Chroman derivatives as 5-hydroxytrytamine-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

• 33
• wherein
• Y is SO2NR9R10 or NR11ZR12;
• Z is SO2, CONH or CSNH;
• R is halogen, CN, OR13, CO2R14, CONR15R16, SOxR17 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloakyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;
• R1, R2, R5, R6, R7, R8 and R11 are each independently H or an optionally substituted C1-C6alkyl group;
• R3 and R4 are each independently H or a C1-C6alkyl, C3-C6cycloalkyl or heterocyclylalkyl group each optionally substituted or R3 and R4 may be taken together with the atom to which they are attached to represent a 3- to 10-membered optionally substituted mono- or bicyclic ring system optionally containing one or two additional heteroatoms selected from N, O or S with the proviso that when R12 is an optionally substituted C1-C6alky or aryl group then R3 and R4 must be other than an optionally substituted C3-C6cycloalkyl or cycloheteroalkyl group;
• m is 0 or an integer of 1, 2 or 3;
• n is an integer of 1, 2, 3 or 4;
• x is 0 or an integer of 1 or 2;
• R9 and R10 are each independently H or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R12 and R17 are each independently a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R13 is H, CO2R18 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl or heteroaryl group each optionally substituted;
• R14 and R18 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloakyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R15 and R16 are each independently H or an optionally substituted C1-C6alkyl group;
• or
• the stereoisomers thereof or a pharmaceutically acceptable salt thereof.

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

• 34
• wherein
• Y is SO2NR9R10 or NR11ZR12;
• Z is SO2, CONH or CSNH;
• R is halogen, CN, OR13, CO2R14, CONR15R16, SOxR17 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;
• R1, R2, R5, R6, R7, R8 and R11 are each independently H or an optionally substituted C1-C6alkyl group;
• R3 and R4 are each independently H or a C1-C6alkyl, C3-C6cycloalkyl or heterocyclylalkyl group each optionally substituted or R3 and R4 may be taken together with the atom to which they are attached to represent a 3- to 10-membered optionally substituted mono- or bicyclic ring system optionally containing one or two additional heteroatoms selected from N, O or S with the proviso that when R12 is an optionally substituted C1-C6alky or aryl group then R3 and R4 must be other than an optionally substituted C3-C6cycloalkyl or cycloheteroalkyl group;
• m is 0 or an integer of 1, 2 or 3;
• n is an integer of 1, 2, 3 or 4;
• x is 0 or an integer of 1 or 2;
• R9 and R10 are each independently H or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R12 and R17 are each independently a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R13 is H, CO2R18 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl or heteroaryl group each optionally substituted;
• R14 and R18 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R15 and R16 are each independently H or an optionally substituted C1-C6alkyl group;
• or
• the stereoisomers thereof or a pharmaceutically acceptable salt thereof.

A process for the preparation of a compound of formula I

• 35
• wherein
• Y is SO2NR9R10 or NR11ZR12;
• Z is SO2, CONH or CSNH;
• R is halogen, CN, OR13, CO2R14, CONR15R16, SOxR17 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;
• R1, R2, R5, R6, R7, R8 and R11 are each independently H or an optionally substituted C1-C6alkyl group;
• R3 and R4 are each independently H or a C1-C6alkyl, C3-C6cycloalkyl or heterocyclylalkyl group each optionally substituted or R3 and R4 may be taken together with the atom to which they are attached to represent a 3- to 10-membered optionally substituted mono- or bicyclic ring system optionally containing one or two additional heteroatoms selected from N, O or S with the proviso that when R12 is an optionally substituted C1-C6alky or aryl group then R3 and R4 must be other than an optionally substituted C3-C6cycloalkyl or cycloheteroalkyl group;
• m is 0 or an integer of 1, 2 or 3;
• n is an integer of 1, 2, 3 or 4;
• x is 0 or an integer of 1 or 2;
• R9 and R10 are each independently H or a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R12 and R17 are each independently a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• R13 is H, CO2R18 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl or heteroaryl group each optionally substituted;
• R14 and R18 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• and
• R15 and R16 are each independently H or an optionally substituted C1-C6alkyl group
• which process comprises reacting a compound of formula XIII
• 36
• wherein Y, m, n, R, R1, R2, R5, R6, R7 and R8 are as defined above and Hal is Cl, Br or I with an amine, HNR3R4, at an elevated temperature optionally in the presence of a solvent to give the desired product of formula I.