Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-07-26
2000-03-28
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514404, 540575, 544364, 544371, 5483717, 546211, 5462754, A61K 31415, A61K 31496, C07D23140, C07D40312
Patent
active
060432462
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention is useful in the field of medicines. More specifically, novel pyrazole derivatives of the present invention are useful as neuropeptide Y receptor antagonists and as agents for the treatment of various diseases of circulatory organs, central nervous system and metabolic system.
BACKGROUND OF THE INVENTION
Neuropeptide Y (to be referred to as NPY hereinafter) is a peptide consisting of 36 amino acids, which was isolated from porcine brain for the first time by Tatemoto et al. in 1982 [Nature, vol.296, p.659 (1982)]. NPY is broadly distributed in central nervous and peripheral nervous systems and has various in vivo functions as one of the peptides most abundantly present in the nervous system. That is, in the central nervous system, NPY acts as an aperitive and significantly promotes a fat accumulation via secretion of various hormones and actions of the nervous system. It is known that a continuous intracerebroventricular administration of NPY induces obesity and insulin resistance based on the above actions. NPY is also associated with the control of mood and functions of the central autonomic nervous system. In addition, in the peripheral nervous system, NPY is present together with norepinephrine in the sympathetic nerve terminal and associated with the tension of the sympathetic nervous system. It is known that a peripheral administration of NPY causes vasoconstriction and enhances actions of other vasoconstrictors including norepinephrine [International Journal of Obesity, vol.19, p.517 (1995); Endocrinology, vol.133, p.1753 (1993); British Journal of Pharmacology, vol.95, p.419 (1988)].
The function of NPY is expressed when it is bound to an NPY receptor present in the central or peripheral nervous system. Therefore, the expression of the function of NPY can be prevented if the binding of NPY to the NPY receptor is inhibited. Consequently, it is expected that compounds capable of inhibiting the binding of NPY to the NPY receptor are useful in the prevention or treatment of various diseases associated with NPY, for example, diseases of circulatory organs such as hypertension, nephropathy, cardiopathy and angiospasm; diseases of central nervous system such as bulimia, depression, epilepsy and dementia; metabolic diseases such as obesity, diabetes and dysendocrisiasis, or glaucoma [Trends in Pharmacological Sciences, vol.15, p.153 (1994)].
Compounds structurally similar to the compounds of the present invention are disclosed in International Publication WO 96/14843, JP 3093774A, JP 2300173A, JP 51146465A and etc. However, these publications do not clearly disclose nor suggest the compound of the present invention. And, an antagonistic action to NPY is not described at all therein.
DISCLOSURE OF THE INVENTION
An object of the present invention is to provide a new medicine having an antagonistic action to NPY.
The present inventors have found that a compound represented by the general formula [I]: ##STR2## wherein A represents a nitrogen atom or a group represented by C--R.sup.5 ; Ar.sup.1 represents an aryl group which may have a substituent selected from the group consisting of a halogen atom and lower alkyl and lower haloalkyl groups; Ar.sup.2 represents an aryl or heteroaryl group which may have a substituent selected from the group consisting of a halogen atom and lower alkyl, lower alkenyl, lower haloalkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower dialkylamino and aryl groups; R.sup.1 represents a hydrogen atom, a lower alkyl group or a bond formed by linking to R.sup.5 ; R.sup.2 represents a hydrogen atom or a lower alkyl group; R.sup.3 and R.sup.4 may be the same or different and each represents a hydrogen atom or a lower alkyl group, or R.sup.3 and R.sup.4 are linked to each other to form an alkylene group containing 2 to 4 carbon atoms which may have a lower alkyl group; and R.sup.5 represents a hydrogen atom or a hydroxyl, lower alkyl or lower alkoxy group or a bond formed by linking to R.sup.1,
Since the compound [I] of the prese
REFERENCES:
patent: 4089962 (1978-05-01), Harrison et al.
Fukami Takehiro
Fukuroda Takahiro
Ihara Masaki
Kanatani Akio
Banyu Pharmaceutical Co. Ltd.
Ramsuer Robert W.
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