne ,  Patrick J. Rebstein ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

IPC分类号： A61K31/38 ,  C07D207/12

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。

公开(公告)号：US20080287522A1

公开(公告)日：2008-11-20

申请号：US12176876

申请日：2008-07-21

申请人： Ronald W. Lauener ,  David L. Burgoyne ,  Patrick J. Rebstein ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

发明人： Ronald W. Lauener ,  David L. Burgoyne ,  Patrick J. Rebstein ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

IPC分类号： A61K31/40 ,  C07D207/12 ,  A61P29/00 ,  A61P35/00 ,  A61P25/00 ,  A61P31/12 ,  A61P33/00

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。

公开(公告)号：US06555572B2

公开(公告)日：2003-04-29

申请号：US09810085

申请日：2001-03-16

申请人： Ronald W. Lauener ,  David L. Burgoyne ,  Patrick J. Rebstein ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

发明人： Ronald W. Lauener ,  David L. Burgoyne ,  Patrick J. Rebstein ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Yaping Shen

IPC分类号： C07D20712

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.

公开(公告)号：US07446129B2

公开(公告)日：2008-11-04

申请号：US10391685

申请日：2003-03-18

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

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

IPC分类号： A61K31/24 ,  C07D209/56

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.

公开(公告)号：US20100168170A1

公开(公告)日：2010-07-01

申请号：US12530592

申请日：2008-03-12

申请人： Benjamin Pelcman ,  Christian Krog-Jensen ,  Yaping Shen ,  James Gee Kan Yee ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Kang Han ,  Jeffery R. Raymond

发明人： Benjamin Pelcman ,  Christian Krog-Jensen ,  Yaping Shen ,  James Gee Kan Yee ,  Lloyd F. Mackenzie ,  Yuanlin Zhou ,  Kang Han ,  Jeffery R. Raymond

IPC分类号： A61K31/445 ,  C07D211/76 ,  A61P29/00 ,  A61P35/00 ,  A61P25/00 ,  A61P11/00 ,  A61P25/28 ,  A61P25/16 ,  A61P35/02

CPC分类号： C07D211/08

摘要： There is provided compounds of formula (I), wherein R1, R2, R3, R4, R5, R6, R7, R8, m, n, q and r have meanings given in the description, and pharmaceutically acceptable derivatives thereof, which compounds are useful in the treatment of diseases and conditions associated with inflammation.

摘要翻译： 提供式（I）化合物，其中R 1，R 2，R 3，R 4，R 5，R 6，R 7，R 8，m，n，q和r在说明书中给出的含义及其药学上可接受的衍生物， 可用于治疗与炎症相关的疾病和病症。

公开(公告)号：US20100168167A1

公开(公告)日：2010-07-01

申请号：US12530578

申请日：2008-03-12

申请人： Benjamin Pelcman ,  Christian Krog-Jensen ,  Yaping Shen ,  James Gee Kan Yee ,  Lloyd F. MacKenzie ,  Yuanlin Zhou ,  Kang Han ,  Jeffery R. Raymond

发明人： Benjamin Pelcman ,  Christian Krog-Jensen ,  Yaping Shen ,  James Gee Kan Yee ,  Lloyd F. MacKenzie ,  Yuanlin Zhou ,  Kang Han ,  Jeffery R. Raymond

IPC分类号： A61K31/4545 ,  A61P11/00 ,  A61P1/00 ,  A61P19/02 ,  A61P19/08 ,  A61P7/12 ,  A61P35/04 ,  C07D211/40 ,  A61K31/445 ,  C07D417/04 ,  A61K31/454 ,  C07D401/02

CPC分类号： C07D211/22 ,  C07D401/06 ,  C07D407/06 ,  C07D409/06

摘要： There is provided compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, m and n have meanings given in the description, and pharmaceutically acceptable derivatives thereof, which compounds are useful in the treatment of diseases and conditions associated with inflammation.

摘要翻译： 提供式（I）化合物：其中R1，R2，R3，R4，R5，R6，R7，m和n具有说​​明书中给出的含义及其药学上可接受的衍生物，该化合物可用于治疗疾病 和与炎症相关的病症。