Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides
Lithium trialkylborohydrides were found to mono-dealkylate dialkylphosphonates rapidly (rate of cleavage Me, Bn > 1°). The reaction was applied to the synthesis of a new GABA C antagonist, 2-aminoethyl methylphosphonate ( 4a). Lithium trialkylborohydrides were found to effect rapid monodealkylati...
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creator | Chowdhury, Sarwat Muni, Niraj J. Greenwood, Nicholas P. Pepperberg, David R. Standaert, Robert F. |
description | Lithium trialkylborohydrides were found to mono-dealkylate dialkylphosphonates rapidly (rate of cleavage Me, Bn
>
1°). The reaction was applied to the synthesis of a new GABA
C antagonist, 2-aminoethyl methylphosphonate (
4a).
Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H
2N(CH
2)
2OP(OH)R,
4], a little-explored class of analogs of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Compound
4a (R
=
Me) proved to be a potent antagonist at human
ρ1 GABA
C receptors (expressed in
Xenopus laevis oocytes), with an IC
50 of 11.1
μM, but is inactive at α
1β
2γ
2 GABA
A receptors. |
doi_str_mv | 10.1016/j.bmcl.2007.04.026 |
format | Article |
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>
1°). The reaction was applied to the synthesis of a new GABA
C antagonist, 2-aminoethyl methylphosphonate (
4a).
Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H
2N(CH
2)
2OP(OH)R,
4], a little-explored class of analogs of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Compound
4a (R
=
Me) proved to be a potent antagonist at human
ρ1 GABA
C receptors (expressed in
Xenopus laevis oocytes), with an IC
50 of 11.1
μM, but is inactive at α
1β
2γ
2 GABA
A receptors.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2007.04.026</identifier><identifier>PMID: 17467985</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; BASIC BIOLOGICAL SCIENCES ; Biological and medical sciences ; Borohydrides - chemistry ; CATALYTIC EFFECTS ; Chemistry, Pharmaceutical - methods ; DEALKYLATION ; Dose-Response Relationship, Drug ; Drug Design ; Esters - chemistry ; GABA antagonists ; GABA C receptors ; GABAC receptors ; Gabaergic and benzodiazepinic system ; gamma-Aminobutyric Acid - analogs & derivatives ; gamma-Aminobutyric Acid - chemistry ; Inhibitory Concentration 50 ; Lithium ; LITHIUM COMPOUNDS ; Lithium trialkylborohydrides ; Magnetic Resonance Spectroscopy ; Medical sciences ; Models, Chemical ; NERVE CELLS ; Neuropharmacology ; Neurotransmitter Agents ; Neurotransmitters. Neurotransmission. Receptors ; OOCYTES ; Oocytes - metabolism ; Organophosphonates - chemical synthesis ; Organophosphonates - chemistry ; Pharmacology. Drug treatments ; Phosphonate esters ; phosphonate estes ; PHOSPHONIC ACID ESTERS ; RECEPTORS ; SYNTHESIS ; Xenopus laevis</subject><ispartof>Bioorganic & Medicinal Chemistry Letters, 2007-07, Vol.17 (13), p.3745-3748</ispartof><rights>2007 Elsevier Ltd</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-8c0b676d088c5fbe461fd1e94788ea0a75f91710d5c2c1e938745426f058e4c43</citedby><cites>FETCH-LOGICAL-c441t-8c0b676d088c5fbe461fd1e94788ea0a75f91710d5c2c1e938745426f058e4c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2007.04.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,885,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18859578$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17467985$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/930910$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Chowdhury, Sarwat</creatorcontrib><creatorcontrib>Muni, Niraj J.</creatorcontrib><creatorcontrib>Greenwood, Nicholas P.</creatorcontrib><creatorcontrib>Pepperberg, David R.</creatorcontrib><creatorcontrib>Standaert, Robert F.</creatorcontrib><creatorcontrib>Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)</creatorcontrib><title>Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides</title><title>Bioorganic & Medicinal Chemistry Letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Lithium trialkylborohydrides were found to mono-dealkylate dialkylphosphonates rapidly (rate of cleavage Me, Bn
>
1°). The reaction was applied to the synthesis of a new GABA
C antagonist, 2-aminoethyl methylphosphonate (
4a).
Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H
2N(CH
2)
2OP(OH)R,
4], a little-explored class of analogs of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Compound
4a (R
=
Me) proved to be a potent antagonist at human
ρ1 GABA
C receptors (expressed in
Xenopus laevis oocytes), with an IC
50 of 11.1
μM, but is inactive at α
1β
2γ
2 GABA
A receptors.</description><subject>Animals</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Biological and medical sciences</subject><subject>Borohydrides - chemistry</subject><subject>CATALYTIC EFFECTS</subject><subject>Chemistry, Pharmaceutical - methods</subject><subject>DEALKYLATION</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Esters - chemistry</subject><subject>GABA antagonists</subject><subject>GABA C receptors</subject><subject>GABAC receptors</subject><subject>Gabaergic and benzodiazepinic system</subject><subject>gamma-Aminobutyric Acid - analogs & derivatives</subject><subject>gamma-Aminobutyric Acid - chemistry</subject><subject>Inhibitory Concentration 50</subject><subject>Lithium</subject><subject>LITHIUM COMPOUNDS</subject><subject>Lithium trialkylborohydrides</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Models, Chemical</subject><subject>NERVE CELLS</subject><subject>Neuropharmacology</subject><subject>Neurotransmitter Agents</subject><subject>Neurotransmitters. Neurotransmission. Receptors</subject><subject>OOCYTES</subject><subject>Oocytes - metabolism</subject><subject>Organophosphonates - chemical synthesis</subject><subject>Organophosphonates - chemistry</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphonate esters</subject><subject>phosphonate estes</subject><subject>PHOSPHONIC ACID ESTERS</subject><subject>RECEPTORS</subject><subject>SYNTHESIS</subject><subject>Xenopus laevis</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhS0EokvhD3BA4QC3hHHixI7EZVvRglQJDiBxsxx70nhJ4sV2Wu2_x-mutDcuHsn63tO8eYS8pVBQoM2nXdFNeixKAF4AK6BsnpENZQ3LKwb1c7KBtoFctOz3BXkVwg6AMmDsJbmgnDW8FfWGPP4YXNgPbrY6U9qaTM1qdPchc312u73aZnHwbrkfMo9m0dE-YGZQjX8Oo4rWzSu2PzsYiyGiD9mjjUM2pscuUxa9fVJ0zrvhYLw1GF6TF70aA745zUvy6-bLz-uv-d3322_X27tcM0ZjLjR0DW8MCKHrvkPW0N5QbBkXAhUoXvct5RRMrUud_ivBWc3KpodaINOsuiTvj74uRCuDthH1oN08o46yraClkJiPR2bv3d8lJZCTDRrHUc3oliBpW9OKcZ7A8ghq70Lw2Mu9t5PyB0lBrpXInVwrkWslEphMlSTRu5P70k1ozpJTBwn4cAJU0GrsvZq1DWdOiLqtuUjc5yOH6V4PFv0aB2eNxvo1jXH2f3v8A_ZHq9c</recordid><startdate>20070701</startdate><enddate>20070701</enddate><creator>Chowdhury, Sarwat</creator><creator>Muni, Niraj J.</creator><creator>Greenwood, Nicholas P.</creator><creator>Pepperberg, David R.</creator><creator>Standaert, Robert F.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>OTOTI</scope></search><sort><creationdate>20070701</creationdate><title>Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides</title><author>Chowdhury, Sarwat ; Muni, Niraj J. ; Greenwood, Nicholas P. ; Pepperberg, David R. ; Standaert, Robert F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-8c0b676d088c5fbe461fd1e94788ea0a75f91710d5c2c1e938745426f058e4c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Biological and medical sciences</topic><topic>Borohydrides - chemistry</topic><topic>CATALYTIC EFFECTS</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>DEALKYLATION</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>Esters - chemistry</topic><topic>GABA antagonists</topic><topic>GABA C receptors</topic><topic>GABAC receptors</topic><topic>Gabaergic and benzodiazepinic system</topic><topic>gamma-Aminobutyric Acid - analogs & derivatives</topic><topic>gamma-Aminobutyric Acid - chemistry</topic><topic>Inhibitory