Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
2001-05-30
2002-09-17
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C514S706000, C562S405000, C562S434000, C562S435000
Reexamination Certificate
active
06452044
ABSTRACT:
The present invention relates to new compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to inhibit NAALADase enzyme activity, detecting diseases where NAALADase levels are altered, inhibit angiogenesis, effect neuronal activity, and treat glutamate abnormalities, neuropathy, pain, prostate diseases, cancers, TGF-&bgr; abnormalities, compulsive disorders, and glaucoma.
The NAALADase enzyme, also known as prostate specific membrane antigen (“PSM” or “PSMA”) and human glutamate carboxypeptidase II (“GCP II”), catalyzes the hydrolysis of the neuropeptide N-acetyl-aspartyl-glutamate (“NAAG”) to N-acetyl-aspartate (“NAA”) and glutamate. Based upon amino acid sequence homology, NAALADase has been assigned to the M28 family of peptidases.
Studies suggest NAALADase inhibitors may be effective in treating ischemia, spinal cord injury, demyelinating diseases, Parkinson's disease, Amyotrophic Lateral Sclerosis (“ALS”), alcohol dependence, nicotine dependence, cocaine dependence, cancer, diabetic neuropathy, pain and schizophrenia, and in inhibiting angiogenesis. In view of their broad range of potential applications, a need exists for new NAALADase inhibitors and pharmaceutical compositions comprising such compounds.
SUMMARY OF THE INVENTION
Specifically, the present invention relates to a compound of formula I
or a pharmaceutically acceptable equivalent, wherein:
X is —W—Z;
W is a bond or a linking group;
Z is a terminal group; and
Y is —COOH oriented meta or para relative to C-1.
Additionally, the present invention relates to a method for inhibiting NAALADase enzyme activity, treating a glutamate abnormality, effecting a neuronal activity (e.g., treating peripheral neuropathy or neuropathic pain), treating a prostate disease, treating cancer, inhibiting angiogenesis, or effecting a TGF-&bgr; activity, comprising administering to a mammal in need of such inhibition, treatment, or effect, an effective amount of a compound of formula I, as described above.
The present invention further relates to method for detecting a disease, disorder, or condition where NAALADase levels are altered, comprising:
(i) contacting a sample of bodily tissue or fluid with a compound of formula I, as defined above, wherein said compound binds to any NAALADase in said sample; and
(ii) measuring the amount of any NAALADase bound to said sample, wherein the amount of NAALADase is diagnostic for said disease, disorder or condition.
The present invention further relates to a method for detecting a disease, disorder or condition where NAALADase levels are altered in an animal or a mammal, comprising:
(i) labeling a compound of formula I, as defined above, with an imaging reagent;
(ii) administering to said animal or mammal an effective amount of the labeled compound;
(iii) allowing said labeled compound to localize and bind to NAALADase present in said animal or mammal; and
(iv) measuring the amount of NAALADase bound to said labeled compound, wherein the amount of NAALADase is diagnostic for said disease, disorder or condition.
The present invention further relates to a diagnostic kit for detecting a disease, disorder or condition where NAALADase levels are altered, comprising a compound of formula I, as defined above, labeled with a marker.
The invention further relates to a pharmaceutical composition comprising:
(i) an effective amount of a compound of formula I or a pharmaceutically acceptable equivalent; and
(ii) a pharmaceutically acceptable carrier.
REFERENCES:
patent: 3898266 (1975-08-01), Feit et al.
patent: 3950380 (1976-04-01), Feit et al.
patent: 4250182 (1981-02-01), Gorvin
patent: 4863636 (1989-09-01), Chang et al.
patent: 5498784 (1996-03-01), Arnold et al.
patent: 5672592 (1997-09-01), Jackson et al.
patent: 5795877 (1998-08-01), Jackson et al.
patent: 5804602 (1998-09-01), Slusher et al.
patent: 5807688 (1998-09-01), Blackburn et al.
patent: 5824662 (1998-10-01), Slusher et al.
patent: 5863536 (1999-01-01), Jackson et al.
patent: 5880112 (1999-03-01), Jackson et al.
patent: 5880309 (1999-03-01), Suzuki et al.
patent: 5902817 (1999-05-01), Jackson et al.
patent: 5962521 (1999-10-01), Jackson et al.
patent: 5968915 (1999-10-01), Jackson et al.
patent: 5977090 (1999-11-01), Slusher et al.
patent: 5981209 (1999-11-01), Slusher et al.
patent: 5985855 (1999-11-01), Slusher et al.
patent: 6004946 (1999-12-01), Slusher et al.
patent: 6011021 (2000-01-01), Slusher et al.
patent: 6017903 (2000-01-01), Slusher et al.
patent: 6025344 (2000-02-01), Jackson et al.
patent: 6025345 (2000-02-01), Jackson et al.
patent: 6028216 (2000-02-01), Morales et al.
patent: 6046180 (2000-04-01), Jackson et al.
patent: 6054444 (2000-04-01), Jackson et al.
patent: 6071965 (2000-06-01), Jackson et al.
patent: 6121252 (2000-09-01), Jackson et al.
patent: 6228888 (2001-05-01), Slusher
patent: 651-91 (1998-02-01), None
patent: 0745673 (1996-12-01), None
patent: 2-204754 (1990-08-01), None
patent: 2-208666 (1990-08-01), None
patent: 11-269182 (1999-10-01), None
patent: 2000-95788 (2000-04-01), None
patent: 2000-159984 (2000-06-01), None
patent: 6606892 (1967-07-01), None
C.A. 66:3730 (Abstract of NL 6606892).
C.A. 79:147536 (Abstract of M. Erickson et al., Acta Chem. Scand. (1973), 27(5), 1673-8).
C.A. 85:177080 (Abstract of V. Kudlacek et al., CS 162594).
C.A. 94:214626 (Abstract of US 4250182).
C.A. 105:190584 (Abstract of A. El-Maghraby et al., Egypt. J. Pharm. Sci. (1985), vol. Date 1983, 24(1-4).
C.A. 124:219572 (Abstract of P. Wentworth et al., Proc. Natl. Acad. Sci. USA (1996), 93(2), 799-803).
C.A. 126:70131 (Abstract of EP 0745673).
C.A. 129:81601 (Abstract of M. Pickert et al., Arch. Pharm. (1998), 331(5), 177-192).
Watson, S., et al., “TiPS Receptor and Ion Channel Nomenclature Supplement 1995,” pp. 1 and 30-32,Elsevier Trends Journals, 6thEd., United Kingdom (ISBN 1357-485X).
Wentworth, et al., “Antibody Catalysis of BAC2 Aryl Carbamate Ester Hydrolysis: A Highly Disfavored Chemical Process,”Journal of the American Chemical Society, 1997, vol. 119, No. 9, pp. 2315-2316.
Wentworth, et al., “Toward antibody-directed ‘abzyme’ prodrug therapy, ADAPT: Carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing,” Proceedings of the National Academy of Sciences of the United States of America, 1996, vol. 93, No. 2, pp. 799-803.
WPINDEX Abstract for JP-2-204754.
WPINDEX Abstract for JP-2-208666.
WPINDEX Abstract for JP-11-269182.
WPINDEX Abstract for JP-2000-95788.
WPINDEX Abstract for JP-2000-159984.
Jackson Paul F.
Slusher Barbara S.
Tsukamoto Takashi
Wang Eric
Guilford Pharmaceuticals Inc.
Higel Floyd D.
Lyon & Lyon LLP
Shameem Golam M. M.
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