ABSTRACT
The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2).
Subject(s)
Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Purines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Drug Design , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Purines/chemical synthesis , Purines/chemistry , Roscovitine , Stereoisomerism , Structure-Activity RelationshipABSTRACT
C-6 Biarylmethylamino purine derivatives of roscovitine (1) inhibit cyclin dependent kinases and demonstrate potent antiproliferative activity. Replacement of the aryl rings of the C-6 biarylmethylamino group with heterobiaryl rings has provided compounds with significantly improved activity. In particular, derivatives 18 g and 9 c demonstrated 1000-fold and 1250-fold improvements, respectively, in the growth inhibition of HeLa cells compared to roscovitine (1).
Subject(s)
Antineoplastic Agents/pharmacology , Cyclin-Dependent Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Purines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Drug Design , Drug Screening Assays, Antitumor , HeLa Cells , Humans , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Purines/chemical synthesis , Purines/chemistry , Roscovitine , Stereoisomerism , Structure-Activity RelationshipABSTRACT
We report a general strategy for the spontaneous segregation of electron-rich and electron-poor pi-conjugated moieties using mutually phobic aliphatic fluorocarbon-hydrocarbon interactions.
ABSTRACT
Solar cells constructed of organic materials are becoming increasingly efficient due to the discovery of the bulk heterojunction concept. This review provides an overview of organic solar cells. Topics covered include: a brief history of organic solar cell development; device construction, definitions, and characteristics; and heterojunction morphology and its relation to device efficiency in conjugated polymer/fullerene systems. The aim of this article is to show that researchers are developing a better understanding of how material structure relates to function and that they are applying this knowledge to build more efficient light-harvesting devices.
