SrasV1, Hal, Checkpoint, bibRecord, 000045

Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles

Identifieur interne : 000045 ( Hal/Checkpoint ); précédent : 000044; suivant : 000046

Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles

Auteurs : Dominik Dolles [Allemagne] ; Matthias Hoffmann [Allemagne] ; Sandra Gunesch [Allemagne] ; Oliviero Marinelli [Italie] ; Jan Möller [Allemagne] ; Giorgio Santoni [Italie] ; Arnaud Chatonnet [France] ; Martin J. Lohse [Allemagne] ; Hans-Joachim Wittmann [Allemagne] ; Andrea Strasser [Allemagne] ; Massimo Nabissi [Italie] ; Tangui Maurice [France] ; Michael Decker [Allemagne]

Source :

Journal of Medicinal Chemistry [ 0022-2623 ] ; 2018.

RBID : Hal:hal-01837661

Abstract

The enzyme butyrylcholinesterase (BChE) and the human cannabinoid receptor 2 (hCB2R) represent promisingtargets for pharmacotherapy in the later stages of Alzheimer’s disease. We merged pharmacophores for both targets into small benzimidazole-based molecules, investigated SARs, and identified several dual-acting ligands with a balanced affinity/inhibitory activity and an excellent selectivity over both hCB1R and hAChE. A homology model for the hCB2R was developed based on the hCB1R crystal structure and used for molecular dynamics studies to investigate binding modes. In vitro studies proved hCB2R agonism. Unwanted μ-opioid receptor affinitycould be designed out. One well-balanced dual-acting and selective hBChE inhibitor/hCB2R agonist showed superior in vivo activity over the lead CB2 agonist with regards to cognition improvement. The data shows the possibility to combine a small molecule with selective and balanced GPCR-activity/enzyme inhibition and in vivo activity for the therapy of AD and may help to rationalize the development of other dual-acting ligands.

Url:

https://hal.archives-ouvertes.fr/hal-01837661

DOI: 10.1021/acs.jmedchem.7b01760

Links toward previous steps (curation, corpus...)

