Cyclic guanidines. X. Synthesis of 2-(2,2-disubstituted ethenyl- and ethyl)-2-imidazolines as potent hypoglycemics.

Ishikawa, Fumiyoshi

doi:10.1248/cpb.28.1394

Cited by 37 publications

(14 citation statements)

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“…DG-5128 was synthesized in this institute (Ishikawa 1980). The following chemicals were used: tolbutamide (Shinnihon Yakugyo Co., Tokyo), t-epinephrine bitartrate (Tokyo Kasei Kogyo Co., Tokyo), yohimbine hydrochloride (Nakarai Chemicals Co., Kyoto), phentolamine hydrochloride (Japan Ciba-Geigy Co., Takarazuka), prazosine hydrochloride (Taito-Pfizer Co., Tokyo), clonidine hydrochloride (C. H. Boehringer Sohn GmbH, Ingelheim), propranolol hydrochloride (Sumitomo Chemicals Co., Osaka), aprotinin (Trasylol, Bayer Co., Leverkusen), bovine serum albumin (Cohn Fraction V, Daiichi Pure Chemicals Co., Tokyo) and collagenase (Type I, Worthington Biochemical Corp., Freehold).…”

Section: Methodsmentioning

confidence: 99%

Insulin releasing action of 2-[2-(4,5-dihydro-1H-imadazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128), a new, orally effective hypoglycaemic agent

Kameda¹,

Ono²,

Koyama³

et al. 1982

Acta Endocrinologica

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2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenyl\x=req-\ ethyl] pyridine dihydrochloride sesquihydrate is a new orally effective hypoglycaemic agent structurally unrelated to the known hypoglycaemics. DG-5128 was found to decrease blood glucose levels by stimulating insulin release, like the sulphonylurea hypoglycaemics. However, the study with the rat Langerhans islets in vitro indicated a great difference in mode of stimulation of insulin release between DG-5128 and a sulphonylurea hypoglycaemic, tolbutamide. DG-5128 significantly reversed \g=a\-adrenergic inhibition of the glucose-primed insulin release from the islets, while tolbutamide did not.From the comparison with the effects of phentolamine, yohimbine and prazosine, DG-5128 was strongly suggested to stimulate the glucose-primed insulin release through antagonizing at \g=a\2-adrenoreceptors on the B cells.In a previous report (Kameda et al., in press), we described the hypoglycaemic and antihyperglycaemic action of 2-[2-(4,5-dihydro-lH-imidazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesqui¬ hydrate in various animal species in¬ cluding mice, rats, dogs, monkeys and genetically diabetic mice of AyKK strain. Since DG-5128 hardly affected blood glucose levels in streptozotocin-induced diabetic rats, this compound was as¬ sumed to exert its hypoglycaemic action through stimulating insulin release, like the sulphonylurea hypoglycaemics. However, some difference was observed in hypo¬ glycaemic action between DG-5128 and tolbut¬ amide; the former was also effective in the geneti¬ cally diabetic AyKK mice, while the latter was not (Kameda et al., in press). In addition to the structural difference between DG-5128 and tolbut¬ amide, this difference in hypoglycaemic action between the 2 compounds has stimulated us to compare the mode of action of DG-5128 with that of tolbutamide. The present report describes the insulin releasing action of DG-5128 in rats in vivo and in vitro in comparison with that of tolbut¬ amide. Materials and MethodsDG-5128 was synthesized in this institute (Ishikawa 1980). The following chemicals were used: tolbutamide (Shinnihon Yakugyo Co., Tokyo), t-epinephrine bitartrate (Tokyo Kasei Kogyo Co., Tokyo), yohimbine hydrochloride (Nakarai Chemicals Co., Kyoto), phentolamine hydrochloride (Japan Ciba-Geigy Co., Takarazuka), prazosine hydrochloride (Taito-Pfizer Co., Tokyo), clonidine hydrochloride (C. H. Boehringer Sohn GmbH, Ingelheim), propranolol hydrochloride (Sumitomo Chemicals Co., Osaka), aprotinin (Trasylol, Bayer Co., Leverkusen), bovine serum albumin (Cohn Fraction V, Daiichi Pure Chemicals Co., Tokyo) and collagenase (Type I, Worthington Biochemical Corp., Freehold). Other chemicals used were of analytical grade.For the experiments in vivo, male Wistar:STD rats weighing 140-170 g were used after fasting overnight. DG-5128 or tolbutamide was dissolved in saline and injected into the tail vein at 2 ml/kg. Control rats received saline alone. For this purpose, tolbutamide was solubilized by the addition of a small amount of rat se...

