Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors

Kopecky, David J.; Hao, Xiaolin; Chen, Yi; Fu, Jiasheng; Jiao, Xiaojin; Jaén, Juan C.; Cardozo, Mario; Liu, Jinsong; Wang, Zhong Lin; Walker, Nigel; Wesche, Holger; Li, Shyun; Farrelly, Ellyn; Xiao, Shou‐Hua; Kayser, Frank

doi:10.1016/j.bmcl.2008.10.092

Cited by 33 publications

(84 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[30]). The original numeration of [30] was retained for cross-reference. only aromatic fluorine compounds were studied in the current analysis, we can make no conclusions about the modulation properties of aliphatic fluorine.…”

Section: Discussionmentioning

confidence: 93%

“…Chemical structures and biological activities of non-fluorinated and fluorinated N 3 ,N 6 -diaryl-N 6 -(3,3-dimethyl-3-methoxypropyl)pyrazolo [3,4-d]pyrimidine-3,6-diamines 7 and 9 (left); docking of the corresponding 4-piperazin-1-yl derivative in the active site of ACK1 (right, adapted from Ref. [30]). The original numeration of [30] was retained for cross-reference.…”

Section: Discussionmentioning

confidence: 99%

“…Introduction of fluorine in the 4-postion of this dimethylphenyl group leads to a significant decrease in activity (almost 300 times). Again, like in the previous case, the rest of the molecule is tightly bound in the active site via a network of hydrogen bonds involving pyrimidine nitrogen and NH groups [30]. In this situation re-orientation of the molecule to avoid the undesirable proximity of the CF fragment to the hydrophobic pocket is not feasible since this re-orientation will result in disruption of the already energyoptimized hydrogen bond network.…”

Section: [ ( ) T D $ F I G ]mentioning

confidence: 95%

“…[ ( ) T D $ F I G ] Another interesting example of significant negative modulation of biological activity also probably involves unfavorable hydrophobic pocket interactions [30]. In this case the dimethyl-phenyl group of compound 7 is positioned in the vicinity of a hydrophobic pocket (Fig.…”

Section: [ ( ) T D $ F I G ]mentioning

confidence: 99%

See 3 more Smart Citations

Extreme modulation properties of aromatic fluorine

Gakh¹,

Burnett²

2011

Journal of Fluorine Chemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: [ ( ) T D $ F I G ]mentioning

confidence: 95%

Section: [ ( ) T D $ F I G ]mentioning

confidence: 99%

See 2 more Smart Citations

Extreme modulation properties of aromatic fluorine

Gakh¹,

Burnett²

2011

Journal of Fluorine Chemistry

View full text Add to dashboard Cite

“…et al 1992;Altmann, Staudacher et al 1999). A few examples of proteins expressed in insect cells that resulted in www.intechopen.com crystal structures are the transferase Ack1 (PDB:3EQP) (Kopecky, Hao et al 2008), a human hydrolase (PDB: 2PMS) (Senkovich, Cook et al 2007) and myosin VI (PDB:2BKI) (Menetrey, Bahloul et al 2005).…”

Section: Insect Cellsmentioning

confidence: 99%

Rational and Irrational Approaches to Convince a Protein to Crystallize

Abts¹,

Schwarz²,

Tschapek³

et al. 2012

Modern Aspects of Bulk Crystal and Thin Film Preparation

View full text Add to dashboard Cite

Ausgeprägte Methyleffekte in der Wirkstoff‐Forschung und der Bedarf an neuen C‐H‐Methylierungsreaktionen

2013

View full text Add to dashboard Cite

Die Methylgruppe gehört zu den häufigsten Kohlenstoffbausteinen in niedermolekularen Wirkstoffen. Dieser einfachste Alkylrest kommt in mehr als 67 % der 2011 meistverkauften Wirkstoffe vor und kann die biologischen und physikalischen Eigenschaften einer Verbindung in bedeutendem Maß modulieren. Den Schwerpunkt dieses Aufsatzes bildet der so genannte magische Methyleffekt auf das Bindungsvermögen, bei dem der scheinbar banale Wechsel von der C‐H‐ zur C‐Me‐Gruppe den IC50‐Wert eines potenziellen Wirkstoffs um mehr als das 100fache verbessert. Anschließend an diese Diskussion folgt ein Überblick über Fortschritte in der Synthesechemie, die eine direkte Methylierung von sp2‐ und sp3‐C‐H‐Bindungen ermöglichen. Wir hoffen, dass die hier besprochene Bedeutung der einfachen Methylgruppe für die Wirkstoff‐Forschung zu Berichten über neue und umfassende C‐H‐Methylierungsreaktionen anregt.

show abstract

Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors

Cited by 33 publications

References 12 publications

Extreme modulation properties of aromatic fluorine

Extreme modulation properties of aromatic fluorine

Rational and Irrational Approaches to Convince a Protein to Crystallize

Ausgeprägte Methyleffekte in der Wirkstoff‐Forschung und der Bedarf an neuen C‐H‐Methylierungsreaktionen

Contact Info

Product

Resources

About