Relativistic description of 3He(e,e'p)2H

The relativistic distorted-wave impulse approximation is used to describe the 3He(e, e′ p)2H process. We describe the 3He nucleus within the adiabatic hyperspherical expansion method with realistic nucleon-nucleon interactions. The overlap between the 3He and the deuteron wave functions can be accurately computed from a three-body calculation. The nucleons are described by solutions of the Dirac equation with scalar and vector (S–V) potentials. The wave function of the outgoing proton is obtained by solving the Dirac equation with a S–V optical potential fitted to elastic proton scattering data on the residual nucleus. Within this theoretical framework, we compute the cross section of the reaction and other observables like the transverse-longitudinal asymmetry, and compare them with the available experimental data measured at JLab.

7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide (IDRA 21), a congener of aniracetam, potently abates pharmacologically induced cognitive impairments in patas monkeys.

We report here on the ability of IDRA 21 and aniracetam, two negative allosteric modulators of glutamate-induced DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization, to attenuate alprazolam-induced learning deficit in patas monkeys working in a complex behavioral task. In one component of a multiple schedule (repeated acquisition or "learning"), patas monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four discriminative stimuli (geometric forms or numerals). In the other component (performance) the four-response chain was the same each session. The response chain in each component was maintained by food presentation under a fixed-ratio schedule. When alprazolam (0.1 or 0.32 mg/kg p.o.) was administered alone, this full allosteric modulator of gamma-aminobutyric acid type A (GABAA) receptors produced large decreases in the response rate and accuracy in the learning component of the task. IDRA 21 (3 or 5.6 mg/kg p.o.) and aniracetam (30 mg/kg p.o.) administered 60 min before alprazolam, having no effect when given alone, antagonized the large disruptive effects of alprazolam on learning. From dose-response studies, it can be estimated that IDRA 21 is approximately 10-fold more potent than aniracetam in antagonizing alprazolam-induced learning deficit. We conclude that IDRA 21, a chemically unrelated pharmacological congener of aniracetam, improves learning deficit induced in patas monkeys by the increase of GABAergic tone elicited by alprazolam. Very likely IDRA 21 exerts its behavioral effects by antagonizing AMPA receptor desensitization.

On the spectrum of non-Denniston maximal arcs in PG(2,2h)

In 1969, Denniston gave a construction of maximal arcs of degree n in Desarguesian projective planes of even order q, for all n dividing q. Recently, Mathon gave a construction method that generalized that of Denniston. In this paper we use that method to give maximal arcs that are not of Dermiston type for all n dividing q, 4 < n < q/2, q even. It is then shown that there are a large number of isomorphism classes of such maximal arcs when n is approximately rootq. (C) 2003 Elsevier Ltd. All rights reserved.

Temperature dependence of the crystal structure and g-values of [(HC(Ph2PO)(3))(2)Cu] (ClO4)(2)center dot 2H(2)O: Influence of dynamic Jahn-Teller coupling and lattice strain interactions

The temperature dependence of the X-ray crystal structure and powder EPR spectrum of [(HC(Ph2PO)(3))(2)CU]-(ClO4)(2)center dot 2H(2)O is reported, and the structure at room temperature confirms that reported previously. Below similar to 100 K, the data imply a geometry with near elongated tetragonal symmetry for the [(HC(Ph2PO)(3))(2)Cu](2+) complex, but on warming the two higher Cu-O bond lengths and g-values progressively converge, and by 340 K the bond lengths correspond to a compressed tetragonal geometry. The data may be interpreted satisfactorily assuming an equilibrium among the energy levels of a Cu-O-6 polyhedron subjected to Jahn-Teller vibronic coupling and a lattice strain. However, agreement with the experiment is obtained only if the orthorhombic component of the lattice strain decreases to a negligible value as the temperature approaches 340 K.