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Section: Methodsmentioning

confidence: 99%

Insulin releasing action of 2-[2-(4,5-dihydro-1H-imadazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128), a new, orally effective hypoglycaemic agent

Kameda¹,

Ono²,

Koyama³

et al. 1982

Acta Endocrinologica

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“…Beyond the chemical and biochemical interest of 4,5‐1 H ‐dihydroimidazole, the synthesis as well as vibrational and structural studies are of pharmacological importance because some substances of this kind present antihypertensive, antihelminthic, hypoglycemic, anti‐inflammatory, and analgesic activities 1–6. These biological effects were attributed to the activation of three groups of imidazoline receptors 7.…”

Section: Introductionmentioning

confidence: 99%

Structural and vibrational study of 2‐(2′‐ furyl)‐4,5‐1H‐dihydroimidazole

Zinczuk

Ledesma

Brandán

et al. 2009

J of Physical Organic Chem

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In this study 2-(2(-furyl)-4,5-1H-dihydroimidazole (1) was prepared and then characterized by infrared, Raman, and multidimensional nuclear magnetic resonance (NMR) spectroscopies. The crystal and molecular structures of 1 were determined by X-ray diffraction methods. The density functional theory (DFT) and second-order Møller-Plesset theory (MP2) with Pople's basis set show that there are two conformers for the title molecule that have been theoretically determined in the gas phase, and that only one of them, conformer I, is present in the solid phase. NMR spectra observed for 1 were successfully compared with the calculated chemical shifts at the B3LYP/6-311RRG ** level theorized for this conformer. The harmonic vibrational frequencies for the optimized geometry of the latter conformer were calculated at the B3LYP/6-311RRG ** level in the approximation of the isolated molecule. For a complete assignment of the IR and Raman spectra in the solid phase of 1, DFT calculations were combined with Pulaý s scaled quantum mechanics force field (SQMFF) methodology to fit the theoretical frequency values to the experimental ones.

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“…1 H -4,5-Dihydroimidazoles (2-imidazolines, I ) are cyclic amidines of pharmacological interest owing to certain properties exhibited by some members of the class, such as antihypertensive [ 1 ], antihelminthic [ 2 , 3 ], hypoglycemic [ 5 ], antiinflamatory and analgesic activity [ 4 ]. These biological effects were attributed to activation of three groups of imidazoline receptors (I 1 , I 2 , I 3 ) [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

1H- and 13C-NMR Analysis of a Series of 1,2-Diaryl-1H-4,5-dihydroimidazoles

Salerno¹,

Perillo²

2005

Molecules

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An analysis of the 1H- and 13C-NMR spectra of a series of 1,2-diaryl-1H-4,5-dihydroimidazoles and comparisons with 4,5-dihydroimidazoles having different substitution patterns are presented. The influence of different 1-aryl and 2-aryl group substituents on spectroscopic parameters of the heterocyclic ring and on the contributions of possible mesomeric structures in the system was determined. Spectroscopic features are coherent with the presence of two conjugated systems (Ar1-N and Ar2-C=N) which compete with the delocalization characteristics of the amidine system.

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Cyclic guanidines. X. Synthesis of 2-(2,2-disubstituted ethenyl- and ethyl)-2-imidazolines as potent hypoglycemics.

Cited by 37 publications

References 0 publications

Insulin releasing action of 2-[2-(4,5-dihydro-1H-imadazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128), a new, orally effective hypoglycaemic agent

Insulin releasing action of 2-[2-(4,5-dihydro-1H-imadazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128), a new, orally effective hypoglycaemic agent

Structural and vibrational study of 2‐(2′‐ furyl)‐4,5‐1H‐dihydroimidazole

1H- and 13C-NMR Analysis of a Series of 1,2-Diaryl-1H-4,5-dihydroimidazoles

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