161803-04-9Relevant academic research and scientific papers
Photoresponsive Formation of an Intermolecular Minimal G-Quadruplex Motif
Thevarpadam, Julie,Bessi, Irene,Binas, Oliver,Gon?alves, Diana P. N.,Slavov, Chavdar,Jonker, Hendrik R. A.,Richter, Christian,Wachtveitl, Josef,Schwalbe, Harald,Heckel, Alexander
, p. 2738 - 2742 (2016)
The ability of three different bifunctional azobenzene linkers to enable the photoreversible formation of a defined intermolecular two-tetrad G-quadruplex upon UV/Vis irradiation was investigated. Circular dichroism and NMR spectroscopic data showed the formation of G-quadruplexes with K+ ions at room temperature in all three cases with the corresponding azobenzene linker in an E conformation. However, only the para-para-substituted azobenzene derivative enables photoswitching between a nonpolymorphic, stacked, tetramolecular G-quadruplex and an unstructured state after E-Z isomerization.
Prodrugs of protein tyrosine kinase inhibitors
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, (2008/06/13)
A compound which comprises a prodrug of a protein tyrosine kinase inhibitor (PTKi) linked to a protecting group which is capable of being cleaved from the compound to release the PTKi, said PTKi prodrugs including tyrphostins, of formula (I), STR1 where X
Self-immolative nitrogen mustard prodrugs for suicide gene therapy
Niculescu-Duvaz, Dan,Niculescu-Duvaz, Ion,Friedlos, Frank,Martin, Janet,Spooner, Robert,Davies, Lawrence,Marais, Richard,Springer, Caroline J.
, p. 5297 - 5309 (2007/10/03)
Four new potential self-immolative prodrugs derived from phenol and aniline nitrogen mustards, four model compounds derived from their corresponding fluoroethyl analogues and two new self-immolative linkers were designed and synthesized for use in the suicide gene therapy termed GDEPT (gene-directed enzyme prodrug therapy). The self-immolative prodrugs were designed to be activated by the enzyme carboxypeptidase G2 (CPG2) releasing an active drug by a 1,6-elimination mechanism via an unstable intermediate. Thus, N-[(4-{[4-(bis{2- chloroethyl}amino)phenoxycarbonyloxy]methyl}phenyl)carbamoyl]-L-glutamic acid (23), N-[(4-{[4(bis{2- chloroethyl}amino)phenoxycarbonyloxy]methyl}phenoxy)carbonyl]-L-glutamic acid (30), N-[(4-{N-(4-(bis[2- chloroethyl]amino}}pheny)carbamoyloxy]methyl}phenoxy)carbonyl]-L-glutmic acid (37), and N-[(4-{[N-(4-{bis[2- chloroethyl]amino}phenyl)carbamoyloxy]methyl}phenyl)carbamoyl]-L-glutamic acid (40) were synthesized. They are bifunctional alkylating agents in which the activating effects of the phenolic hydroxyl or amino functions are masked through an oxycarbonyl or a carbamoyl bond to a benzylic spacer which is itself]inked to a glutamic acid by an oxycarbonyl or a carbamoyl bond. The corresponding fluoroethyl compounds 25, 32, 42, and 44 were also synthesized. The rationale was to obtain model compounds with greatly reduced alkylating abilities that would be much less reactive with nucleophiles compared to the corresponding chloroethyl derivatives. This enabled studies of these model compounds as substrates for CPG2, without incurring the rapid and complicated decomposition pathways of the chloroethyl derivatives. The prodrugs were desired to be activated to their corresponding phenol and aniline nitrogen mustard drugs by CPG2 for use in GDEPT. The synthesis of the analogous novel parent drugs (21b, 51) is also described. A colorectal cell line was engineered to express CPG2 tethered to the outer cell surface. The phenylenediamine compounds were found to behave as prodrugs, yielding IC50 prodrug/IC50 drug ratios between 20- and 33-fold (for 37 and 40) and differentials of 12-14-fold between CPG2-expressing and control LacZ- expressing clones. The drugs released are up to 70-fold more potent than 4- [(2-chloroethyl)(2-mesyloxyethyl)amino]benzoic acid that results from the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid (CMBA) which has been used previously for GDEPT. These data demonstrate the viability of this strategy and indicate that self-immolative prodrugs can be synthesized to release potent mustard drugs selectively by cells expressing CPG2 tethered to the cell surface in GDEPT.
Improvements relating to prodrugs
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, (2008/06/13)
A prodrug of the general formula FTLi-(PRT)m, where m is an integer from 1 to 5; FTLi is a ras inhibitor such as a farnesyltransferase inhibitor compound, such as Ia, Ib, Ic; and PRT represents m protecting groups or a precursor thereof, such as compound
The Synthesis of Precisely Structured Polyurethanes. Part 1. Monomer Synthesis
Denholm, Alistair A.,George, Maurice H.,Hailes, Helen C.,Tiffin, Peter J.,Widdowson, David A.
, p. 541 - 548 (2007/10/02)
The synthesis of a series of bifunctional siloxymethyl isocyanate monomers, required for the solid phase synthesis of structurally defined polyurethane oligomers and copolymers is described.Thus, the MDI mimics 2, 3 were synthesised via a desymmetrisation
