Activity spectra

Pharmacological activity spectrum and toxicological properties of benzimidazole derivatives 99KFZ(5)6. 

Cefpimizole (51) appears to be less active in vitro than cefotaxime and cefoperazone and to have a somewhat narrower activity spectrum although some strains of Pseudomonas are susceptible. It is not orally active, but its performance in vivo appears superior to what would be expected from its in vitro data. Its synthesis begins by acylation of cephaloglycin (48) with the bis acid chloride of imidazole-4,5-dicarboxylic acid (49) to give amide 50. The acetyl moiety at C-3 of this intermediate is displaced with 4-pyridineethanesulfonic acid and sodium iodide to give cef-pimazole (51) [16]. 

Cefpiramide (64) is a third generation cephalosporin with a l-methyl-[lH)-tetra2ol-5-ylthio-methyl moiety at C-3 and an acylated -hydroxyphenylglycine moiety at C-7. It includes in its activity spectrum reasonable potency in vitro against many strains of Pseudomonas. It can be synthesized in a variety of ways including condensation of cephalosporin antibiotic 63 with 6-methyl-4-(l-H)-pyridone-3-carboxylic acid in the form of its active N-hydroxysuccinimide ester (62) to produce cefpiramide (64) [20,21],... 

Three subclasses Bl, B2 and B3 can be distinguished on the basis of the sequences. Bl and B3 enzymes are optimally active with 2 Zn2+ions, while the B2 enzymes are inhibited by the second Zn2+. These B2 enzymes also exhibit a very narrow activity spectrum and only hydrolyse carbapenems. The 3D structures of representative members of each subfamily have been... 

Figure 19.4 The activity spectrum of the benzodiazepines. Motor impairment and CNS depression increases with drug dose. (Based on data for chlordiazepoxide (Sternbach, Randall and Gustafson 1964))...

These new recruits to the activity spectrum were named inverse agonists and subsequent studies confirmed that they reduce the affinity of GABA for its binding site on the GABAa receptor and attenuate the GABAa receptor-mediated increase in Cl conductance (Fig. 19.5). 

Figure 19.7 The activity spectrum for different generic groups of compounds that bind to the benzodiazepine domain on the GABAa receptor...

Firstly, it is intrinsically more active than either compound alone (Figure 15). Secondly, it has a much wider activity spectrum than the two single actives (Figure 16) and thirdly, by its enhanced stability when compared with CIT (Figure 17), required initial addition levels are often similar to those of CIT/MIT blended products. 

HCHO/aldehyde free a Broader microbiological activity spectrum than BIT... 

The compounds are highlighted from the following viewpoints anti-HIV potency and selectivity, mechanism of action, antiviral activity spectrum, clinical or therapeutic potential, and risk of resistance development. 

The antiviral activity spectrum of the ddN analogues should, in principle, extend to all retroviruses as well as hepadnaviruses [i.e., hepatitis B virus (HBV)], since HBV, like retroviruses, replicates through an RNA template-driven RT process. Indeed, various ddN analogues (particularly, the L-enantiomeric forms 3TC, FTC, and L-DDC) have been shown to inhibit HBV replication [36-38]. Consequently, 3TC is, at present, pursued as a potential drug candidate for the treatment of both HIV and HBV infections. 

The antiviral activity spectrum of PMEA, PMEDAP, and their congeners is not confined to retroviruses but also extends to hepadna-viruses (e.g., HBV). PMEA has proved effective against duck HBV infec-... 

The antiviral activity spectrum of the NNRTIs is limited to HIV-1, probably because only HIV-1 RT contains a pocket site at which the... 

The second criteria, a different activity spectrum, is met by oxaliplatin (Figure 1.9A), the l isomer of [oxalatol f ra/rv-1,2-diaminocyclohexane)platinum (II)], oxaliplatin, [Pt(II)(oxalato)(DACH)]. This platinum agent is used for secondary treatment of metastatic colorectal cancer.77 Oxaliplatin, like carboplatin, has a kinetically slower leaving group, and is also less nephrotoxic than cisDDP. The limiting toxicity of oxaliplatin is peripheral sensory neuropathy, also seen with cisDDP. The neuropathy affects the extremities and increases in incidence and... 

The stimulated Raman emission exhibits a threshold and only a few vibrational lines are observed, corresponding to the lines of highest intensity in the normal Raman spectrum. For observation of the inverse Raman spectrum, both the continuum and the monochromatic stimulating radiation are supplied. There is no threshold and therefore the complete Raman active spectrum can be obtained if the continuum light source has a sufficient spectral bandwidth. 

The activity spectrum of a pesticidal compound is often determined by the physical properties of the compound. For example, systemic insecticides usually require both water and lipid solubility since it is necessary for them to pass through... 

The structurally close congener am-picillin (no 4-hydroxy group) has a similar activity spectrum. However, because it is poorly absorbed (<50%) and therefore causes more extensive damage to the gut microbial flora (side effect diarrhea), it should be given only by injection. 

Activity spectrum. Disinfectants inactivate bacteria (gram-positive > gram-negative > mycobacteria), less effectively their sporal forms, and a few (e.g, formaldehyde) are virucidal. 

For this task, easily accessible properties of mixtures or pure metabolites are compared with literature data. This may be the biological activity spectrum against a variety of test organisms. Widely used also is the comparison of UV [90] or MS data and HPLC retention times with appropriate reference data collections, a method which needs only minimal amounts and affords reliable results. Finally, there are databases where substructures, NMR or UV data and a variety of other molecular descriptors can be searched using computers [91]. The most comprehensive data collection of natural compounds is the Dictionary of Natural Products (DNP) [92], which compiles metabolites from all natural sources, also from plants. More appropriate for dereplication of microbial products, however, is our own data collection (AntiBase [93]) that allows rapid identification using combined structural features and spectroscopic data, tools that are not available in the DNP. 

The molecular ion (M ) of 16 was reported in <1998GHE297> and was shown to be unstable and dissociates in a number of directions. The most stable ion has mjz 262, and high-resolution MS showed that this ion is formed by removal of the isopropyl group and ethyl radicals from M. To determine the structure of this ion, the collision-activation spectrum was recorded and was found to be compound 27 <1997GHE1306>. 

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