{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/70435"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/70435","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"I. Molecular Probes for the Progesterone Receptor. II. Design and Synthesis of a Rigidly Constrained Peptidomimetic as a Potential Beta-Turn Mimic. III. Isolation and Characterization of Novel Ion Channel Modulators From Commercial Phenol Red Preparations","abstract":"Chemical probes for steroid receptors have proven useful in providing molecular details about important hormone-receptor interactions. $16\\alpha,17\\alpha$- ((R)-1$\\sp\\prime$-(4-Azidophenyl)-ethylidenedioxy) pregn-4-ene-3,20-dione (12) was prepared in high specific activity tritium-labeled form (20 Ci/mmol), and shown to bind to the PR with an affinity (K$\\sb{\\rm d}$ = 0.801 nM) that is 47% of the affinity of ($\\sp3$H) -R 5020 (K$\\sb{\\rm d}$ = 0.379 nM). ($\\sp3$H) -progestin aryl azide 12 exhibits high photoattachment efficiency (60% at 1 h) compared to the commonly used PR PAL reagent ($\\sp3$H) -R 5020 (2.2% at 1 h), and is the most efficient progesterone receptor PAL reagent prepared to date. $16\\alpha,17\\alpha$-((R)-1$\\sp\\prime$-(4-Fluorophenyl)ethylidenedioxy) pregn-4-ene-3,20-dione (34) was prepared in fluorine-18 labeled form, and evaluated for its in vivo biodistribution in rats. The fluorine-18 labeled progestin showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. The structures of two novel steroids (17$a\\beta$-hydroxy-16$\\alpha,17 \\alpha$-oxacyclopentan-1$\\sp\\prime$-one-D-homoandrost-4-en-3-one (78) and 15$\\alpha$-formyl-16$\\alpha$-hydroxy-16$ \\beta$-methylandrost-4-ene-3,17-dione (79)), formed by treatment of 16-dehydroprogesterone with cetyltrimethyl-ammonium permanganate, have been determined by corroboration of $\\sp1$H and $\\sp $C NMR methods, IR, and mass spectrometry. The X-ray crystal structure of D-homosteroid 78, and putative mechanisms for formation of 78 and 79 are presented.","abstract_html":"Chemical probes for steroid receptors have proven useful in providing molecular details about important hormone-receptor interactions. <span class=\"etd-inline-math\">16&alpha;,17&alpha;</span>- ((R)-1$\\sp\\prime$-(4-Azidophenyl)-ethylidenedioxy) pregn-4-ene-3,20-dione (12) was prepared in high specific activity tritium-labeled form (20 Ci/mmol), and shown to bind to the PR with an affinity (K$\\sb{\\rm d}$ = 0.801 nM) that is 47% of the affinity of ($\\sp3$H) -R 5020 (K$\\sb{\\rm d}$ = 0.379 nM). ($\\sp3$H) -progestin aryl azide 12 exhibits high photoattachment efficiency (60% at 1 h) compared to the commonly used PR PAL reagent ($\\sp3$H) -R 5020 (2.2% at 1 h), and is the most efficient progesterone receptor PAL reagent prepared to date. <span class=\"etd-inline-math\">16&alpha;,17&alpha;</span>-((R)-1$\\sp\\prime$-(4-Fluorophenyl)ethylidenedioxy) pregn-4-ene-3,20-dione (34) was prepared in fluorine-18 labeled form, and evaluated for its in vivo biodistribution in rats. The fluorine-18 labeled progestin showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. The structures of two novel steroids (17<span class=\"etd-inline-math\">a&beta;</span>-hydroxy-16<span class=\"etd-inline-math\">&alpha;,17 &alpha;</span>-oxacyclopentan-1$\\sp\\prime$-one-D-homoandrost-4-en-3-one (78) and 15<span class=\"etd-inline-math\">&alpha;</span>-formyl-16<span class=\"etd-inline-math\">&alpha;</span>-hydroxy-16<span class=\"etd-inline-math\"> &beta;</span>-methylandrost-4-ene-3,17-dione (79)), formed by treatment of 16-dehydroprogesterone with cetyltrimethyl-ammonium permanganate, have been determined by corroboration of $\\sp1$H and $\\sp $C NMR methods, IR, and mass spectrometry. The X-ray crystal structure of D-homosteroid 78, and putative mechanisms for formation of 78 and 79 are presented.","abstract_has_math":true,"creators":["Kym, Philip Ryan"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Katzenellenbogen, John A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-15T23:19:27Z","date_published":"2014-12-15T23:19:27Z","updated_at":"2026-07-22T22:26:02Z","subjects":["Chemistry, Organic","Chemistry, Pharmaceutical"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI9512443"],"render_values":[{"text":"(UMI)AAI9512443","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/70435","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Katzenellenbogen, John A."]