Indolylalkylidenehydrazine-carboximidamide 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

• 34
• wherein
• X is N or CR3;
• Y is N or CR4;
• Q is SO2, CO, CO2, CONR or CSNR12;
• R1, R2, R3 and R4 are each independently H, halogen, CN, OCO2R13, CO2 R14, CONR15 R16, NR17SO2R18, NR19COR28, SOnR20, NR21R22, OR23, COR24 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R5, R6 and R7 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C12cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R5 and R6 maybe taken together with the atoms to which they are attached to form an optionally substituted 5-to 7-membered ring;
• R8 is H or a C1-C6alkyl or C3-C10cycloalkyl group each optionally substituted;
• R9 is H, halogen, CN, NO2, NR25R26, OR27 or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted or R8 and R9 may be taken together with the atoms to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing one or two heteroatoms selected from O, N or S;
• R10 is a C1-C6alkyl, aryl or heteroaryl group each optionally substituted 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 R8 is H or C0-C6alkyl and Q is CO then R10 must be other than C1-C6alkyl or aryl;
• n 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, R18, R20, R23, R24, R27 and R28 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, R19, R21, R22, R25 and R26 are each independently H or an optionally substituted C1-C4alkyl group or R2, 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, the tautomers 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

• 35
• wherein
• X is N or CR3;
• Y is N or CR4;
• Q is SO2, CO, CO2, CONR or CSNR12;
• R1, R2, R3 and R4 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, NR17SO2R18, NR19COR28, SOnR20, NR21R22, OR23, COR24 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R5, R6 and R7 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C12cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R5 and R6 maybe taken together with the atoms to which they are attached to form an optionally substituted 5- to 7-membered ring;
• R8 is H or a C1-C6alkyl or C3-C10cycloalkyl group each optionally substituted;
• R9 is H, halogen, CN, NO2, NR25R26, OR27 or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted or R8 and R9 may be taken together with the atoms to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing one or two heteroatoms selected from O, N or S;
• R10 is a C1-C6alkyl, aryl or heteroaryl group each optionally substituted 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 R8 is H or C1-C6alkyl and Q is CO then R10 must be other than C1-C6alkyl or aryl;
• n 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, R18, R20, R23, R24, R27 and R28 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, R19, R21, R22, R25 and R26 are each independently H or an optionally substituted CO1—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, the tautomers thereof or the pharmaceutically acceptable salts thereof.

A process for the preparation of a compound of formula I

• 36
• wherein
• X is N or CR3;
• Y is N or CR4;
• Q is SO2, CO, CO2, CONR or CSNR12;
• R1, R2, R3 and R4 are each independently H, halogen, CN, OCO2R13, CO2R14, CONR15R16, NR17SO2R18, NR19COR28, SOR20, NR21R22, OR23, COR24 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R5, R6 and R7 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C12cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R5 and R6 maybe taken together with the atoms to which they are attached to form an optionally substituted 5- to 7-membered ring;
• R8 is H or a C1-C6alkyl or C3-C10cycloalkyl group each optionally substituted;
• R9 is H, halogen, CN, NO2, NR25R26, OR27 or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted or R8 and R9 may be taken together with the atoms to which they are attached to form an optionally substituted 5- to 7-membered ring optionally containing one or two heteroatoms selected from O, N or S;
• R10 is a C1-C6alkyl, aryl or heteroaryl group each optionally substituted 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 R8 is H or C1-C6alkyl and 0 is CO then R10 must be other than C1-C6alkyl or aryl;
• n 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, R18, R20, R23, R24, R27 and R28 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, R19, R21, R22, R25 and R26 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 XIV
• 37
• wherein Q, X, Y, R1, R2, R8, R9 and R10 are described hereinabove with an aminoguanidine derivative of formula V
• 38
• wherein R5, R6 and R7 are described hereinabove in the presence of an acid optionally in the presence of a solvent.