Biological isosterism

Baclofen, 121 Bamethan, 39 BAS, 96 BCNU, 12 Becanthone, 413 Beckett-Casey rule, 328 Beloxamide, 56 Benapryzine, 74 Bendazac, 351 Benfurodil, 355, 356 Benorterone, 156 Benoxaprofen, 356 Benperidol, 290 Benproperine, 100 Benzbromarone, 354 Benzetimide, 293 Benzilate esters, 74 Benzilonium bromide, 72 Benzindopyrine, 343 Benzoctamine, 220 Benzodepa, 122 Benzothiadiazines, 383 Benztriamide, 290 Benzydamine, 350 Betahistine, 279 Bioisosterism (see also biological isosterism), 278... 

Bisehler-Napieralski reaetions, 4, 279 carboline synthesis from, 4, 516 Mannieh-type reactions, 4, 279 sulfur isosteres, biological activity, 4, 913 synthesis, 4, 337, 913 Tryptophan... 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

Benzacridine tetrahydroepoxides and did epoxides. The isosteric molecules BA, benz[a]acridine (BaAcr) and benz[c]acridine (BcAcr) and their derivatives provide excellent probes for studying the effect of electronic changes upon biological properties. The... 

Phosphothioates have been explored as analogues that had the potential to be biologically stable phosphate isosteres. Phosphothioate analog 4 (EC50 on SI Pi,3,4, = 49, 600, 860 and 130 nM, respectively) showed a similar SIP receptor selectivity profile to the corresponding phosphate albeit with a ca. 10-fold loss... 

Biological applications and utility of fluoroolefin peptide isosteres 5.1. Background... 

The preparation of the fluoroolefin amide isosteres is reviewed. The incorporation of the amide isosteres in peptidomimetics and the influence of that isosteric substitution on biological activity on inhibition of peptidyl prolyl isomerases cyclophilin (CyP) and Pini, dipeptidyl peptidase IV/CD26 (DPP IV) and thermolysin is described. In addition, select fiuoroolefination procedures which may have utility in the construction of fluoroolefin amide isosteres are illustrated. 

BIOLOGICAL APPLICATIONS AND UTILITY OF FLUOROOLEFIN PEPTIDE ISOSTERES... 

Tertiary amides, such as those associated with prolyl amide bonds frequently influence turn architectures. The importance of the cis Xaa-Pro bond on activity was recognized and proposed to be the source of differentiation in biological activity [86] therefore, isomerization of the prolyl amide bond is central to regulation of protein folding, immunosuppression, and mitosis. These functions are not surprisingly associated with several disease states and thus substitution of the acyl-proline amide bond with the fluoroolefin isostere has received considerable attention. 

Cyclic peptides have been synthesized not only for the purpose of improving biological activities and selectivity, but also to explore basic features of secondary structures in peptides and to investigate with such mimetic compounds the conformational behavior of proteins. For this purpose artificial building blocks have been frequently used or amide bonds have been modified isosterically. Nature also offers a variety of modifications in cyclic peptides that are critically involved in their bioactivity. Some of the most common natural and synthetic modifications including unusual structural elements such as thiazoles (and dihy-drothiazoles) and oxazoles (and dihydrooxazoles) with broad synthetic applications will be presented in the following section. 

Substances that are isosteric equivalents of substances that are toxic or pharmacologically active may also possess these biological properties. It is also possible that biological properties may be bestowed, exacerbated, or attenuated when isosteric modifications are made. This point is illustrated by the following examples. 7-Methyl-benz[a]anthracene (36) is a known carcinogen, whereas 7-methyl-l-fluorobenz[o]... 

Sieburth, S.McN., Manly, C.J. and Gammon, D.W. (1990) Organosilane insecticides. Part I. Biological and physical effects of isosteric replacement of silicon for carbon in etofenprox... 

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