Compounds
AssigneeSmithKline Beecham Corporation
InventorsJohn Duncan Elliott, Jack Dale Leber, Scott Kevin Thompson, Stacie Marie Halbert
Life of this patent
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Abstract
This invention relates to novel carboxylic acid indole compounds and compositions for use in the treatment of disease states mediated by the chemokine, Interleukin-8 (IL-8).
Claims13
A method of treating a chemokine mediated disease state, wherein the chemokine binds to an IL-8 .alpha. or .beta. receptor in a mammal, which comprises administering to said mammal an effective amount of a compound of the formula ##STR45## wherein Ar is an optionally substituted phenyl or naphthyl group;
- R is hydrogen, hydroxy, C.sub.1-8 alkoxy, or O--(CR.sub.8 R.sub.9).sub.n --R.sub.6 ;
- R.sub.6 is an optionally substituted C.sub.3-7 cycloalkyl, optionally substituted C.sub.3-7 cycloalkenyl, or optionally substituted aryl;
- n is 0 or an integer having a value of 1, 2, 3 or 4;
- R.sub.1 is hydrogen, halogen, halosubstituted C.sub.1-8 alkyl, C.sub.1-8 alkyl, hydroxy, C.sub.1-8 alkoxy, halosubstitutedC.sub.1-8 alkoxy, O--CH.sub.2 --O--C.sub.1-8 alkyl, --(CH.sub.2).sub.t aryl, O--(CH.sub.2).sub.t aryl, --O--(CH.sub.2).sub.v C(O)OC.sub.1-4 alkyl, NO.sub.2, S(O).sub.m R.sub.2, N(R.sub.3).sub.2, NHC(O)R.sub.4, --C(O)R.sub.5, or together two R.sub.1 moieties may form a methylene dioxy ring system, or together two R.sub.1 moieties may form a 6 membered saturated or unsaturated ring system which may be optionally substituted;
- t is 0 or an integer having a value of 1, 2, 3, or 4;
- v is an integer having a value of 1, 2, 3, or 4;
- s is an integer having a value of 1, 2, or 3;
- m is 0 or an integer having a value of 1 or 2;
- R.sub.2 is an optionally substituted C.sub.1-8 alkyl;
- R.sub.3 is independently hydrogen, or C.sub.1-4 alkyl, or together with the nitrogen to which they are attached form a 5 to 7 membered saturated or unsaturated ring;
- R.sub.4 is independently hydrogen, or C.sub.1-4 alkyl;
- R.sub.5 is hydrogen, optionally substituted C.sub.1-8 alkyl, or C.sub.1-8 alkoxy;
- R.sub.8 and R.sub.9 are independently hydrogen or C.sub.1-4 alkyl;
- or pharmaceutically acceptable salts thereof.
A method of treating a chemokine mediated disease wherein the disease is inflammation in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of Formula (I) ##STR46## wherein Ar is an optionally substituted phenyl or naphthyl group;
- R is hydrogen, hydroxy, C.sub.1-8 alkoxy, or O--(CR.sub.8 R.sub.9).sub.n --R.sub.6 ;
- R.sub.6 is an optionally substituted C.sub.3-7 cycloalkyl, optionally substituted C.sub.3-7 cycloalkenyl, or optionally substituted aryl;
- n is 0 or an integer having a value of 1, 2, 3 or 4;
- R.sub.1 is hydrogen, halogen, halosubstituted C.sub.1-8 alkyl, C.sub.1-8 alkyl, hydroxy, C.sub.1-8 alkoxy, halosubstitutedC.sub.1-8 alkoxy, O--CH.sub.2 --O--C.sub.1-8 alkyl, --(CH.sub.2).sub.t aryl, O--(CH.sub.2).sub.t aryl, --O--(CH.sub.2).sub.v C(O)OC.sub.1-4 alkyl, NO.sub.2, S(O).sub.m R.sub.2, N(R.sub.3).sub.2, NHC(O)R.sub.4, --C(O)R.sub.5, or together two R.sub.1 moieties may form a methylene dioxy ring system, or together two R.sub.1 moieties may form a 6 membered saturated or unsaturated ring system which may be optionally substituted;
- t is 0 or an integer having a value of 1, 2, 3, or 4;
- v is an integer having a value of 1, 2, 3, or 4;
- s is an integer having a value of 1, 2, or 3;
- m is 0 or an integer having a value of 1 or 2;
- R.sub.2 is an optionally substituted C.sub.1-8 alkyl;
- R.sub.3 is independently hydrogen, or C.sub.1-4 alkyl, or together with the nitrogen to which they are attached form a 5 to 7 membered saturated or unsaturated ring;
- R.sub.4 is independently hydrogen, or C.sub.1-4 alkyl;
- R.sub.5 is hydrogen, optionally substituted C.sub.1-8 alkyl, or C.sub.1-8 alkoxy;
- R.sub.8 and R.sub.9 are independently hydrogen or C.sub.1-4 alkyl;
- or a pharmaceutically acceptable salt thereof.
A method of treating a chemokine mediated disease wherein the disease is asthma in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of Formula (I) ##STR47## wherein Ar is an optionally substituted phenyl or naphthyl group;
- R is hydrogen, hydroxy, C.sub.1-8 alkoxy, or O--(CR.sub.8 R.sub.9).sub.n --R.sub.6 ;
- R.sub.6 is an optionally substituted C.sub.3-7 cycloalkyl, optionally substituted C.sub.3-7 cycloalkenyl, or optionally substituted aryl;
- n is 0 or an integer having a value of 1, 2, 3 or 4;
- R.sub.1 is hydrogen, halogen, halosubstituted C.sub.1-8 alkyl, C.sub.1-8 alkyl, hydroxy, C.sub.1-8 alkoxy, halosubstitutedC.sub.1-8 alkoxy, O--CH.sub.2 --O--C.sub.1-8 alkyl, --(CH.sub.2).sub.t aryl, O--(CH.sub.2).sub.t aryl, --O--(CH.sub.2).sub.v C(O)OC.sub.1-4 alkyl, NO.sub.2, S(O).sub.m R.sub.2, N(R.sub.3).sub.2, NHC(O)R.sub.4, --C(O)R.sub.5, or together two R.sub.1 moieties may form a methylene dioxy ring system, or together two R.sub.1 moieties may form a 6 membered saturated or unsaturated ring system which may be optionally substituted;
- t is 0 or an integer having a value of 1, 2, 3, or 4;
- v is an integer having a value of 1, 2, 3, or 4;
- s is an integer having a value of 1, 2, or 3;
- m is 0 or an integer having a value of 1 or 2;
- R.sub.2 is an optionally substituted C.sub.1-8 alkyl;
- R.sub.3 is independently hydrogen, or C.sub.1-4 alkyl, or together with the nitrogen to which they are attached form a 5 to 7 membered saturated or unsaturated ring;
- R.sub.4 is independently hydrogen, or C.sub.1-4 alkyl;
- R.sub.5 is hydrogen, optionally substituted C.sub.1-8 alkyl, or C.sub.1-8 alkoxy;
- R.sub.8 and R.sub.9 are independently hydrogen or C.sub.1-4 alkyl;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.