133628-28-1Relevant academic research and scientific papers
Synthesis of a series of nitrothiophenes with basic or electrophilic substituents and evaluation as radiosensitizers and as bioreductively activated cytotoxins
Threadgill,Webb,O'Neill,Naylor,Stephens,Stratford,Cole,Adams,Fielden
, p. 2112 - 2120 (1991)
A series of 2- and 3-nitrothiophene-5-carboxamides bearing N-(ω-aminoalkyl) side chains has been prepared by treatment of the thiophenecarbonyl chloride with the appropriate (protected) ω-aminoalkylamine. Analogous N-(oxiranylmethyl)nitrothiophene-5-carboxamides have been synthesized by epoxidation of the corresponding N-allylamide. Compounds in both classes were evaluated in vitro both as radiosensitizers of hypoxic mammalian cells and as selective bioreductively activated cytotoxins. The most potent radiosensitizers were those agents with strong tertiary amine bases or oxiranes in the side chain. Studies in vivo showed that 2-methyl-N-[2-(dimethylamino)ethyl]-3-nitrothiophene-5-carboxamide caused slight radiosensitization of the KHT sarcoma in mice given 0.34 mmol kg-1. However, administration of this and related tertiary amines at higher doses was precluded by systemic toxicity.
Structure-Activity Relationships and Kinetic Studies of Peptidic Antagonists of CBX Chromodomains
Stuckey, Jacob I.,Simpson, Catherine,Norris-Drouin, Jacqueline L.,Cholensky, Stephanie H.,Lee, Junghyun,Pasca, Ryan,Cheng, Nancy,Dickson, Bradley M.,Pearce, Kenneth H.,Frye, Stephen V.,James, Lindsey I.
, p. 8913 - 8923 (2016)
To better understand the contribution of methyl-lysine (Kme) binding proteins to various disease states, we recently developed and reported the discovery of 1 (UNC3866), a chemical probe that targets two families of Kme binding proteins, CBX and CDY chromodomains, with selectivity for CBX4 and -7. The discovery of 1 was enabled in part by the use of molecular dynamics simulations performed with CBX7 and its endogenous substrate. Herein, we describe the design, synthesis, and structure-activity relationship studies that led to the development of 1 and provide support for our model of CBX7-ligand recognition by examining the binding kinetics of our antagonists with CBX7 as determined by surface-plasmon resonance.
