1-Heterocyclylalkyl-3-sulfonyl-indole or -indazole 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

• 27
• wherein
• W is N or CR2;
• R is halogen, CN, OCO2R9, CO2R10, CONR11R12, SOxR13, NR14R15, OR16, COR17 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• 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, n and p are each independently 0 or an integer of 1, 2 or 3;
• q and x are each independently 0 or an integer of 1 or 2;
• R9, R10, R13 and R17 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R11 and R12 are each independently H or an optionally C1-C6alkyl group or R11 and R12 may be taken together with the atom to which they are attached to form a 5- to 7-member ring optionally containing another heteroatom selected from O, N or S;
• R14 and R15 are each independently H or an optionally substituted C1-C4alkyl group or R14 and R15 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, NR18 or SOx;
• R16 is a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R18 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl 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

• 28
• wherein
• W is N or CR2;
• R is halogen, CN, OCO2R9, CO2R10, CONR11R12, SOxR13, NR14R15, OR16, COR17 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• 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, n and p are each independently 0 or an integer of 1, 2 or 3;
• q and x are each independently 0 or an integer of 1 or 2;
• R9, R10, R13 and R17 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R11 and R12 are each independently H or an optionally C1-C6alkyl group or R11 and R12 may be taken together with the atom to which they are attached to form a 5- to 7-member ring optionally containing another heteroatom selected from O, N or S;
• R14 and R15 are each independently H or an optionally substituted C1-C4alkyl group or R14 and R15 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, NR18 or SOx;
• R16 is a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R18 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• or
• the stereoisomers thereof or the pharmaceutically acceptable salts thereof.

A process for the preparation of a compound of formula I

• 29
• wherein
• W is N or CR2;
• R is halogen, CN, OCO2R9, CO2R10, CONR11R12, SOxR13, NR14R15, OR16, COR17 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, aryl or heteroaryl group each optionally substituted;
• 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, n and p are each independently 0 or an integer of 1, 2 or 3;
• q and x are each independently 0 or an integer of 1 or 2;
• R9, R10, R13 and R17 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R11 and R12 are each independently H or an optionally C1-C6alkyl group or R11 and R12 may be taken together with the atom to which they are attached to form a 5- to 7-member ring optionally containing another heteroatom selected from O, N or S;
• R14 and R15 are each independently H or an optionally substituted C1-C4alkyl group or R14 and R15 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, NR18 or SOx;
• R16 is a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R18 is H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• which process comprises reacting a compound of formula VIII
• 30
• wherein W, R, R1 and m are as described hereinabove with a protected azacyclic compound of formula IX
• 31
• wherein P is a protecting group;
• L is a leaving group;
• and R3, R4, R6, R7, R8, n, p and q are as described hereinabove in the presence of a first base to give the protected formula I compound;
• and deprotecting said compound to give the free amine of formula I wherein R5 is H optionally alkylating said amine with an alkylating agent, R5—L′, wherein L′ is a leaving group in the presence of a second base.