943749-63-1Relevant articles and documents
Sulfones as Synthetic Linchpins: Transition-Metal-Free sp3–sp2 and sp2–sp2 Cross-Couplings Between Geminal Bis(sulfones) and Organolithium Compounds
Trost, Barry M.,Kalnmals, Christopher A.
supporting information, p. 9066 - 9074 (2018/06/29)
A valuable umpolung strategy that highlights the ambiphilic nature of the bis(phenylsulfonyl)methyl synthon and demonstrates its utility as a synthetic linchpin is reported. Although the bis(phenylsulfonyl)methyl group is typically introduced as an sp3-carbon nucleophile, it is demonstrated that it can also function as an effective sp2-carbon electrophile in the presence of organolithium nucleophiles. Alkyl- and aryllithiums couple with the central carbon of the bis(phenylsulfonyl)methyl unit to ultimately generate trisubstituted alkenes, comprising formal sp3–sp2 and sp2–sp2 cross-couplings between organolithium reagents and bis(sulfones). This process occurs almost instantaneously at ?78 °C in the absence of any transition metals. By developing this curious transformation, it has been demonstrated that bis(phenylsulfonyl)methane is a valuable synthetic linchpin, which can undergo two C?C bond-forming processes as an sp3-nucleophile, followed by a third C?C bond-forming reaction as an effective sp2-electrophile. This discovery significantly enhances the utility of this ubiquitous, but underutilized, linker group.
4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4 (CDK4)
Tsou, Hwei-Ru,Otteng, Mercy,Tran, Tritin,Floyd Jr., M. Brawner,Reich, Marvin,Birnberg, Gary,Kutterer, Kristina,Ayral-Kaloustian, Semiramis,Ravi, Malini,Nilakantan, Ramaswamy,Grillo, Mary,McGinnis, John P.,Rabindran, Sridhar K.
experimental part, p. 3507 - 3525 (2009/04/07)
The cyclin-dependent kinases (CDKs), as complexes with their respective partners, the cyclins, are critical regulators of cell cycle progression. Because aberrant regulations of CDK4/cyclin D1 lead to uncontrolled cell proliferation, a hallmark of cancer, small-molecule inhibitors of CDK4/cyclin D1 are attractive as prospective antitumor agents. The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. In the headpiece of the 4-(phenylaminomethylene) isoquinoline-1,3(2H,4H)-dione, a basic amine substitutent is required on the aniline ring for the CDK4 inhibitory activity. The inhibitory activity is further enhanced when an aryl or heteroaryl substituent is introduced at the C-6 position of the isoquinoline-1,3(2H,4H)-dione core. We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.
NEW COMPOUNDS AND THEIR USES 707
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Page/Page column 101, (2008/12/04)
The present invention relates to isoquinolinone derivatives of formula (I): should be wherein R1, R2, R3, R4, R5, R6 and R7 are as herein defined; processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
