Lithiation directed by amino alkoxides. Application to the synthesis of new disubstituted dihydrodipyridopyrazines.

The synthesis of new 4,6-disubstituted dihydrodipyridopyrazines starting from corresponding carboxaldehydes via lithiation directed by alpha-amino alkoxides is described. The N,N,N'-trimethylethylenediamine was used as amine component for in situ formation of the alpha-amino alkoxides. After optimization, this reaction allowed easy access to new interesting starting materials for further applications by palladium-catalyzed reactions.

Synthesis of mono- and bisdihydrodipyridopyrazines and assessment of their DNA binding and cytotoxic properties.

Aminoalkyl-substituted monomeric and dimeric dihydrodipyridopyrazines have been synthesized and evaluated as antitumor agents. Potent cytotoxic compounds were identified in both series. Biochemical and biophysical studies indicated that all these compounds strongly stabilized the duplex structure of DNA and some of them elicited a selectivity for GC-rich sequences.

Synthesis and antiproliferative activity of benzocyclobutacarbazol derivatives. A new class of potential antitumor agents.

Several benzocyclobutacarbazol derivatives were synthesized and evaluated for their potential cytotoxic properties. A number of these compounds exhibited significant antiproliferative activity with concomitant interaction with the cell cycle and represent a new class of potential anticancer agents.

Novel indole-2-carboxamide and cycloalkeno[1,2-b]indole derivatives. Structure-activity relationships for high inhibition of human LDL peroxidation.

Series of indole-2-carboxamide and cycloalkeno[1,2-b]indole derivatives were synthesized and evaluated in order to determine the necessary structural requirements for a high inhibition of human LDL copper-induced peroxidation. Various modulations were systematically performed on the indole and cycloalkeno[1,2-b]indole nuclei as well as on the carboxamide moiety. The best compounds (3c, 3e, 7c, 7f, 7h, 7g, and 7o) are between 5 and 30 times more active than probucol itself.

Synthesis and structure of new bronchospasmolytic agents. I.

The crystal structures of two phenylethanolamines showing bronchospasmolytic activity have been determined at room temperature [293 (2) K]. Crystal data are as follows: 11-morpholinotricyclo[6.3.

Chrysops silacea and C.dimidiata seasonality and loiasis prevalence in the Chaillu mountains, Congo.

Seasonal activity of the loiasis vectors Chrysops dimidiata Wulp and Chrysops silacea Austen (Diptera: Tabanidae) was studied during 1987-89 in villages and surrounding forest of the Chaillu Mountains, Congo. Chrysops were captured mainly in the hot rainy season (November-May) and densities of both species were higher in the forest than in villages. C.

Effect of attraction factors on the sampling of Chrysops silacea and C. dimidiata (Diptera: Tabanidae), vectors of Loa loa (Filaroidea: Onchocercidae) filariasis.

The effects of fire and human host density on Chrysops silacea and C. dimidiata abundance and age structure was evaluated at sites of Loa loa filariasis transmission in the Congo rain forest. Fire increased the catch of C.

Novel inhibitors and substrates of bilirubin: UDP-glucuronosyltransferase. Arylalkylcarboxylic acids.

The in vitro inhibitory potency of 20 structurally related alkanoic and arylalkanoic acids has been investigated on rat liver UDP-glucuronosyltransferase. These compounds were tested on the microsomal and purified enzyme, and a cloned cDNA expressed in COS 7 cell cultures. Among all the acids tested, 7,7,7-triphenylheptanoic acid was the most powerful inhibitor of bilirubin:UDP-glucuronosyltransferase with a lower effect on 1-naphtol, androsterone and testosterone glucuronidation.

A new series of tricyclic (aryloximino)propanolamines displaying very high selective beta 2-blocking properties.

A new class of indanones 4 easily obtained by aryne type condensations, followed by transposition of the benzocyclobutanols 3 thus formed, were transformed into the corresponding oximinopropanolamines 7. These compounds were studied for their potential beta-blocking properties. It was found that 7 have generally low beta 1-blocking properties.

Inhibition of bilirubin UDPglucuronosyltransferase activity by triphenylacetic acid and related compounds.

Bilirubin UDPglucuronosyltransferase of rat or human liver microsomes was inhibited, in vitro, by triphenylacetic acid and by structurally related arylcarboxylic acids. This inhibition appeared to be competitive towards bilirubin, and mixed-type towards UDPglucuronic acid. A decrease in the number of phenyl rings or the absence of the carboxyl group in the molecule gave structures which did not affect enzyme activity, showing that both the triphenyl moiety and the carboxyl group were necessary for the inhibition.

Synthesis of a novel series of (aryloxy)propanolamines: new selective beta 2-blocking agents.

A new family of beta-blocking drugs is described. The originality of the new molecules lies in their functionalized hydrophobic folded structure, the basic part of which contains a benzocyclobutene ring. Excellent beta 2-blocker selectivity has been obtained with some of these compounds.