3700-55-8Relevant academic research and scientific papers
Chiral photocages based on phthalimide photochemistry
Soldevilla, Alberto,Griesbeck, Axel G.
, p. 16472 - 16473 (2007/10/03)
A new class of photoremovable protecting groups, based on a photoinduced decarboxylation reaction coupled with the elimination of the caged molecule, is described for 2-phthalimido-3-hydroxy-propionate derivatives. When derived from enantiopure N-phthaloyl- serine or threonine, the chirality of the starting amino acid is transmitted to the protected (caged) molecule. These photocages possess good properties for their use in biological systems, and the introduction of chirality opens new possibilities for the study of diastereoselective photochemistry and stereodifferentiation processes involving the release of the caged molecule. Copyright
Structure-based design, parallel synthesis, structure - Activity relationship, and molecular modeling studies of thiocarbamates, new potent non-nucleoside HIV-1 reverse transcriptase inhibitor isosteres of phenethylthiazolylthiourea derivatives
Ranise, Angelo,Spallarossa, Andrea,Cesarini, Sara,Bondavalli, Francesco,Schenone, Silvia,Bruno, Olga,Menozzi, Giulia,Fossa, Paola,Mosti, Luisa,La Colla, Massimiliano,Sanna, Giuseppina,Murreddu, Marta,Collu, Gabriella,Busonera, Bernardetta,Marongiu, Maria Elena,Pani, Alessandra,La Colla, Paolo,Loddo, Roberta
, p. 3858 - 3873 (2007/10/03)
In this paper we describe our structure-based ligand design, synthetic strategy, and structure-activity relationship (SAR) studies that led to the identification of thiocarbamates (TCs), a novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs), isosteres of phenethylthiazolylthiourea (PETT) derivatives. Assuming as a lead compound O-[2-(phthalimido)ethyl] phenylthiocarbamate 12, one of the precursors of the previously described acylthiocarbamates (Ranise, A.; et al. J. Med. Chem. 2003, 46, 768-781), two targeted solution-phase TC libraries were prepared by parallel synthesis. The lead optimization strategy led to para-substituted TCs 31, 33, 34, 39, 40, 41, 44, 45, and 50, which were active against wild-type HIV-1 in MT-4-based assays at nanomolar concentrations (EC50 range: 0.04-0.01 μM). The most potent congener 50 (EC50 = 0.01 μM) bears a methyl group at position 4 of the phthalimide moiety and a nitro group at the para position of the N-phenyl ring. Most of the TCs showed good selectivity indices, since no cytotoxic effect was detected at concentrations as high as 100 μM. TCs 31, 37, 39, 40, and 44 significantly reduced the multiplication of the Y181C mutant, but they were inactive against K103R and K103N + Y181C mutants. Nevertheless, the fold increase in resistance of 41 was not greater than that of efavirenz against the K103R mutant in enzyme assays. The docking model predictions were consistent with in vitro biological assays of the anti-HIV-1 activity of the TCs and related compounds synthesized.
Acid-mediated intramolecular cationic cyclization using an oxygen atom as internal nucleophile: Synthesis of substituted oxazolo-, oxazino- and oxazepinoisoindolinones
Sikoraiová, Jana,Marchalín, ?tefan,Da?ch, Adam,Decroix, Bernard
, p. 4747 - 4751 (2007/10/03)
Efficient assembly of substituted oxazolo-, oxazino-, and oxazepinoisoindolinones (5-7, 12-15 and 19) is described in three steps according to an acidic α-oxoamidoalkylation reaction from ready available phthalic anhydride by successive imidation, sodium borohydride reduction and intramolecular cationic cyclization involving N-acyliminium species. The relative stereochemistry accompanying these reactions was also discussed.
Photochemical transformations of proteinogenic and non-proteinogenic amino acids
Griesbeck, Axel G.
, p. 272 - 283 (2007/10/03)
The photochemistry of N-activated enantiomerically pure α-amino acids is described with emphasis on chemo-, regio-, stereo-, and spin selectivity. An especially valuable chromophore is the phthalimido group. The first excited singlet states are short-lived and deactivated (chemically) via homolytic CH cleavage or (physically) via electron-transfer steps. The first excited triplet states are chemically deactivated via electron-transfer reactions and subsequent deprotonation/coupling steps. A wide variety of product types were synthesized, and potential target molecules were available by tuning the reaction conditions. Also remote groups can be activated by means of electron-transfer steps, which represents an attractive new synthetic protocol for macrocyclization.
Photochemistry of N-phthaloyl derivatives of electron-donor-substituted amino acids
Griesbeck,Henz,Hirt,Ptatschek,Engel,Loffler,Schneider
, p. 701 - 714 (2007/10/02)
The hydroxy substituted amino acids threonine and serine have been investigated concerning their photochemical behaviour when activated as N-phthaloyl substrates. The methyl esters 1a and 2a solely underwent cleavage of the central C-C single bond to give the glycine derivative 3 and an aldehyde fragment. C-unprotected threonine derivative 1b is converted into a series of products the composition of which depends on solvent polarity and on the electronic state. Three reaction modes were detected for the N-phthaloyl derivatives of the aryl substituted amino acids phenylalanine, tyrosine, and dihydroxyphenylalanine (DOPA): (A) decarboxylation (only for 12a), (B) β-fragmentation, and (C) ring enlargement reaction. Processes B and C are initiated by photo electron transfer (PET), as the solvent dependence revealed. The DOPA derivatives 14a and 14b are the most prominent examples due to their exclusive PET reactivity leading to type C products (18a,b) with high diastereoselectivity (90:10). PET results from the first excited singlet states of 12 and 13, whereas for compounds 14 the corresponding triplet states are involved. The correlation between photochemical reactivity and the fluorescence decay data for compounds 12a,b and 15 is discussed.
Purine acyclic nucleosides. 6-dimethylamino-9-[(2-phenylalanylamido-1-substituted-ethoxy)methyl]purine s as candidate antivirals
Kelley,Selway,Schaeffer
, p. 1302 - 1304 (2007/10/02)
Several acyclic puromycin analogues containing hydrocarbon substituents on the 1'-position of the aminoethoxymethyl moiety were synthesized and tested for antiviral activity. The N-carbobenzoxy intermediate 7c was active in vitro against Mengo and Semliki Forest viruses.
Hypolipidemic activity of phthalimide derivatives. IV: Further chemical modification and investigation of the hypolipidemic activity of N-substituted imides
Chapman Jr.,Cocolas,Hall
, p. 1344 - 1347 (2007/10/02)
A further investigation of N-substituted derivatives of phthalimide for hypolipidemic activity has revealed that the chain length, as well as the type of substitution on the N-alkyl chain of phthalimide is critical for biological activity. In these studies the hypolipidemic activity was not improved by extending the chain length beyond five carbon atoms in the alkyl and alkanoic acid series. Imido nitrogen substitutents, other than alkanoic acids, methyl ketones, and alkyl groups, caused a reduction in hypolipidemic activity, e.g., hydroxy, amino, hydroxymethyl, or carbethoxy. Reduction of the keto group in the side chain to an alcohol, as well as forming derivatives of the keto group, did not improve the hypolipidemic activity with the exception of 1-N-phthalimidobutan-3-one semicarbazone. This compound demonstrated improved hypocholesterolemic activity over phthalimide and 1-N-phthalimidobutan-3-one. Substitution of the 3-position of the aromatic moiety of phthalimide with an amino or nitro group, as well as substituting a pyridine or cyclohexyl ring for the phenyl ring, led to the loss of hypolipidemic activity.
