Corticotropin releasing factor (CRF) receptor modulators: Progress and opportunities for new therapeutic agents

Journal of Medicinal Chemistry

Volumn 43, Issue 9, 2000, Pages 1641-1660

  Gilligan, Paul J ^a   Robertson, David W ^a   Zaczek, Robert ^b  

^a DUPONT COMPANY   (United States)

^b PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOTROPIN RELEASING FACTOR RECEPTOR;

CORTICOTROPIN RELEASE; DRUG EFFECT; DRUG RECEPTOR BINDING; HORMONAL REGULATION; HORMONE INHIBITION; HUMAN; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; NONHUMAN; REVIEW; STRESS;

AMINO ACID SEQUENCE; ANIMALS; HUMANS; MOLECULAR SEQUENCE DATA; RECEPTORS, CORTICOTROPIN-RELEASING HORMONE; STRESS;

EID: 0034124297     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990590f     Document Type: Review

References (246)

1. Selye, H. Stress; Acta Medical Publisher Inc.: Montreal, Quebec, 1950.
2. Selye, H. The stress of life; McGraw-Hill: New York, 1956.
3. Chrousos, G. P.; Gold, P. W. The concept of stress and stress system disorders: overview of physical and behavioral homeostasis. J. Am. Med. Soc. 1992, 267, 1244-1252.
4. Harris, G. W. Neural control of pituitary gland. Physiol. Rev. 1948, 28, 139-179.
5. Owens, M. J.; Nemeroff, C. B. Physiology and pharmacology of corticotropin releasing factor. Pharmacol. Rev. 1991, 43, 425-473.
6. Vale, W.; Spiess, J.; Rivier, C.; Rivier, J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 1981, 213, 1394-1397.
7. DeSouza, E. B.; Grigoriadis, D. E. Corticotropin-releasing factor. Physiology, pharmacology and role in central nervous sytem and immune disorders. In Psychopharmacology: The fourth generation of progress; Bloom, F. E., Kupfer, D. J., Eds.; Raven Press: New York, 1998; pp 505-517.
8. Chalmers, D. T.; Lovenberg, T. W.; Grigoriadis, D. E.; Behan, D. P.; DeSouza, E. B. Corticotropin-releasing factor receptors: from molecular biology to drug design. Trends Pharmacol. Sci. 1996, 17, 166-172.
9. Kretz, O.; Reichardt, H. M.; Schutz, G.; Bock, T. Corticotropin-releasing hormone expression is the major target for glucocorticoid feedback-control at the hypothalamic level. Brain Res. 1999, 818, 488-491.
10. Vale, W.; Rivier, C.; YAnd, L.; Minick, S.; Guillemin, R. Effects of purified hypothalamic corticotropin releasing factor and other substances on the secretion of ACTH and β-endorphin-like immunoreactivities in vitro. Endocrinology 1978, 103, 1910-1915.
11. Sutton, R. E.; Koob, G. F.; LeMoal, M.; Rivier, J.; Vale, W. Corticotropin releasing factor produces behavioral activation in rats. Nature 1982, 297, 331-333.
12. Brown, M. R.; Fisher, L. A.; Spiess, J.; Rivier, C.; Rivier, J.; Vale, W. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 1982, 111, 928-931.
13. Britton, D. R.; Koob, G. F.; Rivier, J.; Vale, W. Intraventricular corticotropin releasing factor enhances behavioral effects of novelty. Life Sci. 1982, 31, 363-367.
14. Sirinathsinghji, D. J. S.; Rees, L. H.; Rivier, J.; Vale, W. Corticotropin-releasing factor is a potent inhibitor of sexual receptivity in the female rat. Nature 1983, 305, 232-235.
15. Anderson, S. M.; Kant, G. J.; De Souza, E. B. Effects of chronic stress on anterior pituitary and brain corticotropin releasing factor receptors. Pharmacol. Biochem. Behav. 1993, 44, 755-761.
16. Gold, P. W.; Chrousos, G.; Kellner, C.; Post, R.; Roy, A.; Augerinos, P.; Schulte, H.; Oldfield, E.; Loriaux, D. L. Psychiatric implications of basic and clinical studies with corticotropin-releasing factor. Am. J. Psychiatry 1984, 141, 619-627.
17. Aguilera, G. Regulation of pituitary ACTH secretion during chronic stress. Front. Neuroendocrinol. 1994, 15, 321-350.
18. Spiess, J.; Rivier, J.; Rivier, C.; Vale, W. Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc. Natl. Acad. Sci. U.S.A. 1981, 78, 6517-6521.
19. Rivier, J.; Rivier, C.; Vale, W. Synthetic competitive antagonists of corticotropin releasing factor: effect on ACTH secretion in rat. Science 1984, 224, 889-891.
20. Battaglia, G.; Webster, E. L.; De Souza, E. B. Characterization of corticotropin-releasing factor (CRF) receptor-mediated stimulation of adenylate cyclase activity in rat brain. Synapse 1987, 1, 572-581
21. Rivier, C.; Rivier, J.; Lederis, K.; Vale, W. In vitro and in vivo ACTH-releasing activity of ovine CRF, sauvagine and urotensin I. Regul. Pept. 1983, 5, 139-143.
22. Britton, D. R.; Hoffman, D. K.; Lederis, K.; Rivier, J. A comparison of the behavioral effects of CRF, sauvagine and urotensin I. Brain Res. 1984, 304, 201-205.
23. Vaughan, J.; Donaldson, C.; Bittencourt, J.; Perrin, M. H.; Lewis, K. Sutton, S.; Chan, R.; Turbull, A. V.; Lovejoy, D.; Rivier, C.; Rivier, J.; Sawchenko, P. E.; Vale, W. Urocortin, a mammalian neuropeptide related to fish urotensin and corticotropin-releasing factor. Nature 1995, 378, 287-292.
24. Jones, D. N. C.; Kortekaas, R.; Slade, P. D.; Middlemiss, D. N.; Hagan, J. J.; The behavioral effects of corticotropin-releasing factor-related peptides in rats. Psychopharmacology 1998, 138, 124-132.
25. Iino, K.; Susano, H.; Oki, Y.; Andoh, N.; Shin, R.-W.; Kitamoto, T.; Takahashi, K.; Suzuki, H.; Tetzuka, F.; Yoshimi, T.; Nagura, H. Urocortin expression in the human central nervous system. Clin. Endocrinol. 1999, 50, 107-114.
26. Valentino, R. J.; Foote, S. L. Brain noradrenergic neurons, corticotropin releasing factor and stress. In Neural and endocrine peptides and receptors; Moody., T., Ed.; Plenum Press: New York, 1986; pp 101-120.
27. Davies, M. The role of the amygdala in fear and anxiety. Annu. Rev. Neurosci. 1993, 15, 353-375.
28. Lehnert, H.; Schulz, C.; Dieterich, K.; Physiological and neurochemical aspects of corticotropin-releasing factor actions in the brain: the role of the locus coeruleus. Neurochem. Res. 1998. 23, 1039-1052.
29. Davis, M.; Are different parts of the extended amygdala involved in fear versus anxiety. Biol. Psychiatry 1998, 44, 1239-1247.
30. Petrusz, P.; Merchenthaler, L.; Ordronneau, P.; Maderdrut, J. L.; Vigh, S.; Schally, A. V. Corticotropin-releasing factor (CRF)-like immunoreactivity in the gastro-entero-pancreatic endocrine system. Peptides 1984, 5 (Suppl.), 71-78.
31. Ritchie, J. C.; Owens, M. J.; O'Connor, L. W.; Kegelmeyer, A. E.; Walker, J. T.; Stanley, M.; Bissette, G.; Nemeroff, C. B. Measurement of ACTH and CRF immunoreactivity in adrenal gland and lymphocytes. Soc. Neurosci. Abstr. 1986, 12, 1041.
32. Stephanou, A.; Jessop, D. S.; Knight, R. A.; Lightman, S. L. Corticotropin-releasing factor immunoreactivity and mRNA in human leukocytes. Brain Behav. Immunol. 1990, 4, 67-73.
