Search results for " Synthesis"

Organocatalytic Enantioselective 1,6-aza -Michael Addition of Isoxazolin-5-ones to p -Quinone Methides

2020

Assignment of the Absolute Configuration and Total Synthesis of (+)-Caripyrin

2014

The antifungal secondary metabolite (+)-caripyrin was studied by vibrational circular dichroism spectroscopy. Analysis of the recorded data, with the Boltzmann weighted-average of the spectra calculated at the B3LYP/6-311G(d,p) level of theory for all relevant conformers, unequivocally proved the (R,R)-configuration for the dextrorotatory natural product. Based on this finding, a short enantioselective synthesis of (+)-caripyrin was developed.

Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter

2001

6-Methoxylated and 8-oxygenated benztropines were prepared and evaluated for their DAT and SERT activity (binding and uptake inhibition). Methoxylation at the two-carbon bridge of benztropine produced a novel class of potent and selective DAT ligands. An interesting enantioselectivity was also observed for this new class of chiral benztropines. The inactivity of the 8-oxygenated analogues seems to point out that, unlike cocaine and its analogues, interactions of benztropine ligands with DAT may be strongly governed by the nitrogen atom.

In vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidin- and N-pyrazin-2-ylbenzenesulfonamides, and N2-(4-nitrophenyl)-N1-propylglyci…

2009

A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmania infantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5 mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease …

Synthesis and cytotoxic activity of novel C7-functionalized spongiane diterpenes.

2003

Based on two lead cytotoxic spongiane diterpenes, a new series of C7-oxygenated derivatives were synthesized and evaluated for their antitumor activity in vitro against the cancer cell lines HeLa and HEp-2. In general, introduction of either hydroxyl or acetoxy groups at C-7 did not improve the resultant cytotoxicity, while the presence of a butyrate ester led to more active compounds (CC(50)=4.0-9.5 microM).

Regioselective substitution of 6,7-dichloroquinoline-5,8-dione: synthesis and X-ray crystal structure of 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dion…

2003

6,7-Dichloroquinoline-5,8-dione (1) was reacted with a number of 2-aminopyridine derivatives. Of the several possible products of this reaction, 4a,10,11-triazabenzo[3,2-a]fluorene-5,6-dione (6), produced by condensation and rearrangement, was obtained as the major product, and its structure was subsequently unambigously determined by X-ray crystallographic study. Ortho-quinones were produced via nucleophilic substitution at position C7, which was unexpected, considering that para-quinones were produced via C6 substitution in the reaction between compound 1 and ethyl acetoacetate in our previous work. Such unexpected nucleophilic substitution at C7 provides an effective, yet simple route, t…

[68Ga]Ga-DO2A-(OBu-l-tyr)2: Synthesis, 68Ga-radiolabeling and in vitro studies of a novel 68Ga-DO2A-tyrosine conjugate as potential tumor tracer for …

2009

The synthesis, (68)Ga-labeling and in vitro study of the novel tyrosine chelate derivative [(68)Ga]Ga-1,4,7,10-tetraazacyclododecane-1,7-diacetic acid-4,10-di-(O-butyl)-l-tyrosine ([(68)Ga]Ga-DO(2)A-(OBu-l-tyr)(2)) as a potential tracer for imaging tumor metabolism by positron emission tomography (PET) is presented. This approach combines the biological amino acid transporter targeting properties of l-tyrosine with the outstanding availability of (68)Ga(III) via the (68)Ge/(68)Ga generator. In vitro studies utilizing the F98-glioblastoma cell line revealed specific uptake of [(68)Ga]Ga-DO2A-(OBu-l-tyr)(2) that was comparable to that of the reference O-(2-[(18)F]fluoroethyl)-l-tyrosine (FET)…

Annelated pyrrolo-pyrimidines from amino-cyanopyrroles and BMMAs as leads for new DNA-interactive ring systems.

2005

The efficient one-pot synthesis of several new tricyclic systems of type 1 and 2, obtained from the reaction of substituted 2-amino-3-cyanopyrroles and 3-amino-4-cyanopyrroles with BMMAs, is reported. The duration and yields of the reaction strongly depend on the reactivity of the starting pyrrole and on the size of the ring to be formed. Mechanist features of the reaction were investigated and proposed by studying also the reactivity of a 3-aminopyrrole-2,4-dicyano substituted. The method reported represents the first example of the use of BMMA reagents in combination with pyrrole derivatives and allows an easy and versatile entry to a large number of hitherto unknown pyrrolo-pyrimidines f…

The introduction of fluorine atoms or trifluoromethyl groups in short cationic peptides enhances their antimicrobial activity

2006

The effect of introducing fluorine atoms or trifluoromethyl groups in either the peptidic chain or the C-terminal end of cationic pentapeptides is reported. Three series of amide and ester peptides were synthesised and their antimicrobial properties evaluated. An enhanced activity was found in those derivatives whose structure contained fluorine, suggesting an increase in their hydrophobicity.

Synthesis and biological evaluation of 2-(3',4',5'-trimethoxybenzoyl)-3-N,N-dimethylamino benzo[b]furan derivatives as inhibitors of tubulin polymeri…

2008

Molecules that target microtubules have an important role in the treatment of cancer. A new class of inhibitors of tubulin polymerization based on the 2-(3,4,5-trimethoxybenzoyl)-2-dimethylamino-benzo[b]furan molecular skeleton was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. The most promising compound in this series was 2-(3,4,5-trimethoxybenzoyl)-3-dimethylamino-6-methoxy-benzo[b]furan, which inhibits cancer cell growth at nanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.