US5118675A
Expired / Lapsed
US
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Quinoxaline phosphono-amino acids
Assignee: Wyeth LLC
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Filing: 1991-02-15
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Granted: 1992-06-02
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Expires: 2011-02-15
Abstract
Abstract The compounds of the formula: ##STR1## in which Q is the quinoxaline nucleus; m is one of the integers 0, 1 or 2; n is one of the integers 1,2 or 3; or a pharmaceutically acceptable salt, alkyl ester or ##STR2## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy, are NMDA antagonists useful in the treatment and prevention of central nervous system related pathological conditions resulting from overstimulation by excitatory amino acids.
Inventors
- 👤 Ivo L. Jirkovsky
- 👤 Reinhardt B. Baudy
- 👤 Lynne P. Greenblatt
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 07:46
CPC Classifications
C; C07; C07F; C07F9/00; C07F9/02; C07F9/547; C07F9/645; C07F9/6509; C07F9/650952; C07F9/650994
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
141 words
A compound of the formula: ##STR6## in which the amino acid and phosphonic acid bearing groups are ortho to each other in the 2-, 3- or 6-, 7-positions of the quinoxaline nucleus and, when the acid bearing groups are in the 2-, 3-positions, R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene, otherwise R 1 and R 2 are hydrogen; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has from 1 to 6 carbon atoms, or a ##STR7## ##STR8## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy.
Claim 2
Dependent Claim
141 words
A compound of the formula: ##STR6## in which the amino acid and phosphonic acid bearing groups are ortho to each other in the 2-, 3- or 6-, 7-positions of the quinoxaline nucleus and, when the acid bearing groups are in the 2-, 3-positions, R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene, otherwise R 1 and R 2 are hydrogen; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has from 1 to 6 carbon atoms, or a ##STR7## ##STR8## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy.
Claim 3
Dependent Claim
64 words
A compound of the formula: ##STR9## in which R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has 1 to 6 carbon atoms, or benzyl ester thereof.
Claim 4
Dependent Claim
64 words
A compound of the formula: ##STR9## in which R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has 1 to 6 carbon atoms, or benzyl ester thereof.
Claim 5
Dependent Claim
62 words
A compound of claim 2 in which the alkyl substituent is of 1 to 4 carbon atoms; the alkoxy substituent is of 1 to 6 carbon atoms; halo is chlorine, bromine or fluorine; m is 1; n is 1 or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 6
Dependent Claim
32 words
The compound of claim 1 which is α-amino-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 7
Dependent Claim
33 words
The compound of claim 1 which is (-) α-amino-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 8
Dependent Claim
32 words
The compound of claim 1 which is α-amino-6,7-dimethyl-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 9
Dependent Claim
32 words
The compound of claim 1 which is α-amino-3-(phosphonomethyl)-2-benzo[g]quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 10
Dependent Claim
32 words
The compound of claim 1 which is α-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 11
Dependent Claim
32 words
The compound of claim 1 which is α-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 12
Dependent Claim
32 words
The compound of claim 1 which is α-amino-5,8-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 13
Dependent Claim
32 words
The compound of claim 1 which is α-amino-6,7-difluoro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 14
Dependent Claim
32 words
The compound of claim 1 which is α-amino-6,7-dimethoxy-3-(phosphonomethyl)-2-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 15
Dependent Claim
29 words
The compound which is α-amino-7-(phosphonomethyl)-6-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 16
Dependent Claim
29 words
The compound which is α-amino-7-(phosphonomethyl)-6-quinoxalinepropanoic acid or a pharmaceutically acceptable salt, alkyl ester in which the alkyl group has from 1 to 6 carbon atoms or benzyl ester thereof.
Claim 17
Dependent Claim
164 words
A process for the treatment of cerebral ischemia which comprises administering to a mammal suffering from such disorder, a neuroprotective amount of an NMDA antagonist of the formula: ##STR10## in which the amino acid and phosphonic acid bearing groups are ortho to each other in the 2-, 3- or 6-, 7-positions of the quinoxaline nucleus and, when the acid bearing groups are in the 2-, 3-positions, R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene, otherwise R 1 and R 2 are hydrogen; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has from 1 to 6 carbon atoms, or a ##STR11## ##STR12## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy.
Claim 18
Dependent Claim
164 words
A process for the treatment of cerebral ischemia which comprises administering to a mammal suffering from such disorder, a neuroprotective amount of an NMDA antagonist of the formula: ##STR10## in which the amino acid and phosphonic acid bearing groups are ortho to each other in the 2-, 3- or 6-, 7-positions of the quinoxaline nucleus and, when the acid bearing groups are in the 2-, 3-positions, R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene, otherwise R 1 and R 2 are hydrogen; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has from 1 to 6 carbon atoms, or a ##STR11## ##STR12## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy.
Claim 19
Dependent Claim
158 words
A pharmaceutical composition for the treatment of cerebral ischemia which comprises a compound of the formula: ##STR13## in which the amino acid and phosphonic acid bearing groups are ortho to each other in the 2-, 3- or 6-, 7-positions of the quinoxaline nucleus and, when the acid bearing groups are in the 2-, 3-positions, R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene, otherwise R 1 and R 2 are hydrogen; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has from 1 to 6 carbon atoms, or a ##STR14## ##STR15## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy; and a pharmaceutically acceptable carrier therefor.
Claim 20
Dependent Claim
158 words
A pharmaceutical composition for the treatment of cerebral ischemia which comprises a compound of the formula: ##STR13## in which the amino acid and phosphonic acid bearing groups are ortho to each other in the 2-, 3- or 6-, 7-positions of the quinoxaline nucleus and, when the acid bearing groups are in the 2-, 3-positions, R 1 and R 2 are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or halo, or taken together, R 1 and R 2 are butadienylene, otherwise R 1 and R 2 are hydrogen; m is one of the integers 0, 1 or 2; n is one of the integers 1, 2 or 3; or a pharmaceutically acceptable salt, alkyl ester, in which the alkyl group has from 1 to 6 carbon atoms, or a ##STR14## ##STR15## where R 3 and R 4 are, independently, hydrogen, nitro, halo or methoxy; and a pharmaceutically acceptable carrier therefor.
References Cited (Backward Citations)
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