33. Laatikainen, T.; Virtanen, T., Raisenen, I.; Salminen, K. Immunoreactive corticotropin-releasing factor and corticotropin during pregnancy, labor and puerperium. Neuropeptides 1987, 10, 343-353.
34. Yoon, D. J.; Sklar, C.; David, R. Presence of immunoreactive corticotropin-releasing factor in rat testis. Endocrinology 1988, 122, 759-761.
35. Wynn, P. C.; Hauger, R. L., Holmes, M. C.; Millan, M. A.; Catt, K. J.; Aguilera, G. Brain and pituitary receptors for corticotropin releasing factor: localization and differential regulation after adrenalectomy. Peptides 1984, 5, 1077-1084.
36. Battaglia; Webster, E. L.; De Souza, E. B.; Characterization of second messengers coupled to corticotropin-releasing factor (CRF) receptors in brain. In Corticotropin-releasing factor: Basic and clinical studies of a neuropeptide; De Souza, E. B., Nemeroff, C. B., Eds.; CRC Press: Boca Raton, FL, 1990; pp 138-151.
37. Perrin, M.; Hass, Y.; Rivier, J.; Vale, W. Corticotropin-releasing factor binding to the anterior pituitary receptor is modulated by divalent cations and guanine nucleotides. Endocrinology 1966, 118, 1171-1179.
38. Nicholson, W. E.; DeCherney, G. S.; Jackson, R. V.; Orth, D. N. Pituitary and hypothalamic hormones in normal and neoplastic adrenal medullae: biologically active corticotropin releasing hormone and corticotropin. Regul. Pept. 1987, 18, 173-188.
39. Brown, M. R.; Fisher, L. A. Corticotropin-releasing factor: effects on the autonomic system and visceral systems. Fed. Proc. 1985, 44, 243-248.
40. Suda, T.; Tomori, N.; Tozawa, F.; Mouri, T.; Demura, H.; Shizume, K. Distribution and characterization on immunoreactive corticotropin-releasing factor in human tissues. J. Clin. Endocrinol. Metab. 1984, 59, 861-866.
41. Grigoriadis, D. E.; Lovenberg, T. W.; Chalmers, D. T.; Liaw. C.; De Souza, E. B. Characterization of corticotropin-releasing factor receptor subtypes. Ann. N. Y. Acad. Sci. 1996, 780, 60-80.
42. Liaw, C. W.; Lovenberg, T. W.; Barry, G.; Oltersdorf, T.; Grigoriadis, D. E.; De Souza, E. B. Cloning and characterization of the human corticotropin releasing factor-2 receptor complementary deoxyribonucleic acid. Endocrinology 1996, 137, 72-77.
43. Chen, R.; Lewis, K. A.; Perrin, M. H. Vale, W. W. Expression cloning of a human corticotropin-releasing factor receptor. Proc. Natl Acad. Sci. U.S.A. 1993, 90, 8967-8971.
44. 2α receptor. Mol. Endocrinol. 1998, 12, 1077-1085.
45. Perrin, M. H.; Donaldson, C. J.; Chen, R.; Lewis, K. A. Vale, W. W. Cloning and functional expression of a rat brain corticotropin-releasing factor receptor. Endocrinology 1993, 133, 3058-3061.
46. Chang, C. P.; Pearse, R. V.; O'Connell, S.; Rosenfeld, M. G. Identification of a seven transmembrane helix receptor for corticotropin releasing factor and sauvagine in mammalian brain. Neuron 1993, 11, 1187-1195.
47. Lovenberg, T. W.; Liaw, C. W.; Grigoriadis, D. E.; Clevenger, W.; Chalmers, D. T.; De Souza, E. B.; Oltersdorf, T. Cloning and characterization of a functionally distinct corticotropin releasing factor receptor subtype from rat brain. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 836-840.
48. Kishimoto, T.; Pearse, R. V.; Lin, C. R.; Rosenfeld, M. G. A sauvagine/corticotropin releasing factor receptor expressed in heart and skeletal muscle. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 1108-1112.
49. Perrin, M.; Donaldson, C.; Chen. R.; Blount, A.; Bergren, T.; Bilezikjian, L.; Sawchenko, P. Vale, W. W. Identification of a second corticotropin-releasing factor receptor gene and characterization of a c-DNA expressed in heart. Proc. Natl. Acad. Sci U.S.A. 1995, 92, 2969-2973
50. 1 receptor mRNA expression. J. Neurosci. 1995, 15, 6340-6350.
51. Aguilera, G.; Millan, M. A.; Hauger, R. L.; Catt, K. J. Corticotropin releasing factor receptors: distribution and regulation in the brain, pituitary and peripheral tissues. The hypothalamic-pituitary-adrenal axis revisited. Ann. N. Y. Acad. Sci. 1987, 512, 48-66.
52. DeSouza, E. B. Corticotropin-releasing factor receptors in the rat central nervous system: characterization and regional distribution. J. Neurosci. 1987, 7, 88-100.
53. 2β receptor mRNAs are differentially distributed between the rat central nervous system and peripheral tissues. Endocrinology 1995, 136, 4139-4142.
54. 0-sauvagine: a novel high affinity radioligand for the pharmacological and biochemical study of human corticotropin-releasing factor 2α receptors. Mol. Pharmacol. 1996, 50, 679-686.
55. 2 receptors: membrane homogenate and autoradiographic studies. J. Pharmacol. Exp. Ther. 1998, 286, 459-468.
56. Donaldson, C. J.; Sutton, S. W.; Perrin, M. H.; Corrigan, A. Z.; Lewis, K. A.; Rivier, J. E.; Vaughan, J. M.; Vale, W. W. Cloning and characterization of human urocortin. Endocrinology 1996, 137, 2167-2170.
57. Millan, M. A.; Jacobowitz, D. M.; Hauger, R. L.; Catt, K. J.; Aguilera, G. Distribution of corticotropin-releasing factor receptors in the primate brain. Proc. Natl. Acad. Sci. U.S.A. 1986, 83, 1921-1925.
58. Grigoriadis, D. E.; Dent, G. W.; Turner, J. G.; Uno, H.; Shelton, S. E.; De Souza, E. B.; Kalin, N. H. Corticotropin-releasing factor (CRF) receptors in infant rhesus monkey brain and pituitary gland: biochemical characterization and autoradiographic localization. Dev. Neurosci. 1995, 17, 357-367.
59. Sanchez, M. M.; Young, L. J.; Plotsky, P. M.; Insel, T. R. Autoradiographic and in situ hybridization localization of corticotropin releasing factor 1 and 2 receptors in nonhuman primate brain. J. Comput. Neurol. 1999, 408, 365-377.
60. 2) in hypothalamus and amygdala of the immature rat by sensory input and food intake. J. Neurosci. 1999, 19, 3982-3991.
61. Kemp, C. F.; Woods, R. J.; Lowry, P. J. The corticotropin-releasing factor-binding protein: an act of several parts. Peptides 1998, 19, 1119-1128.
62. Sutton, S. W.; Behan, D. P.; Lahrichi, S. L.; Kaiser, R. Corrigan A.; Lowry, P.; Potter, E.; Perrin, M. H.; Rivier, J.; Vale, W. Ligand requirements of the human corticotropin-releasing factor-binding protein. Endocrinology 1995, 136, 1097-1102.
63. Lowry, P. J.; Woods, R. J. Corticotropin releasing factor and its binding protein. Pharmacol. Biochem. Behav. 1996, 54, 305-308.
64. Behan, D. P.; Heinrichs, S. C.; Troncoso, J. C.; Liu, X. J.; Kawas, C. H. Ling, N.; DeSouza, E. B. Displacement of corticotropin releasing factor from its binding protein as a possible treatment for Alzheimer's disease. Nature 1995, 378, 284-287.
65. Woods, R.; David, J.; Baigent, S.; Gibbins, J.; Lowry, P. J. Elevated levels of corticotropin-releasing factor binding protein in the blood of patients suffering from arthritis and the presence of novel ligands in synovial fluid. Br. J. Rheumatol. 1996, 35, 120-124.
