944-81-0Relevant academic research and scientific papers
7′-Substituted benzothiazolothio- and pyridinothiazolothio-purines as potent heat shock protein 90 inhibitors
Zhang, Lin,Fan, Junhua,Vu, Khang,Hong, Kevin,Le Brazidec, Jean-Yves,Shi, Jiandong,Biamonte, Marco,Busch, David J.,Lough, Rachel E.,Grecko, Roy,Ran, Yingqing,Sensintaffar, John L.,Kamal, Adeela,Lundgren, Karen,Burrows, Francis J.,Mansfield, Robert,Timony, Gregg A.,Ulm, Edgar H.,Kasibhatla, Srinivas R.,Boehm, Marcus F.
, p. 5352 - 5362 (2007/10/03)
We report on the discovery of benzo- and pyridinothiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7′-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chloro-benzothiazol-2-ylsulfanyl)-9-(2-cyclopropylamino-ethyl) -9H-purin-6-ylamine).
Syntheses of novel hydroxylamine carbanucleosides
Mulvihill, Mark J.,Miller, Marvin J.
, p. 6605 - 6626 (2007/10/03)
Enantiomerically pure 4'-hydroxylamino-adenine-derived carbanucleosides have been synthesized as isosteric 4'-hydroxymetyl analogs to carbovir, ddA, and aristeromycin. The key steps in the syntheses involved an enzymatic desymmetrization, two subsequent Mitsunobu reactions, and a highly diastereoselective ruthenium tetroxide-mediated dithydroxylation, overcoming the syn-directing effect seen in osmium tetroxide-mediated dihydroxylations. Hydroxylamino-propane analogs were also synthesized through similar methodology to afford adenine and cyclopropylamino purine analogs to acyclovir.