to stream Hal, to step Corpus: 000149
to stream Hal, to step Curation: 000149

Links to Exploration step

Hal:hal-01837661

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles</title>
<author><name sortKey="Dolles, Dominik" sort="Dolles, Dominik" uniqKey="Dolles D" first="Dominik" last="Dolles">Dominik Dolles</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Hoffmann, Matthias" sort="Hoffmann, Matthias" uniqKey="Hoffmann M" first="Matthias" last="Hoffmann">Matthias Hoffmann</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Gunesch, Sandra" sort="Gunesch, Sandra" uniqKey="Gunesch S" first="Sandra" last="Gunesch">Sandra Gunesch</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Marinelli, Oliviero" sort="Marinelli, Oliviero" uniqKey="Marinelli O" first="Oliviero" last="Marinelli">Oliviero Marinelli</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539026" status="INCOMING">          <orgName>School of Pharmacy, Department of Experimental Medicine</orgName>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-473150" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-473150" type="direct"><org type="institution" xml:id="struct-473150" status="VALID">          <orgName>University of Camerino</orgName>
          <date type="start">2016-11-24</date>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Moller, Jan" sort="Moller, Jan" uniqKey="Moller J" first="Jan" last="Möller">Jan Möller</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539027" status="INCOMING">          <orgName>Institute of Pharmacology and Toxicology</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Santoni, Giorgio" sort="Santoni, Giorgio" uniqKey="Santoni G" first="Giorgio" last="Santoni">Giorgio Santoni</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539026" status="INCOMING">          <orgName>School of Pharmacy, Department of Experimental Medicine</orgName>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-473150" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-473150" type="direct"><org type="institution" xml:id="struct-473150" status="VALID">          <orgName>University of Camerino</orgName>
          <date type="start">2016-11-24</date>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Chatonnet, Arnaud" sort="Chatonnet, Arnaud" uniqKey="Chatonnet A" first="Arnaud" last="Chatonnet">Arnaud Chatonnet</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-206262" status="OLD">          <idno type="RNSR">199917397U</idno>
          <orgName>Dynamique Musculaire et Métabolisme</orgName>
          <orgName type="acronym">DMEM</orgName>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>INRA 2 place Viala 34060 Montpellier Cedex 1</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www6.montpellier.inra.fr/dmem/</ref>
          </desc>
          <listRelation>            <relation name="UMR 0866" active="#struct-410122" type="direct"></relation>
            <relation active="#struct-92114" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle name="UMR 0866" active="#struct-410122" type="direct"><org type="institution" xml:id="struct-410122" status="VALID">          <idno type="ISNI">0000000120970141</idno>
          <orgName>Université de Montpellier</orgName>
          <orgName type="acronym">UM</orgName>
          <desc>            <address>              <addrLine>163 rue Auguste Broussonnet - 34090 Montpellier</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.umontpellier.fr/</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-92114" type="direct"><org type="institution" xml:id="struct-92114" status="OLD">          <orgName>Institut National de la Recherche Agronomique</orgName>
          <orgName type="acronym">INRA</orgName>
          <date type="start">1946-05-18</date>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <country key="FR"></country>
            </address>
            <ref type="url">http://www.inra.fr</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Lohse, Martin J" sort="Lohse, Martin J" uniqKey="Lohse M" first="Martin J." last="Lohse">Martin J. Lohse</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539027" status="INCOMING">          <orgName>Institute of Pharmacology and Toxicology</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Wittmann, Hans Joachim" sort="Wittmann, Hans Joachim" uniqKey="Wittmann H" first="Hans-Joachim" last="Wittmann">Hans-Joachim Wittmann</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539028" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry II, Institute of Pharmacy</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-303027" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-303027" type="direct"><org type="institution" xml:id="struct-303027" status="VALID">          <orgName>Universität Regensburg</orgName>
          <orgName type="acronym">UR</orgName>
          <date type="start">2016-10-17</date>
          <desc>            <address>              <addrLine>Universitätsstraße 31, 93053 Regensburg</addrLine>
              <country key="DE"></country>
            </address>
            <ref type="url">http://www.uni-regensburg.de</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Strasser, Andrea" sort="Strasser, Andrea" uniqKey="Strasser A" first="Andrea" last="Strasser">Andrea Strasser</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539028" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry II, Institute of Pharmacy</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-303027" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-303027" type="direct"><org type="institution" xml:id="struct-303027" status="VALID">          <orgName>Universität Regensburg</orgName>
          <orgName type="acronym">UR</orgName>
          <date type="start">2016-10-17</date>
          <desc>            <address>              <addrLine>Universitätsstraße 31, 93053 Regensburg</addrLine>
              <country key="DE"></country>
            </address>
