Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-08-10
1996-04-16
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514211, 514217, 514258, 514261, 514266, 540546, 540547, 540524, 544254, 544262, 544264, 544280, C07D47316, C07D48704
Patent
active
055082777
DESCRIPTION:
BRIEF SUMMARY
This is a section 371 of PCT/FR93/01211, filed Dec. 9, 1993.
TECHNICAL FIELD
The present invention relates to new bicyclic pyrimidine compounds, a process for their preparation, and pharmaceutical compositions containing them.
PRIOR ART
The prior art in the pharmaceutical field is illustrated especially by published European Patent Applications Nos. 0.495 982 A.sub.1 and 0 514 540 A.sub.1, which relate to the compounds of formulae: ##STR2## respectively, which formulae essentially differ from the compounds of the present invention in the meaning of the substituents --Y'--Z' and Y"--Z" on the pyrimidine nucleus, and in their pharmacological activity--the said products of the prior art being active against hypoxaemia associated with respiratory disorders whilst the compounds of the present invention partially or completely reverse the resistance of tumour cells to anti-cancer agents.
STATEMENT OF THE INVENTION
The invention relates especially to bicyclic pyrimidine compounds of formula I: ##STR3## wherein: T and U, which are the same or different, each represents a --CH-- radical or a nitrogen atom so as to form with the pyrimidinyl group a heterocycle selected from: purine, pyrazolo[3,4-d]pyrimidine, pyrrolo[2,3-d]pyrimidine and 1,2,3-triazolo[4,5-d]pyrimidine; having from 1 to 5 carbon atoms or an alkenyl radical having from 2 to 5 carbon atoms, each in straight or branched chain; ##STR4## wherein: B represents a radical of formula: ##STR5## wherein R" is a hydrogen atom or an alkyl radical having from 1 to 5 carbon atoms in straight or branched chain and a halogen atom, or an alkyl or alkoxy radical each having from 1 to 5 carbon atoms in straight or branched chain; from 1 to 3; hydrogen atom or an alkyl radical having from 1 to 5 carbon atoms in straight or branched chain, or together represent a single bond, an oxygen or sulphur atom, a radical --(CH.sub.2).sub.r -- in which r represents an integer of from 1 to 3, a radical --CH.dbd.CH--, --O--CH.sub.2 --, --S--CH.sub.2 --, --SO.sub.2 --CH.sub.2 --, --CO--CH.sub.2 --, ##STR6## in each of which R'" represents a hydrogen atom or an alkyl radical having from 1 to 5 carbon atoms in straight or branched chain, or ##STR7## in which the terminal CH.sub.2 is attached to the closest carbon of the adjoining benzene ring so that the whole: ##STR8## forms the tetracyclic radical of formula: ##STR9## R.sub.3 represents a hydrogen atom or a phenyl radical; and also to the chiral compounds and their enantiomers.
The present invention relates also to a process for the preparation of the compounds of formula I which is characterised in that: ##STR10## wherein T, U and R' are as defined above, is condensed with the amine of formula: ##STR11## whichever it is desired to attach in the 6-position, (R, X, Y, m, n, R.sub.1, R.sub.2, R.sub.3, p and A in those formulae being as defined above), formula: ##STR12## is condensed with the other amine of formula III or IV which it is desired to attach in the 2-position--the order of reactivity of the amines with the dichlorinated compounds II being known [cf. Heterocyclic compounds Part II, Ed. D. J. Brown, Wiley-Interscience (1971), Chapter V, p. 160].
Those successive condensations are carried out especially advantageously as follows: 6-position is carried out in a polar solvent, such as, for example, an alcohol containing from 2 to 5 carbon atoms, dimethylformamide or dimethylacetamide, at a temperature of approximately 60.degree. C., in the presence of an acceptor for the hydracid formed during the course of the reaction; that acceptor may be, for example, triethylamine or an excess of the amine used in the reaction.
The condensation product thus obtained is then condensed with the other amine (to be attached in the 2-position) in a polar solvent of the same type as that used for the preceding condensation, the condensation being carried out in an autoclave at a temperature of from 130.degree. to 150.degree. C. in the presence of an acceptor for the hydracid formed during the course of the reaction; that acceptor may be,
REFERENCES:
patent: 4100286 (1978-07-01), Regnier
patent: 4212866 (1980-07-01), Friebe
patent: 5079249 (1990-08-01), Lavielle
patent: 5110818 (1992-05-01), Allgeier
patent: 5204353 (1993-04-01), Meier
patent: 5278165 (1994-01-01), Janssens
patent: 5302596 (1994-04-01), Oshima
patent: 5329007 (1994-07-01), Peet
patent: 5397782 (1995-03-01), Meert
Atassi Ghanem
Dhainaut Alain
Pierre Alain
Regnier Gilbert
Adir et Compagnie
Daus Donald G.
Hueschen Gordon W.
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