US5863536A
Expired / Lapsed
US
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Phosphoramidate derivatives
Assignee: Eisai Inc
•
Filing: 1996-12-31
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Granted: 1999-01-26
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Expires: 2016-12-31
Abstract
Abstract The present invention includes phosphoramidate derivatives, compositions containing the same, and methods of using them as NAALADase inhibitors, particularly for the treatment of glutamate abnormalities and associated nervous tissue insult in a animal 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 15:24
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
192 words
A compound having the following formula: ##STR12## where R and R1 are independently hydrogen, C 1 -C 9 straight or branched chain alkyl or alkenyl group, C 3 -C 8 cycloalkyl, C 5 -C 7 cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or Ar 1 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, 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and phenyl, said Ar 1 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
192 words
A compound having the following formula: ##STR12## where R and R1 are independently hydrogen, C 1 -C 9 straight or branched chain alkyl or alkenyl group, C 3 -C 8 cycloalkyl, C 5 -C 7 cycloalkenyl, or Ar 1 , wherein said alkyl, alkenyl, cycloalkyl, cycloalkenyl or Ar 1 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, 2-indolyl, 3-indolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, or 4-pyridyl, and phenyl, said Ar 1 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
12 words
The compound of claim 1, in combination with an additional therapeutic agent.
Claim 4
Dependent Claim
28 words
A pharmaceutical composition for inhibiting N-Acetylated Alpha-Linked Acidic Dipeptidase activity which comprises: (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 5
Dependent Claim
31 words
A method of inhibiting N-Acetylated Alpha-Linked Acidic Dipeptidase enzyme activity which comprises: (i) administering to said enzyme an effective amount of the compound of claim 1 in a pharmaceutically acceptible carrier.
Claim 6
Dependent Claim
27 words
A pharmaceutical composition for treating ischemia in an animal which comprises: (i) an effective amount of the compound of claim 1 and (ii) a pharmaceutically acceptable carrier.
Claim 7
Dependent Claim
28 words
A method of treating ischemia in an animal which comprises: administering to said animal an effective amount of the compound of claim 1 in a pharmaceutically acceptable carrier.
Claim 8
Dependent Claim
26 words
A prostate tumor cell growth inhibiting pharmaceutical composition which comprises: (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 9
Dependent Claim
29 words
A method of inhibiting prostate 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 10
Dependent Claim
60 words
The prostate tumor cell growth inhibiting pharmaceutical composition of claim 7, further comprising an additional therapeutic agent selected from the group consisting of therapeutic hormones, chemotherapeutic agents, monoclonal antibodies for cancer therapy, anti-angiogenesis agents, radiolabelled compounds selected from the group consisting of (i) Indium-111 labelled Prostate Specific Membrane Antigen antibody and (ii) monoclonal antibody conjugated with strontium-89, and mixtures thereof.
Claim 11
Dependent Claim
16 words
The tumor cell growth inhibiting pharmaceutical composition of claim 7, wherein the tumor is prostatic adenocarcinoma.
Claim 12
Dependent Claim
39 words
A pharmaceutical composition for treating prostate diseases selected from the group consisting of prostate cancer and benign prostatic hyperplasia in an animal comprising: (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 13
Dependent Claim
38 words
A method of treating prostate diseases selected from the group consisting of prostate cancer and benign prostatic hyperplasia in an animal comprising: (i) administering an effective amount of the compound of claim 1 in a suitable pharmaceutical carrier.
Claim 14
Dependent Claim
33 words
A compound selected from the group consisting of: N- Methylhydroxyphosphinyl!glutamic Acid; N- Ethylhydroxyphosphinyl!glutamic Acid; N- Propylhydroxyphosphinyl!glutamic Acid; N- Butylhydroxyphosphinyl!glutamic Acid; N- Phenylhydroxyphosphinyl!glutamic Acid; N- (Phenylmethyl)hydroxyphosphinyl!glutamic Acid; N- ((2-Phenylethyl)methyl)hydroxyphosphinyl!glutamic Acid; and N-Methyl-N- Phenylhydroxyphosphinyl!glutamic Acid.
Claim 15
Dependent Claim
33 words
A compound selected from the group consisting of: N- Methylhydroxyphosphinyl!glutamic Acid; N- Ethylhydroxyphosphinyl!glutamic Acid; N- Propylhydroxyphosphinyl!glutamic Acid; N- Butylhydroxyphosphinyl!glutamic Acid; N- Phenylhydroxyphosphinyl!glutamic Acid; N- (Phenylmethyl)hydroxyphosphinyl!glutamic Acid; N- ((2-Phenylethyl)methyl)hydroxyphosphinyl!glutamic Acid; and N-Methyl-N- Phenylhydroxyphosphinyl!glutamic Acid.
Claim 16
Dependent Claim
12 words
The compound of claim 13, in combination with an additional therapeutic agent.
Claim 17
Dependent Claim
28 words
A pharmaceutical composition for inhibiting N-Acetylated Alpha-Linked Acidic Dipeptidase activity which comprises: (i) an effective amount of the compound of claim 13 and (ii) a suitable pharmaceutical carrier.
Claim 18
Dependent Claim
31 words
A method of inhibiting N-Acetylated Alpha-Linked Acidic Dipeptidase enzyme activity which comprises: (i) administering to said enzyme an effective amount of the compound of claim 13 in a pharmaceutically acceptible carrier.
Claim 19
Dependent Claim
27 words
A pharmaceutical composition for treating ischemia in an animal which comprises: (i) an effective amount of the compound of claim 13 and (ii) a pharmaceutically acceptable carrier.
Claim 20
Dependent Claim
28 words
A method of treating ischemia in an animal which comprises: administering to said animal an effective amount of the compound of claim 13 in a pharmaceutically acceptable carrier.
Claim 21
Dependent Claim
25 words
A prostate tumor cell growth inhibiting pharmaceutical composition containing (i) an effective amount of the compound of claim 13 and (ii) a suitable pharmaceutical carrier.
Claim 22
Dependent Claim
29 words
A method of inhibiting prostate tumor cell growth which comprises: administering to said tumor cell an effective amount of the compound of claim 13 in a suitable pharmaceutical carrier.
Claim 23
Dependent Claim
60 words
The prostate tumor cell growth inhibiting pharmaceutical composition of claim 19, further comprising an additional therapeutic agent selected from the group consisting of therapeutic hormones, chemotherapeutic agents, monoclonal antibodies for cancer therapy, anti-angiogenesis agents, radiolabelled compounds selected from the group consisting of (i) Indium-111 labelled Prostate Specific Membrane Antigen antibody and (ii) monoclonal antibody conjugated with strontium-89, and mixtures thereof.
Claim 24
Dependent Claim
16 words
The tumor cell growth inhibiting pharmaceutical composition of claim 19, wherein the tumor is prostatic adenocarcinoma.
Claim 25
Dependent Claim
39 words
A pharmaceutical composition for treating prostate diseases selected from the group consisting of prostate cancer and benign prostatic hyperplasia in an animal comprising: (i) an effective amount of the compound of claim 1 and (ii) a suitable pharmaceutical carrier.
Claim 26
Dependent Claim
38 words
A method of treating prostate diseases selected from the group consisting of prostate cancer and benign prostatic hyperplasia in an animal comprising: (i) administering an effective amount of the compound of claim 1 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) | 2002-01-25 | 2002-07-27 | 2003-01-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-01-25 | 2006-07-27 | 2007-01-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-01-25 | 2010-07-27 | 2011-01-26 | $7700.00 | Window Closed / Lapsed |