Yael Asscher

ChemInform Abstract: INTRAMOLECULAR FRIEDEL-CRAFTS ACYLATION OF A LACTONE IN POLYPHOSPHORIC ACID. SYNTHESIS OF 2-PHENYLPHENALEN-1-ONE

Chemischer Informationsdienst, Dec 23, 1980

The synthesis of isotopically labeled .beta.-adrenergic agents by reductive amination: unexpected site of deuterium incorporation

Journal of Organic Chemistry, Aug 1, 1984

Synthese de 2 stimulants β-adrenergiques marques D: p-tolylamide et trifluoromethyl-4' phenyl... more

ChemInform Abstract: THE SYNTHESIS OF ISOTOPICALLY LABELED β-ADRENERGIC AGENTS BY REDUCTIVE AMINATION: UNEXPECTED SITE OF DEUTERIUM INCORPORATION

Chemischer Informationsdienst, Aug 1, 1984

Die aus (I) und (II) zugängliche Schiffsche Base (III) liegt im Gleichgewicht mit dem Isomeren (I... more

Conformation of a double dibenzotropone precursor of a bifunctional amitriptyline-type drug: 7,8,15,16-tetrahydrodibenzo[d,d']benzo[1,2-a;4,5-a']dicycloheptene-5,13-dione

Acta Crystallographica Section C Crystal Structure Communications, 1988

This electronic document was scanned from an archival copy of material deposited to accompany a p... more

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Process for producing freeze dried competent cells and use thereof in cloning

Metabolism-dependent inactivation of liver microsomal enzymes by phencyclidine

Drug metabolism and disposition: the biological fate of chemicals

Incubation of phencyclidine (PCP) with rabbit liver microsomes resulted in NADPH-dependent loss o... more Incubation of phencyclidine (PCP) with rabbit liver microsomes resulted in NADPH-dependent loss of N-demethylase activity accompanied by reduction in microsomal cytochrome P-450 content. This effect was concentration-dependent, exhibited pseudo-first order kinetics, and was irreversible, thus exhibiting characteristics of "suicide substrate" inhibition. Cyanide ions at low concentrations, which have been used to trap the iminium intermediate of PCP metabolism as its cyano adduct, antagonized the inhibition of N-demethylase by PCP. PCP iminium ions were effective inhibitors of microsomal enzyme activity but required NADPH. These results support our suggestions that iminium ion formation is an intermediary step in the bioactivation of PCP leading to reactive electrophilic species.

Leptomycin B: An Important Tool for the Study of Nuclear Export

Non-regulated and stimulated mechanisms cooperate in the nuclear accumulation of MEK1

Oncogene, 2001

MEKs, which operate within the ERK cascade, shuttle into the nucleus, but are rapidly exported fr... more MEKs, which operate within the ERK cascade, shuttle into the nucleus, but are rapidly exported from this location, forming an apparent cytosolic distribution both before and after stimulation. Two dierent mechanisms have been proposed for the nuclear translocation of MEKs. One of them involves a constant and nonregulated shuttling of MEKs into the nucleus operating both before and after mitogenic stimulation. The other mechanism seems to require the activity of MEKs and is facilitated in response to mitogenic stimulation. Here we show that these two mechanisms may coexist in the same cells. We found that leptomycin B (LMB), a potent inhibitor of nuclear export, induces a nuclear accumulation of MEKs, and this was signi®cantly facilitated by stimulation of LMB-treated cells with EGF, TPA and peroxovanadate. The EGF-stimulated, but not the LMBinduced translocation was attenuated by MEK inhibitors and by using inactive forms of MEK1. We also show that LMB slightly activates the ERK cascade, but this activity only partially induces the nuclear accumulation of MEKs in cells treated by LMB alone. Thus, MEKs translocate into the nucleus by a combination of nonregulated and stimulated processes that contribute to the nuclear translocation of MEKs either in resting cells or upon mitogenic stimulation. Oncogene (2001) 20, 7588 ± 7596.

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Pharmacokinetics and Excretion of Unique Beta-Adrenergic Agonists

Pharmacology, 1987

beta-Adrenergic agonist analogs (congeners) of isoproterenol in which the N-isopropyl group has b... more beta-Adrenergic agonist analogs (congeners) of isoproterenol in which the N-isopropyl group has been linked to a p-methyl- (119) or p-trifluoromethyl- (143) anilide moiety through a four carbon methylene spacer have been investigated with respect to their plasma pharmacokinetic profiles and biliary and urinary elimination characteristics in rats. In spite of the differences in selectivity of pharmacologic effects and durations of action between these unique beta-adrenergic agonists and isoproterenol, no differences were observed in their pharmacokinetic parameters in plasma after intravenous administration. Plasma clearances were rapid (67-78 ml/min) and the compounds were widely distributed. In contrast to the known elimination characteristics of isoproterenol, biliary excretion was the major pathway for elimination of 119 and 143. Parent drug and &#39;one&#39; major metabolite peak appeared in HPLC chromatograms of bile collected from rats that received 119 and 143 by intravenous administration. Preliminary evidence suggests that this metabolite peak consists of one or more glucuronide and/or sulfate conjugates. Urinary excretion appears to be of lesser quantitative importance for 119 and 143 than for isoproterenol. The protracted duration of residence of the derivatives in the heart may help to explain the unusual effects and tissue-specific pharmacological properties of these unique beta-adrenergic agonists.

Active Conformation of Polycyclic Antidepressants

Journal of Pharmaceutical Sciences, 1982

Intramolecular Friedel-Crafts acylation of a lactone in polyphosphoric acid. Synthesis of 2-phenylphenalen-1-one

The Journal of Organic Chemistry, 1980

... Chem. Ges. 1886, 18, 3470. (b) Weiss, R.; Organic Syntheses; Wiley, New York, 1943; Collect... more

The synthesis of isotopically labeled .beta.-adrenergic agents by reductive amination: unexpected site of deuterium incorporation

The Journal of Organic Chemistry, 1984

Synthese de 2 stimulants β-adrenergiques marques D: p-tolylamide et trifluoromethyl-4' phenyl... more

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