Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.
A series of thiophene PLK1 inhibitors was optimized for increased solubility and reduced protein binding through the appendage of basic amine functionality. Interesting selectivity between PLK1 and PLK3 was also obtained through these modifications.
Emmitte
Kyle A
KA
Five Moore Drive, Research Triangle Park, NC 27709, GlaxoSmithKline, USA.
Adjabeng
George M
GM
Adjebang
George M
GM
Andrews
C Webb
CW
Alberti
Jennifer G Badiang
JG
Bambal
Ramesh
R
Chamberlain
Stanley D
SD
Davis-Ward
Ronda G
RG
Dickson
Hamilton D
HD
Hassler
Daniel F
DF
Hornberger
Keith R
KR
Jackson
Jeffrey R
JR
Kuntz
Kevin W
KW
Lansing
Timothy J
TJ
Mook
Robert A
RA
Nailor
Kristen E
KE
Pobanz
Mark A
MA
Smith
Stephon C
SC
Sung
Chiu-Mei
CM
Cheung
Mui
M
D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008938:Mitosis; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012995:Solubility; D013876:Thiophenes / Q000737:chemistry*; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; D000097868:Polo-like Kinases
D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D013876:Thiophenes; D025521:Tumor Suppressor Proteins; D000097869:Polo-Like Kinase 1; C486256:PLK3 protein, human; D000097868:Polo-like Kinases