Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Aza Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2006

Structurally similar diazenes exhibit significantly different biological activity.

We have previously synthesized various diazenecarboxamides (subsequently referred to as diazenes) that were cytotoxic to several tumor cell lines. To increase their biological activity, the structure has been modified appropriately. In the present study we examined the effects of N(1)-phenyl-N(2)-(2-pyridinylmethyl)diazenedicarboxamide (RL-337) obtained from the previously examined cytotoxic compound N(1)-phenyl-N(2)-(2-pyridinyl)diazenecarboxamide (JK-279), and compared them with those of diazene JK-279. Using a modified colorimetric MTT assay, the cytotoxicity of RL-337 was determined on human cervical carcinoma HeLa cells, glioblastoma A1235 cells, and prostate adenocarcinoma PC-3 cells. The possible synergistic effect of diazene RL-337 with cisplatin, doxorubicin, and vincristine, and its influence on intracellular GSH content was examined on HeLa cells. Diazene RL-337 was cytotoxic against all three human tumor cell lines, being more cytotoxic to HeLa cells than diazene JK-279. The higher efficacy of RL-337 than of JK-279 can be connected with higher basicity of the 2-picoline moiety present in the former diazene comparing with the pyridine fragment that is a part of the latter. The diazene RL-337 acted synergistically with cisplatin, doxorubicin, and vincristine (diazene JK-279 exhibited synergistic effect only with cisplatin). Glutathione (determined by Tietze's method) was not a target molecule of diazene RL-337 (but was for JK-279, as shown earlier). After just 1 h treatment with diazene RL-337, the cells started to lose membrane integrity. There was no cleavage of caspase-3 in RL-337-treated samples, and the majority of cells died 6 h after the treatment through necrosis (previously, apoptosis-like cell death was detected for diazene JK-279). Thus, although diazenes JK-279 and RL-337 are very similar in their structure, they exhibit widely different biological activity.

Antineoplastic Agents↗
PubMed2005

Designing binuclear transition metal complexes: a new example of the versatility of N,N'-bis(2-aminobenzyl)-4,13-diaza-18-crown-6.

N,N'-Bis(2-aminobenzyl)-4,13-diaza-18-crown-6 (L) is a versatile receptor able to adapt to the coordinative preferences of different metal cation guests. With first-row transition metal ions, L tends to form binuclear complexes but, depending on the nature of the particular metal ion, the structure of the binuclear complex may be very different. Herein we report a study of the structure and magnetic properties of the corresponding nickel(II) and cobalt(II) complexes. The X-ray crystal structure of the nickel complex (1), with formula [Ni2(L)(CH3CN)4](ClO4)4.CH3CN, shows that this compound presents a symmetric coordination environment with L adopting an anti arrangement. Each Ni(II) ion is six-coordinate in a distorted octahedral environment, and both metal ions are quite far from each other. On the other hand, the X-ray crystal structure of the cobalt complex (2), with formula [Co(L)(mu-OH)Co(CH3CN)](ClO4)3, reveals a rather different structure. Coordination number asymmetry is found: one of the Co(II) is five-coordinate in a distorted trigonal-bipyramidal coordination environment, while the second Co(II) ion is six-coordinate in a distorted octahedral arrangement. Now L adopts a syn arrangement and a hydroxide group acts as a bridge between both cobalt ions. This hydroxo-bridged Co(II) binuclear complex shows structural features that mimic the active site of methionine aminopeptidases. The magnetic properties of 1 and 2 have been investigated in the temperature range 2.0-300 K. Whereas 1 displays a Curie law except for temperatures below 50 K where zero-field splitting of the S= 1 ground state is observed, antiferromagnetic exchange in the singular asymmetric binuclear Co(II) complex 2 has been observed. This magnetic behaviour has been fitted considering first-order spin-orbit coupling in the assumed axially distorted octahedral site and totally quenched orbital contribution in the five-coordinate site in which zero-field splitting of the S= 3/2 ground state is operative.

Aza Compounds↗
PubMed2005

Effects of dietary administration of CL-20 on Japanese quail Coturnix coturnix japonica.

