公开(公告)号：EP2200564B1

公开(公告)日：2016-05-04

申请号：EP08838096.9

申请日：2008-10-10

申请人： The Regents of the University of California ,  Università degli Studi di Parma ,  Universita degli Studi di Urbino "Carlo Bo"

发明人： PIOMELLI, Daniele ,  TARZIA, Giorgio ,  MOR, Marco ,  DURANTI, Andrea ,  TONTINI, Andrea

IPC分类号： A61K8/00 ,  A61K8/18 ,  A61Q5/00

CPC分类号： A61K31/337 ,  A61K31/165 ,  A61K31/195 ,  A61K31/365 ,  C07D305/10

公开(公告)号：EP2744778A2

公开(公告)日：2014-06-25

申请号：EP12826376.1

申请日：2012-08-17

申请人： The Regents of the University of California ,  Fondazione Istituto Italiano Di Tecnologia ,  Università Degli Studi Di Urbino "Carlo Bo" ,  Università degli Studi di Parma

发明人： PIOMELLI, Daniele ,  MORENO-SANZ, Guillermo ,  BANDIERA, Tiziano ,  MOR, Marco ,  TARZIA, Giorgio

IPC分类号： C07C233/06 ,  C07C233/23 ,  C07D309/14 ,  A61K31/165 ,  A61P29/00

CPC分类号： C07C271/56 ,  C07C269/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D309/14

摘要： The present invention provides methods of making and using peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH). The present invention provides compounds and compositions that suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). The present invention also sets forth methods for inhibiting FAAH as well as methods for treating conditions such as, but not limited to, pain, inflammation, immune disorders, dermatitis, mucositis, the over reactivity of peripheral sensory neurons, neurodermatitis, and an overactive bladder. Accordingly, the invention also provides compounds, methods, and pharmaceutical compositions for treating conditions in which the selective inhibition of peripheral FAAH (as opposed to CNS FAAH) would be of benefit.

摘要翻译： 本发明提供制备和使用外周限制性脂肪酸酰胺水解酶抑制剂（FAAH）的方法。 本发明提供抑制FAAH活性并增加中枢神经系统（CNS）外的氨基酰胺水平的化合物和组合物。 本发明还提出了用于抑制FAAH的方法以及治疗诸如但不限于疼痛，炎症，免疫病症，皮炎，粘膜炎，周围感觉神经元，神经性皮炎和膀胱过度活动症的过度反应的病症的方法 。 因此，本发明还提供了用于治疗其中选择性抑制外周FAAH（与CNS FAAH相反））有益的化合物，方法和药物组合物。

公开(公告)号：EP2744778B1

公开(公告)日：2019-01-16

申请号：EP12826376.1

申请日：2012-08-17

申请人： The Regents of the University of California ,  Fondazione Istituto Italiano di Tecnologia ,  Università Degli Studi Di Urbino "Carlo Bo" ,  Università degli Studi di Parma

发明人： PIOMELLI, Daniele ,  MORENO-SANZ, Guillermo ,  BANDIERA, Tiziano ,  MOR, Marco ,  TARZIA, Giorgio

IPC分类号： C07C269/02 ,  C07C271/56 ,  C07D309/14

公开(公告)号：EP2598477B1

公开(公告)日：2016-03-02

申请号：EP11812991.5

申请日：2011-07-22

申请人： The Regents of the University of California ,  Università Degli Studi Di Urbino "Carlo Bo" ,  Università Degli Studi di Parma

发明人： PIOMELLI, Daniele ,  CLAPPER, Jason, R. ,  MORENO-SANZ, Guillermo ,  DURANTI, Andrea ,  TONTINI, Andrea ,  MOR, Marco ,  TARZIA, Giorgio

IPC分类号： C07C271/56 ,  A61K31/27 ,  A61P29/00 ,  A61P37/00

CPC分类号： C07C271/56 ,  C07C2601/14

公开(公告)号：EP2598477A2

公开(公告)日：2013-06-05

申请号：EP11812991.5

申请日：2011-07-22

申请人： The Regents of the University of California ,  Università Degli Studi Di Urbino "Carlo Bo" ,  Universita Degli Studi di Parma

发明人： PIOMELLI, Daniele ,  CLAPPER, Jason, R. ,  MORENO-SANZ, Guillermo ,  DURANTI, Andrea ,  TONTINI, Andrea ,  MOR, Marco ,  TARZIA, Giorgio

IPC分类号： C07C271/56 ,  A61K31/27 ,  A61P29/00 ,  A61P37/00

CPC分类号： C07C271/56 ,  C07C2601/14

摘要： Peripherally restricted inhibitors of fatty acid amide hydrolase (FAAH) are provided. The compounds can suppress FAAH activity and increases anandamide levels outside the central nervous system (CNS). Despite their relative inability to access brain and spinal cord, the compounds attenuate behavioral responses indicative of persistent pain in rodent models of inflammation and peripheral nerve injury, and suppresses noxious stimulus-evoked neuronal activation in spinal cord regions implicated in nociceptive processing. CBi receptor blockade prevents these effects. Accordingly, the invention also provides methods, and pharmaceutical compositions for treating conditions in which the inhibition of peripheral FAAH would be of benefit. The compounds of the invention are according to the formula (I): in which R
1 is a polar group. In some embodiments, R
1 is selected from the group consisting of hydroxy and the physiologically hydro lysable esters thereof. R
2 and R
3 are independently selected from the group consisting of hydrogen and substituted or unsubstituted hydrocarbyl; each R
4 is independently selected from the group consisting of halogen and substituted or unsubstituted hydrocarbyl and n is an integer from 0 to 4; each R
5 is independently selected from the group consisting of halo and substituted or unsubstituted hydrocarbyl and m is an integer from 0 to 3; and R
6 is substituted or unsubstituted cyclohexyl; and the pharmaceutically acceptable salts thereof.