Bi- and polycyclic substituted isoquinoline and isoquinolinone derivatives

A compound of the formula (I)

• wherein
• R1 is H, OH or NH2;
• R3 is H, halogen, CN, (C1-C6)alkyl, OH, NH2, or NHR′;
• R4 is H, halogen, hydroxy, CN, (C1-C6)alkyl, R′, or (C1-C6)alkylene-R′;
• R5 is H, halogen, CN, (C1-C6)alkyl, or R′;
• R7 is H, halogen, CN, (C1-C6)alkyl, O—(C1-C6)alkyl, R′, or SO2—NH2;
• R8 is H, halogen or (C1-C6)alkyl;
• R6 is one (C1-C4)alkylene bound to the cycloalkyl ring, in which the (C1-C4)alkylene forms a second bond to a different carbon atom of the cycloalkyl ring to form a bicyclic ring system, wherein in the bicyclic ring system one or two carbon atoms are replaced by a group independently selected from O, N—R13, S, SO or SO2;
• or, if m and s are 2, m is 3 and s is 1, or m is 4 and s is 0,
• R6 is CH2—CH—(CH2)2 which is bound with one CH2 to the cycloalkyl ring and the two other CH2 are bound to different carbon atoms of the cycloalkyl ring,
• and, if m is 3 and s is 3,
• R6 are two methylene groups bound to different carbon atoms of the cycloalkyl ring, wherein the methylene groups or the CH2—CH—(CH2)2 group are bound to carbon atoms of the cycloalkyl ring and form an adamantane system of the formula
• wherein L can be bound to any secondary or tertiary carbon atom,
• or R6 together with R11 and the N atom form a (C3-C8)heterocycloalkyl which is connected as a spirocyclic ring system to the cycloalkyl residue to form a residue of the formula
• wherein the bicyclic ring system or adamantane system or the (C3-C8)heterocycloalkyl containing ring system is unsubstituted or optionally substituted by R9;
• R9 is
• R′,
• OH,
• halogen,
• (C1-C6)alkyl,
• O—(C1-C6)alkyl,
• (C1-C6)alkylene-R′,
• (C2-C6)alkenyl,
• (C2-C6)alkynyl,
• (C1-C6)alkylene-O—R′,
• (C1-C6)alkylene-CH[R′]2,
• (C1-C6)alkylene-C(O)—R′,
• (C1-C6)alkylene-C(O)NH2,
• (C1-C6)alkylene-C(O)NH—R′,
• (C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
• (C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
• (C1-C6)alkylene-C(O)N[R′]2;
• (C1-C6)alkylene-C(O)O—(C1-C6)alkyl,
• COOH,
• C(O)O—(C1-C6)alkyl,
• C(O)OR′
• C(O)(C1-C6)alkyl,
• C(O)R′,
• CONH2,
• C(O)—NH—(C2-C6)alkenyl,
• C(O)—NH—(C2-C6)alkynyl,
• C(O)NH—(C1-C6)alkyl,
• C(O)NHR′,
• C(O)—NH(C1-C6)alkylene-R′,
• C(O)N[(C1-C6)alkyl]R′,
• C(O)N[(C1-C6)alkyl]2,
• C(O)—(C1-C6)alkylene-R′, or
• C(O)O(C1-C6)alkylene-R′;
• R11 and R12 are independently of each other
• H,
• R′,
• (C1-C6)alkyl,
• (C1-C6)alkylene-R′,
• (C1-C6)alkylene-O—(C1-C6)alkyl,
• (C1-C6)alkylene-O—R′,
• (C1-C6)alkylene-CH[R′]2,
• (C1-C6)alkylene-C(O)—R′,
• (C1-C6)alkylene-C(O)NH2,
• (C1-C6)alkylene-C(O)NH—R′,
• (C1-C6)alkylene-C(O)NH—(C1-C6)alkyl,
• (C1-C6)alkylene-C(O)N[(C1-C6)alkyl]2,
• (C1-C6)alkylene-C(O)N[R′]2,
• (C1-C6)alkylene-C(O)O—(C1-C6)alkyl,
• C(O)O—(C1-C6)alkyl,
• C(O)OR′,
• C(O)(C1-C6)alkyl,
• C(O)R′,
• C(O)NH—(C1-C6)alkyl,
• C(O)NHR′,
• C(O)N[(C1-C6)alkyl]R′,
• C(O)N[(C1-C6)alkyl]2,
• C(O)—(C1-C6)alkylene-R′,
• C(O)O(C1-C6)alkylene-R′, or
• R11 and R12, together with the N-atom to which they are attached, form a (C3-C8) heterocycloalkyl;
