Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors.
Identifieur interne : 001907 ( Main/Curation ); précédent : 001906; suivant : 001908Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors.
Auteurs : Jacques Le Roux [France] ; Caroline Leriche [France] ; Philippe Chamiot-Clerc [France] ; John Feutrill [Australie] ; Frank Halley [France] ; David Papin [France] ; Nathalie Derimay [France] ; Christelle Mugler [France] ; Claudine Grépin [France] ; Laurent Schio [France]Source :
- Bioorganic & medicinal chemistry letters [ 1464-3405 ] ; 2016.
Descripteurs français
- KwdFr :
- AMP cyclique (biosynthèse), Aminoquinoléines (), Humains, Inhibiteurs de la phosphodiestérase-4 (pharmacologie), Inhibiteurs de la phosphodiestérase-4 (synthèse chimique), Lignée cellulaire tumorale, Modèles moléculaires, Pyrazoles (pharmacologie), Pyrazoles (synthèse chimique), Pyrimidines (pharmacologie), Pyrimidines (synthèse chimique), Relation structure-activité, Sulfones (), Sulfones (pharmacologie), Sulfones (synthèse chimique).
- MESH :
- biosynthèse : AMP cyclique.
- pharmacologie : Inhibiteurs de la phosphodiestérase-4, Pyrazoles, Pyrimidines, Sulfones.
- synthèse chimique : Inhibiteurs de la phosphodiestérase-4, Pyrazoles, Pyrimidines, Sulfones.
- Aminoquinoléines, Humains, Lignée cellulaire tumorale, Modèles moléculaires, Relation structure-activité, Sulfones.
English descriptors
- KwdEn :
- Aminoquinolines (chemistry), Cell Line, Tumor, Cyclic AMP (biosynthesis), Humans, Models, Molecular, Phosphodiesterase 4 Inhibitors (chemical synthesis), Phosphodiesterase 4 Inhibitors (pharmacology), Pyrazoles (chemical synthesis), Pyrazoles (pharmacology), Pyrimidines (chemical synthesis), Pyrimidines (pharmacology), Structure-Activity Relationship, Sulfones (chemical synthesis), Sulfones (chemistry), Sulfones (pharmacology).
- MESH :
- chemical , biosynthesis : Cyclic AMP.
- chemical , chemical synthesis : Phosphodiesterase 4 Inhibitors, Pyrazoles, Pyrimidines, Sulfones.
- chemical , chemistry : Aminoquinolines, Sulfones.
- chemical , pharmacology : Phosphodiesterase 4 Inhibitors, Pyrazoles, Pyrimidines, Sulfones.
- Cell Line, Tumor, Humans, Models, Molecular, Structure-Activity Relationship.
Abstract
A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50=165nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50=0.7nM). Modeling studies based on the PDB structure 3GWT with compound 5 showed the expected overlay with the carboxamide, the aryl moiety and the sulfone. Cyclisation of the primary amide to the 5 position of the pyrazolo[1,5-a]pyrimidines scaffold afforded compounds 15 and 16 with 200-fold enhancement in activity and cellular potency.
DOI: 10.1016/j.bmcl.2015.11.093
PubMed: 26681511
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :002394
- to stream PubMed, to step Curation: Pour aller vers cette notice dans l'étape Curation :002348
- to stream PubMed, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :002348
- to stream Ncbi, to step Merge: Pour aller vers cette notice dans l'étape Curation :002E84
- to stream Ncbi, to step Curation: Pour aller vers cette notice dans l'étape Curation :002E84
- to stream Ncbi, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :002E84
- to stream Main, to step Merge: Pour aller vers cette notice dans l'étape Curation :001902
Links to Exploration step
pubmed:26681511Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors.</title>
<author><name sortKey="Le Roux, Jacques" sort="Le Roux, Jacques" uniqKey="Le Roux J" first="Jacques" last="Le Roux">Jacques Le Roux</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Leriche, Caroline" sort="Leriche, Caroline" uniqKey="Leriche C" first="Caroline" last="Leriche">Caroline Leriche</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris</wicri:regionArea>
<wicri:noRegion>75012 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chamiot Clerc, Philippe" sort="Chamiot Clerc, Philippe" uniqKey="Chamiot Clerc P" first="Philippe" last="Chamiot-Clerc">Philippe Chamiot-Clerc</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris</wicri:regionArea>
<wicri:noRegion>75012 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Feutrill, John" sort="Feutrill, John" uniqKey="Feutrill J" first="John" last="Feutrill">John Feutrill</name>
<affiliation wicri:level="1"><nlm:affiliation>SYN|thesis Med Chem, 399 Royal Parade, Parkville, VIC 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>SYN|thesis Med Chem, 399 Royal Parade, Parkville, VIC 3052</wicri:regionArea>
