Chroman and benzofuran 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 said patient with a therapeutically effective amount of a compound of formula I

• wherein
• R is a substituted C1-C6alkyl group or an aryl or heteroaryl group each optionally substituted;
• R1 is halogen, CN, OR7, CO2R8, CONR9R10, SOxR11 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;
• R2 R3 and R4 are each independently H or an optionally substituted C1-C6 alkyl group with the proviso that when R is a substituted C1-C6alkyl group then R2 R3 and R4 must be H;
• R5 and R6 are each independently H or a C1-C6alkyl, C3-C6cycloalkyl or heterocyclylalkyl group each optionally substituted or R5 and R6 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 R is a substituted C1-C6alkyl group then R5 and R6 must be other than a C3-C6cycloalkyl or cycloheteroalkyl group;
• m is an integer of 1, 2, 3 or 4;
• n is 0 or 1;
• p is 0 or an integer of 1, 2 or 3;
• represents a single bond or a double bond;
• x is 0 or an integer of 1 or 2;
• R7 is H, CO2R12 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl or heteroaryl group each optionally substituted;
• R8 and R12 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R9 and R10 are each independently H or an optionally substituted C1-C6alkyl group;
• and
• R11 is a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• 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

• wherein
• R is a substituted C1-C6alkyl group, or an aryl or heteroaryl group each optionally substituted;
• R1 is halogen, CN, OR7, CO2R8, CONR9R10, SOxR11 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;
• R2, R3 and R4 are each independently H or an optionally substituted C1-C6 alkyl group with the proviso that when R is a substituted C1-C6alkyl group then R2, R3 and R4 must be H;
• R5 and R6 are each independently H or a C1-C6alkyl, C3-C6cycloalkyl or heterocyclylalkyl group each optionally substituted or R5 and R6 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 R is a substituted C1-C6alkyl group then R5 and R6 must be other than a C3-C6cycloalkyl or cycloheteroalkyl group;
• m is an integer of 1, 2, 3 or 4;
• n is 0 or 1;
• p is 0 or an integer of 1, 2 or 3;
• represents a single bond or a double bond;
• x is 0 or an integer of 1 or 2;
• R7 is H, CO2R12 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl or heteroaryl group each optionally substituted;
• R8 and R12 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R9 and R10 are each independently H or an optionally substituted C1-C6alkyl group;
• and
• R11 is a C1-C6alkyl, aryl or heteroaryl group each optionally substituted;
• or
• the stereoisomers thereof or a pharmaceutically acceptable salt thereof.

A process for the preparation of a compound of formula I

• wherein
• R is a substituted C1-C6alkyl group, or an aryl or heteroaryl group each optionally substituted;
• R1 is halogen, CN, OR7, CO2R8, CONR9R10, SOxR11 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, phenyl or heteroaryl group each optionally substituted;
• R2, R3 and R4 are each independently H or an optionally substituted C1-C6 alkyl group with the proviso that when R is a substituted C1-C6alkyl group then R2, R3 and R4 must be H;
• R5 and R6 are each independently H or a C1-C6alkyl, C3-C6cycloalkyl or heterocyclylalkyl group each optionally substituted or R5 and R6 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 R is a substituted C1-C6alkyl group then R5 and R6 must be other than a C3-C6cycloalkyl or cycloheteroalkyl group;
• m is an integer of 1, 2, 3 or 4;
• n is 0 or 1;
• p is 0 or an integer of 1, 2 or 3;
• represents a single bond or a double bond;
• x is 0 or an integer of 1 or 2;
• R7 is H, CO2R12 or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, aryl or heteroaryl group each optionally substituted;
• R8 and R12 are each independently H or a C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted;
• R9and R10 are each independently H or an optionally substituted C1-C6alkyl group;
• and
• R11 is a C1-C6alkyl, aryl or heteroaryl group each optionally substituted
• which process comprises reacting a compound of formula II
• wherein R, R1, R2, R3, R4, m, n and p are as defined hereinabove and Hal represents Cl or Br with an amine, HNR5R6, at an elevated temperature optionally in the presence of a solvent to give the desired product of formula I.