1427296-91-0Relevant articles and documents
Synthesis of novel geldanamycin derivatives
Kitson, Russell R.A.,Moody, Christopher J.
, (2021/02/03)
The toxicity associated with the geldanamycin family of benzoquinone ansamycins when used as heat shock protein-90 inhibitor molecular therapeutics is ameliorated by substitution at the 19-position. The resulting 19-substituted derivatives have greater potential for success in oncology clinical trials and for other medicinal purposes such as the treatment of neurodegenerative conditions. Having overcome hurdles associated with the sensitivity and complexity of these molecules, through a variety of synthetic approaches, the synthesis of a series of 19-substituted geldanamycin derivatives is reported herein using optimised Stille and Suzuki coupling reactions. Further compounds were accessible via copper-mediated coupling and nucleophilic addition reactions The new compounds are of significant medicinal interest, in view of their significantly reduced toxicity previously observed for this class of substrate compared to their 19-unsubstituted counterparts that have been evaluated in the clinic.
An improved route to 19-substituted geldanamycins as novel Hsp90 inhibitors-potential therapeutics in cancer and neurodegeneration
Kitson, Russell R. A.,Moody, Christopher J.
supporting information, p. 8441 - 8443 (2013/09/23)
19-Substituted geldanamycin derivatives are efficient Hsp90 inhibitors, without the toxicity associated with the other benzoquinone ansamycins, thus giving them potential for use as molecular therapeutics in cancer and neurodegeneration. Here a new method of synthesising these important compounds is reported, eliminating the need for toxic metals and metalloids. The Royal Society of Chemistry 2013.
