Search results for "Benzamide"

Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A

2020

Abstract Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were f…

Stochastic dynamics of leukemic cells under an intermittent targeted therapy

2009

The evolutionary dynamics of cancerous cell populations in a model of Chronic Myeloid Leukemia (CML) is investigated in the presence of an intermittent targeted therapy. Cancer development and progression is modeled by simulating the stochastic evolution of initially healthy cells which can experience genetic mutations and modify their reproductive behavior, becoming leukemic clones. Front line therapy for the treatment of patients affected by CML is based on the administration of tyrosine kinase inhibitors, namely imatinib (Gleevec) or, more recently, dasatinib or nilotinib. Despite the fact that they represent the first example of a successful molecular targeted therapy, the development o…

In vitro affinities of various halogenated benzamide derivatives as potential radioligands for non-invasive quantification of D(2)-like dopamine rece…

2007

Abstract Benzamide derivatives as radiotracers have played an important role in diagnosing malfunction in dopaminergic neurotransmission. A variety of halogenated and two unsubstituted benzamide derivatives were synthesised and their in vitro affinities to dopaminergic, serotonergic and adrenergic receptors and their lipophilicities were determined. As references IBZM (3), raclopride (4) and FLB457 (5) were tested as well. The two iodinated compounds NAE (27) and NADE (28) displayed Ki values of 0.68 and 14 nM for the D2 receptor. The well-established radiotracers FP (1) and DMFP (2) showed affinities in the same range as did the brominated compounds NABrE (29) and NABrDE (30). The log D7.4…

Flipping Motion To Bias the Organized Supramolecular Polymerization of N-Heterotriangulenes

2019

Synergistic experimental and theoretical studies have allowed the disentangling of the possible pathways for the supramolecular polymerization of a series of dicyanovinyl-bridged N-heterotriangulene (NHT) derivatives bearing benzamide units with achiral (1a) and chiral (1b,c) side chains. The synthesis of these bowl-shaped, self-assembling units yields a mixture of monomeric species with C3- and C1-symmetry. Both monomeric species are able to self-assemble into different supramolecular aggregates with sufficient stability to coexist in freshly prepared solutions. The dissimilar ratio of the aggregates initially generated results in different spectroscopic features and, more specifically, in…

How Does the Benzamide Antipsychotic Amisulpride get into the Brain?—An In Vitro Approach Comparing Amisulpride with Clozapine

2003

This study evaluated the disposition of the two atypical antipsychotics, amisulpride (AMS) and clozapine (CLZ), and its main metabolite N-desmethylclozapine (DCLZ), to their target structures in the central nervous system by applying an in vitro blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier based on monolayers of porcine brain microvessel endothelial cells (PMEC) or porcine choroid plexus epithelial cells (PCEC). Permeation studies through PMEC- and PCEC-monolayers were conducted for 60 min at drug concentrations of 1, 5, 10, and 30 muM applied to the donor compartment. PMEC were almost impermeable for AMS (permeation coefficient, P1 x 10(-7) cm/s) in the resorptive direct…

Comparative studies of the Pschorr reaction in the pyrazole series. Access to the new dibenzo[e,g]pyrazolo[1,5-a][1,3]diazocine system of pharmaceuti…

2008

The diazonium tetrafluoroborate 11 obtained from 2-amino-N-methyl-N-(1-phenyl-3- methylpyrazol-5-yl)benzamide was transformed in dry acetonitrile via an ionic or radical pathway. Differences were observed with respect to ionic or radical transformations in aqueous media of the analogous diazonium hydrogen sulfate 1 derived from the same amine. In acetonitrile solution, the ionic pathway was characterized by an increased yield of 1,4-dimethyl- 3-phenyl-pyrazolo(3,4-c)isoquinolin-5-one 4 and by the formation of its isomer, the new derivative 7,9-dimethyldibenzo(e,g)pyrazolo(1,5-a)(1,3)diazocin-10(9H)-one 12. When the reaction followed a radical pathway, the pyrazolo(3,4-c)isoquinoline derivat…

1,4-Dimethyl-3-phenyl-3H-pyrazolo[3,4-c]isoquinolin-5(4H)-one

2008

The title compound, C18H15N3O, is the product of the thermal decomposition of the diazonium salt derived from 2-amino-N-methyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)benzamide. It is characterized by a trans orientation of the methyl groups with respect to the tricyclic ring system. The molecule has a nearly planar phenylpyrazolo[3,4-c]isoquinolin-5-one system, the largest deviation from the mean plane being 0.066 (2) angstrom for the O atom. The dihedral angle between the phenyl substituent and the heterotricycle is 67 (1)degrees. The packing is stabilized by C-H center dot center dot center dot N hydrogen-bond interactions, with the formation of molecular chains along the c axis.

Synthesis and biological evaluation of some new 2-phenylpropiolamidobenzamides as potential antagonists of the HDM2-p53 protein-protein interactions

2009

An Improved Rapid Synthesis of Oligo(p -benzamide) Block Copolymers

2008

We describe a new synthesis that allows the preparation of oligo(p-benzamide)s up to the heptamer on solid support without the need of semi-temporary amide N-protective groups. With increase in length, the solubility of oligo(p-benzamide)s reduces dramatically. Even the tetra(p-benzamide) is not soluble in common organic solvents. Therefore, solution syntheses of oligomers beyond the tetramer are not feasible. As will be shown in this paper, solid supported synthesis allows the preparation of even longer oligomers (up to the heptamer) in good yields. The high dilution on the solid support is most likely responsible for their pseudo-solution-like reactivity and the prevention of aggregation.…

Studien zum Vorgang der Wasserstoffübertragung, 52. Zur Kenntnis der elektroreduktiven Spaltung der N - N-Bindung

1978

Am Beispiel von 35 Hydrazinderivaten wird die elektroreduktive Spaltung polarographisch und praparativ untersucht. Es wurde gefunden: 1) Beim mono-, tri- und tetrabenzoylierten Hydrazin 9, 11 bzw. 12 verschiebt sich das Potential proportional der Anzahl der Benzoylgruppen nach positiveren Werten. Beim symmetrischen 1,2-Dibenzoylhydrazin (10) wird das Halbstufenpotential E1/2 — bedingt durch H-Verbruckung und mesomere Stabilisierung — stark nach negativen Werten verschoben. — 2) Bei den cyclischen Hydrazinderivaten 14–16 werden die E1/2-Werte sowohl in Abhangigkeit von der Ringspaltung als auch durch cis-Fixierung der Benzoylgruppen noch zusatzlich nach positiveren Werten verlagert. — 3) Ube…