1192-34-3Relevant articles and documents
Preparation and evaluation of some anti-arrhythmic and cardiac inotropic agents as 'cold' analogs of potential myocardial imaging agents
El-Moselhy, Tarek F.,El-Kersh, Mohamed A.,Nyberg, Fred,Hede, Ragnar,Eldawy, Mohamed A.
, p. 163 - 170 (2007/10/03)
The iodinated anti-arrhythmic analogs of disopyramide (1), procainamide (2) and lidocaine (3) and a new class of imidazolone cardiac inotropic phosphodiesterase inhibitors (4) and (5) (enoximone analogs), were prepared and tested as potential myocardial imaging agents. Compounds 1 and 2 were prepared by direct iodination using iodine monochloride in acetic acid, while 3-5 were prepared from suitable starting materials. The tissue load of the iodinated compounds was determined, in rats, on the basis of their iodine content using adaptation of a recent modification of Sandell and Kolthoff assay. The biodistribution of 125I-iodo derivatives of 2 and 4 were performed in mice. A pharmacokinetic study was performed using 5 to determine the optimal time of imaging post-injection. These compounds have shown significant localization in the heart tissue.
4-(4-Guanidinobenzoyl)-2-imidazolones and related compounds: Phosphodiesterase inhibitors and novel cardiotonics with combined histamine H2 receptor agonist and PDE III inhibitor activity
Glass,Buschauer,Tenor,Bartel,Will-Shahab,Krause
, p. 709 - 719 (2007/10/03)
A series of new positive inotropic agents was synthesized with the aim of combining the pharmacophores of the imidazole-type phosphodiesterase (PDE) inhibitor enoximone and guanidine-type histamine H2 receptor agonists such as arpromidine. All compounds are para-substituted 4-benzoyl-5-alkyl-2-imidazolones. H2 agonism was incorporated by p-(hetero)alkyl substituents, in particular by an imidazolylpropyl guanidine group. In addition analogous ureas, cyanoguanidines carboxylate, and amines were prepared. These functional groups were either directly attached to the phenyl ring or linked by an appropriate spacer. The compounds were screened for positive inotropic activity in the isolated electrically stimulated guinea pig papillary muscle and for inhibition of PDE III (cGMP-inhibited cAMP PDE, isolated from guinea pig heart). The cardiotonics obtained proved to be either PDE III inhibitors, some of them surmounting up to 3-fold the potency of enoximone, or pharmacological hybrids combining both PDE III inhibitor and histamine H2 receptor agonist activities. These hybrids were the most potent positive inotropic substances at the papillary muscle, probably due to their synergistic mechanism of action. The participation of histamine H2 receptors could be demonstrated in the papillary muscle preparation by pretreatment with the H2 antagonist famotidine (10 μM) as well as by further pharmacological experiments using isolated perfused hearts of guinea pigs and rats, isolated guinea pig right atria, adenylyl cyclase and H2 receptor binding assay. At equieffective concentrations the moderate PDE III inhibitor and histamine H2 agonist N1-{4-[(1,3-dihydro-5-methyl-2-oxo-3H-imidazol-4-yl)-carbonyl]phenyl }-N2-[3-(1H-imidazol-4-yl)propyl]guanidine 65 and the 5-ethyl homologue 66 were about 2 and 10 times more potent than enoximone at the papillary muscle. Moreover, both compounds produced a 2.5-fold higher maximal response than the reference compound.
Process for the production of 2-imidazolones
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, (2008/06/13)
The present invention pertains to a process for producing a 2-imidazolone from a ureidoacetal. The ureidoacetal is subjected to an acid catalyzed condensation in order to produce the 2-imidazolone. The reaction is conducted in an alcoholic solvent in order to minimize the production of a polymeric by-product.
RECYCLIZATION REACTIONS. RECYCLIZATIONS OF 3-ACYLMETHYL-2,4-THIAZOLIDINEDIONES BY THE ACTION OF NUCLEOPHILES
Shvaika, O. P.,Korotkikh, N. I.,Chervinskii, A. Yu.,Artemov, V. N.
, p. 1533 - 1543 (2007/10/02)
Four directions were established and investigated in the recyclization of 3-acylmethyl-2,4-thiazolidinediones with the participation of the side chain at the cyclic nitrogen atom and the formation of substituted 2-imidazolones or 2-oxazolones (under the influence of ammonia or hydroxides respectively), 2,5-diarylpyrazines (under the influence of methylamine), 6-monosubstituted or 2,6-disubstituted 4,5-dihydro-1,2,4-triazin-3-ones, and 5-substituted 1-amino-2-imidazolones (under the influence of hydrazine and phenylhydrazine).The directions of recyclization with hydrazines are determined by the stereochemical configuration of the intermediate hydrazones; the E-hydrazones of 3-acylmethyl-2,4-thiazolidenediones are converted into 4,5-dihydro-1,2,4-triazin-3-ones, while the Z izomers are converted into 1-amino-2-imidazolones.
