Discovery of novel sphingosine kinase-1 inhibitors. Part 2.
Building on our initial work, we have identified additional novel inhibitors of sphingosine kinase-1 (SK1). These new analogs address the shortcomings found in our previously reported compounds. Inhibitors 51 and 54 demonstrated oral bioavailability in a rat PK study.
Xiang
Yibin
Y
Department of Medicinal Chemistry, Drug and Biomaterial R&D, Genzyme Corporation, Waltham, MA 02451, USA. yibin.xiang@genzyme.com
Hirth
Bradford
B
Kane
John L
JL
Liao
Junkai
J
Noson
Kevin D
KD
Yee
Christopher
C
Asmussen
Gary
G
Fitzgerald
Maria
M
Klaus
Christine
C
Booker
Michael
M
D000818:Animals; D001547:Benzaldehydes / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008094:Lithium / Q000737:chemistry*; D008862:Microsomes, Liver / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D000099157:Sphingosine Kinase
D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D008094:Lithium; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase; C488327:4-cyanobenzaldehyde