US 5,516,908 AGranted

1,3-dihydro-2H-imidazo-[4,5-.beta.]quinolin-2-one derivatives and intermediates

AssigneeJanssen Pharmaceutica NV

InventorsEddy J. E. Freyne, Alfons H. M. Raeymaekers, Didier R. G. G. de Chaffoy de Courcelles

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Abstract

The present invention relates to novel 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives of formula ##STR1## wherein R is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, phenyl optionally substituted with from 1 to 3 substituents each independently selected from halo, hydroxy, C.sub.1-6 alkyloxy, C.sub.5-6 cycloalkyloxy, C.sub.1-6 alkyl or trifiuoromethyl; pyridinyl; thienyl optionally substituted with halo or C.sub.1-6 alkyl; and >C.dbd.X is a radical of formula >C.dbd.O (a), >C.dbd.N--O--R.sup.1 (b), or >C.dbd.CH--R.sup.2 (c); the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, said compounds being potent inhibitors of both phosphodiesterase III and IV, which are useful in the treatment of warm-blooded animals suffering from allergic disorders, atopic diseases and related afflictions. Intermediates in the preparation thereof. Pharmaceutical compositions containing said compounds as an active ingredient. Methods of preparing said compounds and pharmaceutical compositions.

Claims8

Dependent claims

A compound of the formula:

##STR52## an addition salt thereof or a stereochemically isomeric form thereof, wherein:
R represents hydrogen;
C.sub.1-6 alkyl;
C.sub.3-6 cycloalkyl;
phenyl optionally substituted with from 1 to 3 substituents each independently selected from halo, hydroxy, C.sub.1-6 alkyloxy, C.sub.5-6 cycloalkyloxy, C.sub.1-6 alkyl or trifluoromethyl;
pyridinyl;
or thienyl optionally substituted with halo or C.sub.1-6 alkyl;
and
.dbd.C.dbd.X is a radical of the formula:
.dbd.C.dbd.O (a),
.dbd.C.dbd.N--O--R.sup.1 (b),
or
.dbd.C.dbd.CH--R.sup.2 (c);
wherein:
R.sup.l represents hydrogen, tri(C.sub.1-6 alkyl)silyl or C.sub.1-6 alkyl optionally substituted with COOH, COOC.sub.1-4 alkyl, CONR.sup.3 R.sup.4 or COOCH.sub.2 CONR.sup.5 R.sup.6 ;
and
R.sup.2 represents COOH, COOC.sub.1-4 alkyl, CONR.sup.3 R.sup.4, COOCH.sub.2 CONR.sup.5 R.sup.6 or C.sub.1-6 alkyl optionally substituted with COOH, COOC.sub.1-4 alkyl, CONR.sup.3 R.sup.4 or COOCH.sub.2 CONR.sup.5 R.sup.6,
wherein in the foregoing:
R.sup.3 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.1-4 alkyloxyC.sub.1-4 alkyl, hydroxycarbonylC.sub.1-4 alkyl, or C.sub.1-4 alkyloxycarbonylC.sub.1-4 alkyl;
R.sup.4 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, phenyl, thienyl or pyridinyl;
or
R.sup.3 and R.sup.4 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, morpholinyl or piperazinyl ring, said piperazinyl ring being optionally substituted on the nitrogen atom with C.sub.1-4 alkyl, (C.sub.3-7 cycloalkyl)C.sub.1-4 alkyl, phenylC.sub.1-4 alkyl or C.sub.1-6 alkyl substituted with from one to five hydroxy groups;
R.sup.5 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.1-4 alkyloxyC.sub.1-4 alkyl, hydroxycarbonylC.sub.1-4 alkyl, or C.sub.1-4 alkyloxycarbonylC.sub.1-4 alkyl;
R.sup.6 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, phenyl, thienyl or pyridinyl;
or
R.sup.5 and R.sup.6 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, morpholinyl or piperazinyl ring, said piperazinyl ring being optionally substituted on the nitrogen atom with C.sub.1-4 alkyl, (C.sub.3-7 cycloalkyl)C.sub.1-4 alkyl, phenylC.sub.1-4 alkyl or C.sub.1-6 alkyl substituted with from one to five hydroxy groups,
provided that the configuration about the double bond attached to the tetrahydroimidazolyldione ring is in the (E) configuration.

24 more elements

A compound of the formula:

##STR54## an addition salt thereof or a stereochemically isomeric form thereof, wherein:
R represents hydrogen;
C.sub.1-6 alkyl;
C.sub.3-6 cycloalkyl;
phenyl optionally substituted with from 1 to 3 substituents each independently selected from halo, hydroxy, C.sub.1-6 alkyloxy, C.sub.5-6 cycloalkyloxy, C.sub.1-6 alkyl or trifluoromethyl;
pyridinyl;
or thienyl optionally substituted with halo or C.sub.1-6 alkyl;
and
.dbd.C.dbd.X is a radical of the formula:
.dbd.C.dbd.O (a),
.dbd.C.dbd.N--O--R.sup.1 (b),
or
.dbd.C.dbd.CH--R.sup.2 (c);
wherein:
R.sup.1 represents hydrogen, tri(C.sub.1-6 alkyl)silyl or C.sub.1-6 alkyl optionally substituted with COOH, COOC.sub.1-4 alkyl, CONR.sup.3 R.sup.4 or COOCH.sub.2 CONR.sup.5 R.sup.6 ;
and
R.sup.2 represents COOH, COOC.sub.1-4 alkyl, CONR.sup.3 R.sup.4, COOCH.sub.2 CONR.sup.5 R.sup.6 or C.sub.1-6 alkyl optionally substituted with COOH, COOC.sub.1-4 alkyl, CONR.sup.3 R.sup.4 or COOCH.sub.2 CONR.sup.5 R.sup.6,
wherein in the foregoing:
R.sup.3 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.1-4 alkyloxyC.sub.1-4 alkyl, hydroxycarbonylC.sub.1-4 alkyl, or C.sub.1-4 alkyloxycarbonylC.sub.1-4 alkyl;
R.sup.4 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, phenyl, thienyl or pyridinyl;
or
R.sup.3 and R.sup.4 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, morpholinyl or piperazinyl ring, said piperazinyl ring being optionally substituted on the nitrogen atom with C.sub.1-4 alkyl, (C.sub.3-7 cycloalkyl)C.sub.1-4 alkyl, phenylC.sub.1-4 alkyl or C.sub.1-6 alkyl substituted with from one to five hydroxy groups;
R.sup.5 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.1-4 alkyloxyC.sub.1-4 alkyl, hydroxycarbonylC.sub.1-4 alkyl, or C.sub.1-4 alkyloxycarbonylC.sub.1-4 alkyl;
R.sup.6 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, C.sub.3-7 cycloalkyl, phenyl, thienyl or pyridinyl;
or
R.sup.5 and R.sup.6 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, morpholinyl or piperazinyl ring, said piperazinyl ring being optionally substituted on the nitrogen atom with C.sub.1-4 alkyl, (C.sub.3-7 cycloalkyl)C.sub.1-4 alkyl, phenylC.sub.1-4 alkyl or C.sub.1-6 alkyl substituted with from one to five hydroxy groups.

23 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/423,116Filed 18 Apr 1995 · division
Priority: 30 Oct 1991
Granted: 14 May 1996
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

C07D 215/38
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61P 37/08
Drugs for immunological or allergic disorders: antiallergic agents
C07D 233/76
Two oxygen atoms, e.g. hydantoin: with substituted hydrocarbon radicals attached to the third ring carbon atom
C07D 233/96
Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings: having three double bonds between…