Structure-Spectrum Relationships

P=0 Thomas and Chittenden (5,38 441 have carried out a thorough series of studies on the identification of organophosphorus compounds. The group frequency tables in these studies enable interpretation of many of the characteristic features in the spectra of nerve agents and related chemicals. Several structure-spectrum relationships give specific information on the molecule. One very valuable relation discovered by Thomas is the dependence of the position of the P=0 bond stretching vibration, vp=0, on the substituents on the phosphorus, represented by n constants ... 

Structure-spectrum relationships, in particular the prediction of 3D molecules from spectral information and the prediction of spectral properties, such as H-NMR... 

Expert systems are based on spectral feature-substructure relationship rules that comprise the knowledge base for IR spectral analysis. This is the main difference from neural network techniques, where no prior knowledge about the structure-spectrum relationship is necessary because the network learns inductively from examples. For expert systems a knowledge base has to be established and transformed into a computer operable form. This expert knowledge is expressed in terms of substructure-subspectra relationships. 

The generally accepted structure-activity relationships developed in the early work in the quinolone series held that the N-1 substituent needed to be small and aliphatic. This picture was upset in a dramatic way with the discovery of the excellent potency and antimicrobial spectrum of difloxacin (45) and its congeners in which the substituent on N-1 is an aromatic ring. The synthe-... 

Applications of neural networks are becoming more diverse in chemistry [31-40]. Some typical applications include predicting chemical reactivity, acid strength in oxides, protein structure determination, quantitative structure property relationship (QSPR), fluid property relationships, classification of molecular spectra, group contribution, spectroscopy analysis, etc. The results reported in these areas are very encouraging and are demonstrative of the wide spectrum of applications and interest in this area. 

Effects of Sesquiterpene Lactones on Seed Germination. Sesquiterpene lactones are common constituents of the Asteraceae but are also found in other angiosperm families and in certain liverworts (31,32). These highly bitter substances exhibit a wide spectrum of biological activities (J 3) which include cytotoxicity, anti-tumor, anti-microbial, insecticidal (34) and molluscicidal (35) properties. Furthermore, they are known causes for livestock poisoning and contact dermatitis in humans (33). Structure-activity relationship studies on sesquiterpene lactones have demonstrated that biological activity frequently depend on the presence of the cr... 

The past 30 years have seen the development of a broad spectrum of widely applicable preparative methods for three- and four-membered carbocycles and the accumulation of detailed knowledge about their structure-reactivity relationships. Nowadays, more and more synthetic methodology is being developed, which utilizes the potential of small ring compounds as reactive entities. Cyclopropyl and cyclobutyl moieties in a molecule can be regarded as unique functional groups they allow transformations which are far more difficult or impossible with any of the more conventional functional groups. 

The chemical diversity of pyrrolidine alkaloids indicates a broad spectrum of biological activities, which, however, does not allow, at the present time, structure-activity relationship studies. The available data are inhomogeneous, ranging from investigations of pure compounds to reports of use in folk medecine. 

The final stage of mass spectrum processing involves development of a fragmentation scheme. The scheme should reflect the most characteristic pathways of fragmentation of the molecular ion, composition of the fragment ions (and if possible their structures), the relationship of the fragment ions with one another, and sometimes the relative abundances of their peaks (Schemes 5.23 and 5.24). 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

Many structure—activity relationship studies of host defense peptides have also focused on LL-37. Importantly, LL-37 has a broad spectrum of activities within the immune system but has also displayed cytotoxic activities that would diminish the therapeutic application of this peptide. Thus, structure—activity studies of LL-37 have focused on this cytotoxicity. A study by Nagaoka et al has demonstrated that the cytotoxic and hemolytic activities of LL-37 may reside within different regions of the peptide. Using an 18-mer... 

Traditionally, the structural characterization of designed proteins is carried out by CD spectroscopy, which unfortunately provides only limited structural information at the atomic level. As the understanding of protein design develops more proteins appear that have well-defined structures and the determination of their solution structures by NMR spectroscopy is clearly the main tool for elucidating structure-function relationships. Key information is obtained simply from the ID spectrum (Fig. 7). 

Over the past few years, the heteroaryl-condensed non-natural carbazoles emerged as a rapidly growing class of compounds because of their broad spectrum of useful biological activities (8,249,873). This relatively new class of non-natural carbazoles with a great variety of heterocyclic systems has been extensively investigated in order to understand the structure activity relationships for the various biological activities (843,874—895). 

In the search for structural diversity, and novel therapeutic agents, unique ring structures like the 1,2,5-thiadiazole have always captured the imagination of chemists. Often, as in the case of timolol (4), the interest is rewarded. In the early 1990s, a simple thiadiazole was appended to a penem in the development of the structure-activity relationships for a series of ) -lactamase inhibitors. The result was enhanced penetration of the bacterial membrane and a broader spectrum of activity versus clavulanic acid <9lJAN33l>. 

Anthracyclines are antitumor quinone containing antibiotics produced by different strains of Streptomyces. Some of them, such as adriamycin doxorubicin), and daunorubicin are broad spectrum antitumor compounds. They act by binding to DNA and interfering with DNA replication and gene transcription. Their limitations for clinical use are cardiac toxicity and drug resistance phenomena. Consequently, intense structure-activity relationship studies have been performed to improve the pharmacological profile as well as to enhance the affinity for DNA. In particular, a number of fluorinated anthracyclines have been prepared with introduction of fluorine atoms into D or A cycles, and into the aglycone side chain linked atC-14. ... 

Other P-lactam antibiotics have revolutionized our understanding of the structure-activity relationships in this large group of antibiotics. Thienamycin (9.53), discovered in 1976, is a broad-spectrum antibiotic of high activity. It is lactamase resistant because of its hydroxyethyl side chain but is not absorbed orally as it is highly polar. Unfortunately,... 

Complementary to the synthetic aspects of polyimide chemistry, a wealth of information addressing structure-property relationships of a wide spectrum of polyimides can be found in the literature. Information of this nature can be readily obtained from the literature along with potential application related data [11,131-136]. 

Structure-activity relationships can be inferred by comparison of the antibacterial properties of the clinical agents and related compounds. Different acyl side chains can result In significant changes in the antibacterial activity, both with respect to potency and to breadth of spectrum. The highest activities are observed when the aeylaniino side chain at C-7 is a substituted acetic add. Homologation of the acetic add moiety lowers activity dramatically as exemplified by1 the naturally occurring cephalosporins, which all have weak activity. 

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