Novel nonpeptide CCK-B antagonists: Design and development of quinazolinone derivatives as potent, selective, and orally active CCK-B antagonists

Journal of Medicinal Chemistry

Volumn 41, Issue 7, 1998, Pages 1042-1049

  Padia, Janak K ^a,c   Field, Mark ^b   Hinton, Joanna ^a   Meecham, Ken ^b   Pablo, Julius ^a   Pinnock, Rob ^b   Roth, Bruce D ^a   Singh, Lakhbir ^b   Suman Chauhan, Nirmala ^b   Trivedi, Bharat K ^a   Webdale, Louise ^b  

^a PFIZER INC   (United States)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c Systems Integrated Drug Discovery Co   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLECYSTOKININ B RECEPTOR ANTAGONIST; QUINAZOLINONE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; INTRAVENOUS DRUG ADMINISTRATION; MALE; MAZE TEST; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT; RECEPTOR AFFINITY; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; BEHAVIOR, ANIMAL; CHOLECYSTOKININ; MALE; MAZE LEARNING; RATS; RATS, WISTAR;

EID: 14444274329     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970373j     Document Type: Article

References (34)

1. (a) Preliminary accounts of this work were presented at the 211th National ACS Meeting in New Orleans, LA, 1996.
2. (b) Padia, J. K. Novel heterocycles as cholecystokinin (CCK) ligands. International Patent Application No. WO 96/20178.
3. Larsson, L. I.; Rehfeld, J. F. Localization and molecular heterogeneity of cholecystokinin in the central and peripheral nervous system. Brain Res. 1979, 165, 201-218.
4. Rehfeld, J. F.; Nielsen, F. C. Molecular forms and regional distribution of cholecystokinin in the central nervous system. In Cholecystokinin Anxiety: Neuron Behavior; Bradwejn, J., Vasar, E., Eds.; Landes: Austin, TX, 1995; pp 33-56.
5. Innis, R. B.; Synder, S. H. Distinct cholecystokinin receptors in brain and pancreas. Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 6917-6921.
6. Hays, S. E.; Beinfeld, M. C.; Jensen, R. T.; Goodwin, F. K.; Paul, S. M. Demonstration of a putative receptor site for cholecystokinin in rat brain. Neuropeptides (Edinburgh) 1980, 1 (1), 53-62.
7. Wank, S. A.; Pisegna, J. R.; DeWeerth, A. Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 8691-8695.
8. Lee, Y. M.; Beinbora, M.; McBride, E. W.; Lu, M.; Kolakowski, L. F.; Kopin, A. S. The human brain cholecystokinin-B/gastrin receptor. Cloning and characterization. J. Biol. Chem. 1993, 268, 8164-8169.
9. DeWeerth, A.; Pisegna, J. R.; Hupi, K.; Wank, S. A. Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor. Biochem. Biophys. Res. Commun, 1993, 194, 811-818.
10. Singh, L.; Lewis, A. S.; Field, M. J.; Hughes, J.; Woodruff, G. N. Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 1130.
11. Bradwejn, J. Cholecystokinin and panic disorder. In Cholecystokinin Anxiety: Neuron Behavior; Bradwejn, J., Vasar, E., Eds.; Landes: Austin, TX, 1995; pp 73-86.
12. For reviews, see: (a) Trivedi, B. K. Cholecystokinin receptor antagonists: Current status. Curr. Med. Chem. 1994, 1, 313-327. (b) Trivedi, B. K. Ligands for cholecystokinin receptors: Recent developments. Curr. Opin. Ther. Patents 1994, 4, 31- 44.
13. For reviews, see: (a) Trivedi, B. K. Cholecystokinin receptor antagonists: Current status. Curr. Med. Chem. 1994, 1, 313-327. (b) Trivedi, B. K. Ligands for cholecystokinin receptors: Recent developments. Curr. Opin. Ther. Patents 1994, 4, 31- 44.
14. Horwell, D. C.; Hughes, J.; Hunter, J. C.; Pritchard, M. C.; Richardson, R. S.; Roberts, E.; Woodruff, G. N. Rationally designed "dipeptoid" analogues of CCK. α-Methyltryptophan derivatives as highly selective and orally active gastrin and CCK-B antagonists with potent anxiolytic properties. J. Med. Chem. 1991, 34, 404-414.
15. Feng, R.; Hinton, J. P.; Huffman, K.; Parker, T. D.; Wright, D. S. Pharmacokinetics and oral bioavailability of CI-988 ester prodrugs in Wistar rats, Pharm. Res. 1993, 10 (10), S-346.
