Michael adducts – Synthons for a new class of 1,4-dispirocyclohexane derivatives

808-812A new class of 1,4-dispirocyclohexane derivatives have been prepared from 2,6-diaroyl-3,5-diarylcyclohexane-1,1,4,4-tetra­carboxylic acid tetramethyl ester

Sulfonyl acetic acids — Source for substituted 2-oxazolines

2456-2458A new class of 2-oxazolines have been prepared from N-(2-chloroethyl)sulfonamides by base promoted cyclization with NaH in THF. All the compounds are characterized by IR and 1H NMR spectra

Michael addition of active methylene compounds to <i style=""><img src='/image/spc_char/alpha.gif' border=0> ,</i><i style=""><img src='/image/spc_char/beta.gif' border=0></i>–unsaturated sulfones

2569-2574The Michael addition of dimethyl malonate and ethyl cyanoacetate to ,-unsaturated sulfones in the presence of Triton-B and K2CO3 is studied

Simultaneous CK2/TNIK/DYRK1 inhibition by 108600 suppresses triple negative breast cancer stem cells and chemotherapy-resistant disease

Finding therapeutic strategies for aggressive triple negative breast cancer (TNBC) is an important challenge in clinical practice. Here, the authors identify a multi-kinases inhibitor with antitumor activity and able overcome chemotherapy resistance of TNBC in vivo

Discovery of 8‑Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3‑<i>d</i>]pyrimidine-6-carbonitrile (<b>7x</b>) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multikinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure–activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8<b>-</b>cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido­[2,3-<i>d</i>]­pyrimidine-6-carbonitrile (<b>7x</b>), was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30–100 nM. In vitro kinase profiling revealed that <b>7x</b> is a multikinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARK5 kinases. Here, we report the synthesis, structure–activity relationship, kinase inhibitory profile, in vitro cytotoxicity, and in vivo tumor regression studies by this lead compound