66. Schulkin, J.; Gold, P. W.; McEwen, B. S. Induction of Corticotropin-releasing hormone gene expression by glucocorticoids: Implications for understanding the states of fear and anxiety and allostatic load. Psychoneuroendocrinology 1998, 23, 219-243.
67. Watts, A. G. The impact of physiological stimuli on the expression of corticotropin releasing hormone (CRH) and other neuropeptide genes. Front. Neuroendocrinol. 1996, 17, 281-326.
68. Itoi, K.; Seasholtz, A. F.; Watson, A. J. Cellular and extracellular regulatory mechanisms of hypothalamic corticotropin-releasing hormone neurons. Endocrine J. 1998, 45, 13-33.
69. Hatalski, C. G.; Guirguis, C.; Baram, T. L. Corticotropin releasing factor mRNA expression in the hypothalamic paraventricular nucleus and the central nucleus of the amygdala is modulated by repeated acute stress in the immature rat. J. Neuroendocrinol. 1998, 10, 663-669.
70. Holmes, M. C.; Di Rienzo, G.; Beckford, U.; Gillham, B.; Jones, M. T. Role of serotronin in the control of the secretion of corticotropin relasing factor. J. Endocrinol. 1982, 93, 151-160.
71. Dunn, A. J.; Berridge, C. W. Physiological and behavioral responses to corticotropin-releasing factor administration: Is CRF a mediator of anxiety or stress responses? Brain Res. Rev. 1990, 15, 71-100.
72. Spina, M.; Merlo-Pich, E.; Chan, R. K.; Basso, A. M.; Rivier, J.; Vale, W.; Koob, G. F. Appetite-suppressing effects of urocortin, a CRF-related neuropeptide. Science 1996, 273, 1561-1564.
73. Aguilera, G. Corticotropin releasing hormone, receptor regulation and the stress responses. Trends Endocrinol. Metab. 1998, 9, 329-336.
74. Sutton, R. E.; Koob, G. F.; Le Moal, M.; Rivier, J.; Vale, W. W. Corticotropin-releasing factor produces behavioral activation in rats. Nature 1982, 297, 331-333.
75. Swerdlow, N. R.; Geyer, M. A.; Vale, W. W.; Koob, G. F. Corticotropin-releasing factor potentiates acoustic startle in rats: blockade by chlordiazepoxide. Psychopharmacology 1986, 8, 147-152.
76. Moreau, J. L.; Kilpatrick, G.; Jenck, F. Urocortin, a novel neuropeptide with anxiogenic-like properties. NeuroReport 1997, 8, 1697-1701.
77. Kalin, N. H.; Shelton, S. E.; Kraemer, G. W.; McKinney, W. T. Corticotropin-releasing factor administered intraventricularly to rhesus monkeys. Peptides 1983, 4, 217-221.
78. van Oers, H. J. J.; de Kloet, E. R.; Levine, S. Early vs late maternal deprivation differentially alters the endocrine and hypothalamic responses to stress. Dev. Brain Res. 1998, 111, 245-252.
79. Hsu, D. T.; Chen, F.-L. Takahashi, L. K.; Kalin, N. H. Rapid stress-induced elevation in corticotropin releasing hormone mRNA in rat central amygdala nucleus and hypothalamic paravetricular nucleus: an in situ hybridization analysis. Brain Res. 1998, 788, 305-310.
80. Coplan, J. D.; Andrews, M. W., Rosenblum, L. A.; Ownes, M. J.; Friedman, S.; Gorman, J. M.; Nemeroff, C. B. Persistent elevations of cerebrospinal fluid concentrations of corticotropin-releasing factor in adult nonhuman primates exposed to early life stressors: implications for psychopathology of mood and anxiety disorders. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 1619-1623.
81. Chappell, P. B.; Smith. M. A.; Kilts, C. D.; Bisette, G.; Ritchie, J.; Anderson, C.; Nemeroff, C. B. Alteration in corticotropin-releasing factor-like immunoreactivity in discrete rat brain regions after acute and chronic stress. J. Neurosci. 1986, 6, 2908-2914.
82. Eghbal-Ahmadi, M.; Avishai-Eliner, S.; Hatalski, C. G.; Snodgrass, S. R.; Taram, T. Z. Expression of corticotropin receptor type 2 (CRF2) in the hypothalamus and the amygdala of the immature rat is controlled by maternal cues. Soc. Neurosci. Abstr. 1998, 24, Abstract 243.7.
83. Contarino, A.; Heinrichs, S. C.; Gold, L. H. Understanding corticotropin releasing factor neurobiology: contributions from mutant mice. Neuropeptides 1999, 33, 1-12.
84. Stenzel-Poore, M. P.; Cameron, V. A.; Vaughan, J.; Sawchenko, P. E.; Vale, W. W. Development of Cushing's syndrome in corticotropin releasing factor transgenic mice. Endocrinology 1992, 130, 3378-3386.
85. Stenzel-Poore, M. P.; Heinrichs, S. C.; Rivest, R.; Koob, G. F.; Vale, W. W. Overproduction of corticotropin-releasing factor in transgenic mice: A genetic model of anxiogenic behavior. J. Neurosci. 1994, 14, 2579-2584.
86. Majzoub, J. A.; Muglia, L. J.; Martinez, C.; Jacobson, L. Molecular and Transgenic studies of the cortictropin-releasing hormone gene. Ann. N. Y. Acad. Sci. 1995, 771, 293-300.
87. Muglia, L.; Jacobson, L.; Dikkes, P.; Majzoub, J. A. Corticotropin-releasing hormone deficiency reveals normal fetal but not adult glucocorticoid need. Nature 1995, 373, 427-432.
88. Avishai-Eliner, S.; Yi, S. J.; Baram, T. Z. Developmental profile of messenger RNA for corticotropin-releasing hormone in the rat limbic system. Brain Res. Dev. Brain Res. 1996, 91, 159-163.
89. Smith, G. W.; Aubry, J.-M.; Dellu, F.; Contarino, A.; Bilezekijian, L. M.; Gold, L. H.; Chen, R.; Marchuk, Y.; Hauser, C.; Bentley, C. A.; Sawchenko, P. E.; Koob, G. F.; Vale, W.; Lee, K.-F. Corticotropin releasing factor receptor-1 deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 1998, 20, 1093-1102.
90. Bale, T. L.; Smith, G. W.; Zhao, L.; Vale, W.; Lee, K.-F. Characterization of CRF2 receptor deficient mice. Society for Neuroscience Annual Meeting, Los Angeles, CA, Nov 7-12; Abstract 243.13.
91. Tache, Y.; Gunion, M. M.; Stephens. CRF: Central nervous system action to influence gastrointestinal function and role in the gastrointestinal response to stress In Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide; DeSouza, E. B., Nemeroff, C. B., Eds.; CRC Press: Boca Raton, FL, 1990; pp 299-308.
92. Fisher, L. A. Central actions of corticotropin-releasing factor on autonomic nervous activity and cardiovascular function. In Corticotropin-Reasing Factor: Ciba Foundation Symposium 172; J. Wiley and Sons: Chichester, U.K., 1993; pp 243-257.
93. Brown, M. R.; Fisher, L. A.; Spiess, J.; Rivier, C.; Rivier, J.; Vale, W. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology 1982, 111, 928-931.
94. Fisher, L. A.; Rivier, J.; Rivier, C.; Spiess, J.; Vale, W.; Brown, M. R. Corticotropin-releasing factor (CRF): central effects on mean arterial pressure and heart rate in rats. Endocrinology 1982 111 2222-2224.
95. Tache, Y.; Goto, Y.; Gunion, M. W.; Vale, W.; Rivier, J.; Brown, M. Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor. Science 1983, 222, 935-937.
96. Lenz, H. J.; Hester, S. E.; Brown, M. R. Corticotropin-releasing factor: mechanisms to inhibit gastric acid secretion in conscious dogs. J. Clin. Invest. 1985, 75, 889-895.
97. Pappas, T. N.; Welton, M. Debas, H. T.; Rivier, J.; Tache, Y. Cirticotropin-releasing factor inhibits gastric emptying in dogs: studies on its mechanism of action. Peptides 1987, 8, 1011-1014.