            <ref type="url">http://www.uni-regensburg.de</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Nabissi, Massimo" sort="Nabissi, Massimo" uniqKey="Nabissi M" first="Massimo" last="Nabissi">Massimo Nabissi</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539026" status="INCOMING">          <orgName>School of Pharmacy, Department of Experimental Medicine</orgName>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-473150" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-473150" type="direct"><org type="institution" xml:id="struct-473150" status="VALID">          <orgName>University of Camerino</orgName>
          <date type="start">2016-11-24</date>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Maurice, Tangui" sort="Maurice, Tangui" uniqKey="Maurice T" first="Tangui" last="Maurice">Tangui Maurice</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-3068" status="VALID">          <idno type="RNSR">200716389N</idno>
          <orgName>Mécanismes moléculaires dans les démences neurodégénératives</orgName>
          <orgName type="acronym">MMDN</orgName>
          <desc>            <address>              <addrLine>U1198 - Université de Montpellier, Place Eugène Bataillon 34095 Montpellier Cedex 5</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">https://mmdn.umontpellier.fr/fr/</ref>
          </desc>
          <listRelation>            <relation name="U1198" active="#struct-303623" type="direct"></relation>
            <relation active="#struct-92690" type="direct"></relation>
            <relation name="UMR_S 1198" active="#struct-410122" type="direct"></relation>
            <relation active="#struct-110691" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle name="U1198" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID">          <idno type="IdRef">026388278</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>            <address>              <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-92690" type="direct"><org type="institution" xml:id="struct-92690" status="OLD">          <orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
          <orgName type="acronym">UM2</orgName>
          <date type="end">2014-12-31</date>
          <desc>            <address>              <addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.univ-montp2.fr/</ref>
          </desc>
        </org>
</tutelle>
<tutelle name="UMR_S 1198" active="#struct-410122" type="direct"><org type="institution" xml:id="struct-410122" status="VALID">          <idno type="ISNI">0000000120970141</idno>
          <orgName>Université de Montpellier</orgName>
          <orgName type="acronym">UM</orgName>
          <desc>            <address>              <addrLine>163 rue Auguste Broussonnet - 34090 Montpellier</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.umontpellier.fr/</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-110691" type="direct"><org type="institution" xml:id="struct-110691" status="VALID">          <orgName>École pratique des hautes études</orgName>
          <orgName type="acronym">EPHE</orgName>
          <desc>            <address>              <addrLine>4-14 Rue Ferrus, 75014 Paris</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.ephe.fr</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Decker, Michael" sort="Decker, Michael" uniqKey="Decker M" first="Michael" last="Decker">Michael Decker</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">HAL</idno>
<idno type="RBID">Hal:hal-01837661</idno>
<idno type="halId">hal-01837661</idno>
<idno type="halUri">https://hal.archives-ouvertes.fr/hal-01837661</idno>
<idno type="url">https://hal.archives-ouvertes.fr/hal-01837661</idno>
<idno type="doi">10.1021/acs.jmedchem.7b01760</idno>
<date when="2018">2018</date>
<idno type="wicri:Area/Hal/Corpus">000149</idno>
<idno type="wicri:Area/Hal/Curation">000149</idno>
<idno type="wicri:Area/Hal/Checkpoint">000045</idno>
<idno type="wicri:explorRef" wicri:stream="Hal" wicri:step="Checkpoint">000045</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles</title>
<author><name sortKey="Dolles, Dominik" sort="Dolles, Dominik" uniqKey="Dolles D" first="Dominik" last="Dolles">Dominik Dolles</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Hoffmann, Matthias" sort="Hoffmann, Matthias" uniqKey="Hoffmann M" first="Matthias" last="Hoffmann">Matthias Hoffmann</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Gunesch, Sandra" sort="Gunesch, Sandra" uniqKey="Gunesch S" first="Sandra" last="Gunesch">Sandra Gunesch</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Marinelli, Oliviero" sort="Marinelli, Oliviero" uniqKey="Marinelli O" first="Oliviero" last="Marinelli">Oliviero Marinelli</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539026" status="INCOMING">          <orgName>School of Pharmacy, Department of Experimental Medicine</orgName>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-473150" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-473150" type="direct"><org type="institution" xml:id="struct-473150" status="VALID">          <orgName>University of Camerino</orgName>
          <date type="start">2016-11-24</date>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Moller, Jan" sort="Moller, Jan" uniqKey="Moller J" first="Jan" last="Möller">Jan Möller</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539027" status="INCOMING">          <orgName>Institute of Pharmacology and Toxicology</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Santoni, Giorgio" sort="Santoni, Giorgio" uniqKey="Santoni G" first="Giorgio" last="Santoni">Giorgio Santoni</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539026" status="INCOMING">          <orgName>School of Pharmacy, Department of Experimental Medicine</orgName>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-473150" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-473150" type="direct"><org type="institution" xml:id="struct-473150" status="VALID">          <orgName>University of Camerino</orgName>
