Isoster

Synthesis and antiproliferative activity of furocoumarin isosters (pyrrolo-, thieno-, oxazolo-, and triazolocoumarins, 8- and 4- azapsoralenes) 95F479. 

Cathepsin D. The design of inhibitors of the aspartyl protease cathepsin D started from a virtual library of peptide analogs that contained the typical hydroxyethylamine isoster for the cleavable peptide bond. As the availability of starting materials would have generated a library of about 1 billion compounds, virtual screening was applied to reduce this multitude of candidate structures to a reasonable number. The backbone of a peptide... 

Recently, compound CM 30366 (CAS 82239-52-9), the 4-hydroxyphenyl analogue of minaprine, also has been studied in some detail. Based on the results obtained in a behavioural study in mice and rats, it has been concluded that CM 30366 may be of potential therapeutic usefulness due to a significant atypical dopamine-like activity [159], Also thiophene isosters of minaprine have been claimed as antidepressant agents [131],... 

In the U.S.A. various pyridazine analogues of naturally occurring pyrimidine nucleosides have been prepared [299, 300] for a review on this subject see [13]. Within this series, 3-deaza-6-azauridine (86) has been found to inhibit the growth of L-1210 mouse leukaemic cells with an ID50 value of a 7 X 10 5 M [299, 301], The inhibitory effect of this uridine isoster might be due to interference in pyrimidine biosynthesis [302],... 

Novel highly functionalized dipeptide isosters were synthesized via diastereoselective alkyl-arylation protocol of a glucose-derived (R)-tert-butanesulfinylimine. One of these novel sugar amino acid derivatives, a D-Ala-Ser/Thr isostere, was applied in a peptide synthesis protocol to afford a cyclic tetramer (Fig. 53).69... 

Also considered are adsorption isobars, which are the dependences of q(T) at p — const., and adsorption isosters, that is, dependence ofp T) at q = const. [53]. 

To further evaluate the binding of aminoglycosides to the RRE, Marino and co-workers have developed truncated RRE constructs (RRE IIB) where 2-aminopurine (2-AP), a fluorescent A isoster, replaces A at position 68 or U at position 72 (Figure 10.8). The fluorescent constructs retain their ability to bind Rev and can be used to monitor ligand binding. By measuring fluorescence... 

The precursors for building the heterocyclic rings in the C-nucleoside isosters 923 were 917 and 920. The former was prepared from ethyl bromo-... 

Calcagni, A., Ciattini, P. G., Di Stefano, A., Dupre, S., Luisi, G., Pinnen, F., Rossi, D., and Spirito, A. (1999). psi(S02NH) transition state isosters of peptides. Synthesis and bioactivity of sulfonamido pseudopeptides related to camosine. Farmaco 54, 673-677. 

The Ni—C force constant is not known with certainty, but all quoted values are quite small, and are of the same order as metal-carbon force constants in metal alkyls (34). This indicates that what effect there is does not appreciably strengthen the nickel-carbon bond. Again, the effect is much greater for the anionic isosters. 

Alternatively, the use of dipeptide isosters mimicking the cis- or tram-imide geometry 30 or replacement of the imide bond with Z- or E-alkene units131-36 (see also Section 10.5) have been proposed. 

Dipeptide Isosters (5-Amino Acids) y-Amino Acid p-Amino Acid... 

Analogously, Pelter and co-workers reported that PIFA reacts in CF3CH2OH with readily available rans-2,3-dibenzylbutyrolactones (150) to produce isoste-ganes (32) and steganes (33) (Scheme 22). After that, they improved the yields of 32 and 33 by treating 150 with PIFA in aqueous MeOH followed by treatment with TFA via the quinol intermediate 151 [108]. Related synthetic studies toward lignans have also been performed by the same group [109-111]. 

Fischell TA, Carter AJ, Laird JR, The beta-particle-emitting radioisotope stent (isostent) animal studies and planned clinical trials. Am J Cardiol I 996 78 45-50, van der Giessen WJ, Lincoff AM, Schwartz RS, et al. Marked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 1996 94 1690-1697. 

Lamos and colleagues reported the modification of cyclophilin A (CypA) by binding immunosuppressive cyclosporin A with a benzophenone-Dj j and a biotin moiety (compound 89, Fig. 11a) [91]. As a proof of principle, they used a 1 1 mixture of this TIP and its nondeuterated isoster for the selective PAL and pulldown of CypA among three other proteins. Subsequent tryptic digestion of the elutes and LC-MS/MS analysis allowed the identification of 11 CypA characteristic peptides, two of which were modified with the probe, as evidenced from the double, 11 Da separated, peaks in the mass spectra. The large 11-Da mass difference allowed easy visual recognition of labeled peptides in the mass spectra, which makes this a powerful method for determination of the modification site after PAL however, application in more complex systems still remains to be done. 

Isosters Two or more molecules having same number of atoms and same number of electrons are known... 

Der so gewonnenen Substanz 87> kommt eine Struktur mit acht-gliedrigem Ringsystem zu, die leicht als isoster zu (19—23) erkenntlich ist ... 

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