Synthesis and monoamine uptake inhibiting properties of perisubstituted tricyclic compounds

Persistent Link:
http://hdl.handle.net/10150/291828
Title:
Synthesis and monoamine uptake inhibiting properties of perisubstituted tricyclic compounds
Author:
Peters, Jennifer Margaret, 1956-
Issue Date:
1988
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The synthesis of 1-methyl-promazine, 4-hydroxymethyl-iminodibenzyl, and 4-bromo-5-trimethylsilyl-iminodibenzyl via dilithiation and ¹H-NMR's are described. Molecular modeling was done for the latter compound. The heat of dissociation was 30.6 kcal/mole for the lowest energy conformer. Rotational energies were examined for three bonds. The IC₅₀ values for inhibition of neurotransmitter uptake by rat brain synaptosomes were determined for a series of 1-substituted promazines, and 4-substituted imipramines. 1-Substituted promazines were fair inhibitors of serotonin uptake with an average IC₅₀ of 2000 nm. Their potency for inhibiting norepinephrine uptake was difficult to assess due to poor assay reproducibility, and the average IC₅₀ was estimated at 200 to 1700 nm. Serotonin, but not norepinephrine, uptake inhibition was increased with additional ring substitution at C(2) with a trifluoromethyl group. The 4-substituted imipramines were equal or slightly decreased in potency to unsubstituted imipramine for uptake inhibition of both neurotransmitters. IC₅₀'s were also reported for imipramine and desipramine.
Type:
text; Thesis-Reproduction (electronic)
Keywords:
Heterocyclic compounds -- Synthesis.; Phenothiazine -- Synthesis.; Imipramine -- Synthesis.
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College; Pharmaceutical Sciences
Degree Grantor:
University of Arizona
Advisor:
Martin, Arnold R.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleSynthesis and monoamine uptake inhibiting properties of perisubstituted tricyclic compoundsen_US
dc.creatorPeters, Jennifer Margaret, 1956-en_US
dc.contributor.authorPeters, Jennifer Margaret, 1956-en_US
dc.date.issued1988en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe synthesis of 1-methyl-promazine, 4-hydroxymethyl-iminodibenzyl, and 4-bromo-5-trimethylsilyl-iminodibenzyl via dilithiation and ¹H-NMR's are described. Molecular modeling was done for the latter compound. The heat of dissociation was 30.6 kcal/mole for the lowest energy conformer. Rotational energies were examined for three bonds. The IC₅₀ values for inhibition of neurotransmitter uptake by rat brain synaptosomes were determined for a series of 1-substituted promazines, and 4-substituted imipramines. 1-Substituted promazines were fair inhibitors of serotonin uptake with an average IC₅₀ of 2000 nm. Their potency for inhibiting norepinephrine uptake was difficult to assess due to poor assay reproducibility, and the average IC₅₀ was estimated at 200 to 1700 nm. Serotonin, but not norepinephrine, uptake inhibition was increased with additional ring substitution at C(2) with a trifluoromethyl group. The 4-substituted imipramines were equal or slightly decreased in potency to unsubstituted imipramine for uptake inhibition of both neurotransmitters. IC₅₀'s were also reported for imipramine and desipramine.en_US
dc.typetexten_US
dc.typeThesis-Reproduction (electronic)en_US
dc.subjectHeterocyclic compounds -- Synthesis.en_US
dc.subjectPhenothiazine -- Synthesis.en_US
dc.subjectImipramine -- Synthesis.en_US
thesis.degree.nameM.S.en_US
thesis.degree.levelmastersen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMartin, Arnold R.en_US
dc.identifier.proquest1334360en_US
dc.identifier.oclc22271751en_US
dc.identifier.bibrecord.b17390552en_US
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