Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 1. Synthesis and biological activities of N-benyl-N'-(arylalkyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl) piperazines
Rondu, Frédéric; Le Bihan, Gaëlle; Wang, Xuanet al.
1997 • In Journal of Medicinal Chemistry, 40 (23), p. 3793-3803
Design and synthesis of imidazoline derivatives active on glucose homeostasis in a rat model of type II diabetes. 1. Synthesis and biological activities of N-benyl-N'-(arylalkyl)-2-(4',5'-dihydro-1'H-imidazol-2'-yl) piperazines
Publication date :
1997
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Schmid-Antomarchi, H. S.; De Weille, J.; Fosset, M.; Lazdunski, M. The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells. J. Biol. Chem. 1987, 262, 15840-15844.
Bailey, C. J.; Nattrass, M. Treatment - Metformin. Bailiere's Clin. Endocrinol. Metab. 1988, 2, 455-476.
Jackson, R. A.; Mawa, M. I.; Jaspan, J. B.; Sim, B. M.; Di Silvio, L.; Featherbe, D.; Kurtz, A. B. Mechanisms of metformin action in non-insulin-dependent diabetes. Diabetes 1987, 36, 632-640.
Hermann, L. S.; Melander, A. Biguanides: Basic aspects and clinical uses. In International Textbook of Diabetes Mellitus; Alberti, K. G. M. M., DeFronzo, R. A., Keen, H., Zimmet, P., Eds.; John Wiley & Sons Ltd.: New York 1992, pp 773-795.
Campbell, I. W. Sulphonylureas and Metformin: Efficacy and Inadequacy in New Antidiabetic Drugs; Bailey, C. J., Flatt, P. R., Eds.; Smith-Gordon: London, 1990, pp 33-51.
Berger, W. Incidence des effets secondaires sévères sous traitement par des sulfonylurées et des biguanides. (Incidence of severe side effects under sulfonylureas and biguanides treatment.) J. Diabétol, Hôtel-Dieu, Flammation Ed., Paris 1986, 243-253.
Kameda, K.; Ono, S.; Aboko, Y. Hypoglycemic action of 2-[2-(4′,5′-dihydro-1′H-imidazol-2′-yl)]-1- phenylethylpyridine dihydrochloride sesquihydrate (DG-5128), a new hypoglycemic agent. Arzneim. Forsch. Drug Res. 1982, 32, 39-44.
Kashiwagi, A.; Harano, Y.; Susuki, M.; Kojima, H.; Harada, M.; Nishio, Y.; Shiegeta, Y. New α2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients. Diabetes 1986, 35, 1085-1089.
Use of pyrrolo[3,2,1-hi]indole derivatives in the manufacture of a medicament for the treatment of diabetes. EP 0311467; Synthelabo.
Annual Drug Data Report 1992, 14, 995.
Jonas, J. C.; Garcia-Banado, M. J.; Angel, I.; Henquin, J. C. The imidazoline SL 84.0148 shows stereoselectivity in blocking α2-adrenoceptors but not ATP-sensitive K+ channels in pancreatic B-cells. Eur. J. Pharmacol. 1994, 264, 81-84.
Berritge, T. L.; Doxey, J. C.; Roach, A. G. Comparison of the effects of efaroxan and glibenclamide on plasma glucose and insulin levels in rats. Eur. J. Pharmacol. 1992, 213, 213-218.
Östenson, C. G.; Cattaneo, A. G.; Doxey, J. C.; Efendic, S. Alpha-adrenoceptors and insulin release from pancreatic islets of normal and diabetic rats. Am. J. Physiol. 1989, 257, E439-E443.
Chan, S. L. F. Role of alpha-2 adrenoceptors and imidazoline-binding sites in the control of insulin secretion. Clin. Sci. 1993, 85, 671-677.
Schultz, A.; Hasselblatt, A. An insulin-releasing property of imidazoline derivatives is not limited to compounds that block α-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol. 1989, 340, 321-327.
Michel, M. C.; Brodde, O. E.; Schnepel, B.; Behrendt, T.; Tschada, R.; Motulsky, H. J.; Insel, P. A. (3H)Idazoxan and some other alpha-2-adrenergic drugs also bind with high affinity to a non adrenergic site. Mol. Pharmacol. 1989, 35, 324-330.
Atlas, D.; Diamant, S.; Zonnenschein, R. Is imidazoline site a unique receptor? Am. J. Hyper. 1992, 5, 83S-90S.
Ruffolo, R. R. H.; Bondinelli, W. E.; Hieble, J. P. α- and β-Adrenoceptors: From the gene to the clinic. Structure-activity relationships and therapeutic applications. J. Med. Chem. 1995, 38, 3681-3716.
Wang, X.; Rondu, F.; Lamouri, A.; Dokhan, R.; Marc, S.; Touboul, E.; Pfeiffer, B.; Manechez, D.; Renard, P.; Guardiola-Lemaitre, B.; Godfroid, J. J.; Ktorza, A.; Penicaud, L. Effect of S-21663 (PMS 812), an imidazoline derivative, on glucose tolerance and insulin secretion in a rat model of type II diabetes. J. Pharmacol. Exp. Ther. 1996, 278, 82-89.
6-31G results (see ref 38). All 24 combinations of the mono- and/ or diprotonations of the molecule were studied. These results will be published elsewhere and are available if requested.
