Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving hydrolase
Patent
1993-11-05
1996-05-14
Redding, David A.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving hydrolase
435 772, 435 792, 435 793, 435183, 435810, 548154, 514368, 514393, 546271, C12Q 142, C07D51302
Patent
active
055166474
ABSTRACT:
The present invention discloses novel compounds useful as alkaline phosphatase inhibitors and therapeutic agents. Preferably, the novel compounds are useful as selective inhibitors of human alkaline phosphatases as opposed to Escherichia coli alkaline phosphatases. The novel compounds can also be used as cancer therapeutic agents, anti-depressive agents, anti-anergic agents, and antihelminthic agents. The novel compounds have the following general formula: ##STR1## wherein R' is an aryl, aryl ether, aryl thioether, aromatic heterocyclic, aromatic heterocyclic thioether, or aromatic heterocyclic ether group. More preferably, R' is a phenyl or a pyridine. Most preferably, R' is of the following formula: ##STR2## 2-thiopyridine, or ##STR3## 2-oxypyridine. R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.1 ', R.sub.2 ', R.sub.3 ', R.sub.4 ', and R.sub.5 ' can be the same or different, and at least one of which is selected from the group consisting of: H, C.sub.1 -C.sub.6 alkyl, halo C.sub.1 -C.sub.6 alkyl, phenyl, C.sub.1 -C.sub.6 alkoxy, phenoxy, trifluoromethyl, nitro, amino, carboxy, and halo groups with the proviso that each novel compound has no more than three substituents. Hydrogen is not considered a substituent.
REFERENCES:
patent: 3364112 (1968-01-01), Raeymakers
patent: 3817837 (1974-06-01), Rubenstein
patent: 3852157 (1974-12-01), Rubenstein
patent: 3852458 (1974-12-01), Janssen
patent: 3875011 (1975-04-01), Rubenstein
patent: 3905871 (1975-09-01), Rubenstein
patent: 4005212 (1977-01-01), DeBarre
patent: 4090025 (1978-05-01), Raghu
patent: 4137321 (1979-01-01), Leeming
patent: 4139707 (1979-02-01), Raghu
patent: 4143147 (1979-03-01), Leeming
patent: 4179460 (1979-12-01), Georgiev
patent: 4310672 (1982-01-01), Raghu
patent: 4370482 (1983-01-01), Raghu
patent: 4389406 (1983-06-01), Dorgan
patent: 4584305 (1986-04-01), Brugmans
patent: 5093231 (1992-03-01), Hoke
patent: 5135847 (1992-08-01), Hoke
patent: 5143825 (1992-09-01), Chacko
patent: 5279935 (1994-01-01), Nycz
patent: 5284948 (1994-02-01), Pouticello et al.
Biochim. Biophys. Acta, H. Van Belle, Kinetics and Inhibition of Alkaline Phosphatases from Canine Tissues, 289 (1972) pp. 158-168.
Proc. Natl. Acad. Sci. USA, J. Berger, et al., Cloning and sequencing of human intestinal alkaline phosphatase cDNA, vol. 84, (Feb. 1987) pp. 695-698.
Journal of Medicinal Chemistry, K. Bhargava, et al., Tetramisole Analogues as Inhibitors of Alkaline Phosphatase, an Enzyme Involved in the Resistance of Neoplastic Cells to 6-Thiopurines, vol. 20, No. 4 (1977) pp. 563-566.
Clin. Chem., J. Farley, et al., Alkaline Phosphatase Activity from Human Osteosarcoma Cell Line SaOS-2: an Isoenzyme Standard for Quantifying Skeletal Alkaline Phosphatase Activity in Serum, vol. 35, No. 2 (1969) pp. 223-229.
The American Journal of Medicine, W. Fishmann, Perspectives on Alkaline Phosphatase Isoenzymes, vol. 56, (May 1974) pp. 617-650.
J. Pharmacol. (Paris), C. Gouret, et al., Interaction de Divers Psychotropes Avec Cif Effets De L a Reserpine chez la souris et chez le chat, vol. 8, No. 3 (1977) 333-350.
J. Neurol. Neurosurg. Psychiat., M. Hamilton, A Rating Scale for Depression, 23 (1960) pp. 56-62.
Proc. Natl. Acad. Sci. USA, P. Henthorn, et al., Products of two common alleles at t locus for human placental alkaline phosphatase differ by seven amino acids, vol. 83 (Aug. 1986) pp. 5597-5601.
Proc. Natl. Acad. Sci. USA, W. Kam, et al., Cloning, sequencing, and chromosomal localization of human term placental alkaline phosphatase cDNA, vo. 82 (Dec. 1985) pp. 8715-8719.
The Journal of Biological Chemistry, J. Millan, Molecular Cloning and Sequence Analysis of Human Placental Alkaline Phosphatase, vol. 261, No. 7 (Mar. 5, 1966) pp. 3112-3115.
The New England Journal of Medicine, C. Moertel, et al., Levamisole and Fluoroura for Adjuvant Therapy of Resected Colon Carcinoma, vol. 322 (Feb. 8, 1990) p. 35 358.
Journal of Immunological Methods, R. Morris, et al., Cellular Enzyme-Linked Immunospecific Assay (CELISA). IV. Inhibition of Endogenous Cellular Alkaline Phosphatase Activity, vol. 68 (1984) pp. 11-17.
The Journal of Biological Chemistry, V. Nigam, et al., Catalysis of Phosphoryl Transfer by Prostatic Acid Phosphatase, vol. 234, No. 9 (Sep. 1959) pp. 2394-2398.
The Journal of Biological Chemistry, V. Nigam, et al., Kinetics of Hydrolysis of the Orthophosphate Monoesters of Phenol, p-Nitrophenol, and Glycerol by Human Prostatic Acid Phosphatase*, vol. 234 (1959) pp. 1550-1554.
The Journal of Histochemistry and Cytochemistry, B. Ponder, et al., Inhibition of Endogenous Tissue Alkaline Phosphatase with the Use of Alkaline Phosphatase Conjugates in Immunohistochemistry, vol. 29, No. 8 (1981) pp. 981-984.
Collect. Czech. Chem. Commun., U. Shukla, et al., Synthesis of trans-2[N-(2 -Hydroxy-1,2,3,4-Tetrahydronaphthalene-1-YL)]Iminothiazolidine and Related Compounds --a New Class of Antidepressants, vol. 54 (1992) pp. 415-424.
Proc. Natl. Acad. Sci. USA, M. Weiss, et al., Isolation and characterization of a CDNA encoding a human liver/bone/kidney-type alkaline phosphatase, vol. 83 (Oct. 1986) pp. 7182-7186.
Bieniarz Christopher
Bridon Dominique
Bures Mark
Haviv Fortuna
Husain Mazhar
Abbott Laboratories
Mohamed Abdel A.
Pope Lawrence S.
Redding David A.
LandOfFree
Compounds useful as alkaline phosphatase inhibitors and therapeu does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Compounds useful as alkaline phosphatase inhibitors and therapeu, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Compounds useful as alkaline phosphatase inhibitors and therapeu will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1894932