},{"key":"dc:creator","label":"Author","values":["Kym, Philip Ryan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-15T23:19:27Z","10000-01-01","1994"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Organic","Chemistry, Pharmaceutical"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/70435","(UMI)AAI9512443"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Chemical probes for steroid receptors have proven useful in providing molecular details about important hormone-receptor interactions. $16\\alpha,17\\alpha$- ((R)-1$\\sp\\prime$-(4-Azidophenyl)-ethylidenedioxy) pregn-4-ene-3,20-dione (12) was prepared in high specific activity tritium-labeled form (20 Ci/mmol), and shown to bind to the PR with an affinity (K$\\sb{\\rm d}$ = 0.801 nM) that is 47% of the affinity of ($\\sp3$H) -R 5020 (K$\\sb{\\rm d}$ = 0.379 nM). ($\\sp3$H) -progestin aryl azide 12 exhibits high photoattachment efficiency (60% at 1 h) compared to the commonly used PR PAL reagent ($\\sp3$H) -R 5020 (2.2% at 1 h), and is the most efficient progesterone receptor PAL reagent prepared to date. $16\\alpha,17\\alpha$-((R)-1$\\sp\\prime$-(4-Fluorophenyl)ethylidenedioxy) pregn-4-ene-3,20-dione (34) was prepared in fluorine-18 labeled form, and evaluated for its in vivo biodistribution in rats. The fluorine-18 labeled progestin showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. The structures of two novel steroids (17$a\\beta$-hydroxy-16$\\alpha,17 \\alpha$-oxacyclopentan-1$\\sp\\prime$-one-D-homoandrost-4-en-3-one (78) and 15$\\alpha$-formyl-16$\\alpha$-hydroxy-16$ \\beta$-methylandrost-4-ene-3,17-dione (79)), formed by treatment of 16-dehydroprogesterone with cetyltrimethyl-ammonium permanganate, have been determined by corroboration of $\\sp1$H and $\\sp $C NMR methods, IR, and mass spectrometry. The X-ray crystal structure of D-homosteroid 78, and putative mechanisms for formation of 78 and 79 are presented.","A novel, rigidly constrained 2-azacyclodec-6-enone ring system was designed as a potential $\\beta$-turn mimic. A precursor to the potential $\\beta$-turn mimic, (3R,10S),(3S,10R)-($\\pm$)-(6E)-3,10-diethyl-2-azacyclodec-6-enone dicarboxylate (103), was prepared by classical ring closure via an intramolecular amine condensation on an ethyl ester. Only the enantiomeric pair that positions both the C$\\sb3$ and C$\\sb $ substituents in equatorial positions was formed during the cyclization reaction. This methodology has been used in the asymmetric synthesis of a diester precursor to the putative $\\beta$-turn mimic.","Two novel bisphenol derivatives have been isolated from the lipophilic impurities present in a commercial preparation of phenol red, and their structures have been determined by corroboration of $\\sp1$H and $\\sp $C NMR methods and mass spectrometry. The bisphenol fluorene derivative, 9,9-bis(4$\\sp\\prime$-hydroxyphenyl)-3-hydroxyfluorene (170), has been found to exhibit a dramatic effect on the intracellular concentrations of K$\\sp+$ and Na$\\sp+$ ions in human fibroblasts at low concentrations (EC$\\sb{50}$ between 30 and 60 ng/mL). The bisphenol xanthene derivative, 9,9-bis(4$\\sp\\prime$-hydroxyphenyl)xanthene (169), elicits a similar biological response, but is less potent. Xanthene 169 exhibits a dramatic effect on cell adhesion, causing release of cells from the plastic substrate at concentrations as low as 2 $\\mu$g/mL.","Made available in DSpace on 2014-12-15T23:19:27Z (GMT). No. of bitstreams: 1 9512443.pdf: 8737679 bytes, checksum: c936572616c9045623c01980a12a85f4 (MD5) Previous issue date: 1994","Embargo set by: Seth Robbins for item 70601 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","234 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1994."]