Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors

Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1

The Anti-HIV Actions of 7-and 10-Substituted Camptothecins

Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-1(IIIB) in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1(KM018) in PBMC were 10.3, 3.5 and 66.0, respectively. While the TI of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-2(CBL-20) were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2(ROD) showed the similar values. However, when the antiviral mechanisms were considered, we found there was no inhibition of 7-hydroxymethyl-CPT on viral cell-to-cell transmission, and was no inhibition on reverse transcriptase, protease or integrase in cell-free systems. 7-Hydroxymethyl-CPT showed no selective killing of chronically infected cells after 3 days of incubation. In conclusion, 7-hydroxymethyl-CPT showed more potent anti-HIV activity, while 10-hydroxy-CPT had less efficient activity, compared with the parent CPT. Though the antiviral mechanisms remain to be further elucidated; the modification of -OH residues at C-7 of CPT could enhance the antiviral activity, while of -OH residues at C-10 of CPT had decreased the antiviral activity, which provides the preliminary modification strategy for anti-viral activities enhancement of this compound.

Anti-HIV Actions of 7- and 10-Substituted Camptothecins (vol 15, pg 138, 2010)

The authors thank the anonymous reviewer for helpful comments on the early version of the manuscript. This work was financially supported by the earmarked fund for Modern Agro-industry Technology Research System, the Science Fund for Young Scholars in Sichuan Province (Grant No: ZQ 026-017), and the National 863 Project of China (No. 2008AA101001).

Synthesis of substituted pyridyl ureas by selenium dioxide-catalyzed carbonylation

A series of commercially useful substituted pyridyl ureas have been synthesized via selenium dioxide-catalyzed reductive carbortylation of substituted nitrobenzene or substituted nitropyridine with amine as co-reagent and carbon monoxide as carbonyl reagent instead of phosgene in one-pot reaction. The recycling reusability of catalyst was also tested. It was also found that selenium dioxide-catalyzed reductive carbonylation of nitroaromatics exhibited reaction-controlled phase-transfer phenomena of the catalyst. (C) 2003 Elsevier B.V. All rights reserved.

Effect of drying methods on the structure and catalytic combustion activity of Mn-substituted hexaaluminate catalysts

Conventional oven drying (COD) and supercritical drying (SCD) methods were applied to the preparation of Mn-substituted hexaaluminate (BaMnA(11)O(19-alpha)) catalysts. The effect of drying methods on phase composition, specific surface area, pore structure and combustion activity of the samples was investigated. The samples obtained by SCD have higher surface area, narrower pore size distribution, and higher combustion activity than those obtained by COD.

Preparation of Mn substituted La-hexaaluminate catalysts by using supercritical drying

LaMnxAl12-xO19 catalysts were prepared from NH4OH and metal nitrates solutions. Supercritical drying (SCD) and conventional oven drying (CD) methods were used to extract the water in the hydrogel. The effects of drying methods on properties of the catalysts were investigated by means of TEM, N-2-adsorption, thermogravimetry (TG)-differential thermal analysis (DTA) and X-ray diffraction. SCD method is beneficial to maintain high surface area and improving catalytic activity for methane combustion of the catalyst. The specific surface area and pore volume of LaMn1Al11O19 catalyst prepared by SCD method are 28 m(2)/g and 0.23 cm(3)/g, respectively, and the ignition of methane could be carried out at 450degreesC. However, those of the CD catalyst prepared from the same precursor are 15 m(2)/g, 0.11 cm(3)/g and 530 degreesC, respectively. Suitable Mn content (0 less than or equal to x less than or equal to 2) could promote the formation of LaMnAl11O19 hexaaluminate, while further addition of Mn (2 less than or equal to x less than or equal to 6) cause the formation of LaMnO3. (C) 2003 Elsevier B.V All rights reserved.