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The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements
For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excell...
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| Published in: | Bioorganic & medicinal chemistry letters 2009-11, Vol.19 (22), p.6340-6345 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c416t-d15ce5d3304478173e25aaebc5ae19f1c707f43a3e106a26e691354f90d06bd03 |
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| cites | cdi_FETCH-LOGICAL-c416t-d15ce5d3304478173e25aaebc5ae19f1c707f43a3e106a26e691354f90d06bd03 |
| container_end_page | 6345 |
| container_issue | 22 |
| container_start_page | 6340 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 19 |
| creator | Nordhoff, Sonja Bulat, Stephan Cerezo-Gálvez, Silvia Hill, Oliver Hoffmann-Enger, Barbara López-Canet, Meritxell Rosenbaum, Claudia Rummey, Christian Thiemann, Meinolf Matassa, Victor G. Edwards, Paul J. Feurer, Achim |
| description | For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.
For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes. |
| doi_str_mv | 10.1016/j.bmcl.2009.09.078 |
| format | article |
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For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2009.09.078</identifier><identifier>PMID: 19833514</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Amides - antagonists & inhibitors ; Amides - chemistry ; Aminobutyrates - chemistry ; Biological and medical sciences ; Caco-2 Cells ; Cell Line, Tumor ; Chemistry, Pharmaceutical ; Diabetes Mellitus, Type 2 - drug therapy ; Dipeptidyl peptidase IV ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; DPP-4 ; DPP-IV ; Drug Design ; General and cellular metabolism. Vitamins ; GLP-1 ; Glucagon-like peptide 1 ; Humans ; Hypoglycemic Agents - antagonists & inhibitors ; Hypoglycemic Agents - therapeutic use ; Medical sciences ; Pharmacology. Drug treatments ; Protease Inhibitors - pharmacokinetics ; Protease Inhibitors - pharmacology ; Sodium Channels - metabolism ; Structure-Activity Relationship ; Type 2 diabetes</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009-11, Vol.19 (22), p.6340-6345</ispartof><rights>2009 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-d15ce5d3304478173e25aaebc5ae19f1c707f43a3e106a26e691354f90d06bd03</citedby><cites>FETCH-LOGICAL-c416t-d15ce5d3304478173e25aaebc5ae19f1c707f43a3e106a26e691354f90d06bd03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22092220$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19833514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nordhoff, Sonja</creatorcontrib><creatorcontrib>Bulat, Stephan</creatorcontrib><creatorcontrib>Cerezo-Gálvez, Silvia</creatorcontrib><creatorcontrib>Hill, Oliver</creatorcontrib><creatorcontrib>Hoffmann-Enger, Barbara</creatorcontrib><creatorcontrib>López-Canet, Meritxell</creatorcontrib><creatorcontrib>Rosenbaum, Claudia</creatorcontrib><creatorcontrib>Rummey, Christian</creatorcontrib><creatorcontrib>Thiemann, Meinolf</creatorcontrib><creatorcontrib>Matassa, Victor G.</creatorcontrib><creatorcontrib>Edwards, Paul J.</creatorcontrib><creatorcontrib>Feurer, Achim</creatorcontrib><title>The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.
