Photochemical rearrangement of oxaziridines and nitrones in the hexahydroindole series: a convenient synthetic route to 1-azabicyclo[5.2.0]nonan-2-ones as novel RGD mimetics.

[reaction: see text] Photolysis of oxaziridines a or nitrones b provides a convenient synthetic route to fused bicyclic lactams c adequately substituted on both cycles A and B as scaffolds for mimicking conformationally constrained beta-turn peptides as in the tripeptide RGD signaling motif of fibronectin.

Synthesis and biological evaluation of novel amides of polyunsaturated fatty acids with dopamine.

New amides of different fatty acids from the C18, C20, and C22 series with dopamine were synthesized. Pharmacological characterization in binding assays with rat brain membrane preparations and in the 'tetrad' of cannabinoid behavioral tests showed that, for these compounds, cannabinoid-like activity was dependent on the fatty acid moiety. Our data demonstrate that polyenoic fatty acid amides with dopamine comprise a new family of synthetic cannabimimetics.

Leukotriene B4 photoaffinity probes: design, synthesis and evaluation of new arylazide-1,3-disubstituted cyclohexanes.

The synthesis and the binding affinities of new leukotriene B4 receptor photoaffinity probes, where a 1,3-disubstituted cyclohexane ring replaces the conjugated delta6,7 and delta8,9 double bonds of the natural eicosanoid, are described. One enantiomeric compound, 4b alpha, is specifically cross-linked upon photolysis to the recombinant leukotriene B4 receptor from human origin (h-BLTR) solubilized in a micellar medium. This probe appears as a good candidate for identifying the ligand binding site of this receptor.

Synthesis of 19-[(2-azido-5-iodo)-benzoyloxy]-LTA4 and enzymatic conversion to the LTC4 analogue.

New photoaffinity probes based on C-19 position of leukotriene A4 has been synthesized from 19-hydroxy-LTA4 methyl ester. Enzymatic conversion into the LTC4 analogue yielded a potential tool for the study of cys-LT2 receptors.

Synthesis and structure-activity relationships of new 1, 3-disubstituted cyclohexanes as structurally rigid leukotriene B(4) receptor antagonists.

A series of 1-hydroxy-3-¿3-hydroxy-7-phenyl-1-hepten-1-yl cyclohexane acetic acid derivatives was designed based on postulated active conformation of leukotriene B(4) (LTB(4)) and evaluated as human cell surface LTB(4) receptor (BLTR) antagonists. Binding was determined through ¿(3)HLTB(4) displacement from human neutrophils and receptor antagonistic assays by in vitro measurements of inhibition of leukocyte chemotaxis induced by LTB(4). On the basis of these assays, a structure-affinity relationship was investigated. Optimization of the acid chain length and omega-substitution of a phenyl group on the lipophilic tail were shown to be critical for binding activity. These modifications led to the discovery of compounds with submicromolar potency and selective BLTR antagonism. The most potent compound 3balpha (IC(50) = 250 nM) was found to significantly inhibit oedema formation in a topical model of phorbolester-induced inflammation. Substantial improvement of in vitro potency was achieved by modification of the carboxylic acid function leading to the identification of the N,N-dimethylamide series. Compound 5balpha, free of agonist activity, displayed higher potency in receptor binding with an IC(50) of 40 nM. These results support the hypothesis that the spatial relationship between the carboxylic acid and allylic hydroxyl functions is crucial for high binding affinity with BLTR.

The effect of emigration on human capital formation.

PIP: It is often argued that labor migration has an adverse effect upon the source country. However, Mountford and Stark et al. in 1997, challenged that position and demonstrated the possibility of a brain drain with a brain gain. These researchers emphasized the incentives for human capital formation in the source country. Higher returns to skill in a foreign country impinge upon human capital formation at home. This paper rests upon the same economic grounds and focuses upon the dynamic consequences of labor emigration upon human capital formation and economic growth. It contributes to the international migration literature and the human capital and growth literature. Emigration to a higher returns to skill country provides an incentive to invest in human capital. The level of human capital formation in the source country can therefore be positively correlated with the probability of emigration. A surge in emigration can lead the source country out of an underdevelopment trap. The implications of the model for the convergence controversy are discussed.^ieng

Time preference and labour migration in an OLG model with land and capital.

"This paper constructs a two-country migration model in the lines of Galor (1986), in which the world population consists of individuals of two types who have different time preferences. Production uses three inputs: mobile labour, immobile capital and land. It is shown that both countries are necessarily inhabited by agents of both types and exhibit equal density of population and equal interest rate at the steady state equilibrium of the integrated economy. The steady state welfare implications of international labour migration are studied."

Synthesis and contractile activity of new pseudopeptido and thioaromatic analogues of leukotriene D4.

Seven new pseudopeptido and thioaromatic leukotriene analogues were synthesized and their agonist-antagonist and binding activities investigated. The synthesis led to the pleasing observation that the analogue in which the cysteinyl-glycine moiety was replaced by a 6-mercapto-3-(E)-hexenoic acid, not only exhibited potent affinity (guinea-pig lung parenchyma, IC50: 5 x 10(-9) M) but also showed 30% of the LTD4 agonist activity (guinea-pig ileum, ED 50: 2.7 x 10(-9)) giving very important key information on LTD4 geometry to the receptor. This compound was the first stable new pseudopeptido-leukotriene with such agonist activity and should contribute to the understanding of the metabolism of leukotriene D4. In addition, inversion of chirality at C5 and C6 carbon atoms of the leukotriene chain or replacement of the cysteinyl-glycine moiety by a thioaromatic acid led to new weak antagonists of the LTD4.

Use of Modified Crystal Decanters With No Lead Migration for Cognac Storage.

The lead content of cognac stored in unprotected lead crystal decanters, with the interior protected by a glass sheet, or treated by ion exchange with kaolin has been determined over a period of 9 to 15 months using graphite furnace atomic absorption spectroscopy. After 15 months, lead content of cognac in unprotected crystal decanters is near 800 ppb, but there is no lead migration with the use of the two types of protected crystal decanters.