Concentration 50</topic><topic>Lithium</topic><topic>LITHIUM COMPOUNDS</topic><topic>Lithium trialkylborohydrides</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Medical sciences</topic><topic>Models, Chemical</topic><topic>NERVE CELLS</topic><topic>Neuropharmacology</topic><topic>Neurotransmitter Agents</topic><topic>Neurotransmitters. Neurotransmission. Receptors</topic><topic>OOCYTES</topic><topic>Oocytes - metabolism</topic><topic>Organophosphonates - chemical synthesis</topic><topic>Organophosphonates - chemistry</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphonate esters</topic><topic>phosphonate estes</topic><topic>PHOSPHONIC ACID ESTERS</topic><topic>RECEPTORS</topic><topic>SYNTHESIS</topic><topic>Xenopus laevis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chowdhury, Sarwat</creatorcontrib><creatorcontrib>Muni, Niraj J.</creatorcontrib><creatorcontrib>Greenwood, Nicholas P.</creatorcontrib><creatorcontrib>Pepperberg, David R.</creatorcontrib><creatorcontrib>Standaert, Robert F.</creatorcontrib><creatorcontrib>Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>OSTI.GOV</collection><jtitle>Bioorganic & Medicinal Chemistry Letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chowdhury, Sarwat</au><au>Muni, Niraj J.</au><au>Greenwood, Nicholas P.</au><au>Pepperberg, David R.</au><au>Standaert, Robert F.</au><aucorp>Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides</atitle><jtitle>Bioorganic & Medicinal Chemistry Letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>17</volume><issue>13</issue><spage>3745</spage><epage>3748</epage><pages>3745-3748</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Lithium trialkylborohydrides were found to mono-dealkylate dialkylphosphonates rapidly (rate of cleavage Me, Bn
>
1°). The reaction was applied to the synthesis of a new GABA
C antagonist, 2-aminoethyl methylphosphonate (
4a).
Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H
2N(CH
2)
2OP(OH)R,
4], a little-explored class of analogs of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Compound
4a (R
=
Me) proved to be a potent antagonist at human
ρ1 GABA
C receptors (expressed in
Xenopus laevis oocytes), with an IC
50 of 11.1
μM, but is inactive at α
1β
2γ
2 GABA
A receptors.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>17467985</pmid><doi>10.1016/j.bmcl.2007.04.026</doi><tpages>4</tpages></addata></record> |
fulltext | fulltext |
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language | eng |
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source | Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE |
subjects | Animals BASIC BIOLOGICAL SCIENCES Biological and medical sciences Borohydrides - chemistry CATALYTIC EFFECTS Chemistry, Pharmaceutical - methods DEALKYLATION Dose-Response Relationship, Drug Drug Design Esters - chemistry GABA antagonists GABA C receptors GABAC receptors Gabaergic and benzodiazepinic system gamma-Aminobutyric Acid - analogs & derivatives gamma-Aminobutyric Acid - chemistry Inhibitory Concentration 50 Lithium LITHIUM COMPOUNDS Lithium trialkylborohydrides Magnetic Resonance Spectroscopy Medical sciences Models, Chemical NERVE CELLS Neuropharmacology Neurotransmitter Agents Neurotransmitters. Neurotransmission. Receptors OOCYTES Oocytes - metabolism Organophosphonates - chemical synthesis Organophosphonates - chemistry Pharmacology. Drug treatments Phosphonate esters phosphonate estes PHOSPHONIC ACID ESTERS RECEPTORS SYNTHESIS Xenopus laevis |
title | Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides |
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