Structure activity relationship synthesis

Chen, S.-H. Fairchild, C. Mamber, S. W. Farina, V. Taxol structure-activity relationships synthesis and biological evaluation of 10-deox3daxol. J. Org. Chem., 1993, 58 2927-2928. 

Some structure-activity relationships, synthesis of new brassinosteroids, and new sensitive bioassays for brassinosteroids are presented. 

Chen S-H, Fairchild C, Mamber SW, Farina V (1993) Taxol Structure-Activity Relationships Synthesis and Biological Evaluation of 10-Deoxytaxol. J Org Chem 58 2927... 

A challenging task in material science as well as in pharmaceutical research is to custom tailor a compound s properties. George S. Hammond stated that the most fundamental and lasting objective of synthesis is not production of new compounds, but production of properties (Norris Award Lecture, 1968). The molecular structure of an organic or inorganic compound determines its properties. Nevertheless, methods for the direct prediction of a compound s properties based on its molecular structure are usually not available (Figure 8-1). Therefore, the establishment of Quantitative Structure-Property Relationships (QSPRs) and Quantitative Structure-Activity Relationships (QSARs) uses an indirect approach in order to tackle this problem. In the first step, numerical descriptors encoding information about the molecular structure are calculated for a set of compounds. Secondly, statistical and artificial neural network models are used to predict the property or activity of interest based on these descriptors or a suitable subset. 

Hundreds of flavonols have been isolated and characterized many of them are biologically active. Hence a great synthetic interest has arisen. Some of the efforts have concentrated on the synthesis of naturally oecurring flavonols while others have focused on the synthesis of flavonol derivatives for structure activity relationships. ... 

Finke, P. E., Oates, B., Mills, S. G., MacCoss, M., Malkowitz, L., Springer, M. S., Gould, S. L., DeMartino, J. A., Carella, A. Carver, G., et al. (2001). Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4 synthesis and structure—Activity relationships for l-[7V-(Methyl)-7V-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(7V-(alkyl)-7V-(benzylox-ycarbonyl)amino)piperidin-l-yl)butanes. Bioorg. Med. Chem. Lett. 11 2475-2479. 

Smith PW, Sollis SL, Howes PD, Cherry PC, Starkey ID, Cobley KN, Weston H, Scicinski J, Merritt A, Whittington A, Wyatt P, Taylor N, Green D, BetheU R, Madar S, Fenton RJ, Motley PJ, Pateman T, Beresford A (1998) Dihydropyrancarboxamides related to zanamivir a new series of inhibitors of influenza virus sialidases. 1. Discovery, synthesis, biological activity, and structure-activity relationships of 4-guanidino- and 4-amino H-pyran-6-carboxamides. J Med Chem 41 787-797... 

Schon U, Antel J, Bruckner, Messinger J. Synthesis, pharmacological characterization, and quantitative structure-activity relationship analyses of 3,7,9,9-tetraalkylbispidines derivatives with specific bradycardic activity. J Med Chem 1998 41 318-31. 

Due to their demanding synthesis, diamondoids are helpful models to study structure-activity relationships in carbocations and radicals, to develop empirical computational methods for hydrocarbons, and to investigate orientational disorders in molecular crystals as well [5,32]. 

In 1985, it was reported by Hsiang et al. [43] that the cytotoxic activity of 20-(S)-camptothecin (CPT III) was attributed to a novel mechanism of action involving the nuclear enzyme topo I, and this discovery of unique mechanism of action revived the interest in CPT and its analogues as anticancer agents. CPT stabilizes the covalent, reversible topo I-DNA complex leading to the inhibition of DNA synthesis in mammalian cells and interferes with the topo I breakage-reunion reaction [44]. Clinical trials and structure-activity relationships have demonstrated the requirement of the a-hydroxy group, the... 

Shi DF et al. (2001) Quadruplex-interactive agents as telomerase inhibitors synthesis of porphyrins and structure-activity relationship for the inhibition of telomerase. J Med Chem 44(26) 4509-4523... 

Lopez-Rodriguez ML et al. (1996) Synthesis and structure-activity relationships of a new model of arylpiperazines. 1. 2-[[4-(o-Methoxyphenyl)piperazin-l-yl]methyl]-1, 3-dioxoperhydroimidazo[l,5-alpha]pyridine a selective 5-HTlA receptor agonist. J Med Chem 39(22) 4439-4450... 

The structure/activity relationships for the methisazone, 3a, derivatives against adenoviruses and poxviruses have been shown to be similar [78]. Pearson and Zimmerman [79] demonstrated that all three types of polioviruses are inhibited by 2-acetylpyridine JV-dibutylthiosemicarbazone, which is similar to 3a, by blocking viral RNA synthesis. A 3-substituted triazinoindole derivative of isatin was effective against several strains of rhinovirus in tissue culture the mechanism of action is unknown [80]. 

Previous syntheses An example of this point can be recognized by examination of one known synthesis of thienobenzazepines (Scheme 6.1). This synthetic route involves a key palladinm-catalyzed cross-conpling of stannyl intermediate 3, prepared by method of Gronowitz et al., with 2-nitrobenzyl bromide. Acetal deprotection and reductive cyclization afforded the desired thienobenzazepine tricycle 4. In support of structure activity relationship studies, this intermediate was conveniently acylated with varions acyl chlorides to yield several biologically active componnds of structure type 5. While this synthetic approach does access intermediate 4 in relatively few synthetic transformations for stractnre activity relationship studies, this route is seemingly nnattractive for preparative scale requiring stoichiometric amounts of potentially toxic metals that are generally difficult to remove and present costly purification problems at the end of the synthesis. 

The third step is to optimize the lead molecule through iterative chemical synthesis and biological testing, aiming to obtain molecules with the required potency (typically nanomolar), selectivity, bioavailability, and DMPK (drug metabolism and pharmacokinetics) properties. This step usually requires considerable time and resources usually the synthesis of hundreds of compounds is needed to deduce a robust SAR (structure-activity relationship). Such resources can be considerably reduced and the... 

The pros and cons of oxidative dehydrogenation for alkene synthesis using doped cerianites as solid oxygen carriers are studied. The hydrogen oxidation properties of a set of ten doped cerianite catalysts (Ce0.9X0.1Oy, where X = Bi, In, La, Mo, Pb, Sn, V, W, Y, and Zr) are examined under cyclic redox conditions. X-ray diffraction, X-ray photoelectron spectroscopy, adsorption measurements, and temperature programmed reduction are used to try and clarify structure-activity relationships and the different dopant effects. 

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