1-Heterocyclylalkyl-3-sulfonylazaindole or -azaindazole derivatives as 5-hydroxytryptamine-6 ligands

A method for the treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor in a patient in need thereof which comprises providing to said patient a therapeutically effective amount of a compound of formula I

• wherein
• W is N or CR2;
• X is N or CR9;
• Y is N or CR10;
• Z is N or CR11;
• Q is N or CR12 with the proviso that at least one and not more than two of X, Y, Z and Q must be N;
• R1 is an optionally substituted C1-C6alkyl, C3-C7cycloalkyl, aryl, or heteroaryl group or an optionally substituted 8- to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;
• R2 is H, halogen, or a C1-C6alkyl, C1-C6alkoxy, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• R3 and R4 are each independently H or an optionally substituted C1-C6alkyl group;
• R5 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R6 is a C1-C6alkyl, C3-C7cycloalkyl, C2-C6alkenyl or C2-C6alkynyl group each optionally substituted;
• R7 and R8 are each independently H or a C1-C6alkyl, C3-C7cycloalkyl, C2-C6alkenyl or C2-C6alkynyl group each optionally substituted;
• m and n are each independently 0 or an integer of 1, 2 or 3;
• p is 0 or an integer of 1 or 2;
• R9, R10, R11 and R12 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, SOxR17, NR18R19, OR20, COR21 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• R13, R14, R17 and R21 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15, R16, R18 and R19 are each independently H or an optionally substituted C1-C4alkyl group or R15 and R16 or R18 and R19 may be taken together with the atom to which they are attached to form a 5- to 7-membered ring optionally containing another heteroatom selected from O, NR22 or SOq;
• R20 is a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• x and q are each independently 0 or an integer of 1 or 2;
• and
• R22 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteraryl group each optionally substituted;
• or
• the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and an effective amount of a compound of formula I

• wherein
• W is N;
• X is N or CR9;
• Y is N or CR10;
• Z is N or CR11;
• Q is N or CR12 with the proviso that at least one and not more than two of X, Y, Z and Q must be N;
• R1 is an optionally substituted C1-C6alkyl, C3-C7cycloalkyl, aryl, or heteroaryl group or an optionally substituted 8- to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;
• R2 is H, halogen, or a C1-C6alkyl, C1-C6alkoxy, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• R3 and R4 are each independently H or an optionally substituted C1-C6alkyl group;
• R5 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R6 is a C1-C6alkyl, C3-C7cycloalkyl, C2-C6alkenyl or C2-C6alkynyl group each optionally substituted;
• R7 and R8 are each independently H or a C1-C6alkyl, C3-C7cycloalkyl, C2-C6alkenyl or C2-C6alkynyl group each optionally substituted;
• m and n are each independently 0 or an integer of 1, 2 or 3;
• p is 0 or an integer of 1 or 2;
• R9, R10, R11, and R12 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, SOxR17, NR18R19, OR20, COR21 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• R13, R14, R17 and R21, are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15, R16, R18 and R19 are each independently H or an optionally substituted C1-C4alkyl group or R15 and R16 or R18 and R19 may be taken together with the atom to which they are attached to form a 5- to 7-membered ring optionally containing another heteroatom selected from O, NR22 or SOq;
• R20 is a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• x and q are each independently 0 or an integer of 1 or 2;
• and
• R22 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteraryl group each optionally substituted;
• or
• the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

A process for the preparation of a compound of formula

• wherein
• W is N;
• X is N or CR9;
• Y is N or CR10;
• Z is N or CR11;
• Q is N or CR12 with the proviso that at least one and not more than two of X, Y, Z and Q must be N;
• R1 is an optionally substituted C1-C6alkyl, C3-C7cycloalkyl, aryl, or heteroaryl group or an optionally substituted 8- to 13-membered bicyclic or tricyclic ring system having a N atom at the bridgehead and optionally containing 1, 2 or 3 additional heteroatoms selected from N, O or S;
• R2 is H, halogen, or a C1-C6alkyl, C1-C6alkoxy, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• R3 and R4 are each independently H or an optionally substituted C1-C6alkyl group;
• R5 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R6 is a C1-C6alkyl, C3-C7cycloalkyl, C2-C6alkenyl or C2-C6alkynyl group each optionally substituted;
• R7 and R8 are each independently H or a C1-C6alkyl, C3-C7cycloalkyl, C2-C6alkenyl or C2-C6alkynyl group each optionally substituted;
• m and n are each independently 0 or an integer of 1, 2 or 3;
• p is 0 or an integer of 1 or 2;
• R9, R10, R11, and R12 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, SOxR17, NR18R19, OR20, COR21 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• R13, R14, R17 and R21, are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15, R16, R18 and R19 are each independently H or an optionally substituted C1-C4alkyl group or R15 and R16 or R18 and R19 may be taken together with the atom to which they are attached to form a 5- to 7-membered ring optionally containing another heteroatom selected from O, NR22 or SOq;
• R20 is a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• x and q are each independently 0 or an integer of 1 or 2;
• and
• R22 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteraryl group each optionally substituted
• which process comprises reacting a compound of formula II
• wherein W, X, Y, Z and Q are described hereinabove with a protected azacyclic compound of formula III
• wherein L represents a leaving group;
• P represents a protecting group and R3, R4, R6, R7, R8, n, m and p are as described hereinabove in the presence of a first base to give the protected amine of formula I;
• and deprotecting said amine to give the compound of formula I wherein R5 is H optionally alkylating said formula I compound with a compound, R5-L′, wherein L′ is a leaving group in the presence of a second base.