<wicri:noRegion>VIC 3052</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Halley, Frank" sort="Halley, Frank" uniqKey="Halley F" first="Frank" last="Halley">Frank Halley</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France. Electronic address: frank.halley@sanofi.com.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Papin, David" sort="Papin, David" uniqKey="Papin D" first="David" last="Papin">David Papin</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Derimay, Nathalie" sort="Derimay, Nathalie" uniqKey="Derimay N" first="Nathalie" last="Derimay">Nathalie Derimay</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg</wicri:regionArea>
<wicri:noRegion>67000 Strasbourg</wicri:noRegion>
<placeName><settlement type="city">Strasbourg</settlement>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Alsace (région administrative)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mugler, Christelle" sort="Mugler, Christelle" uniqKey="Mugler C" first="Christelle" last="Mugler">Christelle Mugler</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg</wicri:regionArea>
<wicri:noRegion>67000 Strasbourg</wicri:noRegion>
<placeName><settlement type="city">Strasbourg</settlement>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Alsace (région administrative)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grepin, Claudine" sort="Grepin, Claudine" uniqKey="Grepin C" first="Claudine" last="Grépin">Claudine Grépin</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris</wicri:regionArea>
<wicri:noRegion>75012 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schio, Laurent" sort="Schio, Laurent" uniqKey="Schio L" first="Laurent" last="Schio">Laurent Schio</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2016">2016</date>
<idno type="RBID">pubmed:26681511</idno>
<idno type="pmid">26681511</idno>
<idno type="doi">10.1016/j.bmcl.2015.11.093</idno>
<idno type="wicri:Area/PubMed/Corpus">002394</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002394</idno>
<idno type="wicri:Area/PubMed/Curation">002348</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">002348</idno>
<idno type="wicri:Area/PubMed/Checkpoint">002348</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">002348</idno>
<idno type="wicri:Area/Ncbi/Merge">002E84</idno>
<idno type="wicri:Area/Ncbi/Curation">002E84</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">002E84</idno>
<idno type="wicri:Area/Main/Merge">001902</idno>
<idno type="wicri:Area/Main/Curation">001907</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors.</title>
<author><name sortKey="Le Roux, Jacques" sort="Le Roux, Jacques" uniqKey="Le Roux J" first="Jacques" last="Le Roux">Jacques Le Roux</name>
<affiliation wicri:level="3"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Vitry-sur-Seine</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leriche, Caroline" sort="Leriche, Caroline" uniqKey="Leriche C" first="Caroline" last="Leriche">Caroline Leriche</name>
<affiliation wicri:level="3"><nlm:affiliation>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chamiot Clerc, Philippe" sort="Chamiot Clerc, Philippe" uniqKey="Chamiot Clerc P" first="Philippe" last="Chamiot-Clerc">Philippe Chamiot-Clerc</name>
<affiliation wicri:level="3"><nlm:affiliation>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris</wicri:regionArea>
<placeName><region type="region" nuts="2">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Feutrill, John" sort="Feutrill, John" uniqKey="Feutrill J" first="John" last="Feutrill">John Feutrill</name>
<affiliation wicri:level="1"><nlm:affiliation>SYN|thesis Med Chem, 399 Royal Parade, Parkville, VIC 3052, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>SYN|thesis Med Chem, 399 Royal Parade, Parkville, VIC 3052</wicri:regionArea>
<wicri:noRegion>VIC 3052</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Halley, Frank" sort="Halley, Frank" uniqKey="Halley F" first="Frank" last="Halley">Frank Halley</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France. Electronic address: frank.halley@sanofi.com.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Papin, David" sort="Papin, David" uniqKey="Papin D" first="David" last="Papin">David Papin</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Derimay, Nathalie" sort="Derimay, Nathalie" uniqKey="Derimay N" first="Nathalie" last="Derimay">Nathalie Derimay</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg</wicri:regionArea>
<wicri:noRegion>67000 Strasbourg</wicri:noRegion>
<placeName><settlement type="city">Strasbourg</settlement>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Alsace (région administrative)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mugler, Christelle" sort="Mugler, Christelle" uniqKey="Mugler C" first="Christelle" last="Mugler">Christelle Mugler</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Open innovation Access Plateform, 16 Rue d'Ankara, 67000 Strasbourg</wicri:regionArea>
<wicri:noRegion>67000 Strasbourg</wicri:noRegion>
<placeName><settlement type="city">Strasbourg</settlement>
