Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-09-27
1994-12-20
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548486, C07D20934, A61K 3140
Patent
active
053746520
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new aryl- and heteroarylethenylene 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) ##STR3## wherein Y is a mono- or bicyclic ring system chosen from (A), (B), (C), (D), (E), (F) and (G) ##STR4## R is a group of formula (a), (b), (c), (d), (e), (f), (g), (h), (i) or (j) ##STR5## in which R.sub.3 is --OH or --NH.sub.2 and Ph means phenyl; R.sub.1 is hydrogen, C.sub.1 -C.sub.6 alkyl or C.sub.2 -C.sub.6 alkanoyl; R.sub.2 is hydrogen, halogen, cyano or C.sub.1 -C.sub.6 alkyl; n is zero or an integer of 1 to 3: n is zero or an integer of 1 to 3 when Y is a ring system (A); it is zero, 1 or 2 when Y is a ring system (B), (E), (F) or (G); or it is zero or 1 when Y is a ring system (C) or (D); and the pharmaceutically acceptable salts thereof; and wherein each of the substituents R, OR.sub.1 and R.sub.2 may be independently on either of the aryl or heteroaryl moieties of the bicyclic ring system (A), (E), (F) and (G), whereas only the benzene moiety may be substituted in the bicyclic ring system (B).
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 substituent R is preferably linked to position 1 or 2 in ring system (A) and (B), to position 4 in ring system (C) and (D), to position 5 or 8 in ring system (E) and (F) and to position 3 or 7 in ring system (G). The substituent R.sub.2 may be independently on either of the rings in the bicyclic ring systems (A), (B), (E), (F) and (G).
When Y is a bicyclic ring system as defined under (A), (E) or (F) the --OR.sub.1 groups are preferably on the same benzene moiety as the R group. In any of ring systems (A) to (G), the substituent R.sub.2 is preferably located on the same 6-membered ring as the substituent --OR.sub.1 in the ortho-, meta-or para- position with respect to --OR.sub.1. Preferably R.sub.2 is located in a position ortho- or para- to --OR.sub.1.
A substituent --OR.sub.1 is preferably linked to position 1, 2, 3, 4, 5 or 8, in particular to position 1, 2, 3 or 4, in ring systems (A) and (B). A substituent --OR.sub.1 is preferably linked to position 2, 3, 4 or 5, in particular to position 3, 4 or 5, in ring systems (C) and (D). A substituent --OR.sub.1 is preferably linked to position 3, 4, 5, 6, 7 or 8, in particular to position 5, 6, 7 or 8, in ring system (E) and (F). A substituent --OR.sub.1 is preferably linked to position 3, 4, 5, 6 or 7, in particular to position 4, 5, 6 or 7 in ring system (G). Of course only one of the substituents R, --OR.sub.1 and R.sub.2 can be linked to the same position in ring systems (A) to (G).
When n is 2 or 3, the --OR.sub.1 groups may be the same or different.
The alkyl groups, and the alkyl moiety in the alkanoyl groups, may be a branched or straight alkyl chain. A C.sub.1 -C.sub.6 alkyl group is preferably a C.sub.1 -C.sub.4 alkyl group, e.g. methyl, ethyl, propyl, isopropyl, butyl, sec-butyl or tert-butyl, in particular methyl or ethyl. A C.sub.2 -C.sub.6 alkanoyl group is preferably a C.sub.2 -C.sub.4 alkanoyl group, in particular acetyl, propionyl or butyryl.
A halogen is, preferably, chlorine, bromine or fluorine, in particular bromine.
Pharmaceutically acceptable salts of the compounds of the invention include acid addition salts, with inorganic, e.g. nitric, hydrochloric, hydrobromic, sulphuric, perchloric and phosphoric acids, or organic, e.g. acetic, propionic, glycolic, lactic, oxalic, malonic, malic, maleic, tartaric, citric, benzoic, cinnamic, mandelic and salicylic acids, and salts with inorganic, e.g. alkali metal, especially sodium or potassium, bases or alkaline-earth metal, especially calcium or magnesium bases, or with organic bases, e.g. alkylamines, preferably triethyl-amine.
As stated above the p
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Buzzetti Franco
Colombo Maristella
Longo Antonio
Davis Zinna N.
Farmitalia Carlo Erba S r l
Ivy C. Warren
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