Hexanitrohexaazaisowurtzitane, or CL-20, is an emerging highly energetic compound currently under consideration for military applications. With the anticipated wide use of CL-20, there is the potential for soil and groundwater contamination resulting in adverse toxicologic effects on environmental receptors. Presently, there is a lack of data describing the toxic effects of CL-20 on avian species. The present study describes the effect of CL-20 on Japanese quail (Coturnix coturnix japonica) modified from standard toxicity test guidelines. First, a 14-day subacute assay was adopted using repeated gavage doses (0, 307, 964, 2439, 3475, or 5304 mg CL-20/kg body weight (BW)/d for 5 days followed by no CL-20 exposure (vehicle only) for 10 days. Second, a subchronic feeding assay (0, 11, 114, or 1085 mg CL-20/kg feed) was done for 42 days. During both studies, no overt toxicity was observed in the CL-20-treated birds. During the first 5 days of the subacute study, CL-20-exposed birds showed a dose-dependent decrease in BW gain, whereas increased liver weight, plasma sodium, and creatinine levels were observed in birds receiving the highest dose tested. For the subchronic study, embryo weights were significantly decreased in a dose-dependent manner. Embryos from CL-20-exposed birds were observed to have multiple cranial and facial deformities, beak curvatures, possible mid-brain enlargement, and classic one-sided development with micro-opthalamia (nonstatistical comparisons with control embryos). A trend toward decreased number of eggs laid per female bird was also observed. We conclude that CL-20 (or its degradation products) elicits few effects in adults but may affect avian development, although these preliminary findings should be confirmed.

Administration, Oral↗
PubMed1999

Pharmacokinetics of the 8-methoxyquinolone, moxifloxacin: a comparison in humans and other mammalian species.

The pharmacokinetics of moxifloxacin was investigated in NMRI mice, Wistar rats, rhesus monkeys, beagle dogs, Göttingen minipigs and healthy human volunteers after i.v. and oral administration of moxifloxacin-HCl (single doses of moxifloxacin 9.2 mg/kg bodyweight) in animals and 100 mg moxifloxacin (1.4 mg/kg bodyweight p.o. and 1.2 mg/kg bodyweight i.v.) in humans. The plasma concentration vs time courses of the unchanged compound (determined by HPLC) and the derived pharmacokinetic parameters were used to evaluate the absorption process, to compare the pharmacokinetics in these species and to perform an interspecies scaling. The results of the pharmacokinetic investigations indicate a clear dependence on the species. Moxifloxacin is absorbed quickly (rats, dogs, humans > monkeys): the major portion of the dose reached the systemic circulation within the first 2 h. In the minipig absorption was slower. Bioavailability was high to moderate (91-52%) in all species. Protein binding (f(u)) was low (55-71%) in all species. The volume of distribution at steady state (Vss) was medium to large (2.0-4.9 L/kg) in all species. There were considerable differences in maximum concentrations (C(max,norm), 0.430-0.070 kg/L) and in AUCnorm values (oral, 6.18-0.184 kg x h/L; i.v., 7.51-0.237 kg x h/L). Total body clearance (CL) decreased with increasing bodyweight (4.21-0.132 L/(h x kg)). The mean residence time (MRT) decreased with decreasing bodyweight (15-0.88 h). The half-life (t(1/2)) decreased with decreasing bodyweight (oral, 12-1.3 h, i.v., 13-0.93 h). There was moderate to low renal excretion (i.v., 20-6.2%), the renal clearance, (CL(R)) was in the range 0.615-0.0222 L/(h x kg). Regarding the pharmacokinetic parameters determined after oral administration, the dog was most similar to the human in terms of Cmax, AUC and t(1/2). There was good correlation between bodyweight and CL (coefficient of correlation (r) = 0.959), Vss (r = 0.990) and MRT (r = 0.943). On the basis of preclinical studies a terminal half-life appropriate for once-daily dosing in humans was predicted and confirmed by Phase I data.

Animals↗
PubMed2005

Selective induction of apoptosis in mutant p53 premalignant and malignant cancer cells by PRIMA-1 through the c-Jun-NH2-kinase pathway.