16. Hinton, J. P.; Rutkowski, K.; Johnson, E. L.; Wright, D. S. Single-dose pharmacokinetics and absolute bioavailability of the anxiolytic CI-988 in fasted and fed cynomolgus monkeys. Pharm. Res. 1991, 8 (10), S-330.
17. 14C]CI-988 in cynomolgus monkeys. Pharm. Res. 1993, 10 (10), S-267.
18. Bradwejn, J.; Koszycki, D.; Paradis, M.; Reece, P.; Hinton, J. P.; Sedman, A. Effect of CI-988 on cholecystokinin tetrapeptide-induced panic symptoms in healthy volunteers. Biol. Psychiat. 1995, 38, 742.
19. Trivedi, B. K.; Padia, J. K.; Holmes, A.; Rose, S.; Wright, S. D.; Hinton, J. P.; Prichard, M. C.; Eden, J. M.; Kneen, C.; Webdale, L.; Suman-Chuhan, N.; Boden, P.; Singh, L.; Field, M. J.; Hill, D. R. Second-generation peptoid CCKB antagonists: Identification and development of CI-1015 with an improved pharmacokinetic profile. J. Med. Chem. 1998, 41, 38-45.
20. Chang, R. S. L.; Lotti, V. J.; Monaghan, R. L.; Birnbaum, J.; Stapley, E. O.; Goetz, M. A.; Albers-Schonberg, G.; Patchett, A. A.; Liesch, J. M.; Hensens, O. D.; Springer, J. P. A potent nonpeptide cholecystokinin antagonist selective for peripheral tissues isolated from Aspergillus alliaceus. Science 1985, 230, 177-179.
21. Chang, R. S. L.; Lotti, V. J. Biochemical and pharmacological characterization of an extremely potent and selective nonpeptide cholecystokinin antagonist. Proc. Natl. Acad. Sci. U.S.A. 1986, S3, 4923-4926.
22. Bradwejn, J.; Koszycki, D.; Couetoux du Tertre, A.; Bourin, M.; Palmour, R.; Ervin, F. The cholecystokinin hypothesis of panic and anxiety disorders: a review. J. Psychopharmacol. (Oxford) 1992, 6(3), 345-51.
23. Bock, M. G.; DiPardo, R. M.; Evans, B. E.; Rittle, K. E.; Whitter, W. L.; Garsky, V. M.; Gillbert, K. F.; Leighton, J. L.; Carson, K. L.; Veber, D. F.; Chang, S. L.; Lotti, V. J.; Freedman, S. B.; Smith, A. J.; Patel, S.; Anderson, P. S.; Freidinger, R. M. Development of 1,4-benzodiazepine cholecystokinin type B an- tagonists. J. Med. Chem. 1993, 36, 4276-4292.
24. Guyon, C.; Duboeucq, M.; Bearreau, M.; Chenot, F.; Folcke, N. M.; Boucharinc, S.; Bertrand, P.; Bohme, G. A.; Meartin, G.; Pendley, C. Abstract presented at XIIIth International Sympo- sium on Medicinal Chemistry, Basel, Switzerland, September 1992; Abstracts P-184.A and P-185.A.
25. Yu, M. J.; Thrasher, K. J.; McCowan, J. R.; Mason, N. R.; Mendelsohn, L. G. Quinazolinone cholecystokinin-B receptor ligands. J. Med. Chem. 1991, 34, 1508.
26. Yu, M. J.; McCowan, J. R.; Mason, N. R.; Deeter, J. B.; Mendelsohn, L. G. Synthesis and X-ray crystallographic analysis of quinazolinone cholecystokinin/gastrin receptor ligands. J. Med. Chem. 1992, 35, 2534.
27. Padia, J. K.; Chilvers, H.; Daum, P.; Pinnock, R.; Suman-Chauhan, N.; Webdale, L.; Trivedi, B. K. Design and synthesis of novel nonpeptoid CCK-B receptor antagonists. Bioorg. Med. Chem. Lett. 1997, 7, 805-810.
28. Abdel-Megeid, F. M. E.; Elkaschef, M. A. F.; Mokhatar, K. E. M.; Zaki, K. E. M. Reactions of 2,4(1H,3H)-quinazolinediones. J. Chem. Soc. C 1971, 1055.
29. Laboratorie Roger Bellon. 4-Oxo-3,4-dihydroquinazolines. British Patent No. 1,038,729, 1966; CAN 65:15399g.
30. Bullock, G. A.; Sheeran, P. J. 2-Amino-4(3H)-quinazolinones. U.S. Patent No. 3,867,384, 1975; CAN 82:171037.
31. Kottke, K.; Kuehmstedt, H. Iodine-substituted 2-hydrazino-3-phenylquinazol-4-ones and their cyclization products. Part 6. Synthesis of compounds with an aminoguanidine structure. Pharmazie 1980, 35, 800-801.
32. Bishop, L. A.; Gerskowiteh, V. P.; Hull, R. A. D.; Shankley, N. P.; Black, J. W. The use of receptor desensitization to analyze CCKA and CCKB/gastrin receptors coupled to contraction in guinea pig stomach muscle. Br. J. Pharmacol. 1995, 114, 339348.
33. Singh, L.; Field, M. J.; Hughes, J.; Menzies, R.; Oles, R. J.; Vass, C. A.; Woodruff, G. N. The antagonism of benzodiazepine withdrawal effects by the selective cholecystokininB receptor antagonist CI-988. Br. J. Pharmacol. 1991, 104, 239.
34. Hinton, J. P.; Pablo, J.; Padia, J. P.; Wright, D. S. Bioanalytical discovery support of novel quinazolinone CCK-B receptor antagonists. Pharm. Res. 1996, 13 (9), S-36.