98. Brown, M. R.; Fisher, L. A. Central nervous system effects of corticotropin releasing factor in the dog. Brain Res. 1983, 280, 75-79.
99. Engeland, W. C.; Lilly, M. P.; Bruhn, T. O.; Gann, D. S. Comparison of corticotropin-releasing factor acetylcholine on catecholamine secretion in dogs. Am. J. Physiol. 1987, 253, R209-R215.
100. Richard, D. The role of corticotropin-releasing hormone in the regulation of energy balance. Curr. Opin. Endocrinol. Diabetes 1999, 6, 10-18.
101. Dufau, M. L.; Tinajero, J. C.; Fabbri, A. Corticotropin-releasing factor: An antireproductive hormone of the testis. FASEB J. 1993, 7, 299-307.
102. Nappi, R. E.; Rivest, S. Stress-induced genetic expression of a selective corticotropin-releasing factor receptor subtype within the rat ovaries: An effect dependent on the ovulatory cycle. Biol. Reprod. 1995, 53, 1417-1428.
103. Mastorakos, G.; Webster, E. L.; Friedman, T. C.; Chrousos, G. P. Immunoreactive corticotropin-releasing hormone an its binding sites in the rat ovary. J. Clin. Invest. 1993, 92, 961-968.
104. Clifton, V. L.; Owens, P. C.; Robinson, P. J.; Smith, R. Identification and characterization of a corticotropin-releasing hormone receptor in human placenta. Eur. J. Endocrinol. 1995, 733, 591-597.
105. Cockett, A. T. K.; Elbadawi, A.; Zemjania, R.; Adey, W. R. The effects of immobilization on spermatogenesis in subhuman primates. Fertil. Steril. 1970, 21, 610-614.
106. Chan, E.-C.; Falconer, J.; Madsen, G.; Rice, K. C.; Webster, E. L.; Chrousos, G. P.; Smith, R. A corticotropin-releasing hormone type I receptor antagonist delays parturition in sheep. Endocrinology 1998, 139, 3357-3360.
107. Webster, E. L.; Torpy, D. J.; Elenkov, I. J.; Chrousos, G. P. Corticotropin-releasing hormone and inflammation. Ann. N. Y. Acad. Sci. 1998, 840, 21-32.
108. Chrousos, G. P. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N. Engl. J. Med. 1995, 332, 1351-1362.
109. McCann, S. M.; Lyson, K.; Karanth, S.; Gimeno, M.; Belova, N.; Kamat, A.; Rettori, V. Mechanism of action of cytokines to induce the pattern of pituitary hormone secretion in infection. Ann. N. Y. Acad. Sci. 1995, 771, 386-395.
110. Wilder, R. L. Neuroendcorine-immune system interactions and auto-immunity. Annu. Rev. Immunol. 1995, 13, 307-338.
111. Mosmann, T.; Sad, S. The expanding universe of T-cell subsets: TH1, TH2 and more. Immunol. Today 1995, 17, 138-146.
112. Elenkov, I. J.; Papanicolaou, D. A.; Wilder, R. A.; Chrousos, G. P. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: Clinical implications. Proc. Am. Assoc. Physicians 1996, 108, 374-381.
113. Irwin, M. Stress-induced immune suppression: role of brain corticotropin releasing hormone and autonomic nervous system mechanisms. Adv. Neuroimmunol. 1994, 4, 29-47.
114. Casadevall, M.; Saperas, E.; Panes, J.; Salas, A.; Anderson, D. C.; Malagelada, J. R.; Pique, J. M. Mechanisms underlying the antiinflammatory actions of central corticotropin-releasing factor. Am. J. Physiol. 1999, 276, G1016-G1026.
115. Webster, E. L.; DeSouza, E. B. Corticotropin-releasing factor receptors in mouse spleen: Identification, autoradiographic localization and regulation by divalent cations and guanine nucleotide. Endocrinology 1988, 122, 609-617.
116. Webster, E. L.; Tracey, D. E.; Jutila, M. A.; Wolfe, S. A.; DeSouza, E. B. Corticotropin-releasing factor receptors in mouse spleen: Identification of receptor-bearing cells as resident macrophages. Endocrinology 1990, 127, 440-452.
117. 125I]corticotropin-releasing factor to blood immunocytes and its reduction in Alzheimer's disease. Immunol. Lett. 1988 18, 5-8.
118. Audhya, T.; Jain. R.; Hollander, C. S. Receptor-mediated immune-modulation by corticotropin-releasing factor. Cell Immunol. 1991, 134, 77-84.
119. Crofford, L. J.; Sano, H.; Karalis, K; Webster, E. L.; Goldmuntz, E. A.; Chrousos, G. P.; Wilder, R. L. Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis. J. Clin. Invest. 1992, 90, 2555-2564.
120. Crofford, L. J.; Sano, H.; Karalis, K.; Friedman, T. C.; Epps, H. R.; Remmers, E. F.; Mathern, P.; Chrousos, G. P.; Wilder, R. L. Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid arthritis and osteoarthritis. J. Immunol. 1993, 151, 1587-1596.
121. Scopa, C. D.; Mastorakos, G.; Friedman, T. C. Melachrinou, M.; Merino, M. J.; Chrousos, G. P. Presence of immunoreactive corticotropin-releasing factor in thyroid lesion. Am. J. Pathol. 1994, 195, 1159-1167.
122. Mitchell, A. J. The role of corticotropin releasing factor in depressive illness: a critical review. Neuroscience and Biobehavioral Rev. 1998, 22, 635-651.
123. Holsboer, F. The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J. Psychiatric Res. 1999, 33, 181-214.
124. Carroll, B. J.; Curtis, G. C.; Davies, B. M.; Mendels, J.; Sugarman, A. A. Urinary free cortisol secretion in depression. Psychol. Med. 1976, 6, 43-50.
125. Poland, R. E.; Rubin, R. T.; Lesser, I. M.; Lane, L. A.; Hart, P. J. Neuroendocrine aspects of primary endogenous depression: serum dexamethasone concentrations and hypothalamic-pituitary-adrenal cortical activity as determinants of the dexamethasone suppression test response. Arch. Gen. Psychiatry 1987, 4, 790-795.
126. Rubin, R. T.; Poland, R. E.; Lesser, I. M.; Winston, R. A.; Blodgett, N. A. L. Neuroendocrine aspects of primary endogenous depression: cortisol secretory dynamics in patients and matched controls. Arch. Gen. Psychiatry 1987, 44, 328-336.
127. Sachar, E. J.; Hellman, L.; Fukushima, D. K.; Gallagher, T. F. Cortisol production in depressive illness: a clinical and biochemical clarification. Arch. Gen. Psychiatry 1970, 23, 289-298.
128. Gold, P. W.; Chrousos, G. P. The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. Proc. Assoc. Am. Physicians 1998, 111, 22-34.
129. Gold, P. W.; Licinio, J.; Wong, M.-L.; Chrousos, G. P. Corticotropin releasing hormone in the pahtophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. Ann. N. Y. Acad. Sci. 1995, 771, 716-729.
130. Banki, C. M.; Bisette, G.; Arato, M.; O'Connor, L.; Nemeroff, C. B. CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. Am. J. Psychiatry 1987, 144, 8783-877.
131. Holsboer, F.; Bardeleben, U. V.; Gerken, A.; Stall, G. K.; Mueller, O. A. Blunted corticotropin and normal cortisol response to human corticotropin-releasing factor (h-CRF) in depression. N. Engl. J. Med. 1984, 311, 1127.
132. Gold, P. W.; Loriaux, D. L.; Roy, A.; Kling, M. A.; Calkabrese, J. R.; Kellner, C. H.; Nieman, L. K.; Post, R. M.; Pickar, D.; Gallucci, W.; Augerinos, P.; Paul, S.; Oldfiled, E. H.; Cutler, G. B.; Chrousos, G. P. Responses to corticotropin- releasing hormone in the hypercortisolism of depression and Cushing's disease. N. Engl. J. Med. 1986, 314, 1329-1335.
133. Raadsheer, F. C.; Hoogendijk, W. J. G.; Stam, F. C.; Tilders, F. J. H.; Swaab, D. F. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 1994, 60, 436-444.
