The performance of the MNDO method, as far as the energies of azines and azoles are concerned, is critically evaluated after comparing its results with some ab initio calculations at the 4-31G level and with available experimental data. The lone-pair electronic repulsions between the neighboring pyridine-like nitrogens are systematically underestimated by MNDO. Nevertheless, when corrections are introduced, even the relative stabilities of quite complex heterocyclic systems (tetrazolotriazine and tetrazolobenzotriazine tautomers) are predicted with reasonable accuracy.Semiempirical SCF-MO methods are rather popular within the organic chemists' community since, with a moderate cost, they offer quite reliable results (in specific areas) of either explanatory or predictive value for medium-to-large-sized molecules. Outstanding among which there is the MNDO method of Dewar and Thiel,1 with parameters now available for the second-period elements and also for Al, Si, P, S, Cl, Br, I, and Sn.2 Its utility for searching equilibrium geometries of unusual species before
A series of alkyl lysophospholipid (ALP) analogs of ET-18-OCH3 (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) containing modifications in the long C-1 chain has been synthesized and evaluated in human tumor cell line cytotoxicity assays. The compounds have also been evaluated in platelet activating factor (PAF) receptor agonism and hemolysis tests. Two modifications have been studied, introduction of a carbonyl group at different positions of the C-1 chain and branching of this chain, in some compounds with incorporation of a phenyl group. Several compounds showed a cytotoxic potency comparable to that of the reference compound ET-18-OCH3, associated with reduced proaggregating and hemolytic effects. The two enantiomers of 1-O-(7-oxooctadecyl)-2-O-methyl-rac-glycero-3-phosphocholine (2) showed the same level of cytotoxicity or antiproliferative activity, with the PAF-agonistic effect confined to R-2. The very low stereoselectivity found in the in vitro cytotoxicity confirms earlier results and indicates a lack of stereospecific interactions with a macromolecular target.
The synthesis of the new dihydropyridine diethyl 1,4‐dihydro‐4‐(imidazo[1,5‐α]pyridin‐8‐yl)‐2,6‐dimethyl‐pyridine‐3,5‐dicarboxylate (1) is described. After many attempts to prepare the key intermediate aldehyde 2a by different approaches, this compound has been obtained in good yields from methyl 2‐cyano‐3‐pyridinecar‐boxylate (10). A three‐step procedure involving reduction to the amine, formylation with concomitant cyclization and reduction of the ester group was used.
Four series of potential PAF‐antagonists in which the isoxazole nucleus is condensed with a polyhydrogenated five‐ or six‐carbon ring were prepared. The synthesis of the compounds 3‐aryl‐4,5,6,7‐tetrahydrobenz[c]isoxazoles 1, 3‐arylcyclopent[c]isoxazoles 2, 3‐aryl‐4,5,6,7‐tetrahydrobenz[d]isoxazoles 3, and 3‐arylcyclopent[d]isoxazoles 4, required an extensive optimization and comparison of the methods available in the literature.
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