Search

The novel synthesis of unsymmetrical 1,1'‐bibenzimidazoles is described. The key N−N bond was introduced on 1H‐benzimidazole or 1H‐benzimidazole‐2‐sulfonic acid by N‐amination with hydroxylamine‐O‐sulfonic acid (HASA). The precursors, 1‐[(2‐nitrophenyl)amino]‐1H‐benzimidazoles, were prepared by nucleophilic aromatic substitution of 1‐fluoro‐2‐nitrobenzene with 1H‐benzimidazole‐1‐amines. The synthesis was demonstrated on 11 novel 1,1'‐bibenzimidazoles, which were prepared in the final step by one‐pot reduction/cyclization with DMF or DMA acetals under mild acidic conditions in good overall yields. [ABSTRACT FROM AUTHOR]

Synthesis of [15N4] purine labeled cytokinine glycosides derived from zeatins and topolins containing a 9‐β‐d, 7‐β‐d‐glucopyranosyl, or 9‐β‐d‐ribofuranosyl group is described. These N6‐substituted adenine derivatives are intended as internal analytic standards for phytohormone analysis. All labeled compounds were prepared from 6‐chloro[15N4]purine (1). The equilibrium reaction of 1 with acetobromo‐α‐d‐glucose gave isomeric 7‐β‐d (3) and 9‐β‐d (4) chloro glucosyl precursors, which were treated with the corresponding amines to get desired labeled cytokinin 7‐β‐d (6) and 9‐β‐d (5) glucopyranosides. Cytokinins containing 9‐β‐d‐ribofuranosyl group (8) were obtained by direct enzymatic transglycosylation reaction of cytokinins (7) prepared from 6‐chloro[15N4] purine (1). Synthesis and characterization of some [15N4] purine labeled cytokinin glycosides derived from zeatins and topolins containing 9‐β‐d, 7‐β‐d‐glucopyranosyl, or 9‐β‐d‐ribofuranosyl group with using chemical and enzymatic approaches is described. [ABSTRACT FROM AUTHOR]

Electrochemical oxidation of azoxystrobin, a systemic fungicide commonly used in agriculture to protect a wide variety of crops, was investigated using cyclic voltammetry with a boron‐doped diamond electrode (BDDE) in aqueous buffer solutions. Two pH independent irreversible anodic current peaks controlled mostly by diffusion were observed in wide pH range (2 to 12) at potentials +1600 mV and +2150 mV vs. saturated silver‐silver chloride electrode. Mechanism of the electrochemical oxidation was proposed and supported with high performance liquid chromatography/mass spectrometry analysis of azoxystrobin solutions electrolyzed on carbon fiber brush electrode. The main product of the first two‐electron oxidation step was identified as methyl 2‐(2‐{[6‐(2‐cyanophenoxy)pyrimidin‐4‐yl]oxy}phenyl)‐2‐hydroxy‐3‐oxopropanoate. An analytical method for the determination of azoxystrobin in water samples and pesticide preparation by differential pulse voltammetry with BDDE was developed. The method provides a wide linear dynamic range (3.0×10−7 to 2.0×10−4 mol L−1) with limit of detection 8×10−8 mol L−1. Accuracy of the method was evaluated by the addition and recovery method with recoveries ranging from 96.0 to 105.8 %. Interference study proved sufficient selectivity of the developed voltammetric method for the azoxystrobin determination in presence of azole fungicides as well as pesticides used to prevent the same crops. [ABSTRACT FROM AUTHOR]

Halogenated aminopyrazoles have rarely been utilized in metal-catalysed cross-coupling reactions mainly due to the complexation of the aminopyrazoles to the metal center, which deactivates the catalyst. In this paper we reveal that the appropriate combination of palladium source and ligand enables efficient Suzuki-Miyaura cross-coupling reactions with even challenging substrates such as halogenated aminopyrazoles. The combination of Pd(OAc)2 and XPhos allowed efficient coupling of halogenated N-acetylaminopyrazoles, whereas XPhos Pd G2 was needed when unprotected aminopyrazoles were used. Generally, the halogenated aminopyrazoles underwent facile cross-coupling reactions with a range of aryl-, heteroaryl-, and styrylboronic acids and esters. The resulting biaryl, bisheteroaryl, or arylalkenyl derivatives were obtained in good-to-high isolated yields. [ABSTRACT FROM AUTHOR]