134. Banki, C. M.; Karmacsi, L.; Bissette, G.; Nemeroff, C. B. CSF corticotropin releasing hormone and somatostatin in major depression: response to antidepressant treatment and relapse. Eur. Neuropsychopharmacol. 1992, 2, 107-113.
135. DeBellis, M. D.; Gold, P. W.; Geracioti, T. D.; Listwak, S. J.; Kling, M. A. Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression. Am. J. Psychiatry 1993, 150, 656-657.
136. Kling, M. A.; Geracioti, T. D.; Licinio, D.; Michelson, E. H.; Oldfield, E. H.; Gold. P. W. Effects of electroconvulsive therapy on the CRH-ACTH-cortisol sytem in melancholic depression: preliminary findings. Psychopharmacol. Bull. 1994, 30, 489-494.
137. Nemeroff, C, B,; Bisette, G.; Akil, H.; Fink, M. Neuropeptide concentrations in the cerebrospinal fluid of depressed patients treated with electroconvulsive therapy: Corticotropin-releasing factor, β-endorphin, and somatostatin. Br. J. Psychiatry 1991, 158, 59-63.
138. Kaye, W. H. Neuropeptide abnormalities in anorexia nervosa. Psychiatry Res. 1996, 62, 65-74.
139. Altemus, M.; Swedo, S. E.; Leonard, H. L.; Richter, D.; Rubinow, D. W.; Potter, W. Z.; Rapoport, J. L. Changes in cerebrospinal fluid neurochemistry during treatment of obsessive-compulsive disorder with clomipramine. Arch. Gen. Psychiatry 1994, 51, 794-803.
140. Stout, S. C.; Kilts, C. D.; Nemeroff, C. B. Neuropeptides and stress: Preclinical findings and implications for pathophysiology. In Neurobiological and Clinical Consequences of Stress: From normal adaptation to post-traumatic stress disorder, Friedman, M. J., Charney, G. S., Deutch, Eds.; Lippencott-Raven: Philadelphia, 1995; pp 103-123.
141. Adinoff, B.; Anton, R.; Linnoila, M.; Guidotti, A.; Nemeroff, C.; Bissette, G. Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence. Neuropsychopharmacology 1996, 15, 288-295.
142. Jolkkonnen, J.; Lepola, U.; Bisette, G.; Nemeroff, C. B.; Riekkinen, P. CSF corticotropin-releasing factor is not affected in panic disorder. Biol. Psychiatry 1993, 33, 136-138.
143. Pomara, N.; Sing, R. R.; Deptula, D.; LeWitt, P. A.; Bissette, G.; Stanley, M.; Nemeroff, C. B. Cerebrospinal fluid corticotropin-releasing factor in Alzheimer's disease: Relationship to severity of dementia and monoamine metabolites. Biol. Psychiatry 1989, 26, 500-504.
144. Kornreich, W. D.; Galyean, R.; Hernandez, J. F ; Craig, A. G.; Donaldson, C. J.; Yamamoto, G.; Riveir, C.; Vale, W.; Rivier, J. Alanine series of ovine corticotropin factor oCRF: a structure-activity relationship study. J. Med. Chem. 1992, 35, 1870-1876.
145. Rivier, J.; Rivier, C.; Galyean, R.; Miranda, A.; Miller. C. Craig, A. G.; Yamamoto, G.; Brown, M.; Vale, W. W. Single point D-substituted corticotropin-releasing factor analogues effects on potency and physicochemical characteristics. J. Med. Chem. 1993, 36, 2851-2859.
146. Beyermann, M.; Fechner, K.; Furkert, J.; Krause, E.; Bienert, M. A single point slight alteration set as a tool for structure-activity relationship studies of ovine corticotropin releasing factor. J. Med. Chem. 1996, 39, 3324-3330.
147. Miranda, A.; Lahrichi, S. L.; Gulyas, J.; Koerber, S. C.; Craig, A. G.; Corrigan, A.; Rivier, C.; Vale, W.; Rivier, J. Constrained corticotropin-releasing factor antagonists with I-(I+3) Glu-Lys bridges. J. Med. Chem. 1997, 40, 3651-3658.
148. Rivier, J.; Lahrichi, S. L.; Gulyas, J.; Erchegyi, J.; Koerber, S. C.; Craig, A. G.; Corrigan, A.; Rivier, C.; Vale, W. W. Minimal size-constrained corticotropin-releasing factor agonists with I-(I+3) Glu-Lys and Lys-Gln bridges. J. Med. Chem. 1998, 41, 2614-2620.
149. Pallai, P. V.; Mabilia, M.; Goodman, M.; Vale, W.; Rivier, J. Structural homology of corticotropin-releasing factor, sauvagine and urotensin I: circular dichroism and prediction studies. Proc. Natl. Acad. Sci. U.S.A. 1983, 80, 6770-6774.
150. Britton, K. T.; Lee, G.; Vale, W. W.; Rivier, J.; Koob, G. F. Corticotropin-releasing factor (CRF) receptor antagonist blocks activating and "anxiogenic" actions of CRF in the rat. Brain Res. 1986, 369, 303-306.
151. Fisher. L.; Rivier, C.; Rivier, J. Brown, M. Differential antagonist activity of a-helical CRF(9-41) in three bioassay systems. Endocrinology 1991, 129, 1312-1316.
152. Gulyas, J.; Rivier, C.; Perrin, M.; Koerber, S. C.; Sutton, S.; Corrigan, A.; Lahrichi, S. L. Craig, A. J.; Vale, W.; Rivier, J. Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 10575-10579.
153. Perrin, M. H.; Sutton, S. W.; Cervini, L. A.; Rivier, J. Vale, W. W. Comparison of an agonist, urocortin, and an antagonist, astressin, as radioligands for characterization of corticotropin-releasing factor receptors. J. Pharmacol. Exp. Ther. 1999, 288, 729-734.
154. Nozu, T.; Martinez, V.; Rivier, J.; Tache, Y. Peripheral urocortin delays gastric emptying: role of CRF receptor 2. Am. J. Physiol, 1999, 276, G867-G874.
155. 2β-selective antisauvagine-30. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 15264-15269.
156. Radulovic, J.; Ruhmann, A.; Liepold, J. Spiess, J. Modulation of learning and anxiety by corticotropin-releasing factor (CRF) and stress. Differential roles of CRF receptors 1 and 2. J. Neurosci. 1999, 19, 5016-5025.
157. Nemeroff C. B. Psychopharmacology of Affective Disorders in the 21st Century. Biol. Psychiatry 1998, 44, 517-525.
158. Abreu, M. E.; Rzeszotarski, Kyle, D. J.; Hiner, R. N.; Elliott, R. L. Corticotropin- releasing factor antagonism compounds. U.S. Patent 5063245, 1991.
159. Courtmanche, G.; Gautier, C.; Gully, D.; Roger, P.; Wermuth, C.-G.
160. Courtmanche, G.; Gautier, C.; Gully, D.; Roger, P.; Valette, G.; Wermuth, C.-G. Branched alkylamino derivatives of thiazole, processes for preparing them and pharmaceutical compositions containing them. U.S. Patent 5464847, 1995.
161. Gully, D.; Roger, P.; Wermuth, C.-G. 4-Phenylaminothiazole derivatives, method for preparing same, and pharmaceutical compositions containing said derivatives. International Publication Number WO97/00868, 1997.
162. Fontaine, E.; Gully, D.; Roger, P.; Wermuth, C.-G. Aminothiazole derivatives, method of preparation, and pharmaceutical compositions containing same. International Publication Number WO98/15543, 1998.
163. Gully, D.; Roger, P.; Wermuth, C.-G. Substituted 4-phenylaminothiazoles, their process of preparation and the pharmaceutical compositions containing them. U.S. Patent 5880135, 1999.
164. Wermuth, C.-G. Search for new lead compounds: The example of the chemical and pharmacological dissection of Aminopyridazines. J. Heterocycl. Chem. 1998, 35, 1091-1100.
