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Biomedical subjects

F Gualtieri

Publications and source records attributed to F Gualtieri.

At least 73 records · Page 4Linked to original sources
PubMed1986

Resolution, absolute configuration, and cholinergic enantioselectivity of (+)- and (-)-cis-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodide.

The potent cholinergic agonist (+/-)-cis-2-methyl-5-[(dimethylamino)methyl]-1,3-oxathiolane methiodide (+/-)-1] was resolved into enantiomeric forms. Their absolute configurations were established by a synthetic pathway that also allowed the synthesis of the corresponding diastereomeric (+)- and (-)-trans-2-methyl-5-[(dimethylamino)-methyl]-1,3-oxathiolane methiodide [(+)- and (-)-10]. Compound (+)-1, which is the most potent of the four isomers, showed the same absolute configuration as L-(+)-muscarine and (+)-cis-dioxolane. The four isomers were tested on guinea pig ileum and frog rectus abdominis, and their muscarinic and nicotinic potency (EPMR) and selectivity were determined. The relationships between stereoisomerism and potency are discussed.

Animals↗
PubMed1985

SAR studies in the field of calcium(II) antagonists. Effect of modifications at the tetrasubstituted carbon of verapamil-like compounds.

A number of fluorenyl and diphenylmethane analogues of verapamil, chosen as having the same substituents arranged in different ways around the quaternary carbon, were synthesized in order to evaluate the importance of the stereoisomerism at that point of the molecule. The compounds were tested with the Langendorff technique and coronary perfusion pressure (CPP), left ventricular pressure (LVP), and heart rate (HR) were recorded. While most of the compounds were almost inactive on these parameters, three of them did show interesting cardiovascular action. In particular they produced a more pronounced decrease in CPP than verapamil, with a less marked negative inotropic effect. Structure-activity relationships and the mechanism of action of the compounds are discussed.

Animals↗
PubMed1985

Affinity and efficacy correlate with chemical structure more than potency does in a series of pentatomic cyclic muscarinic agonists.

The efficacy and affinity of nine pentatomic cyclic muscarinic agonists were determined on the guinea-pig ileum, according to the method of Furchgott & Bursztyn (1967). The efficacy and affinity of these agonists are affected differently by structural modifications. Our results suggest that a strong dipole oriented in the same direction as that of the hydroxy group of muscarine, or the presence of a polarizable atom in the same position, are important for efficacy.

Animals↗
PubMed1985

Search for new Ca++ antagonists. Lipophilic oximes and phosphonates.

On the basis of the reported slow channel-inhibiting activity of oximes and phosphonates a series of compounds bearing such functions on lipophilic carriers were synthesized and studied. Among the compounds studied only (VI b) shows a slight cardiovascular activity. The surprising lack of activity of diethyl 3,4-dimethoxybenzyl-phosphonate (XIV), which is closely related to Fostedil, is discussed.

Animals↗
PubMed1982

Molecular requirements of the active sites of the cholinergic receptors. XIX-Size evaluation of the muscarinic subsite.

Several ethers and acetylderivatives of deoxamuscarine (I) and its isomers have been synthesized and tested to evaluate the volumetric requirements of the site interacting with the hydroxyl moiety of the agonist (muscarinic subsite). The good potency and affinity for the muscarinic receptor shown by some of these compounds will allow the insertion of an alkylating function in this position of the molecule. Such compounds will be useful to get more information on the topography of the active site and in the isolation of the receptor molecule.

Animals↗
PubMed1980

Molecular requirements of the active sites of the cholinergic receptors. XI - Synthesis and biological evaluation of isomuscarie and its isomers.

The synthesis of isomuscarine (IIc) and of its three isomers is described. Their structure were established on the basis of N.M.R. and I.R. data. Unlike the dioxolane (I), from which they are formally derived by substituting the oxygen in position 3 by a CHOH group, the isomuscarines are completely devoid of cholinergic activity. This result is explained by the impossibility of the corresponding receptor site of accepting a group larger than the ether oxygen. Interactions of the onium and C-7 methyl groups are assumed to be the driving forces for binding with the muscarinic receptor while a dipole-dipole interaction for oxygenated functions is proposed.

Abdominal Muscles↗
PubMed1976

Cholinergic compounds VII - Synthesis and pharmacological activity of some trimethylammonium iodides related to desethermuscarine.

Some substances similar to desethermuscarine were synthesized and studied as cholinergics on isolated organs. The results show the importance of the cyclopentane nucleus with regard to activity. The activity of 3-methyltrimethylammonium hexane iodide is particularly interesting for, though lacking the oxygenated function in 3 and having a different methyl spatial arrangement, this compound is only ten times less active than desethermuscarone.

Animals↗
PubMed1975

Cholinergic compounds. II - Synthesis and biological activity of epi- and allo-desethermuscarines.

To obtain further clarification of structure-activity relationships of cholinergic substances, which would give better understanding of cholinergic receptors, the carbocyclic analogs of epi-muscarine (I) and allo-muscarine (II) were prepared starting from 6-methyl-3-oxo-2-oxabicyclo[2.2.1]heptane (IV). Pharmacological tests show that these two compounds possess lower muscarinic activity than the carbocyclic analog of muscarine (desethermuscarine), the allo isomer being from 5 to 500 times more active than the epi isomer. Therefore, the activity in the carbocyclic series follows, for these receptors, the same pattern as the oxygenated one. As far as nicotinic activity is concerned. (I) is 2.5 times more active than (II), the effective doses being from 40 to 100 times higher than that of Ach. These results suggest a steric rather than an electronic influence for the ether oxygen, whose principal role seems to be that of contributing to the rigidity of the molecule. For most receptors assayed, an inverse relationship between the potency ratio of the isomers and the sensitivity towards Ach has been observed.

Animals↗
PubMed1975

Cholinergic compounds. III - Synthesis and biological activity of epi-desmethyldesethermuscarine, desmethyldesethermuscarine and desmethyldesethermuscarone.

As a further contribution to better understanding of the nature of the cholinergic receptors, desmethyldesethermuscarone (I), epi-desmethyldesethermuscarine (II a) and desmethyldesethermuscarine (II b) were synthesized. With few exceptions, the drop in muscarinic activity of these compounds compared with that of desethermuscarone and desethermuscarines emphasizes the importance of C-7 methyl (5). As far as nicotinic activity is concerned, C-7 methyl appears much less critical.

Animals↗