3-[2-(N-phenylacetamide)]-1,5-benzodiazepines: Orally active, binding selective CCK-A agonists

Journal of Medicinal Chemistry

Volumn 39, Issue 15, 1996, Pages 3030-3034

  Willson, Timothy M ^a,b   Henke, Brad R ^a,b   Momtahen, Tanya M ^a,b   Myers, Peter L ^a,b,c   Sugg, Elizabeth E ^a,b   Unwalla, Rayomand J ^a,b,d   Croom, Dallas K ^a,b,e   Dougherty, Robert W ^a,b,e   Grizzle, Mary K ^a,b   Johnson, Michael F ^a,b   Queen, Kennedy L ^a,b   Rimele, Thomas J ^a,b   Yingling, Jeffrey D ^a,b   James, Michael K ^a,b,e  

^a GLAXOSMITHKLINE   (United States)

^b NTH M2134 ^*

^c Formerly CombiChem Inc   (United States)

^d NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^e Inspire Pharmaceuticals   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZODIAZEPINE DERIVATIVE; CHOLECYSTOKININ; CHOLECYSTOKININ A RECEPTOR; CHOLECYSTOKININ RECEPTOR STIMULATING AGENT; RECEPTOR SUBTYPE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG SYNTHESIS; GALLBLADDER DISEASE; GALLBLADDER EMPTYING; INTRAPERITONEAL DRUG ADMINISTRATION; LIGAND BINDING; MOUSE; NONHUMAN; OBESITY; SATIETY;

ACETANILIDES; ANIMALS; AZEPINES; CHOLECYSTOKININ; GALLBLADDER; GUINEA PIGS; MICE; MOLECULAR STRUCTURE; MUSCLE CONTRACTION; RECEPTORS, CHOLECYSTOKININ;

EID: 9344219949     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960205b     Document Type: Article

References (19)

1. Crawley, J. N.; Corwin, R. L. Biological Actions of Cholecystokinin. Peptides 1994, 4, 731-755.
2. Schwartz, G. J.; McHugh, P. R.; Moran, T. H. Gastric Loads and Cholecystokinin Synergistically Stimulate Rat Vagal Afferents. Am. J. Physiol. 1993, 265, R872-R876.
3. Dourish, C. T.; Ruckert, A. C.; Tattersall, F. D.; Iversen, S. D. Evidence that Decreased Feeding Induced by Systemic Injection of Cholecystokinin is Mediated by CCK-A Receptors. Eur. J. Pharmacol. 1989, 173, 233-234.
4. Dourish, C. T.; Hill, D. R. Classification and Function of CCK Receptors. Trends Pharmacol. Sci. 1987, 8, 207-208.
5. Pi-Sunyer, F. X.; Kissileff, H. R.; Thornton, J.; Smith, G. P. C-Terminal Octapeptide of Cholecystokinin Decreases Food Intake in Obese Men. Physiol. Behav. 1982, 29, 627-630.
6. (a) Froehlich, F.; Gonvers, J. J.; Fried, M. Role of Nutrient Fat and Cholecystokinin in Regulation of Gallbladder Emptying in Man. Dig. Dis. Sci. 1995, 40, 529-533.
7. (b) Roslyn, J. J.; DenBesten, L.; Pitt, H. A.; Kuchenbecker, S.; Polarek, J. W. Effects of Cholecystokinin on Gallbladder Stasis and Cholesterol Gallstone Formation. J. Surg. Res. 1981, 30, 200-204.
8. Freidinger, R. M. Cholecystokinin and Gastrin Antagonists. Med. Res. Rev. 1989, 9, 271-290.
9. Aquino, C. J.; Armour, D. R.; Berman, J. M.; Birkemo, L. S.; Carr, R. A. E.; Croom, D. K.; Dezube, M.; Dougherty, R. W.; Ervin, G. N.; Grizzle, M. K.; Head, J. E.; Hirst, G. C.; James, M. K.; Johnson, M. F.; Miller, L. J.; Queen, K. L.; Rimele, T. J.; Smith, D. N.; Sugg, E. E. Discovery of 1,5-Benzodiazepines with Peripheral Cholecystokinin (CCK-A) Receptor Agonist Activity I. Optimization of the Agonist "Trigger". J. Med. Chem. 1996, 39, 562-569.
10. Bock, M. G.: DiPardo, R. M.; Evans, B. E.; Rittle, K. E.; Whitter, W. L.; Veber, D. F.; Anderson, P. S.; Freidinger, R. M. Benzodiazepine Gastrin and Brain Cholecystokinin Receptor Ligands; L-365,260. J. Med. Chem. 1989, 32, 13-16.
11. Unwalla, R. J. Unpublished results.
12. (a) Ulrich, C. D.; Ferber, I.; Holicky, E.; Hadac, E.; Buell, G.; Miller, L. J. Molecular Cloning and Functional Expression of the Human Gallbladder Cholecystokinin A Receptor. Biochem. Biophys. Res. Commun. 1993, 193, 204-211.
13. (b) de Weerth, A.; Pisegna, J. R.; Huppi, K.; Wank, S. A. Molecular Cloning, Functional Expression and Chromasomal Localization of the Human Cholecystokinin Type A Receptor. Biochem. Biophys. Res. Commun. 1993, 194, 811-818.
14. (a) Pisegna, J. R.; de Weerth, A.; Huppi, K.; Wank, S. A. Molecular Cloning of the Human Brain and Gastric Cholecystokinin Receptor: Structure, Functional Expression and Chomasomal Localization. Biochem. Biophys. Res. Commun. 1992, 189 , 296-303.
15. (b) Lee, Y. M.; Beinborn, M.; McBride, E. W.; Lu, M.; Kolakowski, L. F., Jr.; Kopin, A. S. The Human Brain Cholecystokinin-B/Gastrin Receptor. Cloning and Characterization. J. Biol. Chem. 1993, 268, 8164-8169.
16. Makovec, F.; Bani, M.; Cereda, R.; Chiste, R.; Pacini, M. A.; Revel, L.; Rovati, L. C. Antispasmodic Activity on the Gallbladder of the Mouse of CR 1409 (Lorglumide), a Potent Antagonist of Peripheral CCK. Pharmacol. Res. Commun. 1987, 19, 41-51.
17. In rodents, CCK may affect feeding behavior by both peripheral and centrally mediated pathways: (a) Della-Fera, M. A.; Coleman, B. D.; Baile, C. A. CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying. Am. J. Physiol. 1990, 258, R1165-R1169. (b) Crawley, J. Clarification of the behavioral functions of peripheral and central cholecystokinin: two separate peptide pools. Peptides 1985, 6, 129-36.
18. In rodents, CCK may affect feeding behavior by both peripheral and centrally mediated pathways: (a) Della-Fera, M. A.; Coleman, B. D.; Baile, C. A. CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying. Am. J. Physiol. 1990, 258, R1165-R1169. (b) Crawley, J. Clarification of the behavioral functions of peripheral and central cholecystokinin: two separate peptide pools. Peptides 1985, 6, 129-36.
19. Subsequent to the completion of our work, a patent application describing 1,4-benzodiazepines as orally active CCK agonists has been published. Badorc, A.; Despeyroux, P.; Gully, D.; De Cointet, P.; Frehel, D.; Maffrand, J-P. Preparation of 3-acylamino-5-phenyl-1,4-benzodiazepin-2-ones as CCK receptor agonists. EP 95 400293, 1995; Chem. Abstr. 1995, 124, 8858.