Synthesis and evaluation of 5-arylated 2(5H)-furanones and 2-arylated pyridazin-3(2H)-ones as anti-cancer agents

Bis-cyclic butenolides, 5-arylated 2(5H)-furanones 6a-c, 7a, b and the 3(2H)-pyridazones 9a-d were prepared by using the aldehyde form of muco halogen acids in electrophilic substitution reactions and in an aldol-like condensation reaction. The cytotoxicity of these simple and bis-cyclic butenolides have been evaluated in tissue culture studies on MAC 13 and MAC 16 murine colon cancer cell lines. The butyl furanone 3 displayed the highest cytotoxicity of 3 μM, as one selected example of a series of dichlorinated pseudoesters. The 5-arylated 2(5H)-furanones 6 and 7 did not show a structure-activity relationship (SAR) depending on the substitution pattern of the aromatic system. An IC50 (concentration inhibiting growth by 50%) was found within a range of 30-50 and 40-50 μM for the MAC 13 and MAC 16 cell lines, respectively. The pyridazine series 9 showed a maximum in-vitro activity for the p-methoxydrivative 9b, having an IC50 of 17 in MAC 13 and 11 μM in MAC 16 cell lines. Selected examples of each series and further novel 2(5H)-furanones such as the hydrazone 5 and the hydantoin 8 have been screened in-vivo in mice and the data are presented. For the pyridazines 9a-d, the in-vitro cytotoxicity correlated with an in-vivo inhibition of tumour growth. The ring expansion of the 5-membered 2(5H)-furanone ring system such as 6a into the 6-membered 3(2H)-pyridazone 9b led to an agent with improved antineoplastic properties. On the resistant MAC 16 cell line the pyridazone 9b displayed 52% tumour inhibition in mice at a dose of 50 mg kg-1 compared with 27% for the 5-FU standard.

Synthesis of substituted 3-anilino-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine-2-ones and their evaluation as cholecystokinin-ligands

3-Amino-1,4-benzodiazepines as well as chemically related diverse amines were prepared from oxazepam and subsequently screened on the cholecystokinin receptor in a radiolabel binding assay. Oxazepam 2 was activated via its 3-chloro-1,4-benzodiazepine intermediate 3 and was reacted with a large series of aliphatic and aromatic amines. The substituted 3-anilino-1,4-benzodiazepine structure was identified as lead structure in a diverse series of 3-amino-1,4-benzodiazepines 4-38 and the full SAR (structure-activity relationship) optimisation provided 3-anilinobenzodiazepines 16-38 with CCK 1 receptor selectivity to CCK 2. The compounds 18, 24, 28 and 33 have shown affinities at the CCK 1 receptor of 11, 10, 11 and 9 nM, respectively. These equipotent CCK 1 ligands were fully evaluated in behaviour pharmacological essays. An antidepressant effect was identified in the tail suspension- and the Porsolt swimming-test. The ED 50 values for 24 and 28 were determined in these assays as 0.46 and 0.49 mg/kg. The mixed antagonist 37 showed in addition to the antidepressant effects anxiolytic properties. © 2006 Wiley-VCH Verlag GmbH & Co. KGaA.

Nuevas aplicaciones sintéticas de pequeños heterocíclos. 2H-Azirinas fosforadas.

238 p.

Effect of the synthetic coumarin, ethyl 2-oxo-2H-chromene-3-carboxylate, on activity of Crotalus durissus ruruima sPLA2 as well as on edema and platelet aggregation induced by this factor

We show that ethyl 2-oxo-2H-chromene-3-carboxylate (EOCC), a synthetic coumarin, irreversibly inhibits phospholipase A(2) (sPLA2) from Crotalus durissus ruruima venom (sPLA2r) with an IC(50) of 3.1 +/- 0.06 nmol. EOCC strongly decreased the V(max) and K(m), and it virtually abolished the enzyme activity of sPLA2r as well as sPLA2s from other sources. The edema induced by 5PLA2r + EOCC was less than that induced by 5PLA2r treated with p-bromophenacyl bromide, which was more efficient at neutralizing the platelet aggregation activity of native 5PLA2r. Native 5PLA2r induced platelet aggregation of 91.54 +/- 9.3%, and sPLA2r +/- EOCC induced a platelet aggregation of 18.56 +/- 6.5%. EOCC treatment also decreased the myotoxic effect of sPLA2r. Mass spectrometry showed that EOCC formed a stable complex with sPLA2r, which increased the mass of native 5PLA2r from 14,299.34 da to 14,736.22 Da. Moreover, the formation of this complex appeared to be involved in the loss of 5PLA2r activity. Our results strongly suggest that EOCC can be used as a pharmacological agent against the 5PLA2 in Crotalus durissus sp. venom as well as other sPLA2s. (C) 2010 Elsevier Ltd. All rights reserved.