Patent ID: 6180675
Filing Date: 2001-01-30
Classification: A61K,A61P,C07C,C07D,Y02A

Abstract:
A method of treating a chemokine mediated disease, wherein the chemokine binds to an IL-8 .alpha. or .beta. receptor in a mammal, which method comprises administering to said mammal an effective amount of a compound of the formula: ##STR15##whereinX is oxygen or sulfur;R is C(O)NR.sub.6 R.sub.7 ;R.sub.1 is independently selected from hydrogen; halogen; nitro; cyano; halosubstituted C.sub.1-10 alkyl; C.sub.1-10 alkyl; C.sub.2-10 alkenyl; C.sub.1-10 alkoxy; halosubstituted C.sub.1-10 alkoxy; azide; S(O).sub.t R.sub.4 ; hydroxy; hydroxy C.sub.1-4 alkyl; aryl; aryl C.sub.1-4 alkyl; aryloxy; aryl C.sub.1-4 alkyloxy; heteroaryl; heteroarylalkyl; heterocyclic, heterocyclic C.sub.1-4 alkyl; heteroaryl C.sub.1-4 alkyloxy; arylC.sub.2-10 alkenyl; heteroaryl C.sub.2-10 alkenyl; heterocyclicC.sub.2-10 alkenyl; NR.sub.4 R.sub.5 ; C.sub.2-10 alkenylC(O)NR.sub.4 R.sub.5 ; C(O)NR.sub.4 R.sub.5 ; C(O)NR.sub.4 R.sub.10 ; S(O).sub.3 H; S(O).sub.3 R.sub.8 ; C.sub.1-10 alkyl C(O)R.sub.11 ; C.sub.2-10 alkenyl C(O)R.sub.11 ; C.sub.2-10 alkenyl C(O)OR.sub.11 ; C(O)R.sub.11 ; C(O)OR.sub.12 ; OC(O)R.sub.11 ; NR.sub.4 C(O)R.sub.11 ; or two R.sub.1 moieties together may form O--(CH.sub.2).sub.s O-- or a 5 to 6 membered unsaturated ring;t is 0, or an integer having a value of 1 or 2;s is an integer having a value of 1 to 3;R.sub.4 and R.sub.5 are independently hydrogen, optionally substituted C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl C.sub.1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C.sub.1-4 alkyl, heterocyclic, heterocyclic C.sub.1-4 alkyl, or R.sub.4 and R.sub.5 together with the nitrogen to which they are attached form a 5 to 7 member ring which may optionally comprise an additional heteroatom selected from O/N/S;R.sub.6 and R.sub.7 are independently hydrogen or a C.sub.1-4 alkyl group, or R.sub.6 and R.sub.7 together with the nitrogen to which they are attached form a 5 to 7 member ring which ring may optionally contain an additional heteroatom which heteroatom is selected from oxygen, nitrogen or sulfur;Y is independently selected from hydrogen; halogen; nitro; cyano; halosubstituted C.sub.1-10 alkyl; C.sub.1-10 alkyl; C.sub.2-10 alkenyl; C.sub.1-10 alkoxy; halosubstituted C.sub.1-10 alkoxy; azide; S(O).sub.t R.sub.4 ; hydroxy; hydroxyC.sub.1-4 alkyl; aryl; aryl C.sub.1-4 alkyl; aryloxy; arylC.sub.1-4 alkyloxy; heteroaryl; heteroarylalkyl; heteroarylC.sub.1-4 alkyloxy; heterocyclic, heterocyclicC.sub.1-4 alkyl; arylC.sub.2-10 alkenyl; heteroaryl C.sub.2-10 alkenyl; heterocyclicC.sub.2-10 alkenyl; NR.sub.4 R.sub.5 ; C.sub.2-10 alkenylC(O)NR.sub.4 R.sub.5 ; C(O)NR.sub.4 R.sub.5 ; C(O)NR.sub.4 R.sub.10 ; [S(O).sub.3 H;] S(O).sub.3 R.sub.8 ; C.sub.1-10 alkylC(O)R.sub.11 ; C.sub.2-10 alkenyl C(O)R.sub.11 ; C.sub.2-10 alkenyl C(O)OR.sub.11 ; C(O)R.sub.11 ; C(O)OR.sub.12 ; OC(O)R.sub.11 ; NR.sub.4 C(O)R.sub.11 ; or two Y moieties together may form O--(CH.sub.2).sub.s O-- or a 5 to 6 membered unsaturated ring;n is an integer having a value of 1 to 3;m is an integer having a value of 1 to 3;R.sub.8 is hydrogen or C.sub.1-4 alkyl;R.sub.10 is C.sub.1-10 alkyl C(O).sub.2 R.sub.8 ;R.sub.11 is hydrogen, C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl C.sub.1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C.sub.1-4 alkyl, optionally substituted heterocyclic, or optionally substituted heterocyclic C.sub.1-4 alkyl;R.sub.12 is hydrogen, C.sub.1-10 alkyl, optionally substituted aryl or optionally substituted arylalkyl;or a pharmaceutically acceptable salt thereof.