PRIMA-1 (p53 reactivation and induction of massive apoptosis) is a chemical compound that was originally identified as a selective mutant p53-dependent growth suppressor by screening a library of low-molecular-weight compounds. However, its mechanism of action is unknown. In this study, we examined toxicity of PRIMA-1 to three premalignant human colorectal adenoma cell lines (RG/C2, BR/C1, and AA/C1) and four colorectal carcinoma cell lines (DLD-1, SW480, LOVO, and HCT116) and its mechanism of action. It selectively induced apoptosis only in the mutant p53 premalignant and malignant colon cell lines, but was not toxic to the wild-type p53 premalignant and malignant colon cell lines. Using stable transfectants of temperature-sensitive p53 mutant Ala(143) in null p53 H1299 lung cancer cells, we found that PRIMA-1 induced significantly more apoptosis in cells with mutant p53 conformation (37 degrees C) than the wild-type p53 conformation (32.5 degrees C). Cell cycle analysis indicated that its inhibition of cell growth was correlated with induction of G(2) arrest. Western blot analysis showed PRIMA-1 increased p21 and GADD45 expression selectively in the mutant p53 cells. However, Fas, Bcl-2 family proteins, and caspases were not involved in PRIMA-1-induced cell death. The c-Jun-NH(2)-kinase (JNK) inhibitor SP 600125, but not p38 mitogen-activated protein kinase inhibitor SB 203580 or extracellular signal-regulated kinase inhibitor PD 98059, blocked PRIMA-1-induced apoptosis. Transfection with a dominant-negative phosphorylation mutant JNK, but not a dominant-negative p38 or wild-type JNK, inhibited PRIMA-1-induced cell death, suggesting that the JNK pathway plays an important role in PRIMA-1-induced apoptosis. PRIMA-1 is a highly selective small molecule toxic to p53 mutant cells and may serve as a prototype for the development of new p53-targeting agents for therapy of premalignant and malignant cells.

Apoptosis↗
PubMed2006

Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake inhibitor.

DOV 216,303 [(+/-)-1-(3,4-dichlorophenyl)-3-azabicyclo-[3.1.0]hexane hydrochloride] is the prototype of a class of compounds referred to as "triple" reuptake inhibitors. Such compounds inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), the three neurotransmitters most closely linked to major depressive disorder. DOV 216,303 inhibits [(3)H]NE, [(3)H]5-HT, and [(3)H]DA uptake to the corresponding human recombinant transporters (expressed in HEK 293 cells) with IC(50) values of approximately 20, 14, and 78 nM, respectively. DOV 216,303 is active in tests predictive of antidepressant activity including the mouse forced swim test and reversal of tetrabenazine-induced ptosis and locomotor depression. The pharmacodynamic, pharmacokinetic, and toxicological profile of DOV 216,303 in animals prompted us to initiate clinical studies. In both single and multiple dose studies using normal volunteers, DOV 216,303 was safe and well-tolerated. Furthermore, both C(max) and AUC values were dose-proportional between 5-150 mg. The plasma concentrations of DOV 216,303 at doses >10 mg were in excess of the IC(50) values for inhibition of biogenic amine reuptake. In a Phase II study designed to explore the safety and tolerability of DOV 216,303 in depressed individuals, patients received either 100 mg DOV 216,303 (50 mg b.i.d.) or 40 mg citalopram (20 mg, b.i.d.) for two weeks. A placebo arm was not employed in this study because several institutional review boards required administration of an active control to severely depressed individuals. Time dependent reductions in HAM-D scores (the primary outcome measure) were observed in both the DOV 216,303 and citalopram groups compared to baseline scores (p < 0.0001). The side effect profile was not remarkably different between treatment arms. These findings provide preliminary evidence of a clinically meaningful antidepressant action with a molecule capable of inhibiting the three transmitters most closely linked to major depressive disorder.

Animals↗
PubMed2005

Variolin B and its derivate deoxy-variolin B: new marine natural compounds with cyclin-dependent kinase inhibitor activity.