165. Wermuth, C.-G. Search for new lead compounds: The example of the chemical and pharmacological dissection of aminopyridazines. Sixth International Symposium on the Chemistry and Pharmacology of Pyridazines, Clearwater Beach, FL, Nov 4-7, 1998; Abstract PL-2.
166. Bright, G. M; Welch, W. M. Substituted pyrazoles as CRF antagonists. International Publication Number WO94/13661, 1994.
167. Bright, G. M. Amino-substituted pyrazoles having CRF antagonistic activity. International Publication Number WO94/13644, 1994.
168. Faraci, W. S.; Welch, W. M. Pyrazoles and pyrazolopyrimidines having CRF antagonist activity. International Publication Number WO 94/13643, 1994.
169. Bright, G. M.; Welch, W. M. Substituted pyrazoles having corticotropin-releasing factor (CRF) antagonist activity. International Publication Number WO9533727,1994.
170. Chen, Y. L.; Braselton, J.; Collins, J.; Costello, D.; Corman, M.; Dunaiskis, A.; Faraci, S.; Heym, J.; Mansbach, R.; et al. CP-154.526: A potent and selective non-peptide antagonist of the CRF receptor. ACS National Meeting, Orlando, FL, Aug 25-29, 1996; MEDI-195.
171. 1 specific ligands. U.S. Patent Number 5760225, 1998.
172. Aldrich, P. E.; Arvanitis, A. G.; Cheeseman, R. S.; Chorvat, R. J.; Christos, T. E.; Gilligan, P. J.; Grigoriadis, D. E.; Hodge, C. N.; Krenitsky, P. J.; Scholfield, E. L.; Tam, S. W.; Wasserman, Z. N-Alkyl-N-arylpyrimidinamines and derivatives thereof. International Publication Number WO Patent 95/10506, 1995.
173. Arvanitis, A. G.; Aldrich, P. E.; Arnold, C. R.; Bakthavatchalam, R.; Beck, J. P.; Bouchard, P. J.; Cheeseman, R. S.; Chidester, D. R.; Cocuzza, A. J.; Culp, S. G.; Curry, M.; Fitzgerald, L. W.; Gilligan, P. J.; Hartig, P. R.; He, L.; Hobbs, F. W.; Hodge, C. N.; Krenitsky, P. J.; McCall. D.; Rescinito, J. T.; Scholfield, EL.; Tam, S. W.; Trainor, G. L.; Wasserman, Z. R.; Wilde, R. G.; Yarem, J.; Zaczek, R. Anilinopyrimidines as Corticotropin Releasing Hormone (CRH) Antagonists. ACS National Meeting, Orlando, FL, 1996; MEDI 194.
174. 1 Receptor Antagonists. ACS National Meeting, Orlando, FL, 1996; MEDI 92.
175. Arvanitis, A. G.; Gilligan, P. J.; Chorvat, R. J.; Cheeseman, R. S.; Christos, T. E.; Bakthavatchalam, R.; Beck, J. P.; Cocuzza, A. J.; Hobbs, F. W.; Wilde, R. G.; Arnold, C.; Chidester, D.; Curry, M.; He, L.; Hollis, A.; Klaczkiewicz, J.; Krenitsky, P. J.; Rescinito, J. P ; Scholfield, E.; Culp, S.; De Souza, E. B.; Fitzgerald, L.; Grigoriadis, D.; Tam, S. W.; Wong, Y. N.; Huang, S.-M.; Shen, H. Non-Peptide Corticotropin-Releasing Hormone (CRH) Antagonists: The Syntheses and Structure-Activity Relationships of 2-Anilino-Pyrimidines and -Triazines. J. Med. Chem. 1999, 42, 808-818.
176. 1 receptor antagonists. J. Med. Chem. 1996, 39, 4358-4360.
177. Chen, Y. L. Corticotropin-releasing factor antagonists. International Publication Number WO 95/33750, 1995.
178. 1) Receptor. Society for Neuroscience, Washington, DC, Nov 16-21, 1996; Abstract 609.13.
179. Nakazato, A.; Okubo, T.; Kumagai, T.; Chaki, S.; Okuyama, S.; Tomisawa, K.; Aryl-1,2,3,6-tetrahydropyridinoyrimidine derivatives as CRF1 receptor antagonists. ACS National Meeting, Boston, MA, Aug 23-27, 1998; MEDI 137.
180. Nakazato, A.; Kumagai, T.; Okubo, T.; Abe, I.; Tanaka, H.; Chaki, S.; Okuyama, S.; Tomisawa, K. 4-Tetrahydropyridylpyrimidine derivatives. International Publication Number WO 98/42699, 1998.
181. Okuyama, S.; Chaki, S.; Kawashima, N.; Suzuki, Y.; Ogawa, S.; Nakazato, A.; Kumagai, T.; Okubo, T.; Tomisawa, K. Behavioral and electrophysiological profile of non-peptide CRF antagonists CRA1000 and CRA1001. Society for Neuroscience, Los Angeles, CA, Nov 7-12, 1998; Abstract 234.2.
182. Okuyama, S.; Chaki, S.; Kawashima, N.; Suzuki, Y.; Ogawa, S.; Nakazato, A.; Kumagai, T.; Okubo, T.; Tomisawa, K. Receptor binding, behavioral and electrophysiological profile of non-peptide corticotropin-releasing factor subtype 1 receptor antagonists CRA1000 and CRA1001. J. Pharmacol. Exp. Ther. 1999, 289, 926-935.
183. Hodge, C. N.; Aldrich, P.; Fernandez, C.; Chorvat, R.; Cheeseman, R.; Christos, T.; Arvanitis, A.; Scholfield, E.; Krenitisky, P.; Gilligan, P.; Ciganek, E.; Strucely, P.; Wasserman, Z.; Novel CRF Antagonist Design Guided by Ligand Conformational Studies. ACS National Meeting, Orlando, FL, Aug 25-29, 1996; MEDI 94.
184. Hodge, C. N.; Aldrich, P. E.; Wasserman, Z. R.; Fernandez, C. H.; Arvanitis, A.; Chorvat, R. J.; Cheeseman, R. S.; Christos, T. E.; Scholfield, E.; Krenitsky, P.; Gilligan, P. J.; Ciganek, E.; Strucely, P. CRH Antagonists. II. New Framework Design and Synthesis Guided by Anilinopyrimidine Conformational Studies. J. Med. Chem. 1999, 42, 819-832.
185. Bakthavatchalam, R.; Aldrich, P. E.; Arvanitis, A. G.; Beck, J. P.; Calabrese, J.; Cheeseman, R. S.; Cocuzza, A. J.; Culp, S. G.; M. Curry, Fitzgerald, L. W.; Gilligan, P. J.; Hobbs, F. W.; Hodge, C. N.; Huang, S.-M.; Krenitsky, P. J.; Rescinito, J. T.; Wasserman, Z.; Wilde, R. G.; Wong, Y. N.; Yarem, J.; Zaczek, R. Novel Imidazolo- and Triazolopyrimidine Derivatives as Corticotropin Releasing Hormone (CRH) Receptor Antagonists. ACS National Meeting, Orlando, FL, 1996; MEDI 93.
186. Chorvat, R. J.; Bakthavatchalam, R.; Beck, J. P.; Gilligan, P. J.; Wilde, R. G.; Cocuzza, A.; Hobbs, F. W.; Cheeseman, R. S.; Curry, M.; Rescinito, J. P.; Krenitsky, P.; Chidester, D.; Yarem, J.; Klackewicz, J. D.; Hodge, C. N.; Aldrich, P. E.; Wasserman, Z. R.; Fernandez, C. H.; Zaczek, R.; Fitzgerald, L.; Huang, S.-M.; Shen, H. L.; Wong, Y. N.; Chien, B. M.; Quon, C. Y.; Arvanitis, A. Synthesis, Corticotropin Releasing Factor Receptor Binding Affinity and Pharmacokinetic Properties of Triazolo-, Imidazo- and Pyrrolo-Pyrimidines and Pyridines. J. Med. Chem. 1999, 42, 833-848.
187. 1 receptor antagonist. J. Med. Chem. 1997, 40, 1749-1754.
