Patent EP-1486205-B1 (EP)
Inventor: HARRIS ROBERT H
IPC: A61K31/165
Filed: 2001-08-24
Granted: 2007-10-17
Abstract: The present invention describes a method for alleviating pain in a patient suffering from chronic pain comprising administering to said patient an analgesic effective amount of a compound of the formula:   
wherein 
R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, and R is unsubstituted or is substituted with at least one electronic withdrawing group or electron donating group; 
R 1  is hydrogen or lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, aryl, heterocyclic lower alkyl, heterocyclic, lower alkyl heterocyclic, lower cycloalkyl, lower, cycloalkyl lower alkyl, each unsubstituted or substituted with an electron donating group or an electron withdrawing group; and 
R 2  and R 3  are independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl lower alkyl, halo, heterocyclic, heterocyclic lower alkyl, lower alkyl heterocyclic, lower cycloalkyl, lower cycloalkyl lower alkyl, or Z-Y wherein R 2  and R 3  may be unsubstituted or substituted with at least one electron withdrawing group or electron donating group wherein the electron donating group or electron withdrawing group is acyclic; and wherein heterocyclic in R 2  and R 3  is furyl, thienyl, pyrazolyl, pyrrolyl, imidazolyl, indolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, piperidyl, pyrrolinyl, piperazinyl, quinolyl, triazolyl, tetrazolyl, isoquinolyl, benzofuryl, benzothienyl, morpholinyl, benzoxazolyl, tetrahydrofuryl, pyranyl, indazolyl, purinyl, indolinyl, pyrazolindinyl, imidazolinyl, imidazolindinyl, pyrrolidinyl, furazanyl, N-methylindolyl, methylfuryl, pyridazinyl, pyrimidinyl, pyrazinyl, epoxy, aziridino, oxetanyl or azetidinyl; 
Z is O, S, S(O) a , NR 6 ', or PR 4 ; 
Y is hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, lower alkynyl, heterocyclic, heterocyclic lower alkyl, and Y may be unsubstituted or substituted with an electron donating group or an electron withdrawing group, or 
ZY taken together is NR 4 NR 5 R 7 , NR 4 OR 5 , ONR 4 R 7 , OPR 4 R 5 , PR 4 OR 5 , SNR 4 R 7 , NR 4 SR 7 ,  SPR 4 R 5 , PR 4 SR 7 , NR 4 PR 5 R 6  or PR 4 NR 5 R 7 ,    
R 6 ' is hydrogen, lower alkyl, lower alkenyl, or lower alkynyl and R 4  may be unsubstituted or substituted with an electron withdrawing group or electron donating group; 
R 4 , R 5  and R 6  are independently hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl, or lower alkynyl, wherein R 4 , R 5  and R 6  may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and R 7  is COOR 8 , COR 8 , hydrogen, lower alkyl, aryl, aryl lower alkyl, lower alkenyl or lower alkynyl, which R 7  may be unsubstituted or substituted with an electron withdrawing group or electron donating group; 
R 8  is hydrogen or lower alkyl, or aryl lower alkyl, and the aryl or alkyl group may be unsubstituted or substituted with an electron withdrawing group or an electron donating group; and 
n is 1-4; and 
a is 1-3.