Testing compound

Coulthard for amoebicidal action. Each kind of activity increases to a peak as the series is ascended and then diminishes. In the 0-n-alkyl series the peak is at 0-n-butylharmol for Bacillus typhosus, at 0-n-amyl-harmol for Staphylococcus aureus and at 0-n-nonylharmol for Entamoeba histolytica. In the 0-io-diethylaminoalkyl series the peak for B. typhosus is at 0-to-diethylaminononylharmol. No trypanocidal or anti-malarial action was observed in a selection of the compounds tested. ... 

Starting from a collection of samples remarkably well resolved (alpha > 6) on Chiralcel OD (Cellulose tris(3,5-dimethylphenylcarbamate) coated on aminopropyl silica), a putative three-point enantiophore for binding to CSR was derived (Fig. 4-10). This enantiophore query was used to search (CFS 3D search) within a list comprising 4203 compounds tested on Chiralcel OD. From this search domain of CHIRBASE 3D, 191 structures were found to match the enantiophore. 

It is essential to determine the concentration of each isomer and define limits for all isomeric components, impurities, and contaminants of the compound tested preclin-ically that is intended for use in clinical trials. The maximum level of impurities in a stereoisomeric product used in clinical studies should not exceed that in the material evaluated in nonclinical toxicity studies. This point is expanded in the ICH impurities guideline (Section 13.5.3). 

N.D. Mason, Impact Sensitivity Determinations of Explosive Compounds Tested During the Period 1 Jan to 1 Nov 1950 , NOL NAVORD Rept 1589 (Nov 1950) 10) A.H. Lamberton,... 

Physical Requirements for the Liquid Polymer and Cured Compounded Test Sheet... 

Coefficients of the Abrasion Equation as Eunction of Log Energy and Log Speed for Six Compounds Tested on Alumna 60 at Nine Testing Conditions... 

A compound tested in one therapeutic area shows some promise in another, but that information is never communicated to the right project team or group. 

The COMPACT (computer-optimized molecular parametric analysis of chemical toxicity) procedure, developed by Lewis and co-workers [92], uses a form of discriminant analysis based on two descriptors, namely, molecular planarity and electronic activation energy (the difference between the energies of the highest occupied and lowest unoccupied molecular orbitals), which predict the potential of a compound to act as a substrate for one of the cytochromes P450. Lewis et al. [93] found 64% correct predictions for 100 compounds tested by the NTP for mutagenicity. 

The compounds 25a-c and 33a-f were tested for analgesic activity [ 14] by oral administration in mice in terms of the inhibition of the writhing syndrome induced by acetic acid. The ED50 which represents the dose producing 50% inhibition of the writhing induced by acetic acid was determined. The ED50 values of the compounds tested are summarized in Table 4. The pyrazolones 25a-c showed more potent analgesic activity than 1 and amino-pyrine. 

It can be seen that though the aldehydic function is important for antiinflammatory activity as observed in compoimd 36, its conversion to the unsaturated cyanoesters 37 shows an increase in the activity. Similarly, the ethers 39 with the ortho aldehydic group upon conversion to benzofurans 6 show a sHght increase in activity. None of the compounds tested showed any analgesic activity. 

The pH-partition hypothesis, now widely accepted in pharmaceutical research, suggests that membrane permeability will be highest at the pH where the molecule is least charged however, this is also the pH where the molecule is least soluble. (In Brodie s work, the compounds tested have relatively high water solu-... 

The Boger group [64-66] has extensively studied the use of a-ketoheterocycles as FAAH inhibitors. In their initial studies, a range of a-ketoheterocycles based on oleic acid was synthesised. A range of five- and six-membered monocyclic heterocycles and three bicyclic heterocycles (benzothiazole, benzimidazole and benzoxazole) was examined. Although many of the compounds tested were found to inhibit FAAH activity with micromolar affinities, the best results were obtained with heterocycles that incorporated a weakly basic nitrogen a - to the heterocycle (Table 6.5) [64]. 

Drawing Conclusions Summarize how the results of this laboratory activity relate to the formulas of the compounds tested. 

Dose-related shifts in predominant EEG frequency for PCP and several phencyclinoids are shown in figure 3. For all 10 compounds tested, there was a shift in predominant EEG frequency into the theta range across the lower doses, associated primarily with increased locomotor activity and stereotyped behaviors. With further increases in dose, PCP and all of its analogues produced shifts to lower predominant frequencies, which typically fell between 2 and 4 Hz. As the dose was incremented geometrically, the lower frequency EEG waves were associated first with ataxia, then with dyskinetic movements, catalepsy, and possibly seizure activity. SKF-10,047 also produced ataxia, but was unique in that it did not cause a shift to a lower predominant frequency and produced only EEG theta activity at all subconvulsant doses. 

In Table 2 we highlight pertinent information from a number of studies. We did not aim to be exhaustive, but rather to provide enough examples to provide a flavor for the type of studies performed. Of the studies in Table 2, one element to note is the small number of compounds tested in five cases. Despite starting with databases that range from 37 K to 2.5 million compounds, most researchers end up actually testing less than 100 in most cases and several hundreds at most. 

---