Aryl fused 2,4-disubstituted pyridines: NK3 receptor ligands
AssigneeNeurogen Corporation
InventorsJun Yuan, George Maynard, Alan Hutchison
Life of this patent
Estimating the term…
Abstract
Disclosed are compounds of formula (I) or pharmaceutically acceptable non-toxic salts or pharmaceutically acceptable solvates thereof wherein: (II) represents (a), (b), (c) or (d) and W, X, Y, A, B, C, D, E are variables as described herein. These compounds are highly selective agonists or antagonists at NK3 receptors or prodrugs thereof. The novel tachykinin NK-3 receptor antagonists contained in this invention have potential utility in the treatment of a broad array of disorders and diseases of the central nervous system (CNS) and periphery in mammals in which activation of NK-3 receptors is of importance.
Claims27
A compound of the formula:
- or pharmaceutically acceptable non-toxic salts or pharmaceutically acceptable solvates thereof wherein:
- Y is
- hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms,
- halogen, amino, hydroxyl, or lower alkoxy having 1-6 carbon atoms;
- or
- Y is
- straight or branched chain lower alkyl having 1-6 carbon atoms or lower alkoxy having 1-6 carbon atoms each of which is substituted on the alkyl chain with an amino or mono or dialkylamino group where each alkyl is independently lower alkyl;
- W is
- phenyl, thienyl, or pyridyl, each of which may be mono or disubstituted with halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms, amino, or mono or dialkylamino where each alkyl is straight or branched chain lower alkyl having 1-6 carbon atoms;
- or
- R1, R3 and R4 are the same or different and represent
- hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, amino, mono or dialkylamino where each alkyl is straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms:
- X is dihydroimidazolyl, —CONR6R7, or —NR7COR6;
- R6 is C3-C8)cycloalkyl(C1-C6)alkyl, alkyl substituted with optionally substituted phenyl, or cycloalkyl fused to phenyl;
- R7 represents hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms;
- or
- R6 and R7 together form a 6-membered ring fused to a benzene to form a tetrahydroisoquinoline group.
4-6. (canceled)
8-19. (canceled)
30-31. (canceled)
34-35. (canceled)
40-43. (canceled)
A packaged pharmaceutical composition comprising a pharmaceutical composition and at least one pharmaceutically acceptable carrier or excipient in a container with instructions for using the composition to treat a patient suffering from anxiety, depression, schizophrenia, obesity or chronic pulmonary obstructive disorder, where the pharmaceutical composition comprises a compound of the formula
- or pharmaceutically acceptable non-toxic salts or pharmaceutically acceptable solvates thereof wherein:
- Y is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, halogen, amino, hydroxyl, or lower alkoxy having 1-6 carbon atoms;
- or
- Y is straight or branched chain lower alkyl having 1-6 carbon atoms or lower alkoxy having 1-6 carbon atoms each of which is substituted on the alkyl chain with an amino or mono or dialkylamino group where each alkyl is independently lower alkyl;
- W is phenyl, thienyl, or pyridyl, each of which may be mono or disubstituted with halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms, amino, or mono or dialkylamino where each alkyl is straight or branched chain lower alkyl having 1-6 carbon atoms;
- R1, R3 and R4 are the same or different and representhydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, amino, mono or dialkylamino where each alkyl is straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms:
- X is dihydroimidazolyl, —CONR6R7, or —NR7COR6;
- and
- R6 is C3-C8)cycloalkyl(C1-C6)alkyl, alkyl substituted with optionally substituted phenyl, or cycloalkyl fused to phenyl;
- R7 represents hydrogen or straight or branched chain lower alkyl having 1-6 carbon atoms;
- or
- R6 and R7 together form a 6-membered ring fused to a benzene to form a tetrahydroisoquinoline group.
(canceled)
Dependencies are inferred from the claim text.