US5795877A
Expired / Lapsed
US
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Inhibitors of NAALADase enzyme activity
Assignee: Eisai Inc
•
Filing: 1996-12-31
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Granted: 1998-08-18
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Expires: 2016-12-31
Abstract
Abstract The present invention includes compounds, compositions, and methods of treatment for glutamate abnormalities and associated nervous tissue insult in a animal by inhibition of NAALADase enzyme. Compositions include phosphonate derivatives and mixtures thereof that inhibit NAALADase enzyme activity and their use for treating glutamate abnormalities such as created by global and focal ischemia and for treatment of prostate disease and prostate cancer by inhibition of NAALADase enzyme.
Inventors
- 👤 Paul F. Jackson
- 👤 Barbara S. Slusher
- 👤 Kevin L. Tays
- 👤 Keith M. Maclin
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 15:05
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/66; A61K31/661; A61K31/185; A61K31/19; A61K31/194; A61K38/00; A61K38/04; A61K38/05; A61K38/06; C; C07; C07F; C07F9/00; C07F9/02; C07F9/28; C07F9/30; C07F9/301; C07F9/38; C07F9/40; C07F9/4071; C07F9/4075; C07F9/44; C07F9/4461; C07F9/4465; C07F9/547; C07F9/553; C07F9/576; C07F9/58; C07F9/655; C07F9/65515; C07F9/6552
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
181 words
A compound having the following formula: ##STR13## where R is hydrogen, C 1 -C 9 straight or branched chain alkyl or alkenyl group, C 3 -C 8 cycloalkyl, C 3 or C 5 cycloalkyl, C 5 -C 7 cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl groups are optionally substituted with C 3 -C 8 cycloalkyl, C 3 or C 5 cycloalkyl, C 5 -C 7 cycloalkenyl, C 1 -C 4 alkyl, C 1 -C 4 alkenyl, hydroxy, halo, hydroxyl, nitro, trifluoromethyl, C 1 -C 6 straight or branched chain alkyl or alkenyl, C 1 -C 4 alkoxy, C 1 -C 4 alkenyloxy, phenoxy, benzyloxy, amino, or Ar 1 , and where Ar 1 is selected from the group consisting of 1-naphthyl, 2-naphthyl, and phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C 1 -C 6 straight or branched alkyl or alkenyl, C 1 -C 4 alkoxy or C 1 -C 4 alkenyloxy, phenoxy, benzyloxy, and amino; or pharmaceutically acceptable salts or hydrates thereof.
Claim 2
Dependent Claim
181 words
A compound having the following formula: ##STR13## where R is hydrogen, C 1 -C 9 straight or branched chain alkyl or alkenyl group, C 3 -C 8 cycloalkyl, C 3 or C 5 cycloalkyl, C 5 -C 7 cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or aryl groups are optionally substituted with C 3 -C 8 cycloalkyl, C 3 or C 5 cycloalkyl, C 5 -C 7 cycloalkenyl, C 1 -C 4 alkyl, C 1 -C 4 alkenyl, hydroxy, halo, hydroxyl, nitro, trifluoromethyl, C 1 -C 6 straight or branched chain alkyl or alkenyl, C 1 -C 4 alkoxy, C 1 -C 4 alkenyloxy, phenoxy, benzyloxy, amino, or Ar 1 , and where Ar 1 is selected from the group consisting of 1-naphthyl, 2-naphthyl, and phenyl, having one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, C 1 -C 6 straight or branched alkyl or alkenyl, C 1 -C 4 alkoxy or C 1 -C 4 alkenyloxy, phenoxy, benzyloxy, and amino; or pharmaceutically acceptable salts or hydrates thereof.
Claim 3
Dependent Claim
25 words
A pharmaceutical composition for inhibiting NAALADase activity which comprises: (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 4
Dependent Claim
28 words
A method of inhibiting NAALADase enzyme activity which comprises: (i) administering to said enzyme an effective amount of the compound of claim 1 in a pharmaceutically acceptable carrier.
Claim 5
Dependent Claim
43 words
A pharmaceutical composition for treating glutamate abnormalities selected from the group consisting of ischemic stroke, ischemic heart attack, epilepsy, and Parkinson's disease in an animal which comprises: (i) an effective amount of the compound of claim 1 and (ii) a pharmaceutically acceptable carrier.
Claim 6
Dependent Claim
44 words
A method of treating glutamate abnormalities selected from the croup consisting of ischemic stroke, ischemic heart attack, epilepsy, and Parkinson's disease in an animal which comprises: administering to said animal an effective amount of the compound of claim 1 in a pharmaceutically acceptable carrier.
Claim 7
Dependent Claim
66 words
A pharmaceutical composition for treating ischemia selected from the group consisting of ischemic stroke, ischemia due to traumatic injury, ischemia due to heart attack, ischemia resulting from spinal cord compression, ischemia due to thromboembolytic occlusion, ischemia due to brain tumors, and ischemia due to edema in an animal which comprises: (i) an effective amount of the compound of claim 1 and (ii) a pharmaceutically acceptable carrier.
