5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives, pr

Details 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives, pr 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives, pr

1998-07-09

1999-11-23

Gerstl, Robert

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

544343, A61K 31495, C07D48704

Patent

active

059901080

DESCRIPTION:

BRIEF SUMMARY
The present invention relates to the compounds of formula: ##STR2## their isomers, their racemates, enantiomers and diastereoisomers, their salts, their preparation, their intermediates and the medicaments containing them.
In the formula (I),
R represents a hydrogen atom or a --COOH radical, an -alk-COOH radical, a --PO.sub.3 H.sub.2 radical, --CH.sub.2 --PO.sub.3 H.sub.2 radical, a --CH.dbd.CH--COOH radical or a phenyl radical substituted with a carboxyl radical,
R.sub.1 represents an -alk-CN, -alk-COOH, -alk-Het, -alk-PO.sub.3 H.sub.2 or -alk-CO--NH--SO.sub.2 R.sub.2 radical,
R.sup.2 represents an alkyl or phenyl radical,
alk represents an alkyl radical,
Het represents a saturated or unsaturated mono- or polycyclic heterocycle containing 1 to 9 carbon atoms and one or more heteroatoms chosen from O, S, N, the heterocycle being optionally substituted with one or more alkyl, phenyl or phenylalkyl radicals,
it being understood that when R represents a hydrogen atom or a --COOH or --PO.sub.3 H.sub.2 radical, R.sub.1 cannot represent -alk-COOH.
Unless otherwise stated, in the preceding definitions and in those which follow, the alkyl or alkoxy radicals contain 1 to 6 carbon atoms in a straight or branched chain.
Preferably, the substituent R.sub.1 is at position 8 or 9.
Preferably, Het represents a tetrazol-5-yl ring.
The compounds of formula (I) for which R represents a --CH.dbd.CH--COOH radical have isomeric forms (E and Z). These isomers and mixtures thereof form part of the invention.
The racemates, enantiomers and diastereoisomers of the compounds of formula (I) for which R represents an -alk-COOH radical and/or R.sub.1 represents an -alk-CN, -alk-COOH, -alk-Het, -alk-PO.sub.3 H.sub.2 or -alk-CO--NH--SO.sub.2 R.sub.2 radical also form part of the invention.
The compounds of formula (I) can be prepared by cyclization, either in the presence of ammonium acetate, or in the presence of ammonia, or in the presence of ammonium acetate and ammonia, of a derivative of formula: ##STR3## in which Ra represents a hydrogen atom or a -COOalk radical, an -alk-COOalk' radical, a --PO(Oalk).sub.2 radical, a --CH.sub.2 --PO(Oalk).sub.2 radical, a --CH.dbd.CH--COOalkl radical or a phenyl radical substituted with an alkoxycarbonyl radical, Rb represents an -alk-CN, -alk-COOalk', -alk-PO(Oalk').sub.2, -alk-CO--NH--SO.sub.2 R.sub.2 or -alk-Het radical, alk and alk' represent an alkyl radical, R.sub.2 and Het have the same meanings as in the formula (I), followed by a hydrolysis.
When Het represents a tetrazolyl-5-yl radical, it is preferable to use a derivative of formula (II) for which Rb represents an -alk-tetrazol-5-yl radical in which the tetrazole is substituted at position 1 or 2 with a benzyl radical and then to debenzylate the final product.
This cyclization is carried out preferably in an organic acid such as acetic acid, at the boiling temperature of the reaction medium, optionally in the presence of ammonia in solution in a lower aliphatic alcohol such as methanol. The hydrolysis of the --COOalk and --PO(Oalk).sub.2 functional groups and the debenzylation are carried out by any known method which makes it possible to go from an ester to the corresponding acid or from a dialkylphosphonate to the corresponding phosphonic acid or to debenzylate without modifying the rest of the molecule. Preferably, the procedure is carried out by means of an inorganic acid such as hydrobromic acid or hydrochloric acid, at a temperature of 100.degree. C.
The derivatives of formula (II) can be obtained by the action of an indanone of formula: ##STR4## in which Rb has the same meanings as in the formula (II) or represents an -alk-Het' radial for which Het' represents a tetrazol-5-yl radical substituted at position 1 or 2 with a benzyl radical and Hal represents a halogen atom (preferably chlorine or bromine), on a derivative of formula: ##STR5## in which Ra has the same meanings as in the formula (II) and alk represents an alkyl radical.
This reaction is generally carried out in an inert solvent such as an alcohol (for example methanol

Affiliated with

Also associated with

Rating

5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives, pr does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives, pr, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazine-4-one derivatives, pr will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1222122