Reaction of 1,2-diarylhydrazines with acetic anhydride catalyzed by 4-(dimethylamino)pyridine

Summary A new method for the synthesis of 1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-ones3 and 4-acetyl-1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-ones5 is presented. The reaction of 4,4-disubstituted 1,2-diarylhydrazines1 with acetic anhydride in the presence of an equimolar amount of 4-(dimethylamino)pyridine leads to mixtures of the corresponding acetyl derivatives2 and3. Under the same conditions, 2,2-disubstituted 1,2-diarylhydrazines yield mixtures of3 and5.

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4-(Dimethylamino)pyridin-katalysierte Reaktion von 1,2-Diarylhydrazinen mit Essigsäureanhydrid

Zusammenfassung Eine neue Methode zur Synthese von 1,2-Diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-onen3 und 4-Acetyl-1,2-diaryl-1,2-dihydro-5-methyl-3H-pyrazol-3-onen5 wird beschrieben. Die Reaktion von 4,4-disubstituierten 1,2-Diaryl-hydrazinen1 mit Essigsäureanhydrid führt in Gegenwart eines Äquivalentes 4-(Dimethylamino)pyridin zu Gemischen der entsprechenden Acetylderivate2 und3. Unter den gleichen Bedingungen werden aus 2,2-disubstituierten 1,2-Diarylhydrazinen Gemische aus3 und5 erhalten.

     

A six-minute determination of carbon and hydrogen with titrimetric finish

Summary A method is described for the C/H determination with a completely titrimetric finish. Both carbon and hydrogen are converted to an equivalent amount of carbon dioxide, which is titrated in a non-aquous medium. The procedure can be applied for the analysis of substances separated by a gas Chromatograph. The determination takes about six minutes.

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Zusammenfassung Ein Verfahren zur C-H-Bestimmung wird beschrieben, bei dem die Endbestimmung volumetrisch erfolgt. Hierbei werden sowohl Kohlenstoff als auch Wasserstoff in äquivalente Mengen Kohlendioxid übergeführt und dieses durch Titration in nichtwäßrigem Medium erfaßt. Die Methode kann auch für die Analyse gaschromatographisch getrennter Substanzen benutzt werden. Eine Bestimmung ist innerhalb von 6 min beendet.

     

Alternate therapeutic pathways for PARP inhibitors and potential mechanisms of resistance

Homologous recombination (HR) repair deficiency impairs the proper maintenance of genomic stability, thus rendering cancer cells vulnerable to loss or inhibition of DNA repair proteins, such as poly(ADP-ribose) polymerase-1 (PARP-1). Inhibitors of nuclear PARPs are effective therapeutics for a number of different types of cancers. Here we review key concepts and current progress on the therapeutic use of PARP inhibitors (PARPi). PARPi selectively induce synthetic lethality in cancer cells with homologous recombination deficiencies (HRDs), the most notable being cancer cells harboring mutations in the BRCA1 and BRCA2 genes. Recent clinical evidence, however, shows that PARPi can be effective as cancer therapeutics regardless of BRCA1/2 or HRD status, suggesting that a broader population of patients might benefit from PARPi therapy. Currently, four PARPi have been approved by the Food and Drug Administration (FDA) for the treatment of advanced ovarian and breast cancer with deleterious BRCA mutations. Although PARPi have been shown to improve progression-free survival, cancer cells inevitably develop resistance, which poses a significant obstacle to the prolonged use of PARP inhibitors. For example, somatic BRCA1/2 reversion mutations are often identified in patients with BRCA1/2-mutated cancers after treatment with platinum-based therapy, causing restoration of HR capacity and thus conferring PARPi resistance. Accordingly, PARPi have been studied in combination with other targeted therapies to overcome PARPi resistance, enhance PARPi efficacy, and sensitize tumors to PARP inhibition. Moreover, multiple clinical trials are now actively underway to evaluate novel combinations of PARPi with other anticancer therapies for the treatment of PARPi-resistant cancer. In this review, we highlight the mechanisms of action of PARP inhibitors with or without BRCA1/2 defects and provide an overview of the ongoing clinical trials of PARPi. We also review the current progress on PARPi-based combination strategies and PARP inhibitor resistance.Subject terms: Cancer therapy, Mechanisms of disease, PolyADP-ribosylation     

