[(5,6,9a-Substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkano ic and cycloalkanoic acids, their analogs, esters, salts, and derivatives
AssigneeMerck & Co., Inc.
InventorsEdward J. Cragoe, Jr., Gerald E. Stokker, Norman P. Gould
Life of this patent
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Abstract
The invention relates to novel [(5,6,9a-substituted-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]alkanoi c and cycloalkanoic acid and their analogs, esters, salts and derivatives. These compounds are synthesized by methods selected from a number of synthetic routes depending on the particular structure, choice of intermediate or preferred reaction sequence. The compounds are useful in the treatment and prevention of injury to the brain and spinal chord due to accidents, ischemic stroke and hydrocephalus; compositions for such uses are also disclosed.
Claims12
A compound of the formula:
- ##STR21## wherein R is C.sub.2 to C.sub.4 alkynyl, branched or unbranched;
- R.sup.1 is H, lower alkyl;
- lower alkenyl;
- lower alkynyl;
- lower cycloalkyl;
- substituted lower alkyl, where the substituent is carboxy, lower alkoxycarbonyl, oxo, hydroxy, lower alkoxy, halo, lower acyloxy, lower dialkylamino, sulfamoyl, pyridyl, furyl, tetrahydrofuryl, aryl, 1-methylpiperidyl, morpholinyl, pyrrolidinyl, 1-methyl-piperazinyl, and thienyl;
- substituted cycloalkyl heterocyclic;
- aryl;
- Y.sup.1 and Y.sup.2 are independently C1 and CH.sub.3 ;
- A is (CH.sub.2).sub.2 or ##STR22## where R.sup.2 is H, methyl or ethyl, R.sup.3 is H, F or methyl and R.sup.2 and R.sup.3, may be joined together to form the ring >C(CH.sub.2).sub.n where n is the integer 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
A compound which is the (+) enantiomer of [(5,6-dichloro-3-oxo-9a-propargyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy] acetic acid.
A compound which is the (+) enantiomer of 1-carboxy-1-methylethyl [(5,6-dichloro-3-oxo-9a-propargyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl) -oxy]acetic acid.
A composition in unit dosage form for the treatment of grey matter edema comprising a compound of the formula:
- ##STR24## wherein R is C.sub.2 to C.sub.4 alkenyl, branched or unbranched;
- R.sup.1 is H, lower alkyl;
- lower alkenyl;
- lower alkynyl;
- lower cycloalkyl;
- substituted lower alkyl, where the substituent is carboxy, lower alkoxycarbonyl, oxo, hydroxy, lower alkoxy, halo, lower acyloxy, lower dialkylamino, sulfamoyl, pyridyl, furyl, tetrahydrofuryl, aryl, 1-methylpiperidyl, morpholinyl, pyrrolidinyl, 1-methylpiperazinyl, and thienyl;
- substituted cycloalkyl;
- heterocyclic;
- aryl;
- Y.sup.1 and Y.sup.2 are independently C1 and CH.sub.3 ;
- A is (CH.sub.2).sub.2 or ##STR25## where R.sup.2 is H, methyl or ethyl, R.sup.3 is H, F or methyl and R.sup.2 and R.sup.3, may be joined together to form the ring >C(CH.sub.2).sub.n where n is the integer 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.