118629-64-4Relevant articles and documents
Initial development of a cytotoxic amino-seco-CBI warhead for delivery by prodrug systems
Twum, Elvis A.,Nathubhai, Amit,Wood, Pauline J.,Lloyd, Matthew D.,Thompson, Andrew S.,Threadgill, Michael D.
, p. 3481 - 3489 (2015)
Abstract Cyclopropabenzaindoles (CBIs) are exquisitely potent cytotoxins which bind and alkylate in the minor groove of DNA. They are not selective for cancer cells, so prodrugs are required. CBIs can be formed at physiological pH by Winstein cyclisation of 1-chloromethyl-3-substituted-5-hydroxy-2,3-dihydrobenzo[e]indoles (5-OH-seco-CBIs). Corresponding 5-NH2-seco-CBIs should also undergo Winstein cyclisation similarly. A key triply orthogonally protected intermediate on the route to 5-NH2-seco-CBIs has been synthesised, via selective monotrifluoroacetylation of naphthalene-1,3-diamine, Boc protection, electrophilic iodination, selective allylation at the trifluoroacetamide and 5-exo radical ring-closure with TEMPO. This intermediate has potential for introduction of peptide prodrug masking units (deactivating the Winstein cyclisation and cytotoxicity), addition of diverse indole-amide side-chains (enhancing non-covalent binding prior to alkylation) and use of different leaving groups (replacing the usual chlorine, allowing tuning of the rate of Winstein cyclisation). This key intermediate was elaborated into a simple model 5-NH2-seco-CBI with a dimethylaminoethoxyindole side-chain. Conversion to a bio-reactive entity and the bioactivity of this system were confirmed through DNA-melting studies (ΔTm = 13°C) and cytotoxicity against LNCaP human prostate cancer cells (IC50 = 18 nM).
Antagonists of the calcium receptor. 2. Amino alcohol-based parathyroid hormone secretagogues
Marquis, Robert W.,Lago, Amparo M.,Callahan, James F.,Rahman, Attiq,Dong, Xiaoyang,Stroup, George B.,Hoffman, Sandra,Gowen, Maxine,DelMar, Eric G.,Van Wagenen, Bradford C.,Logan, Sarah,Shimizu, Scott,Fox, John,Nemeth, Edward F.,Roethke, Theresa,Smith, Brian R.,Ward, Keith W.,Bhatnagar, Pradip
experimental part, p. 6599 - 6605 (2010/04/03)
When administered as a single agent to rats, the previously reported calcium receptor antagonist 3 elicited a sustained elevation of plasma PTH resulting in no increase in overall bone mineral density. The lack of a bone building effect for analogue 3 was
Chiral glycidyl azides as synthetic intermediates to optically active compounds
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, (2008/06/13)
Chiral glycidyl azides, such as (2S)-glycidyl azide, are prepared, and they are useful as intermediates to prepare optically active compounds, particularly optically active, anti-bacterial oxazolidinones.
