Hydroxyindoles, their use as inhibitors of phosphodiesterase 4 and processes for their preparation

A compound of the Formula

• 4
• and their pharmaceutically acceptable salts, wherein
• R1, R5 are independently of each other
• (i) a C1-2 alkyl, straight-chain or branched-chain, optionally mono- or polysubstituted by —OH, —SH, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —NHCOR6, —NO2, —CN, —F, —Cl, —Br, —I, —O—C1-6 alkyl, —O—C6-14 aryl, —O(CO)R6, —S—C1-6 alkyl, —S—C6-14 aryl, —SOR6, —SO3H, —SO2R6, —OSO2C1-6 alkyl, —OSO2C6-14 aryl, —(CS)R6, —COOH, —(CO)R6, mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S, where the C, aryl groups and the included carbocyclic and heterocyclic substituents can optionally be mono- or polysubstituted by R4,
• (ii)—C2-12 alkenyl, mono- or polyunsaturated, straight-chain or branched-chain, optionally mono- or polysubstituted by —OH, —SH, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —NHCOR6, —NO2, —CN, —F, —Cl, —Br, —I, —O—C, alkyl, —O—C6-14 aryl, —O(CO)R6, —S—C1-6 alkyl, —S—C6-14 aryl, —SOR6, —SO3H, —SO2R6, —OSO2C1-6 alkyl, —OSO2C6-14 aryl, —(CS)R6, —COOH, —(CO)R6, mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S, where the C6-14, aryl groups and the included carbocyclic and heterocyclic substituents for their part can optionally be mono- or polysubstituted by R4,
• (iii) mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, optionally mono- or polysubstituted by —OH, —SH, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —NHCOR6, —NO2, —CN, —F, —Cl, —Br, —I, —O—C1-6 alkyl, —O—C6-14 aryl, —O(CO)R6, —S—C1-6 alkyl, —S—C6-14 aryl, —SOR6, —SO3H, —SO2R6, —OSO2C1-6 alkyl, —OSO2C6-14 aryl, —(CS)R6, —COOH, —(CO)R6, mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S, where the C6-14 aryl groups and the included carbocyclic and heterocyclic substituents can optionally be mono- or polysubstituted by R4,
• (iv) mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S, optionally mono- or polysubstituted by —OH, —SH, —NH2, —NHC1-6 alkyl —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —NHCOR6, —NO2,—CN, —F, —Cl, —Br, —I, —O—C1-6 alkyl, —O—C6-14 aryl, —O(CO)R6, —S—C1-6 alkyl, —S—C6-14 aryl, —SOR6, —SO3H, —SO2R6, —OSO2C1-6 alkyl, —OSO2C6-14 aryl, —(CS)R6, —COOH, —(CO)R6, mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S, where the C6-14 aryl groups and the included carbocyclic and heterocyclic substituents for their part can be optionally mono- or polysubstituted by R4, -carbo- or heterocyclic saturated or mono- or polyunsaturated spirocycles having from 3 to 10 ring members, where heterocyclic systems contains from 1 to 6 heteroatoms, which are suitably N, O and S, optionally mono- or polysubstituted by —OH, —SH, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —NHCOR6, —NO2, —CN, —F, —Cl, —Br, —I, —O—C1-6 alkyl, —O—C6-14 aryl, —O(CO)R6, —S—C1-6 alkyl, —S—C6-14 aryl, —SOR6, —SO3H, —SO2R6, —OSO2C1-6 alkyl, —OSO2C6-14 aryl, —(CS)R6, —COOH, —(CO)R6, mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S, where the C6-14 aryl groups and the included carbocyclic and heterocyclic substituents can optionally be mono- or polysubstituted by R4,
• R2, R3 are hydrogen or —OH, where at least one of the two substituents must be —OH;
• R4 is —H, —OH, —SH, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —NHCOR6, —NO2, —CN, —COOH, —(CO)R6, —(CS)R6, —F, —Cl, —Br, —I, —O—C1-6 alkyl, —O—C6-14 aryl, —O(CO)R6, —S—C1-6 alkyl, —S—C6-14 aryl, —SOR6, —SO2R6.
• R6 is —H, —NH2, —NHC1-6 alkyl, —N(C1-6 alkyl)2, —NHC6-14 aryl, —N(C6-14 aryl)2, —N(C1-6 alkyl)(C6-14 aryl), —O—C1-6 alkyl, —O—C6-14 aryl, —S—C1-6 alkyl, —S—C6-14 aryl, —C1-12 alkyl, straight-chain or branched-chain, —C2-12 alkenyl, mono- or polyunsaturated, straight-chain or branched-chain, -mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, -mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S;
• A is either a bond, or —CH2)m—, —(CH2)m—(CH═CH)n—(CH2)p—, —(CHOZ)m—, —(C═O)—, —(C═S)—, —(C═N—Z)—, —O—, —S—, —NZ—, where m and p are cardinal numbers from 0 to 3 and n is a cardinal number from 0 to 2,
• Z is H, or a C1-12 alkyl, straight-chain or branched-chain, C2-12 alkenyl, mono- or polyunsaturated, straight-chain or branched-chain, mono-, bi- or tricyclic saturated or mono- or polyunsaturated carbocycles having from 3 to 14 ring members, mono-, bi- or tricyclic saturated or mono- or polyunsaturated heterocycles having from 5 to 15 ring members and from 1 to 6 heteroatoms, which are suitably N, O and S;
• B is either carbon or sulfur, or —(S═O)—;
• D is oxygen, sulfur, CH2 or N—Z, where D can only be S or CH2 if B is carbon;
• E is a bond, or (CH2)m—, —O—, —S—, —(N—Z)—, where m and Z have the same meanings as above.