188. Chen, Y. L. Pyrrolopyrimidines as CRF antagonists. International Publication Number WO 94/13676, 1994.
189. 1 specific ligands. U.S. Patent 5804685, 1998.
190. Chen, Y. L. Pyrazolopyrimidines as CRF antagonists. International Publication Number WO 94/13677,1994.
191. Chen, Y. L. Pyrazolo- and pyrrolopyridines. International Publication Number WO 95/34563, 1995.
192. Beck, J. P.; Arvanitis, A. G.; Cocuzza, A. J.; Chidester, D. R.; Curry, M. A.; Rescinito, J. T.; Fitzgerald, L. W.; Zaczek, R.; Calabrese, J. C. 8-Oxopurines as CRH receptor antagonists. ACS National Meeting, Las Vegas, NV, Sept 7-11, 1997; MEDI 94.
193. Beck, J. P.; Arvanitis, A. G.; Curry, M. A.; Rescinito, J. T.; Fitzgerald, L. W.; Gilligan, P. J.; Zaczek, R.; Trainor, G. L. Purin-8-ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists. Bioorg. Med. Chem. 1999, 9, 967-972.
194. Beck, J. P.; Curry, M.; Folmer, B. K.; Gilligan, P. J.; Robertson, D. W.; Fitzgerald, L. W.; Zaczek, R.; Calabrese, J. C. Thiazolo-[4,5-d]-pyrimidine thiones and -ones as potent corticotropin releasing hormone (CRH-R1) receptor antagonists. ACS National Meeting, Boston, MA. Aug 23-27, 1998; MEDI 136.
195. Beck, J. P.; Curry, M. A.; Chorvat, R. J.; Fitzgerald, L. W.; Gilligan, P. J.; Zaczek, R.; Trainor, G. L. Thiazolo[4,5-d]pyrimidine-thiones and -ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists. Bioorg. Med. Chem. Lett. 1999, 9, 1185-1188.
196. Horvath, R.; Hutchison, A.; Certain pyrrolopyridine derivatives; novel CRF1 ligands. International Publication Number WO 98/ 45295,1998.
197. Tanaka, H.; Seio, K.; Kimura, K.; Minogachi, M.; Uehata, M.; Kohara, T.; Ohashi, Y.; Morio, Y.; Yamagami, K. Fused pyrimidine compounds and medicinal use thereof. International Publication Number WO 98/29397, 1998.
198. Chen, C.; Webb, T. R.; McCarthy, J. R.; Moran, T. Thiophenopy-rimidines. International Publication Number WO 97/29110, 1997.
199. McCarthy, J. R. CRF receptor antagonists and methods relating thereto. International Publication Number WO 98/35967, 1998.
200. He, L.; Gilligan, P. J.; Arvanitis, A.; Chorvat, R. J. Azolotriazines and pyrimidines. International Publication Number WO 98/ 03510, 1998.
201. Chen, C.; Webb, T. R.; McCarthy, J. R.; Moran, T. J.; Wilcoxen, K. M. Pyrazolopyrimidines as CRF receptor antagonists. International Publication Number WO 97/29109, 1997.
202. Wilcoxen, K.; Chen, C.; Huang, C.; Haddach, M.; Xie, M.; Wing, L.; Grigoriadis, D.; De Souza E. B.; McCarthy, J. R. Design and syntheses of NBI 30545 and analogues as potent CRF receptor antagonists. ACS National Meeting, Anaheim, CA, Mar 21-25, 1999; MEDI 002.
203. Chen, Y. L. Substituted 6,5-hetero-bicyclic derivatives. International Publication Number WO 98/08847, 1998.
204. Wustrow, D. J.; Capiris, T.; Rubin, R.; Knobelsdorf, J. A.; Akunne, H.; Davis, M. D.; MacKenzie, R.; Pugsley, T. A.; Zoski, K. T.; Heffner, T. G.; Wise, L. D. Pyrazolo[1,5-a]pyrimidine CRF-1 Antagonists. Bioorg. Med. Chem. Lett. 1998, 8, 2067-2070.
205. Davis, M. D.; Cooke, L. W. The non-peptide CRF-R1 antagonist, PD171729, inhibits corticotropin releasing factor (CRF)-induced norepinephrine release in the cortex of rats. Society for Neuroscience, Los Angeles, CA, Nov 7-12, 1998; Abstract 583.2.
206. Gilligan, P. J.; Baldauf, C. A.; Cocuzza, A. J.; Chidester, D. R.; Fitzgerald, L. W.; Zaczek, R; Shen, H.-S. L. Pyrazolo-[1,5-a]-pyrimidine CRF antagonists: Synthesis and Structure-Activity Relationships. ACS National Meeting, Boston, MA, Aug 23-27, 1998; MEDI 135.
207. He, L.; Gilligan, P. J.; Fitzgerald, L.; Zaczek, R.; Shen, H.; Trainor, G. L.; Hartig, P. R. Pyrazolo-[1,5-a]-s-triazine as novel hCRF1 receptor antagonists: Design, synthesis and structure activity relationships. ACS National Meeting, Anaheim, CA, Mar 21-25, 1999; MEDI 107.
208. He, L.; Gilligan, P. J.; Zaczek, R.; Fitzgerald, L.; Kalin, N.; McElroy, J.; Saye, J.; Shen, H.: Shelton, S.; Smith, M.; Trainor, G.; Hartig, P. DMP696: A potent orally bioavailable pyrazolo-[1,5-a]-s-triazine corticotropin releasing factor (CRF) antagonist. ACS National Meeting, Anaheim, CA, Mar 21-25, 1999; MEDI 4.
209. L. W. Fitzgerald (DuPont Pharmaceuticals Co.), personal communication.
210. The structures 18, 22, 24-26, and 33-37 were individually minimized using the PCSpartan software package and then superimposed such that the bicyclic cores were coinincident.
211. Wilde, R. G.; Bakthavatchalam, R.; Beck, J.; Arvanitis, A. Imidazopyrimidines and imidazopyridines for the treatment of neurological disorders. International Publication Number WO 99/01454, 1999.
212. Volkmann, R. A. Benzimidazole derivatives and their use as corticotropin releasing factor antagonists. European Patent Application EP 812831, 1997.
213. Wilde, R. G. Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders. International Publication Number WO 97/44038, 1997.
214. Huang, C.; Wilcoxen, K. M.; Chen, C.; Haddach, M.; McCarthy, J. R. CRF antagonistic quino- and quinazolines. International Publication Number WO 98/47874, 1998.
215. Yuan, J.; Hutchison, A. Isoquinolinamine and phthalazinamine derivatives which interact with CRF receptors. International Publication Number WO 98/27066, 1998.
216. Beck, J. P.; Tivitmahaisoon. P.; Folmer, B. K.; Curry, M. A.; Fitzgerald, L. W.; Gilligan, P. J.; Zaczek, R.; Robertson, D. W.; Marshall, M. Imidazo[4,5-c]-pyrazoles: a novel heterocyclic series of corticotropin releasing hormone (CRH R1) antagonists. ACS National Meeting, Anaheim, CA, Mar 25-29, 1999; MEDI 1.
217. Beck, J. P.; Folmer, B. K.; Curry, M. A.; Tivitmahaisoon, P.; Fitzgerald, L. W.; Gilligan, P. J.; Zaczek, R.; Robertson, D. W. Imidazo[4,5-c]pyrazoles as corticotropin releasing hormone (CRH R1) receptor antagonists: detailed pyrazole SAR and synthesis. ACS National Meeting, Anaheim, CA, Mar 25-29, 1999; MEDI 106.
218. Beck, J. P.; Bakthavatcahalam, R.; Curry, M. A.; Fitzgerald, F. W.; Frietze, W. F.; Gilligan, P. J.; Huang, S.-M.; Olson, R. E.; Robertson, D. W.; Shen, H.; Wilde, R. G.; Zaczek, R. N-Aryl aminotriazolopyrimidines as corticotropin releasing hormone (CRH-R1) antagonists. ACS National Meeting, Dallas, TX, Mar 29-Apr 2, 1998; MEDI 140.
