Synthesis of 2-Methylsulfanyl-1H-imidazoles as Novel Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
α‐Aminoketone hydrochlorides 2a—d were synthesized by Dakin‐West reaction from L‐phenylalanine and L‐cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a—d with aqueous potassium thiocyanate afforded 1, 3‐imidazole‐2‐thiones 3a—d which were alkylated with methyl iodide to give...
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| Veröffentlicht in: | Archiv der Pharmazie (Weinheim) 2003-06, Vol.336 (3), p.175-180 |
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| container_title | Archiv der Pharmazie (Weinheim) |
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| creator | Loksha, Yasser M. El-Badawi, Mahmoud A. El-Barbary, Ahmed A. Pedersen, Erik B. Nielsen, Claus |
| description | α‐Aminoketone hydrochlorides 2a—d were synthesized by Dakin‐West reaction from L‐phenylalanine and L‐cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a—d with aqueous potassium thiocyanate afforded 1, 3‐imidazole‐2‐thiones 3a—d which were alkylated with methyl iodide to give 2‐methylsulfanyl‐1H‐imidazoles 4a—d with 4‐benzyl/4‐cyclohexylmethyl and 5‐ethyl/5‐isopropyl substituents. Coupling of 4a—d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N‐1 5a—d and N‐3 6a—h alkylated products. The synthesised compounds were tested for their activity against HIV‐1. The most active compounds have a cyclohexylmethyl group in the 5‐position of 6 and showed an activity against HIV‐1 comparable to the activity of Nevirapine. |
| doi_str_mv | 10.1002/ardp.200390017 |
| format | Article |
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Treatment of 2a—d with aqueous potassium thiocyanate afforded 1, 3‐imidazole‐2‐thiones 3a—d which were alkylated with methyl iodide to give 2‐methylsulfanyl‐1H‐imidazoles 4a—d with 4‐benzyl/4‐cyclohexylmethyl and 5‐ethyl/5‐isopropyl substituents. Coupling of 4a—d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N‐1 5a—d and N‐3 6a—h alkylated products. The synthesised compounds were tested for their activity against HIV‐1. The most active compounds have a cyclohexylmethyl group in the 5‐position of 6 and showed an activity against HIV‐1 comparable to the activity of Nevirapine.</description><identifier>ISSN: 0365-6233</identifier><identifier>EISSN: 1521-4184</identifier><identifier>DOI: 10.1002/ardp.200390017</identifier><identifier>PMID: 12822183</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Cell Line ; HIV-1 - drug effects ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Imidazole-2-thiones ; Imidazoles - chemical synthesis ; Imidazoles - chemistry ; Imidazoles - pharmacology ; Magnetic Resonance Spectroscopy ; Non-nucleoside reverse transcriptase inhibitors ; Reverse Transcriptase Inhibitors - chemical synthesis ; Reverse Transcriptase Inhibitors - chemistry ; Reverse Transcriptase Inhibitors - pharmacology ; Structure-Activity Relationship ; α-Aminoketones</subject><ispartof>Archiv der Pharmazie (Weinheim), 2003-06, Vol.336 (3), p.175-180</ispartof><rights>Copyright © 2003 WILEY‐VCH Verlag GmbH & Co. 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Pharm. Pharm. Med. Chem</addtitle><description>α‐Aminoketone hydrochlorides 2a—d were synthesized by Dakin‐West reaction from L‐phenylalanine and L‐cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a—d with aqueous potassium thiocyanate afforded 1, 3‐imidazole‐2‐thiones 3a—d which were alkylated with methyl iodide to give 2‐methylsulfanyl‐1H‐imidazoles 4a—d with 4‐benzyl/4‐cyclohexylmethyl and 5‐ethyl/5‐isopropyl substituents. Coupling of 4a—d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N‐1 5a—d and N‐3 6a—h alkylated products. The synthesised compounds were tested for their activity against HIV‐1. The most active compounds have a cyclohexylmethyl group in the 5‐position of 6 and showed an activity against HIV‐1 comparable to the activity of Nevirapine.