<region type="region" nuts="2">Grand Est</region>
<region type="old region" nuts="2">Alsace (région administrative)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grepin, Claudine" sort="Grepin, Claudine" uniqKey="Grepin C" first="Claudine" last="Grépin">Claudine Grépin</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Ophthalmology, 17 Rue Moreau, 75012 Paris</wicri:regionArea>
<wicri:noRegion>75012 Paris</wicri:noRegion>
<placeName><settlement type="city">Paris</settlement>
<region type="région" nuts="2">Île-de-France</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schio, Laurent" sort="Schio, Laurent" uniqKey="Schio L" first="Laurent" last="Schio">Laurent Schio</name>
<affiliation wicri:level="1"><nlm:affiliation>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Sanofi Research Center, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine</wicri:regionArea>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
<wicri:noRegion>94400 Vitry-sur-Seine</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Bioorganic & medicinal chemistry letters</title>
<idno type="eISSN">1464-3405</idno>
<imprint><date when="2016" type="published">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aminoquinolines (chemistry)</term>
<term>Cell Line, Tumor</term>
<term>Cyclic AMP (biosynthesis)</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Phosphodiesterase 4 Inhibitors (chemical synthesis)</term>
<term>Phosphodiesterase 4 Inhibitors (pharmacology)</term>
<term>Pyrazoles (chemical synthesis)</term>
<term>Pyrazoles (pharmacology)</term>
<term>Pyrimidines (chemical synthesis)</term>
<term>Pyrimidines (pharmacology)</term>
<term>Structure-Activity Relationship</term>
<term>Sulfones (chemical synthesis)</term>
<term>Sulfones (chemistry)</term>
<term>Sulfones (pharmacology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP cyclique (biosynthèse)</term>
<term>Aminoquinoléines ()</term>
<term>Humains</term>
<term>Inhibiteurs de la phosphodiestérase-4 (pharmacologie)</term>
<term>Inhibiteurs de la phosphodiestérase-4 (synthèse chimique)</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles moléculaires</term>
<term>Pyrazoles (pharmacologie)</term>
<term>Pyrazoles (synthèse chimique)</term>
<term>Pyrimidines (pharmacologie)</term>
<term>Pyrimidines (synthèse chimique)</term>
<term>Relation structure-activité</term>
<term>Sulfones ()</term>
<term>Sulfones (pharmacologie)</term>
<term>Sulfones (synthèse chimique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Cyclic AMP</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Phosphodiesterase 4 Inhibitors</term>
<term>Pyrazoles</term>
<term>Pyrimidines</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Aminoquinolines</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Phosphodiesterase 4 Inhibitors</term>
<term>Pyrazoles</term>
<term>Pyrimidines</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>AMP cyclique</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Inhibiteurs de la phosphodiestérase-4</term>
<term>Pyrazoles</term>
<term>Pyrimidines</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Inhibiteurs de la phosphodiestérase-4</term>
<term>Pyrazoles</term>
<term>Pyrimidines</term>
<term>Sulfones</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Aminoquinoléines</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles moléculaires</term>
<term>Relation structure-activité</term>
<term>Sulfones</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A new series of pyrazolo[1,5-a]pyrimidines exemplified by compound 1, has been identified with moderate activity (IC50=165nM), following GSK256066 rescaffolding. Compound 1 optimization at positions 2, 3, 6 and 7 gave compound 10 with high in vitro activity (IC50=0.7nM). Modeling studies based on the PDB structure 3GWT with compound 5 showed the expected overlay with the carboxamide, the aryl moiety and the sulfone. Cyclisation of the primary amide to the 5 position of the pyrazolo[1,5-a]pyrimidines scaffold afforded compounds 15 and 16 with 200-fold enhancement in activity and cellular potency.</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Main/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001907 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Curation/biblio.hfd -nk 001907 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Asie |area= AustralieFrV1 |flux= Main |étape= Curation |type= RBID |clé= pubmed:26681511 |texte= Preparation and optimization of pyrazolo[1,5-a]pyrimidines as new potent PDE4 inhibitors. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Curation/RBID.i -Sk "pubmed:26681511" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Curation/biblio.hfd \ | NlmPubMed2Wicri -a AustralieFrV1
This area was generated with Dilib version V0.6.33. |