219. Bakthavatchalam, R.; Arnold, C. R.; Arvanitis, A. G.; Beck, J. P.; Chorvat, R. J.; Curry, M. C.; Fitzgerald, L. W.; Frietze, W. E.; Gilligan, P. J.; Olson, R. E.; Rescinito, J. T.; Robertson, D. W.; Smith, S. C.; Wilde, R. G.; Zaczek, R.; Shen, S.; Huang, S.-M.; N-Aryl aminotriazolopyrimidines and -pyridines: Synthesis and evaluation as selective corticotropin-releasing hormone (CRH1) receptor antagonists. ACS National Meeting, Dallas, TX, Mar 29-Apr 2, 1998; MEDI 143.
220. Arvanitis, A. G.; Bakthavatchalam, R.; Beck, J. P.; Rescinito, J. T.; Arnold, C. R.; Fitzgerald, L. W.; Zaczek, R.; Gilligan, P. J.; Olson, R. E.; Hobbs, F. W. Aryl- and anilino-triazolopyridines as corticotropin releasing factor (CRF) receptor antagonists. ACS National Meeting, Dallas, TX, Mar 29-Apr 2, 1998; MEDI 144.
221. Bakthavatchalam, R.; Arvanitis, A. G.; Gilligan, P. J.; Olson, R. E.; Robertson, D. W.; Trainor, G. L.; Smith, S. C.; Fitzgerald, L. W.; Zaczek, R.; Shen, H.; Christ, D. D. The discovery of DMP 695: An orally active corticotropin-releasing hormone (CRH1) receptor antagonist. ACS National Meeting, Boston, MA, Aug 23-27, 1998; MEDI 134.
222. Bakthavatchalam, R.; Arvanitis, A. G.; Beck, J. P.; Cain, G. A.; Chorvat, R. J.; Gilligan, P. J.; Olson, R. E. Preparation of arylamino fused pyridines and pyrimidines as CRF antagonists. International Publication Number WO 97/35539, 1997.
223. Chen, Y. L. Substituted heterocyclic derivatives as CRF antagonists. European Patent Application Number EP 778277, 1997.
224. Arvanitis, A. G.; Gilligan, P. J.; Beck, J. P.; Bakthavatchalam, R. Heterocyclyl-substituted ring-fused pyridines and pyrimidines as corticotropin-releasing hormone (CRH) antagonists, useful for treating CNS and stress-related disorders. International Publication Number WO99/11643, 1999.
225. Arvanitis, A. G.; Bakthavatchalam, R.; Beck, J. P.; Rescinito, J. T.; Arnold, C. R.; Zaczek, R. Gilligan, P. J.; Olson, R. E.; Fitzgerald, L. W. Heterocyclic triazolopyridines and pyrimidines as corticotropin releasing factor (CRF1) receptor antagonists. ACS National Meeting, New Orleans, LA, Aug 22-26, 1999; MEDI 111.
226. Luthin, D. R.; Rabinovich, A. K.; Bhumralkar, D. R.; Youngblood, K. L.; Bychowski, R. A.; Dhanoa, D. S.; May, J. M. Synthesis and biological activity of oxo-7H-benzo-[e]-perimidine-4-carboxylic acid derivatives as potent non-peptide corticotropin-releasing factor (CRF) receptor antagonists. Bioorg. Med. Chem. Lett. 1999, 9, 765-770.
227. Rabinovich, A. K.; Dhanoa, D. S.; Luthin, D. R.; Bychowski, R. A.; Bhumralkar, D. R. Benzoperimidine-carboxylic acids and derivatives thereof. U.S. Patent 5861398, 1999.
228. Whitten, J. P.; McCarthy, J. R.; Liu, Z.; Huang, C. Q.; Erickson, P. E.; Behan, D. P.; Xie, Y. F.; Lowe, R. F. Oxocoumarin and barbituric acid derivatives, their preparation and their use as ligand inhibitors of a corticotropin releasing factor (CRF) and/ or a CRF-binding protein complex. International Publication Number WO 97/45421, 1997.
229. Mitch, C. H.; Quimby, S. J. Thiadiazinyl corticotropin-releasing factor binding protein ligand inhibitors. International Publication Number WO 98/51312, 1998.
230. Spiess, J.; Dautzenberg, F. M.; Sydow, S.; Hauger, R. L.; Ruhmann, A.; Blank, T.; Radulovic, J. Molecular properties of the CRF receptor. Trends Endocrinol. Metab. 1998, 9, 140-145.
231. Dautzenberg, F. M.; Wille, S.; Lohmann, R.; Spiess, J. Mapping the ligand selective domain of the xenopus laevis "CRF" receptor 1: implications for the ligand binding site. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 4941-4946.
232. 1 antagonists: Identification and pharmacological characterization. American Neuroendocrine Society, Neuroendocrine Workshop on Stress, New Orleans, LA, June 21-23, 1998; Abstract 6.
233. Sydow, S.; Flaccus, A.; Fischer, A.; Spiess, J. The role of the fourth extracellular domain of the rat corticotropin-releasing factor receptor type 1 in ligand binding. Eur. J. Biochem. 1999, 259, 55-62.
234. Wille, S.; Sydow, S.; Palchaudhuri, M. R.; Spiess, J.; Dautzenberg, F. M. Identification of amino acids in the N-terminal domain of corticotropin-releasing factor receptor 1 that are important determinants of high affinity ligand binding. J. Neurochem. 1999, 72, 388-395.
235. Strader, C. D.; Sigal, I. S.; Dixon, R. A. F. Structural basis of β-adrenergic receptor function. FASEB J. 1989, 3, 1825-1832.
236. 1 receptor antagonist. Society for Neuroscience, New Orleans, LA, Oct 25-30, 1997; Abstract 689.4.
237. 1 receptor antagonist NBI27914. Society for Neuroscience, New Orleans, LA, Oct 25-30, 1997; Abstract 689.10.
238. Griebel, G.; Perrault, G.; Sanger, D. J. Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents. Psychopharmacology 1998, 138, 55-66.
239. Schulz, D. W.; Mansbach, R. S.; Sprouse, J.; Braselton, J. P.; Collins, J.; Corman, M.; Dunaiskis, A.; Faraci, S.; Schmidt, A. W.; Seeger, T.; Seymour, P.; Tingley, F. D.; Winston, E. N.; Chen, Y. L.; Heym, J. CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 10477-10482.
240. 1 receptor antagonist. Eur. J. Pharmacol. 1997, 323, 21-26.
241. Webster, E. L.; Lewis, D. B.; Torpy, D. J.; Zachman, E. K.; Rice, K. C.; Chrousos, G. P. In vivo and in vitro characterization of antalarmin, a non-peptide corticotropin-releasing hormone (CRF) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation. Endocrinology 1996, 137, 5747-5750.
242. Theoharides, T. C.; Singh, L. K.; Boucher, W.; Pang, X.; Letourneau, R.; Webster, E.; Chrousos, G. Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability. Endocrinology 1998, 139, 403-413.
243. Deak, T.; Nguyen, K. T.; Ehrlich, A. L.; Watkins, L. R.; Spencer, R. L.; Maier, S. F.; Licinio. J.; Wong, M.-L.; Chrousos, G. P.; Webster, E.; Gold, P. W. The impact of the nonpeptide corticotropin-releasing hormone antagonist antalarmin on behavioral and endocrine responses to stress. Endocrinology 1999, 140, 79-86.
244. 1) Antagonist. Bioorg. Med. Chem. 2000, 8, 181-189.
245. He, L.; Gilligan, P. J.; Zaczek, R.; Fitzgerald. L. W.; McElroy, J. F.; Shen, H.-S. L.; Saye, J. A.; Kalin, N. H.; Shelton, S.; Christ, D.; Trainor, G.; Hartig, P. 4-(1,3-Dimethoxypropyl-2-amino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5- a]-1,3,5-triazine: A Potent, Orally Bioavailable CRF1 Antagonist. J. Med. Chem. 2000, 430, 449-456.
246. Owens, M. J.; Nemeroff, C. B. Corticotropin-releasing factor antagonists: therapeutic potential in the treatment of affective disorders. CNS Drugs 1999, 12, 85-92.