Frisch, M. J.; Trucks, G. W.; Head-Gordon, M.; Gill, P. M. W.; Wong, M. W.; Foresman, J. B.; Johnson, B. G.; Schlegel, H. B.; Robb, M. A.; Replogle, E. S.; Gomperts, J. L.; Andres, J. L.; Raghavachari, K.; Binkley, J. S.; Gonzalez, C.; Martin, R. L.; Fox, D. J.; Defrees, D. J.; Baker, J.; Stewart, J. J. P.; Pople, J. A. GAUSSIAN 94; Gaussian Inc.: Pittsburgh, PA, 1992.
Jucker, E.; Rissi, E. Über C-substituerte piperazinederivate. (On C-substituted piperazine derivatives.) Helv. Chem. Acta 1962, 273, 2383-2401.
Jerzy, L.; Pietraseiwick, M.; Duszynska, B.; Cegla, M. T. Structure-activity relationship studies of central nervous system agents. Effect of the hydrocarbon chain on the affinity of 4-substituted 1-(3-chlorophenyl)piperazines for 5-HT1A receptor site. J. Med. Chem. 1992, 35, 2369-2374.
Icke, R.; Wisegarver, N. B. β-Phenylethyldimethylamine. Organic Syntheses; Wiley: New York, 1955; Collect. Vol. 3, pp 723.
Neef, G.; Eder, U.; Sauer, G. One step conversions of esters to 2-imidazolines, benzimidazoles, and benzothiazoles by aluminum organic reagents. J. Org. Chem. 1981, 46, 2824.
Thibault, C.; Laury, M. C.; Bailbe, D.; Ktorza, A.; Portha, B. Effect of prolonged in vivo glucose infusion on insulin secretion in rats with previous glucose intolerance. Endocrinology 1992, 130, 2521-2527.
Chan, S. L. F.; Brown, C. A.; Morgan, N. G. Stimulation of insulin secretion by the imidazoline alpha-2 adrenoceptor antagonist efaroxan is mediated by a novel, stereoselective, binding site. Eur. J. Pharmacol. 1993, 230, 375-378.
Chan, S. L. F.; Brown, C. A.; Scarpello, K. E.; Morgan, N. G.; Pancreatic β-cells express an imidazoline binding site which is distinct from I1- and I2-sites. Int. Symp. Imidazoline Receptors 1994, P3.
Chan, S. L. F.; Dunne, M. J.; Stillings, M. R.; Morgan, N. G. The alpha-2 adrenoceptor antagonist efaroxan modulates K+/ ATP channels in insulin-secreting cells. Eur. J. Pharmacol. 1991, 204, 41-48.
Chan, S. L. F.; Hurst, R. D.; Morgan, N. G. Effects of alpha-2 adrenergic antagonists on insulin secretion from rat pancreatic islets. Biochem. Soc. Trans. 1988, 16, 1005-1006.
Chan, S. L. F.; Morgan, N. G. Stimulation of insulin secretion by efaroxan may involve interaction with potassium channels. Eur. J. Pharmacol. 1990, 176, 97-101.
Chan, S. L. F.; Stillings, M. R.; Morgan, N. G. Mechanisms involved in stimulation of insulin secretion by the hypoglycemic alpha-adrenergic antagonist, DG-5128. Biochem. Biophys. Res. Commun. 1991, 176, 1545-1551.
Olmos, G.; Kulkarni, T. N.; Haque, M.; MacDermot, J. Imidazolines stimulate release of insulin from RIN-5AH cells independently from I1 and I2 receptors. Eur. J. Pharmacol. 1994, 262, 41-48.
Brown, C. A.; Lowett, A. C.; Smith, S. A.; Morgan, N. G.; Stimulation of insulin secretion by imidazoline compounds is not due to interaction with non-adrenoceptor idazoxan binding sites. Br. J. Pharmacol. 1993, 108, 312-317.
Renouard, A.; Widdowson, P. S.; Cordi, A. (3H)-Idazoxan binding to rabbit cortex recognizes multiple imidazoline I2-type receptors: pharmacological characterization and relationship to monoamine oxidase. Br. J. Pharmacol. 1993, 109, 625-631.
Dewar, M. J. S.; Zoebish, E. G.; Healy, E. F. A new general purpose quantium mechanical molecular model. J. Am. Chem. Soc. 1985, 107, 3902.
Dive, G.; Dehareng, D.; Ghuysen, J. M. Energy analysis on small to medium sized H-bonded complexes. Theoret. Chim. Acta 1993, 85, 409-421.
Hehre, W. J.; Ditchfield, R.; Pople, J. A. Theoretical investigations on the solvation process. J. Chem. Phys. 1972, 56, 2557-2562.
Coupry, I.; Podevin, R. A.; Dausse, J. P.; Parini, A. Evidence for imidazoline binding sites in basolateral membranes from rabbit kidney. Biochem. Biophys. Res. Commun. 1987, 147, 1055-1060.
Reis, D. J.; Reunathan, S.; Meeley, P. M. P. Imidazoline receptors and clonidine-displacing substance: implication in regulation of arterial pressure, neuroprotection and medullo-adrenal secretion. Am. J. Hyper. 1992, 5, 45S-46S.
Uhlen, S.; Wikberg, J. Delineation of rat kidney alpha-2A and alpha-2B adrenoceptors with 3H-RX821002 radioligand binding: computer modelling reveals that guanfacine is an alpha-2A selective compound. Eur. J. Pharmacol. 1991, 202, 235-243.