Prodrugs of perzinfotel with improved oral bioavailability

Journal of Medicinal Chemistry

Volumn 52, Issue 3, 2009, Pages 771-778

  Baudy, Reinhardt B ^a   Butera, John A ^a   Abou Gharbia, Magid A ^a,b   Chen, Hong ^a   Harrison, Boyd ^a   Jain, Uday ^a   Magolda, Ronald ^a   Sze, Jean Y ^a   Brandt, Michael R ^a,c   Cummons, Terri A ^a   Kowal, Diane ^a   Pangalos, Menelas N ^a   Zupan, Bojana ^a,d   Hoffmann, Matthew ^a   May, Michael ^a   Mugford, Cheryl ^a   Kennedy, Jeffrey ^a   Childers Jr , Wayne E ^a  

^a PFIZER INC   (United States)

^b TEMPLE UNIVERSITY   (United States)

^c JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [2 [8,9 DIOXO 2,6 DIAZABICYCLO[5.2.0]NON 1(7) EN 2 YL] 3 OXIDO 7 OXO 7 PHENYL 2,4,6 TRIOXA 3 PHOSPHAHEPT 1 YL BENZOATE; [2 (8,9 DIOXO 2,6 DIAZABICYCLO[5.2.0]NON 1(7) EN 2 YL)ETHYL]PHOSPHONIC ACID; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; PERZINFOTEL; PRODRUG; UNCLASSIFIED DRUG; AZABICYCLO DERIVATIVE; BISPHOSPHONIC ACID DERIVATIVE; EAA-090; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHOSPHONIC ACID DERIVATIVE;

ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG POTENCY; DRUG STABILITY; DRUG SYNTHESIS; IN VITRO STUDY; INFLAMMATION; INTESTINE FLUID; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PH; RAT; STOMACH JUICE; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; BILE; BIOAVAILABILITY; DRUG ANTAGONISM; METABOLISM; ORAL DRUG ADMINISTRATION; SPRAGUE DAWLEY RAT; SYNTHESIS;

ADMINISTRATION, ORAL; ANIMALS; AZABICYCLO COMPOUNDS; BILE; BIOLOGICAL AVAILABILITY; DIPHOSPHONATES; DRUG STABILITY; GASTRIC JUICE; MALE; PHOSPHONIC ACIDS; PRODRUGS; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 61449169060     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm8011799     Document Type: Article

References (20)

1. Sluka, K. A.; Westlund, K. N. Spinal cord amino acid release and content in an arthritis model: the effects of pretreatment with non-NMDA, NMDA, and NK1 receptor antagonists. Brain Res. 1993, 627. 89-103.
2. 2+ concentration in the spinal dorsal orn in an animal model of neuropathic pain. Pain 1996, 68, 8596.
3. Dickenson, A. H.; Chapman, V.; Green, G. M. The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. Gen. Pharmacol. 1997, 28, 633-638.
4. Mao, J.; Price, D. D.; Hayes, R. L.; Lu, J.; Mayer, D. J.; et al. Intrathecal treatment with dextrorphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy. Brain Res. 1993, 605, 164-168.
5. Chaplan, S. R.; Malmberg, A. B.; Yaksh, T. L. Efficacy of spinal nmda receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J. Pharmacol. Exp. Ther. 1997, 280, 829-838.
6. Suzuki, R.; Matthews, E. A.; Dickenson, A. H. Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn neurones in a rat model of mononeuropathy. Pain 2001, 91, 101-109.
7. Kristensen, J. D.; Svensson, B.; Gordh, T., Jr. The NMDA-receptor antagonist CPP abolishes neurogenic "wind-up pain" after intrathecal administration in humans. Pain 1992, 51, 249-253.
8. Kinney, W. A.; Abou-Gharbia, M.; Garrison, D. T.; Schmid, J.; Kowal, D. M.; et al. Design and synthesis of [2-(8,9-dioxo-2,6-diazabicyclo- [5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid (EAA-090), a potent N-methyl-D-aspartate antagonist, via the use of 3-cyclobutene-1,2-dione as an achiral alpha-amino acid bioisostere. J. Med. Chem. 1998, 41, 236-246.
9. Childers, W. E.; Abou-Gharbia, M. A.; Moyer, J. A.; Zaleska, M. M. EAA-090, neuroprotectant, competitive NMDA antagonist. Drugs Future 2002, 27, 633-638.
10. Sun, L.; Chiu, D.; Kowal, D.; Simon, R.; Smeyne, M.; et al. Characterization of two novel N-methyl-D-aspartate antagonists: EAA-090 (2-[8,9-dioxo-2,6-diazabicyclo [5.2.0]non-1(7)-en2-yl- ethylphosphonic acid) and EAB-318 (R-alpha-amino-5-chloro-1- (phosphonomethyl)-1 H-benzimidazole-2-propanoic acid hydrochlo- ride). J. Pharmacol. Exp. Ther. 2004, 310, 563-570.
11. Brandt, M. R.; Cummons, T. A.; Potestio, L.; Sukoff, S. J.; Rosenz- weig-Lipson, S. Effects of the N-methyl-D-aspartate receptor antagonist perzinfotel [EAA-090; [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0 non-1(7)- en-2-yl)-ethyl]phosphonic acid] on chemically-induced thermal hy-persensitivity. J. Pharmacol. Exp. Ther. 2005, 313, 1379-1386.
12. Amersham Biosciences, part of GE Healthcare Life Sciences, 800 Centennial Avenue, P.O. Box 1327, Piscataway, NJ 08855.
13. Zimmermann, M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983, 16, 109-110.
14. 3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid to rat membranes: a selective, high-affinity ligand for N-methyl-D- aspartate receptors. J. Pharmacol. Exp. Ther. 1987, 240, 778-783.
15. 3H]kainic acid receptor sites in rat brain. Mol. Pharmacol. 1979, 15, 492-505.
16. 3H]CGP 39653; a new W-methyl- D-aspartate antagonist radioligand with low nanomolar affinity in rat brain. Eur. J. Pharmacol. 1991, 192, 19-24.
17. 3H]glycine recognition site as a modulatory site of the W-methyl-D-aspartate receptor complex. J. Neurochem. 1989, 53, 370-375.
18. 3H]- α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and a filtration assay. Weurochem. Res. 1987, 12, 775-782.
19. 3H]MK-801 binding to the W-methyl-D-aspartate receptor-ion channel complex by L-glutamate, glycine, and polyamines. J. Weurochem. 1988, 51, 830-836.
20. Brandt, M. R.; Furness, M. S.; Mello, N. K.; Rice, K. C.; Negus, S. S. Antinociceptive effects of delta-opioid agonists in rhesus monkeys: effects on chemically-induced thermal hypersensitivity. J. Pharamcol. Exp. Ther. 2001, 296, 939-946.