83962-06-5Relevant academic research and scientific papers
Scope and limitations of the nitro-Mannich reaction for the stereoselective synthesis of 1,2-diamines
Anderson, James C.,Blake, Alexander J.,Howell, Gareth P.,Wilson, Claire
, p. 549 - 555 (2007/10/03)
(Chemical Equation Presented) The acetic acid-promoted addition of lithium nitropropanate and the Lewis acid-catalyzed [Sc-(OTf)3, Cu(OTf) 2, or Ti(OiPr)4] addition of trimethylsilyl nitropropanate to a range of heteroaromatic and simple aliphatic aldimines gave anti-rich (～3-19:1) β-nitroamines in >95% yields as the kinetic products. It was found that a nonpolar N-imine protecting group was essential for reactivity with the o-methoxybenzyl (OMB) group giving better selectivities and yields than p-methoxybenzyl (PMB) or p-methoxyphenyl (PMP) in the Lewis acid-catalyzed addition reactions. Reduction with SmI2, treatment with COCl 2, followed by OMB deprotection gave diastereomerically pure cis-imidazolidinones in 55-79% overall yield from imine. Preliminary results have shown that acetic acid can catalyze the reaction of N-OMB-benzylideneamine with nitropropane, used as solvent, to give the thermodynamically more stable syn-β-nitroamine product.
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.
