N-substituted .alpha.-amino acids and derivatives thereof having pharmaceutical activity
First Claim
1. A compound of Formula I ##STR55## wherein X is --CH2 CH2 --,--CH═
- CH--, ##STR56## wherein R5 and R6 are independently selected from hydrogen, lower alkyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, lower alkoxy, lower alkylthio, halogen, hydroxy, or trifluoromethyl, ##STR57## wherein R5 and R6 are as defined above, ##STR58## wherein n is 1 to 3, or ##STR59## wherein n is as defined above;
A and D are independently selected from --(CH2)m --, wherein m is 0 to 3, --CH═
CH--, or --CH═
CHCH2 --;
R is --OPO3 R7 R8, wherein R7 and R8 are independently selected from hydrogen, lower alkyl, lower alkenyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, or a pharmaceutically acceptable labile group, --PO3 R7 R8, wherein R7 and R8 are as defined above, or --PO2 R7 R8, wherein R7 and R8 are as defined above;
R1 is hydrogen, lower alkyl, lower alkenyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, --CO--alkyl, ##STR60## R2 is hydrogen, --CH3, --CH2 OH, --CH2 --CO2 H, --CH2 --CONH2, --CH2 CH2 --CO2 H, --CH2 CH2 --CONH2, --CH2 SH, ##STR61## R3 is --OR7, wherein R7 is as defined above, or --NR9 R10, wherein R9 and R10 are independently selected from hydrogen, lower alkyl, lower alkenyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, or a pharmaceutically acceptable labile group;
or a pharmaceutically acceptable salt thereof.
0 Assignments
0 Petitions
Accused Products
Abstract
N-substituted α-amino acids and derivatives thereof are described, as well as methods for the preparation and pharmaceutical composition of same, which are useful in selectively blocking the N-methyl-D-aspartate (NMDA) excitatory amino acid receptors in mammals and also are useful in treating cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from thromboembolic or hemorrhagic stroke, cerebral vasospasm, hypoglycemia, cardiac arrest, status epilepticus and cerebral trauma as well as for treating schizophrenia, epilepsy, neurodegenerative disorders, Alzheimer'"'"'s disease or Huntington'"'"'s disease and also additionally useful as anesthetics in surgical procedures where a finite risk of cerebrovascular damage exists.
-
Citations
6 Claims
-
1. A compound of Formula I ##STR55## wherein X is --CH2 CH2 --,
--CH═ - CH--, ##STR56## wherein R5 and R6 are independently selected from hydrogen, lower alkyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, lower alkoxy, lower alkylthio, halogen, hydroxy, or trifluoromethyl, ##STR57## wherein R5 and R6 are as defined above, ##STR58## wherein n is 1 to 3, or ##STR59## wherein n is as defined above;
A and D are independently selected from --(CH2)m --, wherein m is 0 to 3, --CH═
CH--, or --CH═
CHCH2 --;R is --OPO3 R7 R8, wherein R7 and R8 are independently selected from hydrogen, lower alkyl, lower alkenyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, or a pharmaceutically acceptable labile group, --PO3 R7 R8, wherein R7 and R8 are as defined above, or --PO2 R7 R8, wherein R7 and R8 are as defined above; R1 is hydrogen, lower alkyl, lower alkenyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, --CO--alkyl, ##STR60## R2 is hydrogen, --CH3, --CH2 OH, --CH2 --CO2 H, --CH2 --CONH2, --CH2 CH2 --CO2 H, --CH2 CH2 --CONH2, --CH2 SH, ##STR61## R3 is --OR7, wherein R7 is as defined above, or --NR9 R10, wherein R9 and R10 are independently selected from hydrogen, lower alkyl, lower alkenyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, or a pharmaceutically acceptable labile group;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (2, 3, 4, 5, 6)
- CH--, ##STR56## wherein R5 and R6 are independently selected from hydrogen, lower alkyl, phenyl, phenyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, phenyl lower alkyl, phenyl lower alkyl substituted by one to four substituents selected from lower alkyl of from one to six carbon atoms, lower alkoxy of from one to six carbon atoms, halogen or trifluoromethyl, lower alkoxy, lower alkylthio, halogen, hydroxy, or trifluoromethyl, ##STR57## wherein R5 and R6 are as defined above, ##STR58## wherein n is 1 to 3, or ##STR59## wherein n is as defined above;
Specification