Substituted hexahydro arylquinolizines

Claim 1

A compound of structural formula: or a pharmaceutically acceptable salt thereof wherein Ar represents an aromatic heterocycle selected from R 1 ,R 2 -benzo[b]furo-, R 1 ,R 2 -benzo[b]thieno-, pyridino-, thiazolo-, imidazo-, pyrazolo-, thieno- and furo-; R l and R 2 are independently: 1) hydrogen, 2) halo, 3) hydroxy, 4 ) C 1-3 alkoxy, or 5) C 1-6 alkyl; R 3 is 1) hydrogen, 2) wherein R is hydrogen or C 1-3 alkyl, 3) C 1-6 a3kyl, either unsubstituted or substituted with one or more of; a) hydroxy, b) carboxy, c ) C 1-3 alkoxycarbonyl, d) halo, e ) C 1-3 alkoxy, f) -CONR 6 R 7 , wherein R 6 and R 7 are the same or different and are hydrogen or C 1-5 alkyl, or joined together directly to form a 5-7 membered ring or through a heteroatom selected from 0, N and S, to form a 6-membered heterocycle with the nitrogen to which they are attached, or g ) - NR 6 R 7 ; X is R 4 is 1) -OR 8 , wherein R 8 is hydrogen or C 1-6 alkyl, either unsubstituted or substituted with one or more of; a) OR, or b) -NRCOR; 2) -N(R 8 ) 2 , 3) -CO 2 R 8 , 4) -CONR 6 R 7 , 5) C 1-6 alkyl, either unsubstituted or substituted with a) OR 8 , b) halo, c) CO 2 R 8 , d) CONR 6 R 7 , 6) C 2-5 alkenyl, 7 ) C 2 _,alkynyl, 8 ) C 3-6 cycloalkyl, 9) 5 or 6-membered heterocycle with up to 2 heteroatoms selected from N, 0, and S, 10) carbocyclic aryl of 6-10 carbon atoms, either unsubstituted or substituted with one or more of; a) halo, or b) OR; or 5 R is 1) hydrogen, <) C 1-3 alkgl, 2) C 1-6 alkyl, either unsubstituted or substituted with one or more of a) -OR 8 , b) -NR 8 COR 8 , or c) -CO 2 R 8 , 3) -CO 2 R 8 , or 4) -CONR 6 R 7 ; R 3 and R 4 taken together directly or through a - heteroatom selected from O, N and S, form a 5- or 6-membered heterocycle with the nitrogen to which they are attached; or R 3 and R 5 or R 4 and R 5 , if R 5 is in the 1- or 3-position and both are alkyl, can be joined together to form a 5- or 6-membered ring.

Claim 8

A method of antagonizing a 2 -adrenoceptors which comprises administering to a patient in need of such treatment an effective α 2 - adrenoceptor antagonist amount of a compound of structural formula: or a pharmaceutically acceptable salt thereof wherein Ar, R 3 , X , R 4 , and R 5 are as defined in Claiml .

Claim 9

The method of Claim wherein Ar is R 1 ,R 2 -benzo[b]furo or R 1 ,R 2 -benzo[b]thieno; R 1 and R 2 are hydrogen or halo; R 3 is C 1-6 alkyl; X is -S0 2 - and R 4 is C 1-6 alkyl, di(C 1-3 alkyl)amino, halo-C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 2-5 alkenyl, C 6-10 -carbocyclic aryl, 5 or 6-membered heterocycle, -CO 2 R 8 , -C 1-6 alkyl-CO 2 R 8 or C 1-6 alkyl-CONR 6 R 7 ; and R 5 is hydrogen or C 1-6 alkyl.