Variolin B (VAR-B) is a natural product isolated from the sponge Kirkpatrickia variolosa, found in Antarctica. VAR-B has been shown previously to possess potent pro-apoptotic activity. This study was undertaken to investigate the mechanism of action of chemically synthesised VAR-B and its analogue deoxy-variolin B (dVAR-B). In different human cancer cell lines both compounds inhibited colony formation, caused cell cycle perturbations and induced apoptosis at concentrations ranging from 0.1 to 2 microM. LoVo/Dx cells over-expressing Pgp were equally sensitive as the parental cell line to VAR-B and dVAR-B, indicating that variolins are not substrates of Pgp. Although variolins induced an increase in the levels of p53 with an increase in p21, their cytotoxicities did not appear to be dependent on p53 status as their potency was comparable in cells with wild-type p53, or in sub-lines with inactivated p53. Both VAR-B and dVAR-B prevent the cells from entering S phase, blocking cells in G1 and cause an accumulation of cells in G2. The apoptosis induced by VAR-B and dVAR-B occurs very rapidly in some cell lines (e.g., Jurkat leukaemia cells) and is already evident 4h after the beginning of treatment. Although intercalation of dVAR-B in DNA has been demonstrated, neither VAR-B nor dVAR-B produce detectable breaks in DNA. These results are consistent with the in vitro biochemical assays that also demonstrated that dVAR-B is not topoisomerase I or II poison. Instead, each of these variolins appears to inhibit cyclin-dependent kinases (CDKs) in the muM range. CDK1-cyclin B, CDK2-cyclin A and CDK2/cylin E complexes were inhibited in a range of concentrations lower than those required to inhibit the activity of CDK4/cyclin D or CDK7/cyclin H complexes. In conclusion, these variolins are a new class of CDK inhibitors that activate apoptosis in a p53-independent fashion and thus they may be effective against tumours with p53 mutations or deletions.

Adenocarcinoma↗
PubMed2001

Lack of pharmacokinetic interaction between moxifloxacin, a novel 8-methoxyfluoroquinolone, and theophylline.

OBJECTIVE: To investigate the plasma and urinary pharmacokinetics, safety and tolerability of theophylline and moxifloxacin after single and repeated doses of either compound administered alone or concomitantly with the other. DESIGN: This was a randomised, multiple-dose, period-balanced, 3-way crossover study in healthy volunteers. PARTICIPANTS: 12 nonsmoking healthy volunteers, 21 to 30 years of age were included in this study. METHODS: The investigational medications, all given orally, were as follows: treatment A, moxifloxacin 200mg alone; treatment B, theophylline 400mg alone; treatment C, theophylline 400mg plus moxifloxacin 200mg. Each drug or combination was given twice daily on days 2 to 4 of the 5-day study period and as single morning doses on days 1 and 5. The study periods were separated by 1-week washout intervals. The plasma and urinary pharmacokinetics of moxifloxacin and theophylline were characterised after the first (morning of day 1) and eighth (morning of day 5) doses. RESULTS: At steady state, the plasma pharmacokinetics of theophylline for treatments B and C proved equivalent in terms of maximum concentration (Css(max)) and bodyweight- and dose-normalised Css(max) lestimated true ratio 96%, 90% confidence interval (CI) 87 to 105%] and also in terms of area under the concentration-time curve from 0 to 12 hours (AUCss(tau)) and normalised AUCss(tau) (ratio 95%, 90% CI 85 to 107%); the median times to Cmax(tmax) were also similar (5.0 and 6.0 hours for treatments B and C, respectively). The plasma pharmacokinetics of moxifloxacin for treatments A and C were equivalent with respect to Css(max) (estimated true ratio 109%, 90% CI 97 to 123%) and AUCss(tau) (ratio 104%, 90% CI 100 to 108%); the median tmax values were also similar (0.5 and 1.0 hour for treatments A and C, respectively). The treatments were well tolerated. CONCLUSIONS: Moxifloxacin - in contrast to some older quinolones - does not interact pharmacokinetically with theophylline, confirming preclinical results on the absence of cytochrome P450-mediated metabolism.

Adult↗
PubMed2005

Proteomic identification of heat shock protein 90 as a candidate target for p53 mutation reactivation by PRIMA-1 in breast cancer cells.