The synthesis of 1 H-benzimidazol-2-yl-1 H-pyrazole-3,5-diamines has been developed. Synthesized bisheteroaryls contain two privileged medicinal scaffolds, aminopyrazole and benzimidazole, with two diversity positions at N1 of benzimidazole and C3 of pyrazole, respectively. The three-step synthesis includes the Mitsunobu of benzimidazole and subsequent one-pot formation of aminopyrazole involving substitution of methylthio groups with amine and hydrazine followed with final ring closure. Inhibitory activity toward cyclin-dependent kinase 2/cyclin E and cytotoxicity against two cancer cell lines were evaluated for all novel pyrazoles. Two compounds showed modest cyclin-dependent kinase inhibition activity and cytotoxicity against cancer cell lines K562 and MCF7. [ABSTRACT FROM AUTHOR]

Inhibitors of cyclin-dependent kinases 9 have been developed as potential anticancer drugs for the treatment of multiple myeloma. We have previously prepared a library of arylazo-3,5-diaminopyrazole inhibitors of CDKs. Here, we describe a novel member, AAP1742 (CDK9 inhibition with IC50 = 0.28 μ m), that reduces the viability of multiple myeloma cell lines in low micromolar concentrations. Consistent with inhibition of CDK9, AAP1742 decreases the phosphorylation of RNA polymerase II and inhibits mRNA synthesis of anti-apoptotic proteins Mcl-1, Bcl-2, and XIAP, followed by apoptosis in the RPMI-8226 cell line in a dose- and a time-dependent manner. These results are consistent with the biochemical profile of AAP1742 and further suggest cellular inhibition of CDK9 as a possible target for anticancer drugs. [ABSTRACT FROM AUTHOR]

The first nitration of codeine by using bismuth nitrate pentahydrate under mild reaction conditions is described. The resulting 1-nitrocodeine was reduced to 1-aminocodeine, a key precursor for the synthesis of the azo derivative and several hydrazones. Structures of both 1-nitrocodeine and 1-aminocodeine were unequivocally determined by single-crystal X-ray analysis. The reported preliminary synthetic study lays the groundwork for the synthesis of modified codeine derivatives with potential biological activity. [ABSTRACT FROM AUTHOR]

The electrochemical behavior of tolterodine, an antimuscarinic drug used to treat urge incontinence and overactive bladder, was investigated using cyclic and differential pulse voltammetry at glassy carbon electrode. Electrooxidation of tolterodine proceeds as a complex two-step pH-dependent process. Controlled potential electrolysis of tolterodine solutions was performed at platinum gauze electrode in methanolic, aqueous-methanolic and acetonitrile media. Electrolyzed solutions were analyzed using liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry. 5-Hydroxymethyl tolterodine, the main biologically active metabolite of tolterodine, was identified among monomeric oxidation products. Dimeric products, formed by oxidative coupling of phenoxy radicals, were found in all electrolyzed solutions. The mechanism of the electrochemical oxidation of tolterodine has been proposed. [ABSTRACT FROM AUTHOR]

The structure of the title compound, C9H9N3, consists of discrete mol­ecules. The secondary structure is formed by mol­ecules linked by N—H⋯N hydrogen bonds into linear chains. In addition to the conventional hydrogen bonds, there are several weak inter­actions of the type N—H⋯C, and π stacking inter­actions of the type C—H⋯C. [ABSTRACT FROM AUTHOR]

In the crystal structure of the title compound, C9H9N3, the asymmetric unit contains two independent mol­ecules. In the crystal structure, the mol­ecules are involved in networks of N—H⋯N hydrogen-bond inter­actions linking the N atoms from both the amino and the imino groups. The compound also demonstrates an inter­esting stacking formation of a secondary structure. Two crystallographically independent mol­ecules are connected in helical chains, with four mol­ecules per helical turn. [ABSTRACT FROM AUTHOR]