Second generation 'peptoid' CCK-B receptor antagonists: Identification and development of N-(adamantyloxycarbonyl)-α-methyl(R)-tryptophan derivative (CI-1015) with an improved pharmacokinetic profile

Journal of Medicinal Chemistry

Volumn 41, Issue 1, 1998, Pages 38-45

  Trivedi, Bharat K ^a   Padia, Janak K ^a   Holmes, Ann ^a   Rose, Steven ^a   Wright, D Scott ^a   Hinton, Joanna P ^a   Pritchard, Martyn C ^b   Eden, Jon M ^b   Kneen, Clare ^b   Webdale, Louise ^b   Suman Chauhan, Nirmala ^b   Boden, Phil ^b   Singh, Lakhbir ^b   Field, Mark J ^b   Hill, David ^b  

^a PFIZER INC   (United States)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2,3 DIHYDRO 1 METHYL 2 OXO 5 PHENYL 1H 1,4 BENZODIAZEPIN 3 YL) 3 (3 METHYLPHENYL)UREA; 2 HYDROXYPROPYL BETA CYCLODEXTRIN; 4 [[2 [2 [[(2 ADAMANTYLOXY)CARBONYL]AMINO] 3 (1H INDOL 3 YL) 2 METHYLPROPIONAMIDO] 1 PHENYLETHYL]AMINO] 4 OXOBUTYRIC ACID MEGLUMINE; [2 [(2 HYDROXYCYCLOHEXYL)AMINO] 1 (1H INDOL 3 YLMETHYL) 1 METHYL 2 OXOETHYL]CARBAMIC ACID 2 ADAMANTYL ESTER; BENZOTRIAZOLE DERIVATIVE; CHOLECYSTOKININ B RECEPTOR ANTAGONIST; DICYCLOHEXYLCARBODIIMIDE; DRUG VEHICLE; MACROGOL 400; METHYLCELLULOSE; N (ADAMANTYLOXYCARBONYL) ALPHA METHYL TRYPTOPHAN DERIVATIVE; N,N DIMETHYLACETAMIDE; SODIUM CHLORIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANXIETY; ARTICLE; BLOOD BRAIN BARRIER; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DESIGN; DRUG PENETRATION; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; FOREBRAIN; INTRAVENOUS DRUG ADMINISTRATION; MOUSE; NONHUMAN; ORAL DRUG ADMINISTRATION; PANIC; RAT; STRUCTURE ACTIVITY RELATION; SUBCUTANEOUS DRUG ADMINISTRATION; TRANQUILIZING ACTIVITY; ZONA INCERTA;

ADAMANTANE; ANIMALS; ANTI-ANXIETY AGENTS; BIOLOGICAL AVAILABILITY; BLOOD-BRAIN BARRIER; MAZE LEARNING; MICE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PEPTOIDS; RATS; RATS, WISTAR; RECEPTOR, CHOLECYSTOKININ A; RECEPTOR, CHOLECYSTOKININ B; RECEPTORS, CHOLECYSTOKININ; TETRAGASTRIN; TRYPTOPHAN;

EID: 15444340232     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm970065l     Document Type: Article

References (23)

