US 7,592,346 B2
Quinoline and quinazoline derivatives having affinity for 5HT1-type receptors
Markus Bergauer, Verona (Italy); Barbara Bertani, Verona (Italy); Matteo Biagetti, Verona (Italy); Steven Mark Bromidge, Verona (Italy); Alessandro Falchi, Verona (Italy); Colin Philip Leslie, Verona (Italy); Giancarlo Merlo, Verona (Italy); Domenica Antonia Pizzi, Verona (Italy); Marilisa Rinaldi, Verona (Italy); Luigi Piero Stasi, Verona (Italy); Jessica Tibasco, Veroa (Italy); Antonio Kuok Keong Vong, Harlow (United Kingdom); and Simon Edward Ward, Harlow (United Kingdom)
Assigned to Glaxo Group Limited, Greenford, Middlesex (United Kingdom)
Filed on Jul. 02, 2008, as Appl. No. 12/166,547.
Application 12/166547 is a continuation of application No. 11/687098, filed on Mar. 16, 2007, granted, now 7,459,456.
Application 11/687098 is a continuation of application No. 10/565066, granted, now 7,279,481, previously published as PCT/EP2004/008000, filed on Jul. 15, 2004.
Claims priority of application No. 0316915.8 (GB), filed on Jul. 18, 2003.
Prior Publication US 2008/0280919 A1, Nov. 13, 2008
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/496 (2006.01); A61K 31/517 (2006.01)
U.S. Cl. 514—253.06  [514/252.17] 25 Claims
 
1. A method of treatment of depression or anxiety in a human in need thereof which comprises administering to said human an effective amount of:
a compound of formula (Ib), or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Drawing
wherein:
R1 is halogen, cyano, C1-6alkyl, C1-6alkoxy, haloC1-6alkoxy or haloC1-6alkyl;
X is N or CH;
R3 and R4 are independently hydrogen, C1-6alkyl, C1-6alkylsulfonyl, a group having the formula (IIa):

OG Complex Work Unit Drawing
wherein A is oxygen or sulfur, D is —(CH2)t—, —(CH2)tO— or —O(CH2)t—, wherein t is 0, 1, 2, 3 or 4; and E is C1-6alkyl; C3-7cycloalkyl, optionally substituted by one or more substituents independently selected from halogen, hydroxy, oxo, C1-6alkyl, cyano, CF3, OCF3, C1-6alkoxy and C1-6alkanoyl; or aryl, optionally substituted by one or more substituents independently selected from halogen, C1-6alkyl, CF3, cyano, hydroxy, C1-6alkanoyl, and C1-6alkoxy;
or a group having the formula (IIb)

OG Complex Work Unit Drawing
wherein A is oxygen or sulfur, D is —(CH2)t—, —(CH2)tO— or —O(CH2)t—, wherein t is 0, 1, 2, 3 or 4; and E is C1-6alkyl; C3-7cycloalkyl, optionally substituted by one or more substituents independently selected from halogen, hydroxy, oxo, C1-6alkyl, cyano, CF3, OCF3, C1-6alkoxy and C1-6alkanoyl; or aryl optionally substituted by one or more substituents independently selected from halogen, C1-6alkyl, CF3, cyano, hydroxy, C1-6alkanoyl, and C1-6alkoxy;
or R3 and R4, together with the nitrogen atom to which R3 and R4 are attached, combine to form a 3-7 membered monocyclic heterocyclic group or a 8-11 membered bicyclic heterocyclic group, wherein each group is optionally substituted by one or more substituents selected from halogen, oxo, C1-6alkyl, cyano, CF3, C1-6alkoxy, C1-6alkanoyl, aryl and arylC1-6alkyl, wherein the aryl and arylC1-6alkyl are further optionally substituted by one or more halogen, oxo, C1-6alkyl, cyano, CF3, C1-6alkoxy and C1-6alkanoyl;
and another active substance selected from the group consisting of a 5HT3 antagonist, a serotonin agonist, an NK-1 antagonist, a selective serotonin reuptake inhibitor, a noradrenaline re-uptake inhibitor, a tricyclic antidepressant, and a dopaminergic antidepressant.