For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.</description><subject>Amides - antagonists & inhibitors</subject><subject>Amides - chemistry</subject><subject>Aminobutyrates - chemistry</subject><subject>Biological and medical sciences</subject><subject>Caco-2 Cells</subject><subject>Cell Line, Tumor</subject><subject>Chemistry, Pharmaceutical</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Dipeptidyl peptidase IV</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>DPP-4</subject><subject>DPP-IV</subject><subject>Drug Design</subject><subject>General and cellular metabolism. Vitamins</subject><subject>GLP-1</subject><subject>Glucagon-like peptide 1</subject><subject>Humans</subject><subject>Hypoglycemic Agents - antagonists & inhibitors</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Protease Inhibitors - pharmacokinetics</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Sodium Channels - metabolism</subject><subject>Structure-Activity Relationship</subject><subject>Type 2 diabetes</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp9kU1rFTEYhYMo9lr9Ay4kG-1qbt98TGYibkpbq9DSLiq4C5nkHZvLfDWZW2h_vRnvpe4KL8nmOYfDOYR8ZLBmwNTxZt30rltzAL1erqpfkRWTShZCQvmarEArKGotfx-QdyltAJgEKd-SA6ZrIUomV6S_vUPqMYU_Ax1bOo0zDjO1g6cJO3RzeEAahrvQhHmMaUHObm4K-ZVeT3Pow5Odw_hPeXJ2dU6nOE4Y54CJNo_U9sEjjTh11mGffdN78qa1XcIP-_-Q_Pp-fnv6o7i8vvh5enJZOMnUXHhWOiy9EDltVbNKIC-txcaVFplumaugaqWwAhkoyxUqzUQpWw0eVONBHJKjnW8OdL_FNJs-JIddZwcct8lUuSCtObBMfnmR5IwpqSqeQb4DXRxTitiaKYbexkfDwCxzmI1Z5jDLHGa5qs6iT3v3bdOj_y_Z95-Bz3vAJme7NtrBhfTMcQ6a5ydz33Yc5tYeAkaTXMDBoQ8xr2T8GF7K8Rf9ragB</recordid><startdate>20091115</startdate><enddate>20091115</enddate><creator>Nordhoff, Sonja</creator><creator>Bulat, Stephan</creator><creator>Cerezo-Gálvez, Silvia</creator><creator>Hill, Oliver</creator><creator>Hoffmann-Enger, Barbara</creator><creator>López-Canet, Meritxell</creator><creator>Rosenbaum, Claudia</creator><creator>Rummey, Christian</creator><creator>Thiemann, Meinolf</creator><creator>Matassa, Victor G.</creator><creator>Edwards, Paul J.</creator><creator>Feurer, Achim</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20091115</creationdate><title>The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements</title><author>Nordhoff, Sonja ; Bulat, Stephan ; Cerezo-Gálvez, Silvia ; Hill, Oliver ; Hoffmann-Enger, Barbara ; López-Canet, Meritxell ; Rosenbaum, Claudia ; Rummey, Christian ; Thiemann, Meinolf ; Matassa, Victor G. ; Edwards, Paul J. ; Feurer, Achim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-d15ce5d3304478173e25aaebc5ae19f1c707f43a3e106a26e691354f90d06bd03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Amides - antagonists & inhibitors</topic><topic>Amides - chemistry</topic><topic>Aminobutyrates - chemistry</topic><topic>Biological and medical sciences</topic><topic>Caco-2 Cells</topic><topic>Cell Line, Tumor</topic><topic>Chemistry, Pharmaceutical</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Dipeptidyl peptidase IV</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</topic><topic>DPP-4</topic><topic>DPP-IV</topic><topic>Drug Design</topic><topic>General and cellular metabolism. Vitamins</topic><topic>GLP-1</topic><topic>Glucagon-like peptide 1</topic><topic>Humans</topic><topic>Hypoglycemic Agents - antagonists & inhibitors</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Medical sciences</topic><topic>Pharmacology. 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These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.
For a series of β-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19833514</pmid><doi>10.1016/j.bmcl.2009.09.078</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-11, Vol.19 (22), p.6340-6345 |
| issn | 0960-894X 1464-3405 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_734099201 |
| source | ScienceDirect Freedom Collection |
| subjects | Amides - antagonists & inhibitors Amides - chemistry Aminobutyrates - chemistry Biological and medical sciences Caco-2 Cells Cell Line, Tumor Chemistry, Pharmaceutical Diabetes Mellitus, Type 2 - drug therapy Dipeptidyl peptidase IV Dipeptidyl-Peptidase IV Inhibitors - therapeutic use DPP-4 DPP-IV Drug Design General and cellular metabolism. Vitamins GLP-1 Glucagon-like peptide 1 Humans Hypoglycemic Agents - antagonists & inhibitors Hypoglycemic Agents - therapeutic use Medical sciences Pharmacology. Drug treatments Protease Inhibitors - pharmacokinetics Protease Inhibitors - pharmacology Sodium Channels - metabolism Structure-Activity Relationship Type 2 diabetes |
| title | The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements |
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