US 5,182,386 AGranted

Certain imidazoquinoxalinones; a new class of gaba brain receptor ligands

AssigneeNeurogen Corporation

InventorsPamela Albaugh, Alan J. Hutchinson

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Abstract

This invention encompasses compounds of the formula: ##STR1## and the pharmaceutically acceptable non-toxic salts thereof wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 are variables; X and Y represent hydrogen, halogen, hydroxy or amino substituents, with the proviso that when Y is a hydrogen, halogen, or amino substituent, X is hydroxy; and W represent aryl groups unsubstituted or substituted with halogen, hydroxy, alkyl, alkoxy or amino groups. These compounds or prodrugs thereof are highly selective agonists, antagonists or inverse agonists or GaBAa brain receptors or prodrugs thereof and are useful in the diagnosis and treatment of anxiety, sleep, and seizure disorder, overdose with benzodiazepine drugs, and enchancement of memory.

Claims37

Dependent claims

A compound of the formula:

##STR20## and the pharmaceutically acceptable non-toxic salts thereof wherein:
R.sub.1 and R.sub.4 are the same or different and represent
hydrogen, halogen or straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms;
X and Y are
hydrogen, halogen, hydroxy or amino with the proviso that when X is hydrogen, halogen, or amino, Y is hydroxy, and when Y is hydrogen, halogen, or amino, X is hydroxy;
W is
2- or 3-thienyl;
or
phenyl, or 2- or 3-thienyl each of which is mono or disubstituted with halogen, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms, amino, or mono- or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
and
R.sub.2 and R.sub.3 are the same or different and represent
hydrogen, halogen, hydroxy, or straight or branched chain lower alkyl having 1-6 carbon atoms;
or
R.sub.5, OR.sub.5, COR.sub.5, CO.sub.2 R.sub.5, or OCOR.sub.5, where R.sub.5 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--CONR.sub.6 R.sub.7 or --(CH.sub.2).sub.n NR.sub.6 R.sub.7, where n is 0, 1, or 2, R.sub.6 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, and R.sub.7 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--CONR.sub.6 R.sub.7 or --(CH.sub.2).sub.n NR.sub.6 R.sub.7, where n is 0, 1, or 2, and NR.sub.6 R.sub.7 forms a heterocyclic group which is morpholyl, piperidyl, pyrrolidyl, or N-alkylpiperizyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--NR.sub.8 CO.sub.2 R.sub.9 where R.sub.8 and R.sub.9 are the same or different and represent hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms, or
--C(OH)R.sub.10 R.sub.11 where R.sub.10 and R.sub.11 are the same or different and represent straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms.

18 more elements

A compound of the formula:

##STR21## and the pharmaceutically acceptable non-toxic salts thereof wherein:
R.sub.1 and R.sub.4 are the same or different and represent
hydrogen, halogen or straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms;
X is
hydrogen, halogen, or amino;
W is
phenyl, 2- or 3-thienyl, or 2-, 3-, or 4-pyridyl;
or
phenyl, 2- or 3-thienyl, or 2-, 3-, or 4-pyridyl each of which is mono or disubstituted with halogen, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms, amino, or mono- or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
and
R.sub.2 and R.sub.3 are the same or different and represent
hydrogen, halogen, hydroxy, or straight or branched chain lower alkyl having 1-6 carbon atoms;
or
R.sub.5, OR.sub.5, COR.sub.5, CO.sub.2 R.sub.5, or OCOR.sub.5, where R.sub.5 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--CONR.sub.6 R.sub.7 or --(CH.sub.2).sub.n NR.sub.6 R.sub.7, where n is 0, 1, or 2, R.sub.6 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, and R.sub.7 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--CONR.sub.6 R.sub.7 or --(CH.sub.2).sub.n NR.sub.6 R.sub.7, where n is 0, 1, or 2, and NR.sub.6 R.sub.7 forms a heterocyclic group which is morpholyl, piperidyl, pyrrolidyl, or N-alkylpiperizyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--NR.sub.8 CO.sub.2 R.sub.9 where R.sub.8 and R.sub.9 are the same or different and represent hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms, or
--C(OH)R.sub.10 R.sub.11 where R.sub.10 and R.sub.11 are the same or different and represent straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms.

18 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of the formula:

##STR20## and the pharmaceutically acceptable non-toxic salts thereof wherein:
R.sub.1 and R.sub.4 are the same or different and represent
hydrogen, halogen or straight or branched chain lower alkyl having 1-6 carbon atoms, or straight or branched chain lower alkoxy having 1-6 carbon atoms;
X and Y are
hydrogen, halogen, hydroxy or amino with the proviso that when X is hydrogen, halogen, or amino, Y is hydroxy, and when Y is hydrogen, halogen, or amino, X is hydroxy;
W is
2- or 3-thienyl;
or
phenyl, or 2- or 3-thienyl each of which is mono or disubstituted with halogen, hydroxy, straight or branched chain lower alkyl having 1-6 carbon atoms, straight or branched chain lower alkoxy having 1-6 carbon atoms, amino, or mono- or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
and
R.sub.2 and R.sub.3 are the same or different and represent
hydrogen, halogen, hydroxy, or straight or branched chain lower alkyl having 1-6 carbon atoms;
or
R.sub.5, OR.sub.5, COR.sub.5, CO.sub.2 R.sub.5, or OCOR.sub.5, where R.sub.5 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--CONR.sub.6 R.sub.7 or --(CH.sub.2).sub.n NR.sub.6 R.sub.7, where n is 0, 1, or 2, R.sub.6 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, and R.sub.7 is hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--CONR.sub.6 R.sub.7 or --(CH.sub.2).sub.n NR.sub.6 R.sub.7, where n is 0, 1, or 2, and NR.sub.6 R.sub.7 forms a heterocyclic group which is morpholyl, piperidyl, pyrrolidyl, or N-alkylpiperizyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
or
--NR.sub.8 CO.sub.2 R.sub.9 where R.sub.8 and R.sub.9 are the same or different and represent hydrogen, straight or branched chain lower alkyl having 1-6 carbon atoms, phenyl, or phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms, or
--C(OH)R.sub.10 R.sub.11 where R.sub.10 and R.sub.11 are the same or different and represent straight or branched chain lower alkyl having 1-6 carbon atoms, phenylalkyl where the alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms.

18 more elements