Synthesis and cardiotonic activity of novel biimidazoles

Abstract

A series of substituted 2,2'-bi-1H-imidazoles and related analogues was synthesized and evaluated for inotropic activity. Structure-activity relationship studies based on a nonclassical bioisosteric approach indicated the necessity of a cyano group on one of the imidazole rings to obtain the desired pharmacological profile. 4(5)-Cyano-2,2'-bi-1H-imidazole (15a) was the most potent inotropic agent in the series. It produced a 25% increase in left ventricular dP/dt at 0.16 mg/kg iv (ED25% = 0.16 mg/kg) and increased left ventricular contractile force 60% at 1 mg/kg iv in anesthetized dogs. Compound 15a is a good inhibitor of type IV cyclic nucleotide phosphodiesterase isolated from dog heart having a potency similar to that of amrinone. Neither 5'-cyano-2,4'-bi-1H-imidazole (44) nor 4-cyano-2,4'-bi-1H-imidazole (48) demonstrated inotropic activity. In addition, the two possible 1,1'-dimethylcyano-2,2'-bi-1H-imidazoles (24 and 25) were inactive, indicating that an acidic NH as well as a cyano group are essential for inotropic activity.

Regioselective symmetrical bromination of protected 2,2′‐biimidazole

“…The chemistry of 2,2'-biimidazole (1), first obtained by Debus in 1858 by reaction of glyoxal and ammonia ( Figure 1) [1], has received little attention despite its potential uses in research areas such as material science [2] or pharmacology [3,4]. The reasons for such lack of interest lie in the fact that the synthesis of the bicyclic structure is extremely laborious, not easily allowing the synthesis of substituted 2,2'-biimidazole rings.…”

Benzoic acid–2,2′-biimidazole (2/1)

“…For background to the use of 2,2 0 -biimidazoles in crystal engineering, see: Matthews et al (1990); Tadokoro & Nakasuji (2000). For similar structures, see: Gao et al (2009); Li & Yang (2006); Mori & Miyoshi (2004).…”

Three new extended Preyssler-type polyoxometalates modified by transition metal-2,2′-biimidazole complexes

“…Moreover, some organic groups can be introduced into the POM skeletons, resulting in new POMs based on organic-inorganic hybrids. The nitrogen donor ligand H 2 biim has versatile coordination behavior and applications in many fields [17][18][19][20][21], but few compounds involving transition metal bridged H 2 biim ligands and polyoxoanions with coordination bonds have been reported [22,23]. Inspired by the above observations, in the present work, we endeavored to prepare new inorganic-organic hybrid compounds based on the TM-2,2 0 -biimidazole complexesmodified {P 5 W 30 } clusters, in order to measure the crystal structures, thermal stabilities and electrochemical properties of these Preysslertype POMs, and preliminarily explore the electrocatalytic activities toward the reduction of hydrogen peroxide, and the catalytic activities for the oxidation of cyclohexanol.…”