Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-11-21
1997-07-29
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514357, 514447, 514438, 514613, 546141, 546142, 546143, 546145, 546153, 546155, 546159, 546164, 548465, 548483, 548505, 564164, 564166, 564167, 564168, C07D21526, C07C25541, A61K 3133
Patent
active
056522509
DESCRIPTION:
BRIEF SUMMARY
This application is a 35 USC 371 National Stage filing of PCT/EP95/00758 published as WO 95/26341 on Oct. 5, 1995.
The present invention relates to new N-substituted .beta.-aryl- and .beta.-heteroaryl-.alpha.-cyanoacrylamide derivatives to a process for their preparation, to pharmaceutical compositions containing them and to their use as therapeutic agents.
The present invention provides compounds having the following general formula (I) ##STR2## wherein A is a bicyclic ring chosen from naphthalene, tetrahydronaphthalene, quinoline, isoquinoline and indole; thiophene ring; group NR.sup.3 R.sup.4 wherein each of R.sup.3 and R.sup.4 is independently hydrogen or C.sub.1 -C.sub.6 alkyl; carboxy, hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkanoyloxy, or a group NR.sup.3 R.sup.4 wherein R.sup.3 and R.sup.4 are as defined above;
In the compounds of formula (I) when A is naphthalene, quinoline, isoquinoline or indole, then each of the substituents R and OR' may be independently on either of the two rings constituing the bicyclic system, when A is tetrahydronaphthalene whilst they are only on the benzene ring of the bicyclic system.
When n is 2, the OR' groups may be the same or different.
The invention includes within its scope all the possible isomers, stereoisomers, in particular Z and E isomers and their mixtures, and the metabolites and the metabolic precursors or bio-precursors (otherwise known as pro-drugs) of the compounds of formula (I).
The alkyl groups and the alkyl moieties in the alkoxy, alkanoyl or alkanoyloxy groups may be branched or straight alkyl chains.
A C.sub.1 -C.sub.6 alkyl is preferably a C.sub.1 -C.sub.4 alkyl, e.g. methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl, in particular methyl or ethyl.
A C.sub.1 -C.sub.6 alkoxy group is preferably a C.sub.1 -C.sub.3 alkoxy, in particular methoxy.
A C.sub.1 -C.sub.6 alkanoyl group is preferably a C.sub.2 -C.sub.3 alkanoyl group, in particular acetyl or propionyl.
A C.sub.1 -C.sub.6 alkanoyloxy group is preferably a C.sub.2 -C.sub.3 alkanoyloxy group, in particular acetyloxy or propionyloxy.
A halogen is preferably fluorine, chlorine or bromine, in particular fluorine or chlorine.
A group ##STR3## is, preferably, amino.
Under tetrahydronaphthalene more precisely we intend 5,6,7,8-tetrahydronaphthalene.
When A is naphthalene the R and R.sup.1 O substituents and the acrylamide side chain are preferably on the same benzene moiety.
When A is 5,6,7,8-tetrahydronaphthalene the R and R.sup.1 O substituent and the acrylamide side chain are preferably on the aromatic benzene moiety.
When A is quinoline the acrylamide side chain is preferably attached to the 4- or 5-position of the quinoline ring and the R and R.sup.1 O substituents are preferably on the same aryl or heteroaryl moiety of said ring.
When A is isoquinoline the acrylamide side chain is preferably attached to the 3 or 5-position of the isoquinoline ring and the R and R.sup.1 O substituents are preferably on the benzene moiety of said ring.
When A is indole ring the acrylamide side chain is preferably attached to the pyrrole moiety and the R and R.sup.1 O substituents are preferably on the benzene moiety of said ring. In this case preferably A is a 3-indolyl group.
Of course only one of the substituents R, R.sup.1 O and acrylamide side chain can be linked to the same carbon of the A ring.
The R.sup.2 substituent is preferably in para position on the benzene ring.
When one of R and R.sup.2 is NO.sub.2, COOH or NR.sup.3 R.sup.4, then the other has preferably a different meaning.
Pharmaceutically acceptable salts of the compounds of the invention include acid addition salts, with inorganic acids, e.g. hydrochloric, sulphuric, perchloric and phosphoric acid, or organic acids, e.g. acetic, glycolic, lactic, oxalic, malonic, malic, maleic, tartaric, citric, benzoic, cinnamic, mandelic and salicylic acid, and salts with inorganic bases, e.g. sodium, potassium, calcium or magnesium base, or with organic bases, e.g. alkylamines, preferably triethylamine.
As stated above, the presen
REFERENCES:
patent: 5122537 (1992-06-01), Buzzetti et al.
patent: 5130472 (1992-07-01), Buzzetti et al.
patent: 5196446 (1993-03-01), Levitzki et al.
patent: 5397787 (1995-03-01), Buzzetti et al.
patent: 5409949 (1995-04-01), Buzzetti et al.
patent: 5436235 (1995-07-01), Buzzetti et al.
patent: 5488057 (1996-01-01), Buzzetti et al.
Ryabova, S.Y., Alekseeva, L.M., Granik, V.G. "Acetals of lactams and acid amides". 70. Reaction of 2-(aminomethylene)indolin-3-one derivatives with CH-acids. Synthesis of substituted pyrrolo[1,2-a]indoles. Khim. Geterotsikl. Soedin. 9, pp. 1199-1204, 1 1991.
Ballinari Dario
Brasca Maria Gabriella
Buzzetti Franco
Crugnola Angelo
Longo Antonio
Pharmacia S.p.A.
Rotman Alan L.
Smith Lyman H.
LandOfFree
N-substituted .beta.-aryl- and .beta.-heteroaryl-.alpha.-cyanoac 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-substituted .beta.-aryl- and .beta.-heteroaryl-.alpha.-cyanoac, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-substituted .beta.-aryl- and .beta.-heteroaryl-.alpha.-cyanoac will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-634041