INTRODUCTION: A loss of p53 function resulting from mutation is prevalent in human cancers. Thus, restoration of p53 function to mutant p53 using small compounds has been extensively studied for cancer therapy. We previously reported that PRIMA-1 (for 'p53 reactivation and induction of massive apoptosis') restored the transcriptional activity of p53 target genes in breast cancer cells with a p53 mutation. By using functional proteomics approach, we sought to identify molecular targets that are involved in the restoration of normal function to mutant p53. METHODS: PRIMA-1 treated cell lysates were subjected to immunoprecipitation with DO-1 primary antibody against p53 protein, and proteins bound to p53 were separated on a denaturing gel. Bands expressed differentially between control and PRIMA-1-treated cells were then identified by matrix-assisted laser desorption ionization-time-of-flight spectrometry. Protein expression in whole cell lysates and nuclear extracts were confirmed by Western blotting. The effect of combined treatment of PRIMA-1 and adriamycin in breast cancer cells was determined with a cytotoxicity assay in vitro. RESULTS: PRIMA-1 treated cells distinctly expressed a protein band of 90 kDa that was identified as heat shock protein 90 (Hsp90) by the analysis of the 90 kDa band tryptic digest. Immunoblotting with isoform-specific antibodies against Hsp90 identified this band as the alpha isoform of Hsp90 (Hsp90alpha). Co-immunoprecipitation with anti-Hsp90alpha antibody followed by immunoblotting with DO-1 confirmed that p53 and Hsp90alpha were interacting proteins. PRIMA-1 treatment also resulted in the translocation of Hsp90alpha to the nucleus by 8 hours. Treatment of cells with PRIMA-1 alone or in combination with adriamycin, a DNA-targeted agent, resulted in increased sensitivity of tumor cells. CONCLUSION: The studies demonstrate that PRIMA-1 restores the p53-Hsp90alpha interaction, enhances the translocation of the p53-Hsp90alpha complex and reactivates p53 transcriptional activity. Our preliminary evidence also suggests that PRIMA-1 could be considered in combination therapy with DNA-targeted agents for the treatment of breast cancer, especially for tumors with aberrant p53 function.

Amino Acid Substitution↗
PubMed2006

The beta-turn scaffold of tripeptide containing an azaphenylalanine residue.

The conformational preferences of azaphenylalanine-containing peptide were investigated using a model compound, Ac-azaPhe-NHMe with ab initio method at the HF/3-21G and HF/6-31G(*) levels, and the seven minimum energy conformations with trans orientation of acetyl group and the 4 minimum energy conformations with cis orientation of acetyl group were found at the HF/6-31G(*) level if their mirror images were not considered. An average backbone dihedral angle of the 11 minimum energy conformations is phi=+/-91 degrees +/-24 degrees , psi =+/-18 degrees +/-10 degrees (or +/-169 degrees +/-8 degrees ), corresponding to the i+2 position of beta-turn (delta(R)) or polyproline II (beta(P)) structure, respectively. The chi(1) angle in the aromatic side chain of azaPhe residue adopts preferentially between +/-60 degrees and +/-130 degrees, which reflect a steric hindrance between the N-terminal carbonyl group or the C-terminal amide group and the aromatic side chain with respect to the configuration of the acetyl group. These conformational preferences of Ac-azaPhe-NHMe predicted theoretically were compared with those of For-Phe-NHMe to characterize the structural role of azaPhe residue. Four tripeptides containing azaPhe residue, Boc-Xaa-azaPhe-Ala-OMe [Xaa=Gly(1), Ala(2), Phe(3), Asn(4)] were designed and synthesized to verify whether the backbone torsion angles of azaPhe reside are still the same as compared with theoretical conformations and how the preceding amino acids of azaPhe residue perturb the beta-turn skeleton in solution. The solution conformations of these tripeptide models containing azaPhe residue were determined in CDCl(3) and DMSO solvents using NMR and molecular modeling techniques. The characteristic NOE patterns, the temperature coefficients of amide protons and small solvent accessibility for the azapeptides 1-4 reveal to adopt the beta-turn structure. The structures of azapeptides containing azaPhe residue from a restrained molecular dynamics simulation indicated that average dihedral angles [(phi(1), psi(1)), (phi(2), psi(2))] of Xaa-azaPhe fragment in azapeptide, Boc-Xaa-azaPhe-Ala-OMe were [(-68 degrees, 135 degrees ), (116 degrees, -1 degrees )], and this implies that the intercalation of an azaPhe residue in tripeptide induces the betaII-turn conformation, and the volume change of a preceding amino acid of azaPhe residue in tripeptides would not perturb seriously the backbone dihedral angle of beta-turn conformation. We believe such information could be critical in designing useful molecules containing azaPhe residue for drug discovery and peptide engineering.

Aza Compounds↗
PubMed2005

Penetration pharmacokinetics of topically administered 0.5% moxifloxacin ophthalmic solution in human aqueous and vitreous.

