Substituted Heteroarylpiperidine Derivatives As Melanocortin-4 Receptor Modulators

A compound according to formula (I)

• and the enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof,
• wherein
• R1 is —N(R10)—(C(R6)2)m-T
• —(C(R6)2)l-T, or
• —O—(C(R6)2)m-T;
• R6 is independently selected from
• H,
• F,
• OH,
• OCH3,
• C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN, OH and OCH3, and
• C3-6-cycloalkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN, OH and OCH3;
• T is NR7R8,
• R7 and R8 are independently from each other selected from
• H,
• C1-6-alkyl,
• C2-6-alkenyl,
• C2-6-alkinyl, and
• C2-6-alkylene-O—C1-6-alkyl,
• wherein each alkyl, alkenyl and alkinyl is optionally substituted by one or more halogen atoms, CN or OH;
• R9 is independently selected from
• halogen,
• CN,
• OH,
• C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN and OH, and
• O—C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN and OH,
• C1-6-alkylene-O—C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN and OH, or
• NR12R13;
• R10 is H, or
• C1-6-alkyl;
• R11 is independently selected from
• halogen,
• CN,
• OH,
• C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN and OH,
• C2-6-alkenyl,
• C2-6-alkinyl,
• O—C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN and OH,
• C1-6-alkylene-O—C1-6-alkyl, optionally substituted with 1 to 3 substituents selected from halogen, CN and OH,
• C0-6-alkyl-C3-6-cycloalkyl,
• —OC(O)C1-6-alkyl,
• —NH2,
• —NH(C1-6-alkyl), and
• —N(C1-6-alkyl)2;
• R12 and R13 are independently from each other selected from
• C1-6-alkyl, optionally substituted with OH,
• C2-6-alkenyl,
• C2-6-alkinyl,
• C2-6-alkylene-O—C1-6-alkyl, and
• C2-6-alkylene-N—(C1-6-alkyl)2;
• W is CH, O or NR10;
• X is CH or N;
• Y is CH or N;
• Z is CH or N;
• A is a 3-7-membered saturated, unsaturated or aromatic ring containing 0-2 nitrogen atoms;
• B is CR2 or N;
• G is CR2 or N;
• D is CR2 or N;
• E is CR2 or N;
• with the proviso that one or two of the variables B, G, D and E must be N;
• R2 is independently selected from
• H,
• F,
• Cl,
• CH3,
• OCH3, and
• CF3;
• R3 is H,
• Cl,
• F, or
• CH3;
• R4 is Cl,
• F or
• CH3;
• R5 is
• morpholine, optionally substituted by 1 to 3 same or different substituents R14,
• 4 to 7 membered, saturated or partially unsaturated heterocycle containing in the ring one nitrogen atom and optionally a further heteroatom selected from O, N and S, wherein heterocycle is optionally substituted by 1 to 4 same or different substituents R11, or
• NR12R13;
• R14 is C1-6-alkyl,
• C1-6-alkylene-O—C1-6-alkyl,
• C1-6-alkylene-OH,
• C1-6-alkylene-NH2,
• C1-6-alkylene-NH—C1-6-alkyl, or
• C1-6-alkylene-N(C1-6-alkyl)2;
• R16 is H or
• C1-6-alkyl;
• l is 0, 1, 2, 3, or 4;
• m is 0, 1, 2, 3, or 4;
• o is 0, 1, or 2;
• p is 0, 1, 2, 3, or 4;
• r is 0, 1, 2, 3, or 4;
• s is 1, or 2 and
• t is 0 or 1.