Potential biological activity

The general interest in the pteridines is due to their widespread occurrence in both the animal and plant kingdoms, implying potential biological activity and drug-type properties in structural analogues. 

Aminomethylated V-aryl- and V-azaheteroaryl-2,5-dimethylpyrroles, compounds with potential biological activity 95F431. 

Papers dealing with this topic are exhaustively reviewed in Comprehensive Heterocyclic Chemistry I (84CHEC-I(6)235) and II (96CHEC-II(3)373). Nevertheless, little information is available on the 5-oxides. Recently, the heteroaromaticity of thiazole compared with isothiazole and thiadiazole 5,5-dioxide systems was studied (97MI1). Quantum-chemical calculations and X-ray studies were performed on 3,3 -di[l,3-thiazolidin-4-one] derivatives (95JCC(25)589) studied for their potential biological activity (97FA(52)43). 

Although non-exhaustive, this review shows that a large variety of new difunc-tionalized mixed phosphorus and sulfur molecular structures have been described during the last ten years. It also demonstrates that such compounds are powerful synthetic tools or building blocks and, in some cases, molecules (or precursors of more complex molecules) with potential biological activities. 

Phosphonyl radicals have been used to functionalize the (60)-, (70)- and (76)-fullerenes [35]. Radical phosphonylation (Scheme 12) of alkenes has been developed by Motherwell et al. [36] for the preparation of fluorophosphony-lated analogs of riboses that exhibit high potential biological activity [37]. 

In general, the described techniques provide an effective, flexible, and relatively fast solution for library design based on analysis of bioscreening data. The quantitative relationships, based on the assessment of contribution values of various molecular descriptors, not only permit the estimation of potential biological activity of candidate compounds before synthesis but also provide information concerning the modification of the structural features necessary for this activity. Usually these techniques are applied in the form of computational filters for constraining the size of virtual combinatorial libraries and... 

In his approach toward selenium-containing heterocycles with potential biological activity, Abdel-Hafez reacted 2-amino-3-(4,5-dihydro-17/-imidazol-2-yl)-4,5,6,7-tetrahydro-l-benzoselenophene 297 with triethyl orthoformate and benzaldehyde to generate the tricyclic systems 296 and 298, respectively (Scheme 21) <2005RJ0396>. Similarly, reaction with carbon disulfide gave the corresponding thiourea 299. 

The clinical significance of protein-based impurities relates to (a) their potential biological activities and (b) their antigenicity. Whereas some contaminants may display no undesirable biological activity, others may exhibit activities deleterious to either the product itself (e.g. proteases that could modify/degrade the product) or the recipient patient (e.g. the presence of contaminating toxins). 

This process was carried out with the use of diastereomerically and enan-tiomerically pure five-membered cyclic nitronates (213). After selective silylation of the hydroxy group and intramolecular cycloaddition, these compounds give enantiomerically pure fused systems, which are similar precursors of enantiomer-ically pure hydroxyamino acids and other polyfunctional compounds possessing potential biological activity. 

Additional data on the use of oxazine (539) and products of its modifications in syntheses of compounds having potential biological activity and their precursors are presented in Scheme 3.274 (541). Catalytic hydrogenation of the imino and oximino fragments is primarily used for this purpose. This approach made it possible to prepare a representative series of nitrogen-containing heterocycles and of other previously unknown compounds. 

The condensation of DMDP with carbon disulfide/dicyclohexylcarbodiimide (DCC) afforded the indolizine derivative—potentially biological active thionocarbamate on carbohydrate scaffold, fused from the nitrogen side. 

The method was first applied to the preparation of a number of simple alkyl and aryl C-l glycals,71 but since then the scope of this approach have been extended with the preparation of a small library of significant C-l glycals including steroidal, and glycerolipidic residues endowed with potential biological activity.72... 

General Comment. The foregoing examples clearly show that poly(vinyl alcohol) can be modified readily and that some of these derivatives have potential (and/or actual) biological activity. This survey is definitely not encyclopedic in scope but rather illustrative. No doubt many more examples of potentially biologically active poly(vinyl alcohol) derivatives will be developed in the future and it is entirely possible that some of these may become of value in chemotherapy and other areas where biologically active polymers are now being studied. 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

Thus, hydrogenated heteroannulated azocines, while relatively little known, are of interest for potential biological activity and their synthesis has attracted attention. 

Extension of the linkage to hve atoms as in 285 provides routes to pyrazolines or pyrazoles 286, or 1,2,4-triazoles 287, fused to a seven-membered ring. The products are potentially biologically active and examples have been reported for X=N (177-181), X = 0 (181-185) and for a pyrazolo fused analogue (186) and X = S (187). In some cases, [e.g., (183)], these reactions are accompanied by tandem intramolecular-intermolecular reactions leading to the formation of macrocycles (see the section Tandem Intermolecular-Intramolecular Cycloaddition Reactions). 

Many constituents with potential biological activity have been extracted from the flowers and leaves, the parts of the plant used for medicinal purposes. These include naphthodianthrones, flavonoids, phlorogluci-nols, and xanthones. Hypericin, one of the naphthodianthrones, has traditionally been considered the main active ingredient, but it is not known whether this is the compound with antidepressant activity. Recent data suggest that a component called hyperforin may be more important than hypericin for the antidepressant activity. 

Alkyl- and aryl-substituted furo[2,3- / thiazolidine derivatives 279, with potential biological activity, have been synthesized by the reaction of methoxycarbonylmethylenetriphenylphosphorane with 4-thiazolidinone derivatives... 

Metals that are potentially biologically active, either therapeutically or toxicologically, may be divided into the following groups, based upon their electron configuration and position in the periodic table of the elements ... 

TABLE 15.3 Other potential biological activities from peptides derived from various fish proteins... 

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