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.
METABOTROPIC GLUTAMATE RECEPTOR 5 MODULATORS AND METHODS OF USE THEREOF
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, (2013/02/27)
Compounds that modulate GluR5 activity and methods of using the same are disclosed.
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.
Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment
Mayer, Scott C.,Banker, Annette L.,Boschelli, Frank,Di, Li,Johnson, Mark,Kenny, Cynthia Hess,Krishnamurthy, Girija,Kutterer, Kristina,Moy, Franklin,Petusky, Susan,Ravi, Malini,Tkach, Diane,Tsou, Hwei-Ru,Xu, Weixin
experimental part, p. 3641 - 3645 (2009/04/06)
Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. This receptor is over-expressed or activated in tumor cells and is emerging as a novel target in cancer therapy. Efforts in our "Hit to Lead" group have generated a novel series of submicromolar IGF-1R inhibitors based on a isoquinolinedione template originating from a Lance enzyme HTS screen. Chemical triage and parallel synthesis incorporating focused library arrays were instrumental in moving these investigations through the Wyeth exploratory medicinal chemistry process. The strategies, synthesis, and SAR behind this interesting kinase scaffold will be described.
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.