OBJECTIVE: To investigate the penetration of 0.5% moxifloxacin hydrochloride into the aqueous and vitreous after topical administration in humans. METHODS: A prospective, nonrandomized study of 20 patients scheduled for vitrectomy surgery between September 1 and December 31, 2003. Aqueous and vitreous samples were obtained and analyzed after topical administration of 0.5% moxifloxacin hydrochloride, every 2 hours (q2h) or every 6 hours (q6h), for 3 days before surgery. Assays were performed using high-performance liquid chromatography. RESULTS: Mean +/- SD moxifloxacin concentrations in the q2h group for the aqueous (n = 9) and vitreous (n = 10) were 2.28 +/- 1.23 and 0.11 +/- 0.05 microg/mL, respectively. Mean +/- SD moxifloxacin concentrations in the q6h group for the aqueous (n = 10) and vitreous (n = 9) were 0.88 +/- 0.88 and 0.06 +/- 0.06 microg/mL, respectively. The minimum inhibitory concentration for 90% of isolates (MIC(90)) was far exceeded in the aqueous for a wide spectrum of key pathogens, whereas it was not exceeded in the vitreous for several organisms. However, the minimum inhibitory concentration for 50% of the isolates was exceeded in the q2h vitreous group for Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Bacillus cereus, and other gram-negative pathogens. CONCLUSIONS: The Endophthalmitis Vitrectomy Study revealed that 94.2% of isolates from postoperative endophthalmitis are gram-positive pathogens. Moxifloxacin has a spectrum of coverage that appropriately encompasses the most common organisms in endophthalmitis. The pharmacokinetic findings of this investigation show that relatively high aqueous levels can be achieved after topical administration. Further studies will help define the precise role of 0.5% moxifloxacin ophthalmic solution in the treatment of or prophylaxis against intraocular infections.

Administration, Topical↗
PubMed2006

Vitreous and aqueous penetration of orally administered moxifloxacin in humans.

OBJECTIVE: To investigate intraocular penetration of moxifloxacin hydrochloride after oral administration. METHODS: Prospective study of 15 patients scheduled for vitrectomy between September and November 2004 at the Barnes Retina Institute, St Louis, MO. Aqueous, vitreous, and serum samples were analyzed from 15 patients after oral administration of 2 tablets containing 400 mg of moxifloxacin. Assays were performed using high-performance liquid chromatography. RESULTS: The mean +/- SD moxifloxacin concentrations in plasma (n = 15), vitreous (n = 13), and aqueous (n = 13) samples were 3.56 +/- 1.31 microg/mL, 1.34 +/- 0.66 microg/mL, and 1.58 +/- 0.80 microg/mL, respectively. Mean +/- SD sampling times after oral administration of the second moxifloxacin tablet for plasma, vitreous, and aqueous were 2.94 +/- 0.81 hours, 3.77 +/- 0.92 hours, and 3.71 +/- 0.89 hours, respectively. The percentages of plasma moxifloxacin concentration in the vitreous and aqueous were 37.6% and 44.3%, respectively. Minimal inhibitory concentrations against 90% levels were exceeded against a wide spectrum of gram-positive and gram-negative pathogens in the vitreous and aqueous. CONCLUSIONS: Moxifloxacin has a spectrum of coverage that encompasses the most common organisms in endophthalmitis. The pharmacokinetic findings of this investigation reveal that orally administered moxifloxacin achieves therapeutic levels in the noninflamed eye. Because of their broad spectrum of coverage, low minimal inhibitory concentration against 90% levels, good tolerability, and excellent oral bioavailability, fourth-generation fluoroquinolones may represent a major advance for managing posterior segment infections.

Administration, Oral↗
PubMed1997

Synthesis and mass spectrometric behavior of some new nucleosides as potential anti-HIV agents.

The electron-impact (EI) mass spectrometric behaviour of a series of 8-aza-purines derivatized with hydroxymethylcyclopentane and exhibiting cis-trans isomerization in the cyclopentane ring has been studied in detail with the aid of metastable-ion data. Specific fragmentation processes, present in both EI and mass analysed ion kinetic energy spectra of molecular species, allow characterization of the different pairs of stereoisomers. Contrary to what is observed in the case of purine analogs, the presence of a nitrogen atom in position 8 strongly inhibits fragmentation processes related to the heterocycle.

Anti-HIV Agents↗