Centrally acting and metabolically stable thyrotropin-releasing hormone analogues by replacement of histidine with substituted pyridinium

Journal of Medicinal Chemistry

Volumn 47, Issue 24, 2004, Pages 6025-6033

  Prokai, Laszlo ^a   Prokai Tatrai, Katalin ^a   Zharikova, Alevtina D ^a   Nguyen, Vien ^a   Perjesi, Pal ^a,b   Stevens Jr , Stanley M ^a  

^a UNIVERSITY OF FLORIDA   (United States)

^b UNIVERSITY OF PÉCS   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

1 [3 [2 (AMINOCARBONYL)PYRROLIDIN 1 YL] 3 OXO 2 [[(5 OXOPYRROLIDIN 2 YL)CARBONYL]AMINO]PROPYL] 1,4 DIHYDROPYRIDINE 3 CARBOXAMIDE; 3 AMINOCARBONYL 1 [3 [2 (AMINOCARBONYL)PYRROLIDIN 1 YL] 3 OXO 2 [[(5 OXOPYRROLIDIN 2 YL)CARBONYL]AMINO]PROPYL]PYRIDINIUM; CENTRAL STIMULANT AGENT; PRODRUG; PROTIRELIN; PROTIRELIN DERIVATIVE; PROTIRELIN RECEPTOR; PYRIDINIUM DERIVATIVE; UNCLASSIFIED DRUG;

ANESTHESIA; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; CHEMICAL MODIFICATION; CONTROLLED STUDY; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DESIGN; DRUG MECHANISM; DRUG PENETRATION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG RETENTION; DRUG STABILITY; DRUG UPTAKE; HIPPOCAMPUS; MALE; MICRODIALYSIS; MOUSE; NONHUMAN; RAT; REDUCTION;

ACETYLCHOLINE; ANIMALS; BRAIN; CENTRAL NERVOUS SYSTEM STIMULANTS; DRUG STABILITY; HIPPOCAMPUS; HISTIDINE; MASS SPECTROMETRY; MEMBRANES, ARTIFICIAL; MICE; MICRODIALYSIS; PERMEABILITY; PRODRUGS; PYRIDINIUM COMPOUNDS; RADIOLIGAND ASSAY; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; THYROTROPIN-RELEASING HORMONE; TISSUE DISTRIBUTION;

EID: 8644224096     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020531t     Document Type: Article

References (47)

