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US 5,182,290 AGranted
Certain oxazoloquinolinones; a new class of GABA brain receptor ligands
AssigneeNeurogen Corporation
InventorPamela Albaugh
Life of this patent
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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, and W are variables These compounds are highly selective agonists, antagonists or inverse agonists for GABA.sub.a brain receptors or prodrugs thereof and are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs, and enhancement of memory.
Claims22
A compound of the formula:
- ##STR16## and the pharmaceutically acceptable non-toxic salts thereof 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;
- W is
- 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, straight or branched chain lower alkyl having 1-6 carbon atoms, amino, mono or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
- or
- 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-alkylpiperazyl 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.
15 more elements
A pharmaceutical composition suitable for treatment of conditions in mammals mediated by the use of compounds which selectively bind to GABA receptors comprising a non-toxic pharmaceutically acceptable carrier and a compound of the formula:
- ##STR19## 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;
- 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, straight or branched chain lower alkyl having 1-6 carbon atoms, amino, mono or dialkylamino where each alkyl portion is straight or branched chain lower alkyl having 1-6 carbon atoms;
- or
- 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.
15 more elements
Dependencies are inferred from the claim text.