Merck & Company, Inc.

University of Pittsburgh

Otto W Woltersdorf, Jr

Edward J Cragoe, Jr

Adolph M Pietruszkiewicz

William F Hoffman

Donald J Abraham

Susan J DeSolms

Harvey Schwam

Stuart R Michelson

John M Sondey

Mark G Bock

Robert L Smith

Gerald E Stokker

S Jane deSolms

Haydn W Williams

Jacob M Hoffman, Jr

Everett M Schultz

Charles N Habecker

The invention relates to novel [5,6-dichloro-3-oxo-9a-propyl-2,3,9,9a -tetrahydrofluoren-7-yl)]alkanoic acids and alkanimidamides, their derivatives and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections, various brain concussions and elevated intracranial pressure.

(5,6-dichloro-3-oxo-9.alpha.-propyl-2,3,9,9.alpha.-tet

The invention relates to novel [(5,6-dichloro-3-oxo-9,9a-disubstituted-2,3,9,9a-tetrahydro-fluoren-7-yl)o xy]alkanoic acids and alkanimidamides, their derivatives and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections, various brain concussions and elevated intracranial pressure.

((5,6-dichloro-3-oxo-9,9a-d

The invention relates to novel [(3,4-dichloro-6,7,8,8a,9,10-hexahydro-6-oxo-8a-substituted-2-phenanthreny l)ox yl]-alkanoic acids and -ethanimidamides and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections and various brain concussions.

[3,4-dichloro-6,7,8,8a,9,10-hexahydro-6-oxo-8a-substituted-2-phenanthreny

This invention relates to novel substituted amidinoalkoxy and amidinoalkylamino indanones and salts thereof. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, the neurological problems caused by AIDS, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections, various brain concussions, and elevated intracranial pressure.

Substituted amidinoalkoxy and amidinoalkylamino indanones and salts

The invention relates to novel (1,2-dichloro-8-oxo-5a-substituted-5a,6,7,8-tetrahydrodibenzofuran-3-yl)al kanoic acids and alkanimidamides, their derivatives and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections including that due to AIDS virus, various brain concussions and elevated intracranial pressure.

(1,2-dichloro-8-oxo-5a-substituted-5a,6,7,8

The invention relates to novel substituted (2,3-dihydro-1-oxo-1H-inden-5-yl)alkanoic acids, their derivatives and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections and various brain concussions.

Substituted (2,3-dihydro-1-oxo-1H-inden-5-yl)alkanoic acids, their

The present invention is directed to compounds of the general formula I and pharmaceutically acceptable salts thereof: ##STR1## wherein: R.sup.1 =HO or HOOC(CH.sub.2).sub.x CHR.sup.2 NH--;

Compounds useful in treating sickle cell anemia

The invention relates to novel [(5,6-dichloro-3-oxo-2,3,9,9a-tetrahydrofluoren-7-yl)]alkanoic acids and alkanimidamides bearing novel functional 9a-substituents, their derivatives and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, the neurological problems caused by AIDS, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections, various brain concussions and elevated intracranial pressure.

(5,6-dichloro-3-oxo-2,3,9,9a-tetrahydrofluoren-7-yl)-alkanoic acids and

The invention relates to novel [(5,6-dichloro-3-oxo-9a-propyl-2,3,9,9a-tetrahydrofluoren-7-yl)]alkanoic acids and alkanimidamides, their derivatives and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections, various brain concussions and elevated intracranial pressure.

(5,6-dichloro-3-oxo-9A-propyl-2,3,9,9A-tetrahydrofluoren-7-yl)alkanoic

The present invention is directed to compounds of the general formula I and pharmaceutically acceptable salts thereof: ##STR1## wherein: R=ethyl, propyl or isopropyl; and

The present invention is directed to a method of treating a person for sickle cell anemia comprising administering to the person a therapeutically effective dosage of a compound of the general formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein: R=ethyl, propyl or isopropyl; and ##STR2##

Method of treating a person for sickle cell anemia

The invention relates to novel [(5,6-dichloro-3-oxo-2,9a-alkano--2,3,9,9a-tetrahydro-1H-fluoren-7-yl)oxy] alkanoic acids and alkanimidamides, their derivatives, and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections including that due to AIDS virus, various brain concussions and elevated intracranial pressure.

[(5,6-dichloro-3-oxo-2,9a-alkano-2,3,9,9a-tetrahydro-1H-fluoren-7-yl)oxy]

The invention relates to novel ester and amide substituted [2,3-dihydro-4-(3-oxo-1-cyclohexen-1-yl)phenoxy]alkanoic acids and their salts. The compounds are useful for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections and various brain concussions.

Ester and amide substituted

The present invention is directed to compounds of the general formula I and pharmaceutically acceptable salts thereof: ##STR1## wherein R=H or lower alkyl;

The invention relates to novel substituted-3-(2,3-dihydro-1H-inden-5-yl)-4-hydroxy-1H-pyrrole-2,5-diones, their analogs and their salts. 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 for the treatment and prevention of injury to the brain and of edema due to head trauma, stroke (particularly ischemic), arrested breathing, cardiac arrest, Reye's syndrome, cerebral thrombosis, cerebral embolism, cerebral hemorrhage, cerebral tumors, encephalomyelitis, spinal cord injury, hydrocephalus, post-operative brain injury trauma, edema due to cerebral infections and various brain concussions.

Growing community of inventors

Chalfont, PA, United States of America

Otto W Woltersdorf, Jr