1. Horita, A.; Carino, M. A.; Lai, H. Pharmacology of Thyrotropin Releasing Hormone. Annu. Rev. Pharmacol. Toxicol. 1986, 26, 311-332.
2. Prokai, L. Central Nervous System Effects of Thyrotropin-Releasing Hormone and Its Analogues: Opportunities and Perspectives for Drug Discovery and Development. In Progress in Drug Research; Jucker, E., Ed.; Birkhäuser Verlag: Basel, 2002; Vol. 59, p 133.
3. (a) Yarbrough, G. G. TRH Potentiates Excitatory Actions of Acetylcholine on Cerebral Cortical-Neurons. Nature 1976, 263, 523-524.
4. (b) Yarbrough, G. G. Thyrotropin Releasing Hormone and CNS Cholinergic Neurons. Life Sci. 1983, 33, 111-118.
5. Stwertka, S. A.; Vincent, G. P.; Gamzu, E. R.; MacNeil, D. A.; Vederese, A. TRH Protection Against Memory Retrieval Deficits Is Independent of Endocrine Effects. Pharmacol. Biochem. Behav. 1991, 41, 145-152.
6. (a) Breese, G.; Cott, J.; Cooper, B.; Prange, A.; Lippton, M.; Plotnikoff, N. Effect of Thyrotropin-Releasing Hormone (TRH) on Actions of Pentobarbital and Other Centrally Acting Drugs. J. Pharmacol. Exp. Ther. 1975, 193, 11-22.
7. (b) Horita, A.; Carino, M.; Lai, H. Analeptic Activity Produced by TRH Microinjection into Basal Forebrain Area in the Rat. FASEB J. 1986, 45, 795.
8. (c) Horita, A.; Carino, M.; Smith, J. Effects of TRH on the Central Nervous System of Rabbit. Pharmacol. Biochem. Behav. 1976, 5, 111-116.
9. Kalivas, P.; Horita, A. Thyrotropin-Releasing Hormone: Neurogenesis of Action in the Pentobarbital Narcotized Rat. J. Pharmacol. Exp. Ther. 1980, 212, 203-210.
10. White, S. R.; Crane, G. K.; Rane, G. K.; Jackson, D. A. Thyrotropin-Releasing-Hormone (TRH) Effects on Spinal-Cord Neuronal Excitability. Ann. N.Y. Acad. Sci. 1989, 553, 337-350.
11. Hashimoto, T.; Fukuda, N. Effect of Thyrotropin-Releasing-Hormone on the Neurologic Impairment in Rats with Spinal-Cord Injury-Treatment Starting 24-h and 7 Days after Injury. Eur. J. Pharmacol. 1991, 203, 25-32.
12. Schröder, H.; Giacobini, E.; Struble, R.; Zilles, Z.; Maelicke, A. Nicotinic Cholinoceptive Neurons of the Frontal-Cortex are Reduced in Alzheimer's Disease. Neurobiol. Aging 1991, 12, 259-262.
13. (a) Zlokovic, B. V.; Segal, M. B.; Begley, D. J.; Davson, H.; Rakic, L. Permeability of the Blood-Cerebrospinal Fluid and the Blood-Brain Barriers to Thyrotropin-Releasing Hormone. Brain Res. 1985, 358, 191-199.
14. (b) Zlokovic, B. V.; Lipovac, M. N.; Begley, D. J.; Davson, H.; Rakic, L. Slow Penetration of Thyrotropin-Releasing Hormone Across the Blood-Brain Barrier of an In Situ Perfused Guinea Pig Brain. J. Neurochem. 1988, 51, 252-257.
15. Meisenberg, G.; Simmons, W. Peptides and the Blood Brain Barrier. Life Sci. 1983, 32, 2611-2623.
16. Szirtes, T.; Kisfaludy, L.; Palosi, E.; Szporny, L. Synthesis of Thyrotropin-Releasing Hormone Analogues. I. Complete Dissociation of Central Nervous System Effects from Thyrotropin-Releasing Activity. J. Med. Chem. 1984, 27, 741-745.
17. (a) Kroll, R. A.; Neuwelt, E. A. Outwitting the Blood-Brain Barrier for Therapeutic Purposes: Osmotic Opening and Other Means. Neurosurgery 1998, 42, 1083-1099.
18. (b) Fortin, D. Altering the properties of the blood-brain barrier: disruption and permeabilization. In Progress in Drug Research; Prokai, L., Prokai-Tatrai, K., Eds.; Birkhäuser Verlag: Basel, 2003; Vol. 61, p 127.
19. (a) Prokai, L. Delivery of Peptides into the Central Nervous System. Drug Discovery Today 1996, 1, 161-167.
20. (b) Prokai, L. Peptide Delivery into the Central Nervous System: Invasive Physiological and Chemical Approaches. Exp. Opin. Ther. Pat. 1997, 7, 233-245.
21. (c) Prokai, L.; Prokai-Tatrai, K. Metabolism-Based Drug Design and Drug Targeting. Pharm. Sci. Technol. Today 1999, 2, 457-463.
22. (d) Prokai-Tatrai, K.; Prokai, L. Modifying Peptide Properties by Prodrug Design for Enhanced Transport into the CNS. In Progress in Drug Research; Prokai, L., Prokai-Tatrai, K., Eds.; Birkhäuser Verlag: Basel, 2003; Vol. 61, p 155.
23. Anderson, B. D. Prodrugs for Improved CNS Delivery. Adv. Drug Del. Rev. 1996, 19, 171-202.
24. Prokai, L.; Prokai-Tatrai, K.; Bodor, N. Targeting Drugs to the Brain by Redox Chemical Delivery Systems. Med. Res. Rev. 2000, 20, 367-416 and references therein.
25. Prokai, L.; Prokai-Tatrai, K.; Ouyang, X.; Kim, H. S.; Wu, W. M.; Zharikova, A. D.; Bodor, N. Metabolism-Based Brain-Targeting System for a Thyrotropin-Releasing Hormone Analogue. J. Med. Chem. 1999, 42, 4563-4571.
