Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1996-07-09
1998-02-17
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
5142345, 514255, 514300, 544127, 544362, 546 21, 546 23, 546113, A61K 31675, A61K 3144, C07D40100, C07D47102
Patent
active
057191352
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/04247, filed Oct. 30, 1995.
The present invention relates to 3-arylidene-7-azaoxindole compounds, 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) ##STR6## wherein A is benzene, naphthalene, 5,6,7,8,-tetrahydronaphthalene, quinoline, isoquinoline, indole or 7-azaindole; ##STR7## --COOR.sub.6, --CONHCH.sub.2 (CHOH).sub.n CH.sub.2 OH, ##STR8## --NR.sub.7 R.sub.8, --N(CH.sub.2 CH.sub.2 OH).sub.2, --NHCH.sub.2 (CHOH).sub.n CH.sub.2 OH, --NHCONH.sub.2, --NH--C(NH.sub.2).dbd.NH, --NHCO(CHOH).sub.n CH.sub.2 OH, ##STR9## --NHSO.sub.2 R.sub.9, --OR.sub.10, --OCH.sub.2 (CHOH).sub.n CH.sub.2 OH, --OOC(CHOH).sub.n CH.sub.2 OH, --PO(OH).sub.2, --CH.sub.2 NH.sub.2, --C(NH.sub.2).dbd.NH, --CH.sub.2 NHC(NH.sub.2).dbd.NH, ##STR10## --CH.sub.2 OH, --CH.sub.2 OOC(CHOH).sub.n CH.sub.2 OH, --CH.sub.2 OPO(OH).sub.2 or --PO(OH).sub.2 ; OH; or --(CH.sub.2).sub.m NMe.sub.2 ; OH;
The invention includes within its scope all the possible isomers, stereoisomers, in particular Z- and E-isomers, as well as the metabolites and the metabolic precursors or bio-precursors (otherwise known as pro-drugs) of the compounds of formula (I).
The substituents R.sub.1 and R.sub.2 may be independently on either of the ring moieties when A is bicyclic.
The azaoxindolylidene substituent is preferably linked to position 1 or 2 when A is naphthalene or 5,6,7,8-tetrahydronaphthalene, to position 4 or 5 when A is quinoline, to position 1 or 3 when A is isoquinoline, to position 3 when A is indole, or 7-azaindole.
The R.sub.1 substituent with reference to the azaoxindolylidene substituent is preferably linked to the other ring moiety when A is naphthalene, 5,6,7,8-tetrahydronaphthalene, quinoline, isoquinoline, indole or azaindole.
The alkyl group and the alkyl moiety in the alkanoyl group may be branched or straight alkyl chains.
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 t-butyl, in particular methyl or ethyl.
A C.sub.2 -C.sub.6 alkanoyl group is preferably a C.sub.2 -C.sub.3 alkanoyl group, in particular acetyl or propionyl.
A halogen is preferably fluorine, chlorine or bromine, in particular fluorine.
Pharmaceutically acceptable salts of the compounds of the invention include acid addition salts with inorganic, e.g. nitric, hydrochloric, hydrobromic, sulfuric, perchloric and phosphoric acids or organic, e.g. acetic, trifluoroacetic, 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. acyclic or cyclic amines, preferably triethylamine or piperidine.
As stated above, the present invention also includes within its scope pharmaceutically acceptable bio-precursors (otherwise known as pro-drugs) of the compounds of formula (I), i.e. compounds which have a different formula to formula (I) above but which, nevertheless, upon administration to a human being are converted directly or indirectly in vivo into a compound of formula (I).
Preferred compounds of the invention are the compounds of formula (I), wherein 7-azaindole; NH.sub.2, ##STR11## --COOMe, --N (CH.sub.2 CH.sub.2 OH).sub.2, --NHCH.sub.2 CHOHCH.sub.2 OH, --NHCONH.sub.2, --NHC(NH.sub.2)=NH, --NHCOCHOHCH.sub.2 OH, ##STR12## --NHSO.sub.2 Me, --OCH.sub.2 CHOHCH.sub.2 OH, --OOCCH.sub.2 OH, --OOCCHOHCH.sub.2 OH, --OH, --OMe, --OPO(OH).sub.2, --CH.sub.2 NH.sub.2, --C(NH.sub.2).dbd.NH, ##STR13## --CH.sub.2 OH, --OPO(OH).sub.2, --PO(OH).sub.2 ; R.sub.2 is C.sub.1 -C.sub.6 alkyl or hydroxy; 2 when A is naphthalene or 5,6,7,8-tetrahydronaphthalene, to position 4 or 5 when A is quinoline, to position 3 when A is indole or 7-azaindole, whereas the R.sub.1 substituent is preferably linked
Ballinari Dario
Brasca Gabriella Maria
Buzzetti Franco
Longo Antonio
Coleman Brenda
Pharmacia S.p.A.
Shah Mukund J.
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