Azaindolylalkylamine derivatives as 5-hydroxytryptamine-6 ligands

A method for the treatment of a disorder of the central nervous system 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

• 31
• wherein
• W is SO2, CO, CONR11 or CSNR12;
• X is N or CR1;
• Y is N or CR2;
• Z is N or CR3;
• Q is N or CR4 with the proviso that no more than two of X, Y, Z and Q may be N;
• n is an integer of 2 or 3;
• R1, R2, R3 and R4 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, CNR17NR18R19, SOmR20, NR21R22, OR23, COR24 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R5 and R6 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted, or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S;
• R7 and R8 are each independently H or an optionally substituted C1-C6alkyl group;
• R9 is H, halogen, or a C1-C6alkyl, C1-C6alkoxy, aryl or heteroaryl group each optionally substituted;
• R10 is an optionally substituted C1-C6alkyl, 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 with the proviso that when Q is N and X, Y and Z are CH then R10 must be other than phenyl;
• m is 0 or an integer of 1 or 2;
• R11 and R12 are each independently H or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R13, R14, R20, R23 and R24 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15, R16 are each independently H or an optionally substituted C1-C6alkyl group;
• and
• R17, R18, R19 R21 and R22 are each independently H or an optionally substituted C1-C4alkyl group;
• or R21 and R22 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, N or S;
• 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

• 32
• wherein
• W is SO2, CO, CONR11 or CSNR12;
• X is N or CR1;
• Y is N or CR2;
• Z is N or CR3;
• Q is N or CR4 with the proviso that no more than two of X, Y, Z and Q may be N;
• n is an integer of 2 or 3;
• R1, R2, R3 and R4 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, CNR17NR18R19, SOmR20, NR21R22, OR23, COR24 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R5 and R6 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted, or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S;
• R7 and R8 are each independently H or an optionally substituted C1-C6alkyl group;
• R9 is H, halogen, or a C1-C6alkyl, C1-C6alkoxy, aryl or heteroaryl group each optionally substituted;
• R10 is an optionally substituted C1-C6alkyl, 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 with the proviso that when Q is N and X, Y and Z are CH then R10 must be other than phenyl;
• m is 0 or an integer of 1 or 2;
• R11 and R12 are each independently H or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R13, R14, R20, R23 and R24 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15, and R16 are each independently H or an optionally substituted C1-C6alkyl group;
• and
• R17, R18, R19, R21 and R22 are each independently H or an optionally substituted C1-C4alkyl group;
• or R21 and R22 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, N or S;
• or
• the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

A process for the preparation of a compound of formula Ib

• 33
• wherein
• X is N or CR1;
• Y is N or CR2;
• Z is N or CR3;
• Q is N or CR4 with the proviso that no more than two of X, Y, Z and Q may be N;
• n is an integer of 2 or 3;
• R1, R2, R3 and R4 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, CNR17NR18R19, SOmR20, NR21R22, OR23, COR24 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R5 and R6 are each independently a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted, or R5 and R6 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing an additional heteroatom selected from O, N or S;
• R7 and R8 are each independently H or an optionally substituted C1-C6alkyl group;
• R9 is H, halogen, or a C1-C6alkyl, C1-C6alkoxy, aryl or heteroaryl group each optionally substituted;
• R10 is an optionally substituted C1-C6alkyl, 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 with the proviso that when Q is N and X, Y and Z are CH then R10 must be other than phenyl;
• m is 0 or an integer of 1 or 2;
• R11 and R12 are each independently H or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R13, R14, R20, R23 and R24 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R15, and R16 are each independently H or an optionally substituted C1-C6alkyl group;
• and
• R17, R18, R19, R21 and R22 are each independently H or an optionally substituted C1-C4alkyl group;
• or R21 and R22 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, N or S
• which process comprises reacting a compound of formula II
• 34
• wherein X, Y, Z, Q, n, R5, R6, R7, R8 and R9 are as defined hereinabove for formula Ib with a sulfonyl chloride R10SO2Cl, in the presence of a base optionally in the presence of a solvent.