Claim 8
Dependent Claim
67 words
A method of treating ischemia selected from the group consisting of ischemic stroke, ischemia due to traumatic injury, ischemia due to heart attack, ischemia resulting from spinal cord compression, ischemia due to thromboembolytic occlusion, ischemia due to brain tumors, and ischemia due to edema in an animal which comprises: administering to said animal an effective amount of the compound of claim 1 in a pharmaceutically acceptable carrier.
Claim 9
Dependent Claim
26 words
A prostatic adenocarcinoma tumor cell growth inhibiting pharmaceutical composition containing (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 10
Dependent Claim
30 words
A method of inhibiting prostatic adenocarcinoma tumor cell growth which comprises: administering to said tumor cell an effective amount of the compound of claim 1 in a suitable pharmaceutical carrier.
Claim 11
Dependent Claim
27 words
A pharmaceutical composition for treating prostate cancer in an animal comprising: (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 12
Dependent Claim
26 words
A method of treating prostate cancer in an animal comprising: (i) administering an effective amount of the compound of claim 1 in a suitable pharmaceutical carrier.
Claim 13
Dependent Claim
29 words
A compound selected from the group consisting of: 2- Methylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Ethylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Propylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Butylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Phenylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- (Phenylmethyl)hydroxyphosphinyl!oxy!pentanedioic Acid; 2- ((2-Phenylethyl)methyl)hydroxyphosphinyl!oxy!pentanedioic Acid.
Claim 14
Dependent Claim
29 words
A compound selected from the group consisting of: 2- Methylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Ethylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Propylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Butylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- Phenylhydroxyphosphinyl!oxy!pentanedioic Acid; 2- (Phenylmethyl)hydroxyphosphinyl!oxy!pentanedioic Acid; 2- ((2-Phenylethyl)methyl)hydroxyphosphinyl!oxy!pentanedioic Acid.
Claim 15
Dependent Claim
25 words
A pharmaceutical composition for inhibiting NAALADase activity which comprises: (i) an effective amount of the compound of claim 12 and (ii) a suitable pharmaceutical carrier.
Claim 16
Dependent Claim
28 words
A method of inhibiting NAALADase enzyme activity which comprises: (i) administering to said enzyme an effective amount of the compound of claim 12 in a pharmaceutically acceptable carrier.
Claim 17
Dependent Claim
43 words
A pharmaceutical composition for treating glutamate abnormalities selected from the group consisting of ischemic stroke, ischemic heart attack, epilepsy, and Parkinson's disease in an animal which comprises: (i) an effective amount of the compound of claim 12 and (ii) a pharmaceutically acceptable carrier.
Claim 18
Dependent Claim
44 words
A method of treating glutamate abnormalities selected from the group consisting of ischemic stroke, ischemic heart attack, epilepsy, and Parkinson's disease in an animal which comprises: administering to said animal an effective amount of the compound of claim 12 in a pharmaceutically acceptable carrier.
Claim 19
Dependent Claim
25 words
A pharmaceutical composition for treating nervous tissue which comprises: (i) an effective amount of the compound of claim 12 and (ii) a pharmaceutically acceptable carrier.
Claim 20
Dependent Claim
27 words
A method of treating nervous tissue which comprises: administering to said nervous tissue an effective amount of the compound of claim 12 in a pharmaceutically acceptable carrier.
Claim 21
Dependent Claim
66 words
A pharmaceutical composition for treating ischemia selected from the group consisting of ischemic stroke, ischemia due to traumatic injury, ischemia due to heart attack, ischemia resulting from spinal cord compression, ischemia due to thromboembolytic occlusion, ischemia due to brain tumors, and ischemia due to edema in an animal which comprises: (i) an effective amount of the compound of claim 12 and (ii) a pharmaceutically acceptable carrier.
Claim 22
Dependent Claim
67 words
A method of treating ischemia selected from the group consisting of ischemic stroke, ischemia due to traumatic injury, ischemia due to heart attack, ischemia resulting from spinal cord compression, ischemia due to thromboembolytic occlusion, ischemia due to brain tumors, and ischemia due to edema in an animal which comprises: administering to said animal an effective amount of the compound of claim 12 in a pharmaceutically acceptable carrier.
Claim 23
Dependent Claim
26 words
A prostatic adenocarcinoma tumor cell growth inhibiting pharmaceutical composition containing (i) an effective amount of the compound of claim 12 and (ii) a suitable pharmaceutical carrier.
Claim 24
Dependent Claim
30 words
A method of inhibiting prostatic adenocarcinoma tumor cell growth which comprises: administering to said tumor cell an effective amount of the compound of claim 12 in a suitable pharmaceutical carrier.
Claim 25
Dependent Claim
27 words
A pharmaceutical composition for treating prostate cancer in an animal comprising: (i) an effective amount of the compound of claim 12 and (ii) a suitable pharmaceutical carrier.
Claim 26
Dependent Claim
26 words
A method of treating prostate cancer in an animal comprising: (i) administering an effective amount of the compound of claim 12 in a suitable pharmaceutical carrier.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-08-17 | 2002-02-16 | 2002-08-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-08-17 | 2006-02-16 | 2006-08-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-08-17 | 2010-02-16 | 2010-08-18 | $7700.00 | Window Closed / Lapsed |