},{"key":"dc:title","label":"Title","values":["I. Molecular Probes for the Progesterone Receptor. II. Design and Synthesis of a Rigidly Constrained Peptidomimetic as a Potential Beta-Turn Mimic. III. Isolation and Characterization of Novel Ion Channel Modulators From Commercial Phenol Red Preparations"]}]}],"canonical_facts":{"dc:contributor":["Katzenellenbogen, John A."],"dc:creator":["Kym, Philip Ryan"],"dc:date":["2014-12-15T23:19:27Z","10000-01-01","1994"],"dc:description":["Chemical probes for steroid receptors have proven useful in providing molecular details about important hormone-receptor interactions. $16\\alpha,17\\alpha$- ((R)-1$\\sp\\prime$-(4-Azidophenyl)-ethylidenedioxy) pregn-4-ene-3,20-dione (12) was prepared in high specific activity tritium-labeled form (20 Ci/mmol), and shown to bind to the PR with an affinity (K$\\sb{\\rm d}$ = 0.801 nM) that is 47% of the affinity of ($\\sp3$H) -R 5020 (K$\\sb{\\rm d}$ = 0.379 nM). ($\\sp3$H) -progestin aryl azide 12 exhibits high photoattachment efficiency (60% at 1 h) compared to the commonly used PR PAL reagent ($\\sp3$H) -R 5020 (2.2% at 1 h), and is the most efficient progesterone receptor PAL reagent prepared to date. $16\\alpha,17\\alpha$-((R)-1$\\sp\\prime$-(4-Fluorophenyl)ethylidenedioxy) pregn-4-ene-3,20-dione (34) was prepared in fluorine-18 labeled form, and evaluated for its in vivo biodistribution in rats. The fluorine-18 labeled progestin showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. The structures of two novel steroids (17$a\\beta$-hydroxy-16$\\alpha,17 \\alpha$-oxacyclopentan-1$\\sp\\prime$-one-D-homoandrost-4-en-3-one (78) and 15$\\alpha$-formyl-16$\\alpha$-hydroxy-16$ \\beta$-methylandrost-4-ene-3,17-dione (79)), formed by treatment of 16-dehydroprogesterone with cetyltrimethyl-ammonium permanganate, have been determined by corroboration of $\\sp1$H and $\\sp $C NMR methods, IR, and mass spectrometry. The X-ray crystal structure of D-homosteroid 78, and putative mechanisms for formation of 78 and 79 are presented.","A novel, rigidly constrained 2-azacyclodec-6-enone ring system was designed as a potential $\\beta$-turn mimic. A precursor to the potential $\\beta$-turn mimic, (3R,10S),(3S,10R)-($\\pm$)-(6E)-3,10-diethyl-2-azacyclodec-6-enone dicarboxylate (103), was prepared by classical ring closure via an intramolecular amine condensation on an ethyl ester. Only the enantiomeric pair that positions both the C$\\sb3$ and C$\\sb $ substituents in equatorial positions was formed during the cyclization reaction. This methodology has been used in the asymmetric synthesis of a diester precursor to the putative $\\beta$-turn mimic.","Two novel bisphenol derivatives have been isolated from the lipophilic impurities present in a commercial preparation of phenol red, and their structures have been determined by corroboration of $\\sp1$H and $\\sp $C NMR methods and mass spectrometry. The bisphenol fluorene derivative, 9,9-bis(4$\\sp\\prime$-hydroxyphenyl)-3-hydroxyfluorene (170), has been found to exhibit a dramatic effect on the intracellular concentrations of K$\\sp+$ and Na$\\sp+$ ions in human fibroblasts at low concentrations (EC$\\sb{50}$ between 30 and 60 ng/mL). The bisphenol xanthene derivative, 9,9-bis(4$\\sp\\prime$-hydroxyphenyl)xanthene (169), elicits a similar biological response, but is less potent. Xanthene 169 exhibits a dramatic effect on cell adhesion, causing release of cells from the plastic substrate at concentrations as low as 2 $\\mu$g/mL.","Made available in DSpace on 2014-12-15T23:19:27Z (GMT). No. of bitstreams: 1 9512443.pdf: 8737679 bytes, checksum: c936572616c9045623c01980a12a85f4 (MD5) Previous issue date: 1994","Embargo set by: Seth Robbins for item 70601 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","234 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1994."],"dc:identifier":["http://hdl.handle.net/2142/70435","(UMI)AAI9512443"],"dc:subject":["Chemistry, Organic","Chemistry, Pharmaceutical"],"dc:title":["I. Molecular Probes for the Progesterone Receptor. II. Design and Synthesis of a Rigidly Constrained Peptidomimetic as a Potential Beta-Turn Mimic. III. Isolation and Characterization of Novel Ion Channel Modulators From Commercial Phenol Red Preparations"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:02Z"}