          <date type="start">2016-11-24</date>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Chatonnet, Arnaud" sort="Chatonnet, Arnaud" uniqKey="Chatonnet A" first="Arnaud" last="Chatonnet">Arnaud Chatonnet</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-206262" status="OLD">          <idno type="RNSR">199917397U</idno>
          <orgName>Dynamique Musculaire et Métabolisme</orgName>
          <orgName type="acronym">DMEM</orgName>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>INRA 2 place Viala 34060 Montpellier Cedex 1</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www6.montpellier.inra.fr/dmem/</ref>
          </desc>
          <listRelation>            <relation name="UMR 0866" active="#struct-410122" type="direct"></relation>
            <relation active="#struct-92114" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle name="UMR 0866" active="#struct-410122" type="direct"><org type="institution" xml:id="struct-410122" status="VALID">          <idno type="ISNI">0000000120970141</idno>
          <orgName>Université de Montpellier</orgName>
          <orgName type="acronym">UM</orgName>
          <desc>            <address>              <addrLine>163 rue Auguste Broussonnet - 34090 Montpellier</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.umontpellier.fr/</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-92114" type="direct"><org type="institution" xml:id="struct-92114" status="OLD">          <orgName>Institut National de la Recherche Agronomique</orgName>
          <orgName type="acronym">INRA</orgName>
          <date type="start">1946-05-18</date>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <country key="FR"></country>
            </address>
            <ref type="url">http://www.inra.fr</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Lohse, Martin J" sort="Lohse, Martin J" uniqKey="Lohse M" first="Martin J." last="Lohse">Martin J. Lohse</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539027" status="INCOMING">          <orgName>Institute of Pharmacology and Toxicology</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Wittmann, Hans Joachim" sort="Wittmann, Hans Joachim" uniqKey="Wittmann H" first="Hans-Joachim" last="Wittmann">Hans-Joachim Wittmann</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539028" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry II, Institute of Pharmacy</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-303027" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-303027" type="direct"><org type="institution" xml:id="struct-303027" status="VALID">          <orgName>Universität Regensburg</orgName>
          <orgName type="acronym">UR</orgName>
          <date type="start">2016-10-17</date>
          <desc>            <address>              <addrLine>Universitätsstraße 31, 93053 Regensburg</addrLine>
              <country key="DE"></country>
            </address>
            <ref type="url">http://www.uni-regensburg.de</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Strasser, Andrea" sort="Strasser, Andrea" uniqKey="Strasser A" first="Andrea" last="Strasser">Andrea Strasser</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539028" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry II, Institute of Pharmacy</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-303027" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-303027" type="direct"><org type="institution" xml:id="struct-303027" status="VALID">          <orgName>Universität Regensburg</orgName>
          <orgName type="acronym">UR</orgName>
          <date type="start">2016-10-17</date>
          <desc>            <address>              <addrLine>Universitätsstraße 31, 93053 Regensburg</addrLine>
              <country key="DE"></country>
            </address>
            <ref type="url">http://www.uni-regensburg.de</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
<author><name sortKey="Nabissi, Massimo" sort="Nabissi, Massimo" uniqKey="Nabissi M" first="Massimo" last="Nabissi">Massimo Nabissi</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539026" status="INCOMING">          <orgName>School of Pharmacy, Department of Experimental Medicine</orgName>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-473150" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-473150" type="direct"><org type="institution" xml:id="struct-473150" status="VALID">          <orgName>University of Camerino</orgName>
          <date type="start">2016-11-24</date>
          <desc>            <address>              <country key="IT"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Italie</country>
</affiliation>
</author>
<author><name sortKey="Maurice, Tangui" sort="Maurice, Tangui" uniqKey="Maurice T" first="Tangui" last="Maurice">Tangui Maurice</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-3068" status="VALID">          <idno type="RNSR">200716389N</idno>
          <orgName>Mécanismes moléculaires dans les démences neurodégénératives</orgName>
          <orgName type="acronym">MMDN</orgName>
          <desc>            <address>              <addrLine>U1198 - Université de Montpellier, Place Eugène Bataillon 34095 Montpellier Cedex 5</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">https://mmdn.umontpellier.fr/fr/</ref>
          </desc>
          <listRelation>            <relation name="U1198" active="#struct-303623" type="direct"></relation>
            <relation active="#struct-92690" type="direct"></relation>
            <relation name="UMR_S 1198" active="#struct-410122" type="direct"></relation>
            <relation active="#struct-110691" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle name="U1198" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID">          <idno type="IdRef">026388278</idno>
          <orgName>Institut National de la Santé et de la Recherche Médicale</orgName>
          <orgName type="acronym">INSERM</orgName>