26. Prokai-Tatrai, K.; Perjesi, P.; Zharikova, A. D.; Li, X.; Prokai, L. Design, Synthesis, and Biological Evaluation of Novel, Centrally-Acting Thyrotropin-Releasing Hormone Analogues. Bioorg. Med. Chem. Lett. 2002, 12, 2171-2174.
27. Rivier, J.; Burgus, R.; Vale, W.; Ling, N.; Monahan, M. Synthetic Thyrotropin-Releasing Factor Analogs. 3. Effect of Replacement or Modification of Histidine Residue on Biological-Activity. J. Med. Chem. 1972, 15, 479-451.
28. Bycroft, B. W.; Chan, W. C.; Chabra, S. R.; Hone, N. D. A Novel Lysine-Protecting Procedure for Continuous-Flow Solid-Phase Synthesis of Branched Peptides. J. Chem. Soc., Chem. Commun. 1993, 778-779.
29. Aletras, A.; Barlos, K.; Gatos, D.; Koutsogianni, S.; Mamos, P. Preparation of the Very Acid-Sensitive Fmoc-Lys(Mtt)-OH - Application in the Synthesis of Side-Chain to Side-Chain Cyclic-Peptides and Oligolysine Cores Suitable for the Solid-Phase Assembly of MAPS and TASP. Int. J. Pept. Protein Res. 1995, 45, 488-496.
30. Augustyns, K.; Kraas, W.; Jung, G. Investigation on the Stability of the Dde Protecting Group Used in Peptide Synthesis: Migration to an Unprotected Lysine. J. Pept. Res. 1998, 51, 127-133.
31. Eda,. M. E.; Kurth, M. J. Polymer Site-Site Interactions: Mechanistic Implication in the Solid-Phase Zincke Reaction. J. Chem. Soc., Chem. Commun. 2001, 723-724
32. Ong, S. W.; Liu, H. L.; Pidgeon, C. Immobilized Artificial-Membrane Chromatography: Measurements of Membrane Partition Coefficient and Predicting Drug Membrane Permeability. J. Chromatogr. A 1996, 728, 113-128.
33. (a) Braddy, A. C.; Janaky, T.; Prokai, L. Immobilized Artificial Membrane Chromatography Coupled with Atmospheric Pressure Ionization Mass Spectrometry. J. Chromatogr. A 2002, 966, 81-87.
34. (b) Prokai, L.; Prokai-Tatrai, K.; Zharikova, A. D.; Li, X. X.; Rocca, J. R. Combinatorial Lead Optimization of a Neuropeptide FF Antagonist. J. Med. Chem. 2001, 44, 1623-1626 .
35. An atom fragment method implemented in the molecular modeling package HyperChem version 6.0 (Hypercube, Gainesville, FL): Ghose, A. K.; Pritchett, A.; Crippen, G. M. Atomic Physicochemical Parameters for 3-Dimensional Structure Directed Quantitative Structure - Activity-Relationships. 3. Modeling Hydrophobic Interactions. J. Comput. Chem. 1988, 9, 80-90.
36. Semiempirical quantum chemical (AM1) approach: Bodor, N.; Gabanyi, Z.; Wong, C. K. A New Method for the Estimation of Partition-Coefficient. J. Am. Chem. Soc. 1989, 111, 3783-3786.
37. Molecular-volume based method: Buchwald, P.; Bodor, N. Octanol-Water Partition of Nonzwitterionic Peptides: Predictive Power of a Molecular Size-Based Model. Proteins 1998, 30, 86-99.
38. Bundgaard, H.; Møss, J. Prodrugs of Peptides. 6. Bioreversible Derivatives of Thyrotropin-Releasing-Hormone (TRH) with Increased Lipophilicity and Resistance to Cleavage by the TRH-Specific Serum Enzyme. Pharm. Res. 1990, 7, 885-892.
39. 2]TRH and its Chemical Brain-Targeting System. Brain Res. 2002, 952, 268-274.
40. Prokai, L.; Zharikova, A. D.; Janaky, T.; Li, X. X.; Braddy, A. C.; Perjesi, P.; Matveeva, L.; Powell, D. H.; Prokai-Tatrai, K. Integration of Mass Spectrometry into Early-Phase Discovery and Development of Central Nervous System Agents. J. Mass Spectrom. 2001, 36, 1211-1219.
41. Stewart, B. H.; Chung, F. Y.; Tait, B.; John, C.; Chan, O. H. Hydrophobicity of HIV Protease Inhibitor by Immobilized Artificial Membrane Chromatography: Application and Significance to Drug Transport. Pharm. Res. 1998, 15, 1401-1406.
42. Reichel, A.; Begley, D. J. Potential of Immobilized Artificial Membranes for Predicting Drug Penetration across the Blood-Brain Barrier. Pharm. Res. 1998, 15, 1270-1274.
43. Hansch, C.; Björkroth, J. P.; Leo, A. Hydrophobicity and Central Nervous System Agents: On the Principle of Minimal Hydrophobicity in Drug Design. J. Pharm. Sci. 1987, 76, 663-687.
44. Cornford, E. M.; Braun, L. D.; Oldendorf, W. H.; Hill, M. A. Comparison of Lipid-Mediated Blood-Brain-Barrier Penetrability in Neonates and Adults. Am. J. Physiol. 1982, 243, C161-C168.
45. 1H-NMR Reinvestigation. Magn. Reson. Chem. 1995, 34, 283-88.
46. (a) Burt, D. R.; Snyder, S. H. Thyrotropin Releasing Hormone (TRH): Apparent Receptor Binding in Rat Brain Membranes. Brain Res. 1975, 93, 309-328.
47. 2)Thyrotropin Releasing Hormone Receptors in Rat Brain. Life Sci. 1982, 30, 1793-1799.