N-(1-thienylcycloalkyl)alkenylamines for treatment of neurotoxic injury
AssigneesG. D. Searle & Co., National Institutes of Health
InventorsKenner C. Rice, Arthur E. Jacobson, Andrew Thurkauf, Mariena V. Mattson, Thomas L. O'Donohue, Patricia C. Contreras, Nancy M. Gray
Life of this patent
Estimating the term…
Abstract
Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of an N-(1-thienylcycloalkyl)alkenylamine compound as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of most interest are those of the formula ##STR1## wherein R.sup.1, R.sup.2, and R.sup.5 are defined in specification.
Claims13
Compound of the formula ##STR28## wherein each R.sup.1 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl, alkoxy or halo, wherein at least two of said R.sup.1 groups are hydrido;
- each R.sup.2 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl, oxo, alkoxy or halo, wherein at least two of said R.sup.2 groups are hydrido;
- each R.sup.5 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl or alkoxy, wherein at least two of said R.sup.5 groups are hydrido;
- and
- wherein the broken line within the N-containing ring represents a double bond between any two adjacent carbon atoms involving the 2-, 3-, 4-, 5-, and 6-positions of said N-containing ring.
A pharmaceutical composition comprising a therapeutically-effective amount of a compound to treat or prevent a neurodegenerative disease and a pharmaceutically-acceptable carrier or diluent, said compound having the formula ##STR30## wherein each R.sup.1 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl, alkoxy or halo, wherein at least two of said R.sup.1 groups are hydrido;
- each R.sup.2 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl, oxo, alkoxy or halo, wherein at least two of said R.sup.2 groups are hydrido;
- each R.sup.5 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl or alkoxy, wherein at least two of said R.sup.5 groups are hydrido;
- and
- wherein the broken line within the N-containing ring represents a double bond between any two adjacent carbon atoms involving the 2-, 3-, 4-, 5-, and 6-positions of said N-containing ring.
Method to control neuropathological processes and the neurodegenerative consequences thereof in mammals, which method comprises treating a mammal susceptible to neurotoxic injury with an effective amount of a compound of the formula ##STR32## wherein each R.sup.1 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl, alkoxy or halo, wherein at least two of said R.sup.1 groups are hydrido;
- each R.sup.2 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl, oxo, alkoxy or halo, wherein at least two of said R.sup.2 groups are hydrido;
- each R.sup.5 is independently hydrido, alkyl of one to ten carbon atoms, cycloalkyl of three to ten carbon atoms, alkenyl of two to ten carbon atoms, hydroxyl or alkoxy, wherein at least two of said R.sup.5 groups are hydrido;
- and
- wherein the broken line within the N-containing ring represents a double bond between any two adjacent carbon atoms involving the 2-, 3-, 4-, 5-, and 6-positions of said N-containing ring.
Dependencies are inferred from the claim text.