Pyridyl imidazole derivatives and processes for the preparation

Details Pyridyl imidazole derivatives and processes for the preparation Pyridyl imidazole derivatives and processes for the preparation

1996-12-08

1997-11-25

Dentz, Bernard

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546118, A61K 31435, C07D47104

Patent

active

056913486

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/KR/00075 filed Jun. 7, 1995.


FIELD OF THE INVENTION

The present invention relates to novel pyridyl imidazole derivatives substituted with N-oxide, processes for preparing them and pharmaceutical compositions containing same as active ingredients.


DESCRIPTION OF THE PRIOR ART

Various imidazole derivatives, which can inhibit the action of angiotensin II, have been used for the treatment of hypertension caused by angiotensin II. Angiotensin II is produced by an angiotensin converting enzyme from angiotensin I, which is formed from angiotensinogen by the action of renin. Angiotensin II, which is a potent vaso-constrictor interacting with specific receptors on cell membrane, has been reported to cause hypertension in mammals including human beings.
Many studies have been made to search for an antagonist which inhibits the action of angiotensin II on the receptors of its target cell in order to suppress the elevation of blood pressure. As a result, many imidazole derivatives have been developed (see A. T. Chiu et al., Eur. J. Pharm., 157, 13(1981); P. C. Wong et al., J. Pharmacol. Exp. Ther., 247, 1(1988); and, P. C. Wong et al., Hypertension, 13, 489(1989)).
As a representative of these compounds, for example, D. J. Carini et al. reported in J. Med. Chem., 34, 2525(1990) imidazole derivatives of the following formula(A): ##STR3##
Further, EP No. 400,974 discloses imidazole derivatives of the following formula(B): ##STR4## wherein: --A'--B'--C'--D'-- represents the constituent atoms of a 6-membered heterocycle having 1 to 3 nitrogen atoms such as --C(R.sup.7).dbd.C(R.sup.7)--C(R.sup.7).dbd.N-- wherein each of R.sup.7 's is independently a hydrogen atom, or a substituted alkyl or aryl group or heterocycle (e.g., --C(CH.sub.3).dbd.CH--C(CH.sub.3).dbd.N--).
Despite these discoveries, however, needs have continued to exist for the development of more effective agents which possess enhanced antagonistic properties against angiotensin II.


SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to provide novel pyridyl imidazole derivatives of formula(I) and pharmacologically acceptable salts thereof, having an enhanced ability to suppress the activity of angiotensin II: ##STR5## wherein: A is a straight, branched or cyclic C.sub.1 -C.sub.6 alkyl or alkenyl group, OR.sup.1 (wherein R.sup.1 is a hydrogen, or a straight, branched or cyclic C.sub.1 -C.sub.6 alkyl or alkenyl radical), or NR.sup.2 R.sup.3 (wherein R.sup.2 and R.sup.3 are independently a hydrogen, or a straight, branched or cyclic C.sub.1 -C.sub.6 alkyl radical); ##STR6## D is a hydrogen; a halogen; a straight, branched or cyclic C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl group which is optionally substituted with OH, a C.sub.1 -C.sub.4 alkoxy radical, CO.sub.2 R.sup.1, COR.sup.1, CON(R.sup.1).sub.2 or N(R.sup.1).sub.2, wherein R.sup.1 is the same as defined above; tetrazol-5-yl; a perfluoro-C.sub.1 -C.sub.4 alkyl group; or N(R.sup.1).sub.2, OR.sup.1, CO.sub.2 R.sup.1 or CON(R.sup.1).sub.2, wherein R.sup.1 is the same as defined above; C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl group which is optionally substituted with OH, a C.sub.1 -C.sub.4 alkoxy radical, CO.sub.2 R.sup.1, COR.sup.1, CON(R.sup.1).sub.2 or N(R.sup.1).sub.2, wherein R.sup.1 is the same as defined above; a perfluoro-C.sub.1 -C.sub.4 alkyl group; NO.sub.2 ; or N(R.sup.1).sub.2 or OR.sup.1, wherein R.sup.1 is the same as defined above; and n is 0 or an integer of 1 to 4.
Another object of the present invention is to provide processes for preparing the inventive derivatives, and to provide pharmaceutical compositions containing same as active ingredients.


DESCRIPTION OF THE DRAWING

FIG. 1 is a HPLC chart showing the result of the enzyme digestion test of a reference "Merck" compound (FIG. 1A) and a compound prepared in Example 3 (FIG. 1B), respectively.


DETAILED DESCRIPTION OF THE INVENTION

Among the compounds of formula(I), preferred are those wherein: OR.sup.1 (wherein R.sup.1 is

REFERENCES:
patent: 5332744 (1994-07-01), Chakravarty et al.

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