Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-04-29
1999-05-04
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514255, 544295, 544360, 544374, 544377, 544379, 544392, 544393, 544394, 544364, A61K 31495, C07D295096, C07D40704, C07D40904
Patent
active
059004150
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to certain substituted benzylamine derivatives which selectively bind to human Neuropeptide Y1 (NPY1) receptors. This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds and compositions in treating feeding disorders and certain cardiovascular diseases.
2. Description of the Related Art
Neuropeptide Y, a peptide first isolated in 1982, is widely distributed in the central and peripheral neurons and is responsible for a multitude of biological effects in the brain and the periphery. Various animal studies have shown that activation of Neuropeptide Y.sub.1 receptors is related to vasoconstriction, Wahlestedt et al., Regul. Peptides, 13: 307-318 (1986), McCauley and Westfall, J. Pharmacol. Exp. Ther. 261: 863-868 (1992), and Grundemar et al., Br. J. Pharmacol. 105: 45-50 (1992); and to stimulation of consummatory behavior, Flood and Morley, Peptides, 10: 963-966 (1989). Leibowitz and Alexander, Peptides, 12: 1251-1260 (1991), and Stanley et al., Peptides, 13: 581-587 (1992). animals, Neuropeptide Y is a powerful stimuli of food intake, and an inducer of vasoconstriction leading to hypertension. They further point out that low levels of Neuropeptide Y is associated with loss of appetite. These reports clearly indicate that compounds that inhibit the activity of this protein will reduce hypertension and appetite in animals.
SUMMARY OF THE INVENTION
Compounds that interact with NPY1 receptors and inhibit the activity of Neuropeptide Y at those receptors are useful in treating eating disorders such as, for example, obesity and bulimia, and certain cardiovascular diseases, such as, for example, hypertension.
This invention provides novel compounds of Formula I which selectively bind to Neuropeptide Y.sub.1 (NPY1) receptors. Such compounds are useful in treating feeding disorders such as obesity and bulimia as well as certain cardiovascular diseases such as essential hypertension.
The invention also provides pharmaceutical compositions comprising compounds of Formula I. The invention thus further relates to the use of such compounds and compositions in the treatment of eating as well as certain cardiovascular diseases. Accordingly, a broad embodiment of the invention is directed to a compound of Formula I: ##STR2## where Ar is an aryl group disubstituted carbon atom; hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms; branched chain lower alkyl having 1-6 carbon atoms; and straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms.
These compounds are highly selective partial agonists or antagonists at human NPY1 receptors and are useful in the diagnosis and treatment of feeding disorders such as obesity and bulimia as well as certain cardiovascular diseases such as essential hypertension and congestive heart failure.
DETAILED DESCRIPTION OF THE INVENTION
The novel compounds encompassed by the instant invention can be described by general formula I: ##STR3## where Ar is an aryl group preferably selected from the group consisting of phenyl, 2-, 3-, or 4-pyridyl, 2- or 3-thienyl, 2-, 4- or 5-pyrimidyl, each of which is optionally mono- or disubstituted with halogen, hydroxy, or straight or branched chain lower alkyl having 1-6 carbon atoms; hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms; straight or branched chain lower alkyl having 1-6 carbon atoms; straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms; atoms. phenyl, 2-, 3-, or 4-pyridyl, or phenyl, 2-, 3-, or 4-pyridyl straight or branched chain lower alkyl having 1-6 carbon atoms; and 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms, phenyl, 2-, 3-
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Blum Charles Albert
Cai Guolin
Hutchison Alan Jeffrey
Peterson John Matthew
Benson Gregg C.
Bernhardt Emily
Brokke Mervin E.
Pfizer Inc.
Richardson Peter C.
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