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N L Allinger

Publications and source records attributed to N L Allinger.

12 recordsLinked to original sources
PubMed2000

Molecular mechanics calculations of 10-vertex boron cage compounds.

The model proposed earlier for molecular mechanics calculations of 7- and 12-vertex boranes, carboranes, and metallocarboranes has been extended to the case of 10-vertex borane cage compounds. To use the MM3 program with the standard connectivity file, and to avoid program alterations, the 10-vertex cages of the molecules were presented as a superposition of four formally independent fragments. Interactions between the fragments were described with a Hill-like potential, with the parameters adjusted for valence interactions. Standard values for the bond lengths and bond angles in the 10-vertex boron cage have been found by statistical analysis of X-ray data on borane cage compounds stored in the Cambridge Structural Database. Several substituted neutral molecules and anions have been considered, and good agreement of the calculated and experimental data has been obtained. Using the approach developed, the unknown structure of the [mu-B20H16O(CH2)4O(CH2)2CH(CH3)2]3- ion has been calculated.

Journal Article↗
PubMed1987

Conformational analysis of 2-aminoindans and 2-(aminomethyl)indans in relation to their central dopaminergic effects and a dynamic dopamine receptor concept.

Conformational analyses on differently substituted 2-aminoindans of significant pharmacological interest were carried out by the molecular mechanics method (MM2). An X-ray structure of (R)-4-methoxy-2-aminoindan has shown the ammonium nitrogen [-)-D-tartaric acid salt) in an axial position. From comparison with other, highly potent, centrally acting dopamine (DA) receptor agonists, it can be predicted that the active enantiomer (R)-4-hydroxy-2-(di-n-propylamino)indan should have its nitrogen atom in an equatorial position. This places it close to the aromatic ring plane, which is one of several prerequisites for potent DA receptor agonism. MM2 correctly calculates (R)-4-methoxy-2-aminoindan and (R)-4-hydroxy-2-(dialkylamino)indan to be more stable in the N-axial and N-equatorial conformations, respectively. Conformational analysis of the dimethyl model compound of the moderately potent dopaminergic phenylpropylamine analogue 4-hydroxy-2-[(di-n-propylamino)methyl]indan was also carried out, in order to see if any conformations of this compound satisfy the requirements for dopaminergic agonism. Two such stable conformations were found.

Brain↗
PubMed1987

Resolved cis-10-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b- octahydrobenzo[f]quinoline : central serotonin stimulating properties.

cis-10-Hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b -octahydrobenzo[f]quinoline (4) is a centrally acting serotonin (5-HT) receptor agonist of moderate potency. Due to its semirigid character and the obvious similarity between (4aR,10bS)-4 and more potent, centrally acting 5-HT receptor agonist cis-(1S,2R)-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (2), we carried out the preparation (via resolution of 6, a precursor of 4) and the pharmacological testing of the enantiomers of 4. We were able to show that the active enantiomers of 4 and 2 coincide in terms of stereochemistry, i.e., that it is the 4aR,10bS enantiomer of 4 that is the more active one. The absolute configuration was assigned on the basis of single-crystal X-ray analysis of the precursor (+)-6 of the active enantiomer (-)-4. Conformational analysis with molecular mechanics (MM2) calculations were performed on the N-methyl analogues of compounds cis-(1S,2R)-2 (cis-(1S,2R)-3) and cis-(4aR,10bS)-4 (cis-(4aR,10bS)-7). Both ammonium and free amine forms were subjected to these calculations. The results show a preference for the N-equatorial conformation, which is corroborated by the X-ray structure of (+)-6.HCl. The relatively low potency of compound cis-(4aR,10bS)-4 might be explained by unfavorable direction of the N-lone pair (or ammonium hydrogen) bond in this compound as compared to cis-(1S,2R)-2 and trans-(4aR,10bR)-5, which can be predicted to be the more active enantiomer of compound 5.

Animals↗
PubMed1987

The dopaminergic moiety of the ergots: a controversial topic studied with molecular mechanics.

Conformational analyses of the side chain of model compounds of the in vivo active dopamine receptor agonist 4-[2-(di-n-propylamino)ethyl]indole (DPAI) were performed with molecular mechanics calculations. The results from these calculations, together with the possibility of meta hydroxylation of indoles in vivo, led to the proposal of fitting 6-hydroxy-4-[2-(di-n-propylamino)ethyl]indole (6-OH-DPAI), (S)-5-hydroxy-N,N-dialkyl-6,7,8,9-tetrahydro-3H-benzo[e]indol-8-ylami nes and (S)-5-hydroxy-2-(dialkylamino)tetralins in a common concept, considering both stereochemistry and hydrogen-bond function in such an overlap. This study emphasizes the importance of considering both conformational analysis and the possibilities of metabolic activation when performing structure-activity studies based on flexible compounds and in vivo data. The answer to the question as to which part of the ergot molecule is responsible for its dopaminergic effect is thus ambiguous. It is possible that the pyrrolylethylamine moiety of the ergots contributes to both in vitro and in vivo effects, and that their 13-OH metabolites contribute, possibly significantly, to their in vivo effects.

Chemical Phenomena↗
PubMed1975

Androsterone. The structure by force-field calculations.

The structure of androsterone was calculated by the force-field (molecular mechanics) method. Plots of the calculated structure are compared with those of the X-ray structure, and found to have all of the atoms in the same positions to within 0.1 A. The regular Dreiding model structure differs substantially from these calculated and experimental structures, atomic positions being up to 0.9 A removed from where they should be.

Androsterone↗