7-azaindoles, their use as inhibitors of phosphodiesterase 4, and a method for synthesizing them

1. A method comprising administering a therapeutically effective amount of a 7-azaindole of the formula 1

or a physiologically tolerated salt thereof

wherein

n is 2;

R 1 is a —C 1 to —C 10 linear or branched alkyl; which may be unsubstituted or substituted

with at least one of —OH, —SH, —NH 2 ,—NHC 1 to —NHC 6 alkyl, —N(C 1 to C 6 —alkyl) 2 , —NHC 6 to —NHC 14 aryl, —N(C 6 to C 14 aryl) 2 , —N(C 1 to C 6 alkyl)(C 6 to C 14 aryl), —NO 2 , —CN, —F, —Cl, —Br, —I, —O—C 1 to —O —C 6 alkyl, —O—C 6 to —O—C 14 aryl, —S—C 1 to —S—C 6 alkyl, —S—C 6 to —S—C 14 aryl, —SO 3 H, —SO 2 C 1 to —SO 2 C 6 alkyl, —SO 2 C 6 to —SO 2 C 14 aryl,—OSO 2 C 1 to —OSO 2 C 6 alkyl, —OSO 2 C 6 to —OSO 2 C 14 aryl, —COOH, —(CO)C 1 to —(CO)C 5 alkyl;

with mono-, bi— or tri-cyclic, saturated or monounsaturated or multiunsaturated carboxylic groups with 3 to 14 ring elements; with mono-, bi— or tri-cyclic saturated or monounsaturated or multiunsaturated heterocyclic groups with 5 to 15 ring elements and 1 to 6 heteroatoms selected from the group consisting of N, O and S;

or R 1 is a —C 2 to —C 10 alkenyl, monounsaturated, multiunsaturated, linear or branched; which may be unsubstituted. monosubstituted or multi-substituted with at least one of —OH, —SH, —NH 2 , —NHC 1 to —NHC 6 alkyl, —N(C 1 to C 6 —alkyl) 2 ,—NHC 6 to —NHC 14 aryl, —N(C 6 to C 14 aryl) 2 —N(C 1 to C 6 alkyl)(C 6 to C 14 aryl), —NO 2 —, —CN, —F, —Cl, —Br, —I, —O—C 1 to —O—C 6 alkyl, —O—C 6 to —O—C 14 aryl, —S—C 1 to —S—C 6 alkyl, —S—C 6 to —S—C 14 aryl, —SO 3 H,—SO 2 C 1 , to —SO 2 C 6 alkyl, —SO 2 C 14 aryl, —OSO 2 C 1 to —OSO 6 alkyl, —OSO 2 C 6 to —OSO 2 C 14 aryl, —COOH, —(CO)C 1 to —(CO)C 5 alkyl;

with mono-, bi- or tri-cyclic, saturated or monounsaturated or multiunsaturated carbocyclic group with 3 to 14 ring elements, with mono-, bi- or tri-cyclic saturated or monounsaturated or multiunsaturated heterocylic groups with 5 to 15 ring elements and 1 to 6 heteroatoms selected from N, O and S;

wherein said C 6 to 14 aryl groups and the carbocyclic and heterocyclic substituents may optionally be substituted at least once with R 4;

R 2 and R 3 are independently selected from the group consisting of —H, —C 1 to —C 5 alkyl, unsubstituted or monosubstituted or multi-substituted with —OH,—SH,—NH 2 to —NCH 1 to —NCH 6 alkyl, —N(C 1 to C 3 -alkyl) 2 , —NO 2 , —CN, —F, —CI, —Br, —I, —O— 1 to —O—C 6 alkyl, —S—C 1 to-S—C 6 alkyl, -phenyl, -pynidyl;

or -phenyl unsubstituted or monosubstituted or multi-substituted with —OH, —SH, NH 2 , —NHC 1 to NHC 3 alkyl, —N(C 1 to C 3 -alkyl) 2 , —NO 2 , —CN, —COOH, —COOC 1 to —COOC 3 -alkyl, —F, —Cl, —Br—, —O—C 3 alkyl, —S—C 1 , to —S—C 3 alkyl;

or pyridyl, unsubstituted or monosubstituted or multisubstituted with NO 2 , —CN, —COOH, —COOC 1 to —COOC 3 alkyl, —Cl, —Br, —O—C 1 to —O—C 3 alkyl, —S—C 1 to —S—C 3 alkyl, or

wherein —NR 2 R 3 can be

R 4 is —H, —OH, —NH 2 , —NHC 1 to —NHC 6 alkyl, —N(C 1 to C 6 alkyl) 2 , —NHC 6 to —NHC 14 aryl, —N(C 6 to C 14 aryl) 2, —N(C 1 to C 6 alkyl) (C 6 to C 14 aryl), —NHCOC 1 to —NHCOC 6 alkyl, —NO 2 , —CN, —COOH, —COOC 1 to —COOC 6 alkyl, —(CO)C 1 to —(CO)C 6 alkyl, —(CS)C 1 to —(CS)C 6 alkyl, —F, —Cl, —Br, —I, —O—C 1 to —O—C 6 alkyl, —O—C 6 to —O—C 14 aryl, —S—C 1 to —S—C 6 alkyl, —S—C 6 to —S—C 14 aryl, —SOC 1 , to SOC 6 alkyl, —SO 2 C 1 to —SO 2 C 6 alkyl;

to a subject afflicted with at least one condition selected from the group consisting of dermatitis, atopic dermatitis, eczema, fascitis, eosinophilic fascitis, urticaria, uveitis, neurodermatitis, pyodermatitis, acne, rosacea-like dermatitis, lupus erythematosus, allergic skin disease, psoriasis and keratosis.

2. The method of claim 1 , wherein the 7-azaindole is N-(3,5-dichIoro-pyridine-4 -yl) -[(1 -(4-fluorobenzyl)-7-azaindole 3 -yl ]glyoxylic acid amide.