Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-10-16
2000-08-01
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544319, C07D40306
Patent
active
060967544
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to N-3 substituted pyrimidin-4-ones with AII antagonistic activity.
The modulation of the renin-angiotensin system (RAS) by means of antagonism of angiotensin II (AII) at the receptor level, recently proved to be a valuable alternative to renin inhibitors or to ACE inhibitors, in the control of blood pressure. Examples of compounds having antagonistic activity of angiotensin II are disclosed in EP-A-0465323. Said compounds are derivatives of 5-diphenylmethyl-pyrimidine. A preceding patent application PCT WO 93/03018 in the Applicant's name disclosed pyrimidinone derivatives having antagonistic properties on the AII receptor, which derivatives have, in particular on the nitrogen atom at the 3-position of the pyrimidinone ring, a benzyl, thienylmethylene or furanylmethylene, substituted by a carboxylic or ester group.
The present invention relates to novel derivatives with a pyrimidinone structure having AII-antagonistic properties, characterized in particular, compared with the above described structures, by the presence of a different heterocycle bound to the 3-position of the pyrimidinone ring and/or of a different substituent bound to the heterocycle itself.
The compounds of the invention have the general formula I ##STR1## wherein: R can be a straight, branched or cyclic lower alkyl of 1 to 5 carbon atoms, optionally substituted by a OR.sub.4 group, wherein R.sub.4 can be hydrogen or a C.sub.1 -C.sub.4 alkyl; or a lower alkenyl group of 1 to 5 carbon atoms, alkyl, hydrogen or a C.sub.1 -C.sub.4 alkyl; a COR.sub.6 group wherein R.sub.6 can be a C.sub.1 -C.sub.4 alkyl or a NR.sub.7 R.sub.8 group wherein R.sub.7 and R.sub.8, which are the same or different, can be hydrogen, C.sub.1 -C.sub.4 alkyl, phenyl or benzyl, wherein m=1,2, with the proviso that at least one be a heteroatom, and they form, together with two carbon atoms, a 5- or 6-membered heterocyclic ring. -C.sub.4 alkyl; a NHSO.sub.2 CF.sub.3 group; a CN group; a NO.sub.2 group; a SO.sub.2 NHR.sub.10 group, wherein R.sub.10 can be hydrogen, COR.sub.11, wherein R.sub.11 can be an optionally substituted phenyl, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 alkoxy, or CONHR.sub.12, wherein R.sub.12 is a straight or branched C.sub.1 -C.sub.4 alkyl; a tetrazol-5-yl group optionally protected by a group preferably selected from the following: triphenylmethyl, tert-butyl, C.sub.1 -C.sub.4 alkoxymethyl, 4-methoxybenzyl, 2,4,6-trimethylbenzyl, tetrahydropyranyl or 2-trimethylsilylethyl.
In the compounds I, R is preferably a straight, branched or cyclic lower alkyl of 1 to 5 carbon atoms, optionally substituted by a OR4 group, wherein R.sub.4 can be hydrogen or a C.sub.1 -C.sub.4 alkyl, and, more preferably, be a C.sub.1 -C.sub.4 alkyl or a NR.sub.7 R.sub.8 group wherein R.sub.7 and R.sub.8, which are the same or different, can be hydrogen, C.sub.1 -C.sub.4 alkyl, and more preferably, is selected from a CN group or a group CONR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8, which are the same or different, can be hydrogen or C.sub.1 -C.sub.4 alkyl, carbon atoms which they are bound to, the following heterocyclic rings: furan, thiophene, thiazole, isothiazole, oxazole, isoxazole, pyridine, pyrimidine, pyrazine, pyridazine, C.sub.1 -C.sub.4 alkyl; a group NHSO.sub.2 CF.sub.3 ; a tetrazol-5-yl group optionally protected by a group preferably selected from the following: triphenylmethyl, tert-butyl, C.sub.1 -C.sub.4 alkoxymethyl, 4-methoxybenzyl, 2,4,6-trimethylbenzyl, tetrahydropyranyl or 2-trimethylsilylethyl and, more preferably, is a tetrazol-5-yl group.
The compounds of the invention form, with various inorganic and organic acids and bases, pharmaceutically acceptable salts which also are object of this invention.
Said salts include ammonium salts, salts with alkali metals such as sodium and potassium, with alkaline-earth metals such as calcium and magnesium, with organic bases, such as dicyclohexylamine, N-methyl-D-glucamine, with amino acids such as arginine, lysine and the like.
The novel compounds can be prepared according to v
REFERENCES:
patent: 5565464 (1996-10-01), Salimbeni et al.
Canevotti Renato
Poma Davide
Salimbeni Aldo
Istituto Luso Farmaco D'Italia S.p.A.
Patel Sudhaber B.
Shah Mukund J.
LandOfFree
N-3 substituted pyrimidin-4-ones with AII antagonistic activity does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with N-3 substituted pyrimidin-4-ones with AII antagonistic activity, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-3 substituted pyrimidin-4-ones with AII antagonistic activity will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-664290