          <desc>            <address>              <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.inserm.fr</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-92690" type="direct"><org type="institution" xml:id="struct-92690" status="OLD">          <orgName>Université Montpellier 2 - Sciences et Techniques</orgName>
          <orgName type="acronym">UM2</orgName>
          <date type="end">2014-12-31</date>
          <desc>            <address>              <addrLine>Place Eugène Bataillon - 34095 Montpellier cedex 5</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.univ-montp2.fr/</ref>
          </desc>
        </org>
</tutelle>
<tutelle name="UMR_S 1198" active="#struct-410122" type="direct"><org type="institution" xml:id="struct-410122" status="VALID">          <idno type="ISNI">0000000120970141</idno>
          <orgName>Université de Montpellier</orgName>
          <orgName type="acronym">UM</orgName>
          <desc>            <address>              <addrLine>163 rue Auguste Broussonnet - 34090 Montpellier</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.umontpellier.fr/</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-110691" type="direct"><org type="institution" xml:id="struct-110691" status="VALID">          <orgName>École pratique des hautes études</orgName>
          <orgName type="acronym">EPHE</orgName>
          <desc>            <address>              <addrLine>4-14 Rue Ferrus, 75014 Paris</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.ephe.fr</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Decker, Michael" sort="Decker, Michael" uniqKey="Decker M" first="Michael" last="Decker">Michael Decker</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-539025" status="INCOMING">          <orgName>Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry </orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-539024" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-539024" type="direct"><org type="institution" xml:id="struct-539024" status="INCOMING">          <orgName>Julius Maximilian University</orgName>
          <desc>            <address>              <country key="DE"></country>
            </address>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Allemagne</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1021/acs.jmedchem.7b01760</idno>
<series><title level="j">Journal of Medicinal Chemistry</title>
<idno type="ISSN">0022-2623</idno>
<imprint><date type="datePub">2018</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">              <p>The enzyme butyrylcholinesterase (BChE) and the human cannabinoid receptor 2 (hCB2R) represent promisingtargets for pharmacotherapy in the later stages of Alzheimer’s disease. We merged pharmacophores for both targets into small benzimidazole-based molecules, investigated SARs, and identified several dual-acting ligands with a balanced affinity/inhibitory activity and an excellent selectivity over both hCB1R and hAChE. A homology model for the hCB2R was developed based on the hCB1R crystal structure and used for molecular dynamics studies to investigate binding modes. In vitro studies proved hCB2R agonism. Unwanted μ-opioid receptor affinitycould be designed out. One well-balanced dual-acting and selective hBChE inhibitor/hCB2R agonist showed superior in vivo activity over the lead CB2 agonist with regards to cognition improvement. The data shows the possibility to combine a small molecule with selective and balanced GPCR-activity/enzyme inhibition and in vivo activity for the therapy of AD and may help to rationalize the development of other dual-acting ligands.</p>
            </div>
</front>
</TEI>
<hal api="V3">          <titleStmt>            <title xml:lang="en">Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles</title>
            <author role="aut">              <persName>                <forename type="first">Dominik</forename>
                <surname>Dolles</surname>
              </persName>
              <idno type="halauthorid">11241719</idno>
              <affiliation ref="#struct-539025"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Matthias</forename>
                <surname>Hoffmann</surname>
              </persName>
              <idno type="halauthorid">485529</idno>
              <affiliation ref="#struct-539025"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Sandra</forename>
                <surname>Gunesch</surname>
              </persName>
              <idno type="halauthorid">11241720</idno>
              <affiliation ref="#struct-539025"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Oliviero</forename>
                <surname>Marinelli</surname>
              </persName>
              <idno type="halauthorid">11241721</idno>
              <affiliation ref="#struct-539026"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Jan</forename>
                <surname>Möller</surname>
              </persName>
              <idno type="halauthorid">11241722</idno>
              <affiliation ref="#struct-539027"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Giorgio</forename>
                <surname>Santoni</surname>
              </persName>
              <idno type="halauthorid">11241723</idno>
              <affiliation ref="#struct-539026"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Arnaud</forename>
                <surname>Chatonnet</surname>
              </persName>
              <email type="md5">6b15f2f43b384683aea44267aff7f6a3</email>
              <email type="domain">inra.fr</email>
              <idno type="halauthorid">1633671</idno>
              <affiliation ref="#struct-206262"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Martin J.</forename>
                <surname>Lohse</surname>
              </persName>
              <idno type="halauthorid">715442</idno>
              <affiliation ref="#struct-539027"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Hans-Joachim</forename>