• R13 is H or (C1-C6)alkyl;
• n is 0, 1, 2, 3 or 4;
• m is 1, 2, 3 or 4;
• s is 0, 1, 2, or 3;
• L is O(CH2)p, S(CH2)p, S(O)(CH2)p, SO2(CH2)p, NH(CH2)p, N(C1-C6)alkyl-(CH2)p, N(C3-C6)cycloalkyl-(CH2)p;
• or N[(C1-C3)alkylene-R′]—(CH2)p;
• p is 0, 1, 2, 3 or 4;
• R′ is
• (C3-C8)cycloalkyl,
• (C5-C10)heteroaryl,
• (C3-C8)heterocycloalkyl,
• (C6-C10)aryl;
• wherein in residues R3 to R13 alkyl or alkylene is unsubstituted or optionally substituted one or more times by OH, OCH3, C(O)OH, C(O)OCH3, NH2, NHCH3, N(CH3)2, C(O)NH2, C(O)NHCH3 or C(O)N(CH3)2;
• wherein in residues R3 to R13 cycloalkyl or heterocycloalkyl is unsubstituted or optionally substituted one or more times by (C1-C6)alkyl, halogen, OH, OCH3, C(O)OH, C(O)OCH3, NH2, NHCH3, N(CH3)2, C(O)NH2, C(O)NHCH3 or C(O)N(CH3)2;
• wherein in residues R3 to R13 alkyl or alkylene is unsubstituted or optionally substituted one or more times by halogen;
• wherein in residues R3 to R13 (C6-C10)aryl and (C5-C10)heteroaryl are unsubstituted or optionally substituted one or more times by a group independently selected from halogen, OH, NO2, N3, CN, C(O)—(C1-C6)alkyl, C(O)—(C6-C10)aryl, C(O)OH, C(O)O(C1-C6)alkyl, C(O)NH2, C(O)NH(C1-C6)alkyl, C(O)N[(C1-C6)alkyl]2, (C3-C8)cycloalkyl, (C1-C6)alkyl, (C1-C6)alkylene-NH(C1-C6)alkyl, (C1-C6)alkylene-N[(C1-C6)alkyl]2, (C2-C6)alkenyl, (C2-C6)alkynyl, O—(C1-C6)alkyl, O—C(O)—(C1-C6)alkyl, PO3H2, SO3H, SO2—NH2, SO2NH(C1-C6)alkyl, SO2N[(C1-C6)alkyl]2, S—(C1-C6)alkyl;
• SO—(C1-C6)alkyl, SO2—(C1-C6)alkyl, SO2—N═CH—N[(C1-C6)alkyl]2, SF5, C(NH)(NH2), NH2, NH—(C1-C6)alkyl, N[(C1-C6)alkyl]2, NH—C(O)—(C1-C6)alkyl, NH—C(O)O—(C1-C6)alkyl, NH—SO2—(C1-C6)alkyl, NH—SO2—(C6-C10)aryl, NH—SO2—(C5-C10)heteroaryl, NH—SO2—(C3-C8)heterocycloalkyl, N(C1-C6)alkyl-C(O)—(C1-C6)alkyl, N(C1-C6)alkyl-C(O)O—(C1-C6)alkyl, N(C1-C6)alkyl-C(O)—NH—(C1-C6)alkyl], (C6-C10)aryl, (C1-C6)alkylene-(C6-C10)aryl, O—(C6-C10)aryl, O—(C1-C6)alkylene-(C6-C10)aryl, (C5-C10)heteroaryl, (C3-C8)heterocycloalkyl, (C1-C6)alkylene-(C5-C10)heteroaryl, (C1-C6)alkylene-(C3-C8)heterocycloalkyl, O—(C1-C6)alkylene-(C5-C10)heteroaryl, O—(C1-C6)alkylene-(C3-C8)heterocycloalkyl,
• wherein said (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C8)heterocycloalkyl, or (C3-C8)cycloalkyl may be substituted one to three times by a group independently selected from halogen, OH, NO2, CN, O—(C1-C6)alkyl, (C1-C6)alkyl, NH2, NH(C1-C6)alkyl, N[(C1-C6)alkyl]2, SO2CH3, C(O)OH, C(O)O—(C1-C6)alkyl, C(O)NH2, (C1-C6)alkylene-O—(C1-C6)alkyl, (C1-C6)alkylene-O—(C6-C10)aryl, or O—(C1-C6)alkylene-(C6-C10)aryl;
• or wherein (C6-C10)aryl is vicinally substituted by a O—(C1-C4)alkylene-O group whereby a 5-8-membered ring is formed together with the carbon atoms the oxygen atoms are attached to;
• and wherein aryl substituents of (C6-C10)aryl, (C5-C10)heteroaryl, (C3-C8)heterocycloalkyl and (C3-C8)cycloalkyl groups may not be further substituted by an aryl, heteroaryl, heterocycloalkyl, or cycloalkyl containing group;
• their stereoisomeric and/or tautomeric forms or a pharmaceutically acceptable salt.