Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-12-29
1999-07-13
Mach, D. Margaret M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
546 17, 546 15, 546 18, 514278, C07D21100, C07D21500, C07D40100
Patent
active
059228750
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new aromatic acid amide derivatives which may be represented by the general formula (I) shown below: ##STR2## in which:
Ar is or di-substituted with a group selected independently from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, phenyl, cyano, nitro, amino, hydroxyl, halogens such as fluorine, chlorine, bromine, trifluoromethyl or
n.sub.1 is selected independently from 1 and 2;
n.sub.2 is selected independently from 0 (zero) and 1;
Y is selected independently from CH.sub.2 and O (oxygen);
m, r and t are integers independently selected one from the others, having a value from 0 (zero) to 2;
z is 0 (zero) or 1;
R.sub.1 is selected independently from H (hydrogen) and methyl
R.sub.2 is selected independently from a phenyl group unsubstituted or mono- or di-substituted with methyl or with chlorine, a 1- (or 2-)naphthyl, a 2-(or 3-) indolyl, a 2-(or 3-)quinolinyl group. (I) may be, independently, D (dextro), L (laevo) or DL (racemic). Preferably the two amide groups bonded directly to Ar are in the ortho positions to each other and Ar is preferably naphthyl or the group 3, 5-dimethylphenyl; Y is CH.sub.2, n.sub.1 is 1 and n.sub.2 is 0 (zero); R.sub.1 is H (hydrogen) and R.sub.2 is 1-naphthyl; m and r are both 1; t and z are both 0 (zero).
The compounds of the present invention have been shown to be powerful antagonists to the gastrin receptors at the peripheral level, that is in the gastrointestinal system, and on cholecystokinin (CCK) receptors in the central nervous system (CCK-B-antagonists). It may thus be thought that they may be usable to advantage in the treatment of various illnesses in man linked to imbalances in the physiological levels of gastrin and CCK or other bioactive polypeptides correlated therewith, both in the gastrointestinal tract and the central nervous system (CNS) or other organs or systems in which these bioactive peptides play a physiological or pathological role. Thus, for example, one may foresee an advantageous use of these compounds in the treatment, at the gastrointestinal level, of illnesses linked to disturbances in motility and mucous trophism such as, for example, gastritis, peptic ulcers, colitis and certain forms of gastrointestinal tumours supported by gastrin or polypeptide hormones correlated therewith, and at the level of the CNS for treating mental disorders such as anxiety, panic attacks, psychosis, such as, for example schizophrenia, depression, anorexia etc. Another use could be in the treatment and prevention of some pathological conditions of the eye such as, for example, myosis induced during surgical treatment for cataract or chronic eye inflammation or other disorders of the sensory organs.
Pharmaceutical forms of the compounds which are the subject of the invention may be prepared by conventional techniques as, for example, tablets, capsules, suspensions, solutions and suppositories, or patches and may be administered orally, parenterally, rectally, to the eyes or transdermally or in other forms suitable for achieving the therapeutic effect, for example as solid preparations for oral use with a protracted action which allow the controlled release of the active ingredient over a period of time.
The active ingredient is administered to the patient typically in doses of from 0.01 to 10 mg/kg body weight per dose. For parenteral and ocular administration it is preferable to use a water-soluble salt of the compounds in question, such as the sodium salt or another non-toxic and pharmaceutically acceptable salt. The inactive ingredients used may be those substances commonly used in pharmaceutical preparations as eccipients, binders, aromatising compounds, dispersants, colouring agents, humectants etc.
The process for the preparation of the derivatives of the invention consists of a series of reactions including: ##STR3## in which Ar and R.sub.1 have the meanings given above with a quantity of carbobenzoxy chloride (Z--Cl) under Schotten-Bauman conditions at a temperature of 0 to 15.degree. C. to give the acid carbamates of formula
Makovec Francesco
Peris Walter
Rovati Lucio C.
Rovati Luigi A.
M. Mach D. Margaret
Rotta Research Laboratorium S.p.A.
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