C. Purna Chander, G. Raju, George Mathai
Jan 30, 2012
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Rapid communications in mass spectrometry : RCM
Abstract
Many pharmaceuticals are synthetic compounds, and a large number of them are heterocycles. Common examples are the widely used arylpyrazoles in medicinal and pesticide chemistry. Several of the pyrazole derivatives are known to exhibit a wide range of biological activities such as anti-hyperglycemic, analgesic, anti-inflammatory, anti-pyretic, anti-bacterial, hypoglycemic, sedative–hypnotic activity and anticoagulant activity. Recently, some arylpyrazoles were reported to have non-nucleoside HIV-1 reverse transcriptase inhibitory activity. They may prove to be clinically useful compounds and extensive studies have been devoted to arylpyrazole derivatives such as Celecoxib, a well-known COX-2 inhibitor. As a part of an ongoing synthetic research program towards the synthesis of novel and alternative non-steroidal antiinflammatory drugs, we have synthesized a new series of 3-phenyl-N-[3-(4-phenylpiperazin-1-yl)propyl]-1H-pyrazole-5carboxamide derivatives and evaluated their anti-inflammatory activity to inhibit carrageenan-induced paw edema in rats. An initial examination of the electrospray ionization (ESI) mass spectra of these compounds revealed an interesting and unusual apparently impossible fragmentation involving loss of 11 u. As there exist no reports in the literature on mass spectrometric studies of the title compounds and also because of the observed unusual fragmentation, we have undertaken a detailed study of these compounds using ESI tandemmass spectrometry (MS/MS) in combinationwith accuratemassmeasurements and density functional theory (DFT) calculations. ESI mass spectra of 3-phenyl-1H-pyrazole-5-carboxamide derivatives (Scheme 1) were recorded using a LCQ ion trap mass spectrometer (Thermo Finnigan, San Jose, CA, USA), equipped with an ESI source. The data acquisition was under the control of Xcalibur software (Thermo Finnigan). The typical source conditions were: spray voltage, 5 kV; capillary voltage, 15–20 V; heated capillary temperature, 200 C; tube lens offset voltage, 20 V; sheath gas (N2) pressure, 30 psi; and helium was used as damping gas. For the ion trap mass analyzer, the automatic gain control (AGC) settings were 2 10 counts for a full-scanmass spectrum and 2 10counts for a full product ion mass spectrum with a maximum ion injection time of 200 ms. In the full-scan MS and MS modes, the precursor ion of interest was first isolated by applying an appropriate waveform across the end-cap electrodes of the ion trap to resonantly eject all trapped ions, except those ions of the m/z ratio of interest. The isolated ions were then subjected to a supplementary ac signal to resonantly excite them and to induce the collision-activated dissociation (CAD) process. The collision energies used were 20–35 eV. The excitation time used was 30 ms and isolation width used was 1.0 Da.