Patent CA-2591415-A1 (CA)
Title: N-pyrrolidin-3-yl-amide derivatives as serotonin and noradrenalin re-uptake inhibitors
Inventor: ANDREWS MARK DAVID
IPC: C07D211/58
Filed: 2005-12-08
Abstract: A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein: R1 is H, C1-6alkyl, -C(A)Y, C3-8cycloalkyl, aryl, het, aryl-C1-4alkyl or het-Cl-4alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted; A is S or O; Y is H, C1-6alkyl, aryl, het, aryl-C1-4alkyl or het~-C1-4alkyl; aryl is independently selected from phenyl, naphthyl, anthracyl or phenanthryl; het is independently selected from an aromatic or non-aromatic 4-, 5- or 6- membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6- membered carbocyclic group or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom; R2 is aryl1 or het1, each optionally substituted; aryl1 is independently selected from phenyl, naphthyl, anthracyl, phenanthryl, or indanyl; het1 is an aromatic 5 to 10 membered heterocyclic ring system which contains at least one N, O or S heteroatom, optionally containing an aryl group; R3 is H, C1-8alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, C1-8alkylSC1-8alkyl, het3, or het3-C1-4alkyl, wherein the alkyl, cycloalkyl and het3 groups are each optionally substituted; het3 is a non-aromatic 4-, 5- or 6- membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6- membered carbocyclic group or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S  heteroatom; or R3 is (CH2)a ,K, wherein a' is 0, 1 or 2 and K is a group selected from: Formula (i) wherein: Z is O, S, NR12, (CH2)V or a bond; a is 1, 2, 3 or 4; b is 1, 2 or 3; v is 1 or 2; R10 and R11 are each independently H  or C1-4alkyl; R12 is H, C1-6 alkyl, C(O)C1-6 alkyl, SO2-C1-6 alkyl; and wherein one or more pairs of hydrogen atoms on adjacent carbon or nitrogen atoms may be replaced by a corresponding number of double bonds, provided the ring system is not aromatic; Formula (ii) a carbocyclic spiro group containing 6 to 12 carbon atoms; Formula(iii) wherein: c is 1, 2, 3 or 4; d is 1, 2 or 3;  e is 1 or 2; and R30 is H or C1-4 alkyl; and wherein one or more pairs of hydrogen atoms on adjacent carbon atoms may be replaced by a corresponding number of double bonds, provided the ring system is not aromatic; Formula (iv) wherein: f is 0, 1, 2 or 3; L is SO, SO2 or NR40;and R40 is H, C1-6 alkyl, C(O)C1-6alkyl, SO2-C1-6alkyl; and wherein one or more pairs of hydrogen atoms on adjacent carbon atoms may be replaced by a corresponding number of double bonds, provided the ring system is not aromatic; Formula (v) wherein: g is 0, 1, 2 or 3; and R50 is H, C1-8alkyl, C1-8alkoxy, OH, halo, CF3, OCHF2, OCF3,SCF3, hydroxy-C1-6alkyl, C1-4alkoxy-C1-6alkyl and C1-4alkyl-S-C1-4alkyl;  and Formula (vi) CH(cyclopropane)2; X is a covalent bond, C1-8alkyl or C3-8cycloalkyl, wherein if X is C3-8cycloalkyl, then R2-X may form a fused aryl-cycloalkyl ring system; and n is 1 or 2, provided that when n is 1, m is 0 or 1 and when n is 2, m is 0, wherein if m is 0, then * represents a chiral centre.