628-12-6Relevant articles and documents
Synthesis and in vitro evaluation of S-acyl-3-thiopropyl prodrugs of Foscarnet
Gagnard, Valerie,Leydet, Alain,Morere, Alain,Montero, Jean-Louis,Lefebvre, Isabelle,Gosselin, Gilles,Pannecouque, Christophe,De Clercq, Erick
, p. 1393 - 1402 (2004)
A new enzyme-labile group called S-acyl-3-thiopropyl group (SATP) has been synthesized from allylic esters of phosphonate. After demonstration of the enzyme-labile character of the SATP in cellular extracts, it has been introduced onto the phosphonate moiety of PFA (Foscarnet) to obtain potential lipophilic prodrugs. To ponder the lipophilicity of the triesters of PFA, esters of monomethylether of polyethyleneglycols and of thioglycerol were introduced on the PFA carboxylate moiety. The SATP groups were introduced in an attempt to deliver PFA after bioactivation inside the cells. The PFA prodrugs were evaluated in vitro for their activity against human immunodeficiency viruses (HIV-1 and HIV-2).
Polyethylene glycol-based homologated ligands for nicotinic acetylcholine receptors
Scates, Bradley A.,Lashbrook, Bethany L.,Chastain, Benjamin C.,Tominaga, Kaoru,Elliott, Brandon T.,Theising, Nicholas J.,Baker, Thomas A.,Fitch, Richard W.
supporting information; experimental part, p. 10295 - 10300 (2009/04/12)
A homologous series of polyethylene glycol (PEG) monomethyl ethers were conjugated with three ligand series for nicotinic acetylcholine receptors. Conjugates of acetylaminocholine, the cyclic analog 1-acetyl-4,4-dimethylpiperazinium, and pyridyl ether A-84543 were prepared. Each series was found to retain significant affinity at nicotinic receptors in rat cerebral cortex with tethers of up to six PEG units. Such compounds are hydrophilic ligands which may serve as models for fluorescent/affinity probes and multivalent ligands for nAChR.
Topical delivery of a model phenolic drug: Alkyloxycarbonyl prodrugs of acetaminophen
Wasdo, Scott C.,Sloan, Kenneth B.
, p. 940 - 946 (2007/10/03)
Purpose. To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown. Methods. Flux through hairless mouse skin from suspensions in isopropyl myristate (JMIPM), solubilities in IPM (SIPM) and water (SAQ), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K IPM:4.0) were measured for two series of AOC derivatives of acetaminophen (APAP); their solubilities in pH 4.0 buffer (S4.0) were estimated from SIPM/KIPM: 4.0. Log JMIPM values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (Δ log J′IPM) was calculated. The J MIPM, SIPM, S4.0, and molecular weight (MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log JMIPM = x + y log SIPM (1 - y) log S4.0 - z MW. Results. All of the 4-AOC-APAP derivatives underperformed based on their predicted log JMIPM (Δ log J′MIPM = 0.275 ± 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: 2 = -0.322, 0.530, 0.00337 and 0.92, respectively. Conclusions. The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on SIPM, S 4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.