Naproxen: Hydroxypropyl-β-Cyclodextrin:Polyvinylpyrrolidone Ternary Complex Formation

The aim of the present study was to investigate the effect of the presence of thewater-soluble polymer polyvinylpyrrolidone (PVP) MW = 24000 g/mol, on thecomplexation of the phototoxic anti-inflammatory drug naproxen, in its sodiumsalt form, with hydroxypropil-β-cyclodextrin (HP-β-CD). The datashown that the polymer interacts with the free naproxen and with thenaproxen:HP-β-CD inclusion complex. The presence of different proportions of PVP, in the 0–1%(w/w) rangesystematically increased the K_app of the naproxen:HP-β-CD inclusioncomplex formation. The cause of this increase is that the polymer interactswith the HP-β-CD with a binding constant of K₂ = 29000 ± 53 M^-1; and with the naproxen:HP-β-CD inclusion complex, to givea ternary complex naproxen:HP-β-CD:PVP. The binding constant of thisprocess was K₃ = 5350 ± 1 M^-1. NMR data revealed that in the ternary system, PVP is outside of the cyclodextrin, and therefore must be wholly or partially recovering the naproxen:HP-β-CD inclusion complex.     

Polyfunctional compounds containing the 4,6-dialkoxy-7-arylthioheptene moiety as synthetically useful intermediates. The course of lewis acid-induced transformations

Data on the selectivity of the Lewis acids induced transformations of the title compounds are presented, and the routes leading to formation of products containing either cyclohexane or 1,3-diene units are described.     

Vectorization of a classical trajectory code on a floating point systems,Inc. Model 164 attached processor

A triatomic classical trajectory code has been modified by extensive vectorization of the algorithms to achieve much improved performance on an FPS 164 attached processor. Extensive timings on both the FPS 164 and a VAX 11/780 with floating point accelerator are presented as a function of the number of trajectories simultaneously run. The timing tests involve a potential energy surface of the LEPS variety and trajectories with 1000 time steps. The results indicate that vectorization results in timing improvements on both the VAX and the FPS. For larger numbers of trajectories run simultaneously, up to a factor of 25 improvement in speed occurs between VAX and FPS vectorized code.     

Matrices with Heterogeneous Distribution of the Binding Sites for Immobilization of Biomacromolecules

The coupling of photosensitive reagents has been carried out with the goal of obtaining the predetermined distribution of binding sites either for “surface” or “spacial” immobilization of biomacromolecules. The correlation holds between light intensity and the number of readant groups emerged in a matrix.     

A direct synthesis of denbinobin

Denbinobin was made in seven steps from quinone 3. The cyclization of aldehyde 12 using P₄-tBu and the oxidation of a hindered alcohol with MnO₂ were key steps.     

Synthesis of a model system for the preparation of phloroglucinol containing natural products

A model system for the synthesis of phloroglucinol containing natural products was synthesized. Key steps include a manganic acetate-mediated cyclization and the facile conversion of an alkene into a β-bromoenone.     

A reflectometric sensor for ammonia and hydrocarbons

Summary Optical reflection measurements in the visible wavelength range may be used for fast analysis of changes in optical thickness of thin polymer layers caused by swelling of the film in contact with various gaseous analytes. Including an absorbing species into the sensitive layer, the applicability of this sensor can be extended to gases with acidic or basic character. The method is demonstrated using bromocresol purple as pH-indicator in a polydimethylsiloxane layer. Principal component analysis is used for qualitative analysis of a two-component gas.Dedicated to Professor Dr. Wilhelm Fresenius on the occasion of his 80th birthday