1. Bourine, M.; Malinge, M.; Vasar, E.; Bradwejn, J. Two faces of cholecystokinin: anxiety and schizophrenia. Fundam. Clin. Pharmacol. 1996, 10, 116-126.
2. Trivedi, B. K. Ligands for cholecystokinin receptors: recent developments. Curr. Opin. Ther. Pat. 1994, 4 (1), 31-44.
3. Trivedi, B. K. Cholecystokinin Receptor Antagonists: Current Status. Curr. Med. Chem. 1994, 1, 313-327.
4. 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. Methyltryptophan derivatives as highly selective and orally active gastrin and CCK-B antagonists with potent anxiolytic properties. J. Med. Chem. 1991, 34, 404-414.
5. Hughes, J.; Boden, P.; Costall, B.; Domeney, A.; Kelly, E.; Horwell, D. C.; Hunter, J. C.; Pinnock, R. D.; Woodruff, G. N. Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc. Natl. Acad. Sci. U.S.A. 1991, 87, 6728.
6. 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.
7. 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-267.
8. 14]CI-988 in cynomolgus monkeys. Pharm. Res. 1993, 10 (10), S-330.
9. 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. Psychiatry 1995, 38, 742-746.
10. Chen, I-W.; Dorley, J. M.; Ranjit, H. G.; Pitzenberger, S. M.; Lin, J. H. Physiological disposition and metabolism of L-365260, a potent antagonist of brain cholecystokinin receptor in laboratory animals. Drug Metab. Dispos. 1992, 20(3), 390-395.
11. Bock, M. J.; Mellin, E. C.; Newton, R. C.; Veber, D. F.; Freedman, S. B.; Smith, A. J.; Patel, S.; Kemp, J. A.; Marshall, G. R.; Fletcher, A. E.; Chapman, K. L.; Andersen, P. S.; Freidinger, R. M. Second-generation benzodiazepine CCK-B antagonists. Development of subnanomolar analogues with selectivity and water solubility. J. Med. Chem. 1994, 37, 722-724.
12. Showell, G. A.; Bourrain, S.; Neduvelil, J. G.; Fletcher, S. R.; Baker, R.; Watt, A. P.; Fletcher, A. E.; Freedman, S. B.; Kemp, J. A.; Marshall, G. R.; Patel, S.; Smith, A. J.; Matassa, V. G. High affinity and potent, water soluble 5-amino-1,4-benzodiazepine CCK-B/gastrin receptor antagonists containing a cationic solubilizing group. J. Med. Chem. 1994, 37, 719-721.
13. Boden, P. R.; Higginbottom, M.; Hill, D. R.; Horwell, D. C.; Hughes, J.; Rees, D. C.; Roberts, E.; Singh, L.; Suman-Chauhan, N.; Woodruff, G. N. Cholecystokinin dipeptoid antagonists: design, synthesis and anxiolytic profile of some novel CCK-A and CCK-B selective and mixed antagonists. J. Med. Chem. 1993, 36, 552-565.
14. Overman, L. E.; Sugai, S. A convenient method for obtaining trans-2-amino cyclohexanol and trans-2-amino cyclopentanol in enantiomerically pure form. J. Org. Chem. 1985, 50, 4154-4155.
15. Aubé, J.; Wolfe, M, S.; Yantiss, R. K.; Cook, S. M.; Takusagawa, F, Synthesis of enantiopure N-tert-butoxycarbonyl-2-amino-cycloalkanones. Synth. Commun. 1992, 22 (20), 3003-3012.
16. Andre Michel, personal communication. X-ray coordinates will be deposited in Cambridge Database.
17. Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Whitter, W. L.; Veber, D. F.; Anderson, P. S.; Freidinger, R. M.; Gould, N. P.; Lundell, G. F.; Homnick, C. F.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. Design of nonpeptidal ligands for a peptide receptor: cholecystokinin antagonists. J. Med. Chem. 1987, 30, 1229.
18. Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.; Friedinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.; Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T. B.; King, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists. J. Med. Chem. 1988, 31, 2235.
19. Boden, P. R.; Pinnock, R. D.; Pritchard, M. C.; Woodruff, G. N. Br. J. Pharmacol. 1994, 112, 666-670.
20. Singh, L.; Field, M. J.; Hughes, J.; Menzies, R.; Oles, R. J.; Vass, C. A.; Woodruff, G. N. The behavioral prperties of CI-988, a selective cholecystokinin B receptor antagonist. Br. J. Pharmacol. 1991, 104, 239-245.
21. Szejtli, J. Cyclodextrins: Properties and Applications. Drug Invest. 1990, 2 (4), 11-21.
22. Frijlink, H. W.; Visser, J.; Hefting, N. R.; Oosting, R.; Meijer, D. K. F.; Lerk C. F. The Pharmacokinetics of β-cyclodextrin and hydroxypropyl-β-cyclodextrin in the rat. Pharm. Res. 1990, 7 (12), 1248-1252.
23. Hinton, J. P.; Pablo, J.; Bjorge, S.; Hoffman, K.; Jennings, K.; Wright, D. S. Three complementary liquid Chromatographic methods for determination of the peptoid cholecystokinin-B antagonist, CI-988, in rat plasma. J. Pharm Biomed. Anal. 1996, 14, 815-824.