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Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia
A series of 2-methoxyacylhydrazones were optimized to yield compounds with high affinity for PDE10A. Several compounds demonstrated efficacy in animal models of schizophrenia, including conditioned avoidance response and a pro-psychotic phencyclidine hyperactivity model.
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| Published in: | Bioorganic & medicinal chemistry letters 2012-09, Vol.22 (17), p.5595-5599 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c419t-3e9775009ab3a15b332f223b1427c8af4617aa8c9c9f3837e0838b745d88efb3 |
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| cites | cdi_FETCH-LOGICAL-c419t-3e9775009ab3a15b332f223b1427c8af4617aa8c9c9f3837e0838b745d88efb3 |
| container_end_page | 5599 |
| container_issue | 17 |
| container_start_page | 5595 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 22 |
| creator | Cutshall, Neil S. Onrust, Rene Rohde, Alex Gragerov, Sasha Hamilton, Lauren Harbol, Kevin Shen, Hui-Rong McKee, Shawn Zuta, Charles Gragerova, Galina Florio, Vince Wheeler, Thomas N. Gage, Jennifer L. |
| description | A series of 2-methoxyacylhydrazones were optimized to yield compounds with high affinity for PDE10A. Several compounds demonstrated efficacy in animal models of schizophrenia, including conditioned avoidance response and a pro-psychotic phencyclidine hyperactivity model. |
| doi_str_mv | 10.1016/j.bmcl.2012.07.007 |
| format | article |
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Drug treatments ; Phosphodiesterase ; Phosphodiesterase Inhibitors - chemistry ; Phosphodiesterase Inhibitors - pharmacokinetics ; Phosphodiesterase Inhibitors - therapeutic use ; Phosphoric Diester Hydrolases - metabolism ; Schizophrenia ; Schizophrenia - drug therapy ; Schizophrenia - enzymology ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry letters, 2012-09, Vol.22 (17), p.5595-5599</ispartof><rights>2012 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2012 Elsevier Ltd. 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Drug treatments</subject><subject>Phosphodiesterase</subject><subject>Phosphodiesterase Inhibitors - chemistry</subject><subject>Phosphodiesterase Inhibitors - pharmacokinetics</subject><subject>Phosphodiesterase Inhibitors - therapeutic use</subject><subject>Phosphoric Diester Hydrolases - metabolism</subject><subject>Schizophrenia</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenia - enzymology</subject><subject>Structure-Activity Relationship</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNqNkT2P1DAQhi0E4paDP0CB3CBRkOCvxI5EczqOD-kEFFfQWY4zUbxy4sX2LuR-PV7tAh2immKedzQzD0LPKakpoe2bbd3P1teMUFYTWRMiH6ANFa2ouCDNQ7QhXUsq1YlvF-hJSltCqCBCPEYXjClBBW83KH8OB_CYVTPkKfxcjV39tA7R3IcFEjYJ70KGJb_GCTzY7A6Av767oeQKu2VyvcshJvzD5QmbY9fltTSwWdxsPJ7DAD7hMOJkJ3cfdlOExZmn6NFofIJn53qJ7t7f3F1_rG6_fPh0fXVbWUG7XHHopGwI6UzPDW16ztnIGO-pYNIqM4qWSmOU7Ww3csUlEMVVL0UzKAVjzy_Rq9PYXQzf95Cynl2y4L1ZIOyTpoSrtvyLNf-DioY2SsiCshNqY0gpwqh3sRwb1wLpoxe91Ucv-uhFE6mLlxJ6cZ6_72cY_kR-iyjAyzNgkjV-jGaxLv3l2qKUK1K4tyeu_BUODqJO1sFiYXCx6NFDcP_a4xcc36vO</recordid><startdate>20120901</startdate><enddate>20120901</enddate><creator>Cutshall, Neil S.</creator><creator>Onrust, Rene</creator><creator>Rohde, Alex</creator><creator>Gragerov, Sasha</creator><creator>Hamilton, Lauren</creator><creator>Harbol, Kevin</creator><creator>Shen, Hui-Rong</creator><creator>McKee, Shawn</creator><creator>Zuta, Charles</creator><creator>Gragerova, Galina</creator><creator>Florio, Vince</creator><creator>Wheeler, Thomas N.</creator><creator>Gage, Jennifer L.</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>7X8</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20120901</creationdate><title>Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia</title><author>Cutshall, Neil S. ; Onrust, Rene ; Rohde, Alex ; Gragerov, Sasha ; Hamilton, Lauren ; Harbol, Kevin ; Shen, Hui-Rong ; McKee, Shawn ; Zuta, Charles ; Gragerova, Galina ; Florio, Vince ; Wheeler, Thomas N. ; Gage, Jennifer L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-3e9775009ab3a15b332f223b1427c8af4617aa8c9c9f3837e0838b745d88efb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antipsychotic Agents - chemistry</topic><topic>Antipsychotic Agents - pharmacokinetics</topic><topic>Antipsychotic Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cognitive</topic><topic>Enzyme inhibitor</topic><topic>Hydrazide</topic><topic>Hydrazone</topic><topic>Hydrazones - chemistry</topic><topic>Hydrazones - pharmacokinetics</topic><topic>Hydrazones - therapeutic use</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>PDE</topic><topic>PDE10</topic><topic>PDE10A</topic><topic>Pharmacology. 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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2012-09, Vol.22 (17), p.5595-5599 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | Elsevier |
| subjects | Animals Antipsychotic Agents - chemistry Antipsychotic Agents - pharmacokinetics Antipsychotic Agents - therapeutic use Biological and medical sciences Cognitive Enzyme inhibitor Hydrazide Hydrazone Hydrazones - chemistry Hydrazones - pharmacokinetics Hydrazones - therapeutic use Medical sciences Mice PDE PDE10 PDE10A Pharmacology. Drug treatments Phosphodiesterase Phosphodiesterase Inhibitors - chemistry Phosphodiesterase Inhibitors - pharmacokinetics Phosphodiesterase Inhibitors - therapeutic use Phosphoric Diester Hydrolases - metabolism Schizophrenia Schizophrenia - drug therapy Schizophrenia - enzymology Structure-Activity Relationship |
| title | Novel 2-methoxyacylhydrazones as potent, selective PDE10A inhibitors with activity in animal models of schizophrenia |
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