                <surname>Wittmann</surname>
              </persName>
              <idno type="halauthorid">575068</idno>
              <affiliation ref="#struct-539028"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Andrea</forename>
                <surname>Strasser</surname>
              </persName>
              <idno type="halauthorid">642133</idno>
              <affiliation ref="#struct-539028"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Massimo</forename>
                <surname>Nabissi</surname>
              </persName>
              <idno type="halauthorid">11241724</idno>
              <affiliation ref="#struct-539026"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Tangui</forename>
                <surname>Maurice</surname>
              </persName>
              <email type="md5">1930fe38c793005f6531202464f7ad79</email>
              <email type="domain">umontpellier.fr</email>
              <idno type="idhal" notation="string">tangui-maurice</idno>
              <idno type="idhal" notation="numeric">179841</idno>
              <idno type="halauthorid">414464</idno>
              <idno type="ORCID">https://orcid.org/0000-0002-4074-6793</idno>
              <affiliation ref="#struct-3068"></affiliation>
            </author>
            <author role="aut">              <persName>                <forename type="first">Michael</forename>
                <surname>Decker</surname>
              </persName>
              <idno type="halauthorid">11241725</idno>
              <affiliation ref="#struct-539025"></affiliation>
            </author>
            <editor role="depositor">              <persName>                <forename>Archive Ouverte</forename>
                <surname>ProdInra</surname>
              </persName>
              <email type="md5">32842db32e322d32df54caa7e75d71a2</email>
              <email type="domain">inrae.fr</email>
            </editor>
          </titleStmt>
          <editionStmt>            <edition n="v1" type="current">              <date type="whenSubmitted">2018-07-12 20:32:11</date>
              <date type="whenModified">2020-03-17 02:27:17</date>
              <date type="whenReleased">2018-07-12 20:32:11</date>
              <date type="whenProduced">2018</date>
            </edition>
            <respStmt>              <resp>contributor</resp>
              <name key="132775">                <persName>                  <forename>Archive Ouverte</forename>
                  <surname>ProdInra</surname>
                </persName>
                <email type="md5">32842db32e322d32df54caa7e75d71a2</email>
                <email type="domain">inrae.fr</email>
              </name>
            </respStmt>
          </editionStmt>
          <publicationStmt>            <distributor>CCSD</distributor>
            <idno type="halId">hal-01837661</idno>
            <idno type="halUri">https://hal.archives-ouvertes.fr/hal-01837661</idno>
            <idno type="halBibtex">dolles:hal-01837661</idno>
            <idno type="halRefHtml">Journal of Medicinal Chemistry, American Chemical Society, 2018, 18 p. ⟨10.1021/acs.jmedchem.7b01760⟩</idno>
            <idno type="halRef">Journal of Medicinal Chemistry, American Chemical Society, 2018, 18 p. ⟨10.1021/acs.jmedchem.7b01760⟩</idno>
          </publicationStmt>
          <seriesStmt>            <idno type="stamp" n="INRA">INRA - Institut national de la recherche agronomique</idno>
            <idno type="stamp" n="EPHE">Ecole Pratique des Hautes Etudes</idno>
            <idno type="stamp" n="BS">Biologie-Santé</idno>
            <idno type="stamp" n="UNIV-MONTPELLIER">Université de Montpellier</idno>
            <idno type="stamp" n="DMEM" corresp="UNIV-MONTPELLIER">Dynamique Musculaire Et Métabolisme</idno>
            <idno type="stamp" n="MMDN">Mécanismes moléculaires dans les démences neurodégénératives</idno>
            <idno type="stamp" n="PSL">Paris Sciences et Lettres (PSL) Research University</idno>
            <idno type="stamp" n="TEST-DEV">TEST-DEV</idno>
            <idno type="stamp" n="INRAE">Institut National de Recherche en Agriculture, Alimentation et Environnement</idno>
          </seriesStmt>
          <notesStmt>            <note type="audience" n="1">Not set</note>
            <note type="popular" n="0">No</note>
            <note type="peer" n="1">Yes</note>
          </notesStmt>
          <sourceDesc>            <biblStruct>              <analytic>                <title xml:lang="en">Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles</title>
                <author role="aut">                  <persName>                    <forename type="first">Dominik</forename>
                    <surname>Dolles</surname>
                  </persName>
                  <idno type="halauthorid">11241719</idno>
                  <affiliation ref="#struct-539025"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Matthias</forename>
                    <surname>Hoffmann</surname>
                  </persName>
                  <idno type="halauthorid">485529</idno>
                  <affiliation ref="#struct-539025"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Sandra</forename>
                    <surname>Gunesch</surname>
                  </persName>
                  <idno type="halauthorid">11241720</idno>
                  <affiliation ref="#struct-539025"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Oliviero</forename>
                    <surname>Marinelli</surname>
                  </persName>
                  <idno type="halauthorid">11241721</idno>
                  <affiliation ref="#struct-539026"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Jan</forename>
                    <surname>Möller</surname>
                  </persName>
                  <idno type="halauthorid">11241722</idno>
                  <affiliation ref="#struct-539027"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Giorgio</forename>
