Response to Aminoglutethimide After Failure of Tamoxifen Therapy in Breast Cancer

Cm, Sutherland; Jh, Muchmore; Rd, Carter

doi:10.1097/00007611-198508000-00024

Cited by 3 publications

(2 citation statements)

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“…The findings that D in eqs [1][2][3][4][5][6] of Table 6 and the AF of speci fie regions in space, see Table 7, correlate w ith -log (EC50) suggests an intermolecular hydrogen bond (or strong electrostatic interaction) between a nitrogen in the inhibitor heterocycle and the receptor. Both D and AF, by the way they are defined, relate a property of a particular site in space to inhibition potency.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Shape and QSAR Analyses of a Family of Substituted Dichlorodiphenyl Aromatase Inhibitors

Tokarski¹,

Hopfinger²

1994

J. Chem. Inf. Comput. Sci.

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Conformational analyses of three families of substituted dichlorodiphenyl aromatase inhibitors indicated that both potent and weak inhibitors adopt a common global minimum energy conformation. Further, this global minimum energy conformation is the only meaningful intramolecular conformer state that can be energetically realized and is virtually identical to the crystal structure of one of the analogs. Quantitative structure-activity relationships, QSARs, were separately, and jointly, developed for two series of inhibitors. The distance, D, of a nitrogen atom in the variable heterocycle from the core Cc atom is the most important activity descriptor. The optimum distance between the nitrogen and Cc to maximize inhibitor potency is about 3.6 A for both classes of analogs. Integrated potential energy field difference calculations were also carried out using a proton probe and some of the variable heterocycles. The field calculations coupled with the QSAR studies suggest that the nitrogen 3.6 A from Cc acts as a hydrogen bond acceptor. Two possible three-dimensional pharmacophores are proposed for effective aromatase inhibitors.

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Section: Discussionmentioning

confidence: 99%

“…(2) What physicochemical properties of the heterocycle govern activity? (3) Is enough structure-activity information available to construct a 3D-QSAR and corresponding 3D-pharmacophore? angles searched are defined in Figure 1A.…”

Section: Introductionmentioning

confidence: 99%