</description><subject>Cell Line</subject><subject>HIV-1 - drug effects</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Imidazole-2-thiones</subject><subject>Imidazoles - chemical synthesis</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - pharmacology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Non-nucleoside reverse transcriptase inhibitors</subject><subject>Reverse Transcriptase Inhibitors - chemical synthesis</subject><subject>Reverse Transcriptase Inhibitors - chemistry</subject><subject>Reverse Transcriptase Inhibitors - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>α-Aminoketones</subject><issn>0365-6233</issn><issn>1521-4184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUGP0zAQhS0EYsvClSPKCcHBy9jT2PFxtdBt0VJQqcTRcpOJanCSrp0shF9PVl3KkcuMRvO90dM8xl4KuBAA8p2L1eFCAqABEPoRm4lcCj4XxfwxmwGqnCuJeMaepfQdJgxk_pSdCVlIKQqcsebr2PZ7Sj5lXZ1J_on6_RjSEGrXjoGLJfeNr9zvLlDKXMrW3R2Fqba8HcpAXfIVZRu6o5go20bXpjL6Q--madXu_c73XUzZm_V6s12lt8_Zk9qFRC8e-jnbLj5sr5b85vP16uryhnuUSnOnnaO6KsBI6QzIAglKAYRK1VXupNmVc1M7uUPUmkqpAQVi7ozIoTIKz9nr49lD7G4HSr1tfCopBNdSNySrEQtTKP1fUAqBejIwga8ewGHXUGUP0TcujvbvIyfAHIGfPtD4bw_2PiZ7H5M9xWQvN--_nKZJy49an3r6ddK6-MNOHnVuv62vrfpoNssFKrvAP3FylOk</recordid><startdate>200306</startdate><enddate>200306</enddate><creator>Loksha, Yasser M.</creator><creator>El-Badawi, Mahmoud A.</creator><creator>El-Barbary, Ahmed A.</creator><creator>Pedersen, Erik B.</creator><creator>Nielsen, Claus</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>200306</creationdate><title>Synthesis of 2-Methylsulfanyl-1H-imidazoles as Novel Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)</title><author>Loksha, Yasser M. ; El-Badawi, Mahmoud A. ; El-Barbary, Ahmed A. ; Pedersen, Erik B. ; Nielsen, Claus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3267-a7aaefd80922a90283e0c10e366fd5a29bc49fa2b3377ec27031335a9150d963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Cell Line</topic><topic>HIV-1 - drug effects</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Imidazole-2-thiones</topic><topic>Imidazoles - chemical synthesis</topic><topic>Imidazoles - chemistry</topic><topic>Imidazoles - pharmacology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Non-nucleoside reverse transcriptase inhibitors</topic><topic>Reverse Transcriptase Inhibitors - chemical synthesis</topic><topic>Reverse Transcriptase Inhibitors - chemistry</topic><topic>Reverse Transcriptase Inhibitors - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>α-Aminoketones</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Loksha, Yasser M.</creatorcontrib><creatorcontrib>El-Badawi, Mahmoud A.</creatorcontrib><creatorcontrib>El-Barbary, Ahmed A.</creatorcontrib><creatorcontrib>Pedersen, Erik B.</creatorcontrib><creatorcontrib>Nielsen, Claus</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Archiv der Pharmazie (Weinheim)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Loksha, Yasser M.</au><au>El-Badawi, Mahmoud A.</au><au>El-Barbary, Ahmed A.</au><au>Pedersen, Erik B.</au><au>Nielsen, Claus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of 2-Methylsulfanyl-1H-imidazoles as Novel Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)</atitle><jtitle>Archiv der Pharmazie (Weinheim)</jtitle><addtitle>Arch. Pharm. Pharm. Med. Chem</addtitle><date>2003-06</date><risdate>2003</risdate><volume>336</volume><issue>3</issue><spage>175</spage><epage>180</epage><pages>175-180</pages><issn>0365-6233</issn><eissn>1521-4184</eissn><abstract>α‐Aminoketone hydrochlorides 2a—d were synthesized by Dakin‐West reaction from L‐phenylalanine and L‐cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a—d with aqueous potassium thiocyanate afforded 1, 3‐imidazole‐2‐thiones 3a—d which were alkylated with methyl iodide to give 2‐methylsulfanyl‐1H‐imidazoles 4a—d with 4‐benzyl/4‐cyclohexylmethyl and 5‐ethyl/5‐isopropyl substituents. Coupling of 4a—d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N‐1 5a—d and N‐3 6a—h alkylated products. The synthesised compounds were tested for their activity against HIV‐1. The most active compounds have a cyclohexylmethyl group in the 5‐position of 6 and showed an activity against HIV‐1 comparable to the activity of Nevirapine.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>12822183</pmid><doi>10.1002/ardp.200390017</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0365-6233 |
| ispartof | Archiv der Pharmazie (Weinheim), 2003-06, Vol.336 (3), p.175-180 |
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| source | MEDLINE; Access via Wiley Online Library |
| subjects | Cell Line HIV-1 - drug effects Human immunodeficiency virus Human immunodeficiency virus 1 Humans Imidazole-2-thiones Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - pharmacology Magnetic Resonance Spectroscopy Non-nucleoside reverse transcriptase inhibitors Reverse Transcriptase Inhibitors - chemical synthesis Reverse Transcriptase Inhibitors - chemistry Reverse Transcriptase Inhibitors - pharmacology Structure-Activity Relationship α-Aminoketones |
| title | Synthesis of 2-Methylsulfanyl-1H-imidazoles as Novel Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) |
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