                    <surname>Santoni</surname>
                  </persName>
                  <idno type="halauthorid">11241723</idno>
                  <affiliation ref="#struct-539026"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Arnaud</forename>
                    <surname>Chatonnet</surname>
                  </persName>
                  <email type="md5">6b15f2f43b384683aea44267aff7f6a3</email>
                  <email type="domain">inra.fr</email>
                  <idno type="halauthorid">1633671</idno>
                  <affiliation ref="#struct-206262"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Martin J.</forename>
                    <surname>Lohse</surname>
                  </persName>
                  <idno type="halauthorid">715442</idno>
                  <affiliation ref="#struct-539027"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Hans-Joachim</forename>
                    <surname>Wittmann</surname>
                  </persName>
                  <idno type="halauthorid">575068</idno>
                  <affiliation ref="#struct-539028"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Andrea</forename>
                    <surname>Strasser</surname>
                  </persName>
                  <idno type="halauthorid">642133</idno>
                  <affiliation ref="#struct-539028"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Massimo</forename>
                    <surname>Nabissi</surname>
                  </persName>
                  <idno type="halauthorid">11241724</idno>
                  <affiliation ref="#struct-539026"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Tangui</forename>
                    <surname>Maurice</surname>
                  </persName>
                  <email type="md5">1930fe38c793005f6531202464f7ad79</email>
                  <email type="domain">umontpellier.fr</email>
                  <idno type="idhal" notation="string">tangui-maurice</idno>
                  <idno type="idhal" notation="numeric">179841</idno>
                  <idno type="halauthorid">414464</idno>
                  <idno type="ORCID">https://orcid.org/0000-0002-4074-6793</idno>
                  <affiliation ref="#struct-3068"></affiliation>
                </author>
                <author role="aut">                  <persName>                    <forename type="first">Michael</forename>
                    <surname>Decker</surname>
                  </persName>
                  <idno type="halauthorid">11241725</idno>
                  <affiliation ref="#struct-539025"></affiliation>
                </author>
              </analytic>
              <monogr>                <idno type="halJournalId" status="VALID">15785</idno>
                <idno type="issn">0022-2623</idno>
                <idno type="eissn">1520-4804</idno>
                <title level="j">Journal of Medicinal Chemistry</title>
                <imprint>                  <publisher>American Chemical Society</publisher>
                  <biblScope unit="pp">18 p.</biblScope>
                  <date type="datePub">2018</date>
                </imprint>
              </monogr>
              <idno type="doi">10.1021/acs.jmedchem.7b01760</idno>
              <idno type="prodinra">421333</idno>
            </biblStruct>
          </sourceDesc>
          <profileDesc>            <langUsage>              <language ident="en">English</language>
            </langUsage>
            <textClass>              <classCode scheme="halDomain" n="sdv">Life Sciences [q-bio]</classCode>
              <classCode scheme="halTypology" n="ART">Journal articles</classCode>
            </textClass>
            <abstract xml:lang="en">              <p>The enzyme butyrylcholinesterase (BChE) and the human cannabinoid receptor 2 (hCB2R) represent promisingtargets for pharmacotherapy in the later stages of Alzheimer’s disease. We merged pharmacophores for both targets into small benzimidazole-based molecules, investigated SARs, and identified several dual-acting ligands with a balanced affinity/inhibitory activity and an excellent selectivity over both hCB1R and hAChE. A homology model for the hCB2R was developed based on the hCB1R crystal structure and used for molecular dynamics studies to investigate binding modes. In vitro studies proved hCB2R agonism. Unwanted μ-opioid receptor affinitycould be designed out. One well-balanced dual-acting and selective hBChE inhibitor/hCB2R agonist showed superior in vivo activity over the lead CB2 agonist with regards to cognition improvement. The data shows the possibility to combine a small molecule with selective and balanced GPCR-activity/enzyme inhibition and in vivo activity for the therapy of AD and may help to rationalize the development of other dual-acting ligands.</p>
            </abstract>
          </profileDesc>
        </hal>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/Hal/Checkpoint

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000045 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Hal/Checkpoint/biblio.hfd -nk 000045 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Sante
   |area=    SrasV1
   |flux=    Hal
   |étape=   Checkpoint
   |type=    RBID
   |clé=     Hal:hal-01837661
   |texte=   Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles
}}

This area was generated with Dilib version V0.6.33.
Data generation: Tue Apr 28 14:49:16 2020. Site generation: Sat Mar 27 22:06:49 2021

	Serveur d'exploration SRAS
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.

Serveur d'exploration SRAS

Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles

Structure–activity relationships and computational investigations into the development of potent and balanced dual-acting butyrylcholinesterase inhibitors and human cannabinoid receptor 2 ligands with pro-cognitive in vivo profiles

Source :

Abstract

Links toward previous steps (curation, corpus...)

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri