Structure-activity relationships aryl substitution

Finke, P.E. etal. (2001) Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 2 structure-activity relationships for substituted 2-aryl-l-[N-(methyl)-N-(phenylsulfonyl)amino]-4-(piperidin-l-yl)butanes. Bioorganic C Medicinal Chemistry Letters, 11 (2), 265-270. 

In the field of isospecific propylene polymerization, systematic structure-activity relationship studies of metalloeenes have shown that the combination of 2-alkyl and 4-aryl substitution is cmcial for a technically suitable catalyst performance (high catalytic activity, excellent stereoselectivity, high melting point of the polymer, certain copolymer properties, etc.) [7, 8]. Consequently, there is a consider-... 

Replacement of the normal pyrethroid ester by alternative linkages usually leads to diminution of biological activity. One important exception to this general phenomena is several oxime ether derivatives, in particular, 3-phenoxybenzyl derivatives of various alkyl aryl ketones. Pyrethroid esters derived from certain 2-substituted-[1,1 -biphenyl]-3-methanols have been shown to possess initial and residual activity surpassing that of esters derived from 3-phenoxybenzyl alcohol. Now it has been demonstrated that the same enhancement of activity was observed for alkyl aryl oxime ethers of certain [1,1 -biphenyl]-3-methanols compared to the corresponding 3-phenoxybenzyl alcohol derived oximes. The synthesis, biological activity, including soil activity, structure-activity relationships and toxicity of several of these biphenylmethyl oxime ethers are described. 

DiJoseph, J. F., Sung, A., Sharr, M. A., Killar, L. M., Walter, T., Jin, G., Cowling, R., Tillett, J., Zhao, W., McDevitt, J., Xu, Z. B. Synthesis and structure-activity relationship of A-substituted 4-aryl-sulfonylpiperidine-4-hydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis. J. Med. Chem. 2003, 46(12), 2376-2396. 

Table 10-6 represents a summary of empirically arrived at structure-activity relationships, The exception of para-aryl substitutions for cardioselective P-blockers (IIB 1 and 4) should be noted but cannot be satisfactorily explained. In fact, not all the para substituents are as lipophilic as the amide ones in practolol, acebutolol (No. 11), atenolol (No. 12), or the ester group in esmolol (No. 14). The methoxyethyl group of metoprolol (No. 15) and the large hydrocarbon nature of the cyclopropylmethoxyethyl function of betaxolol (No. 13) would hardly be expected to increase aqueous solubility of these compounds (see Table 10-4). Still, all the -selective compounds are much less lipophilic than propranolol. Such apparent data correlations may have contributed to a belief that a cardioselectivity-hydrophilicity relationship exists due to some putative hydrophilic site on the Pj receptor. This notion, however, was dispelled by a study comparing hydrophilicity, substituent positions, and cardioselectivity in three sets of l-(2-propylamino)-3-phenoxy-2-propanols. The data clearly show that for each set of compounds even with identical lipophilicities (log P) the Pi-activity resided primarily in the para isomer.

H.P.L. Steenackers, D.S. Ermolat ev, B. Savaliya, A. De Weerdt, D. De Coster, A. Shah, E.V. van der Eycken, D.E. De Vos, J. Vanderleyden, S.C.J. De Keersmaecker, Structure-activity relationship of 4(5)-aryl-2-amino-lH-imidazoles, Nl-substituted 2-aminoimidazoles and imidazo[l,2-a]pyrimidinium salts as inhibitors of biofilm formation by Salmonella typhimuriiun and Pseudomonas aeruginosa, J. Med. Chem. 54 (2011) 472 84. 

Diary] and triaryl or naphthyl carbamates exhibit low herbicidal activity. The substitution of the aryl radical for a heterocyclic radical gives heterocyclic alkyl and dialkyl ureas, of which many examples have been prepared in recent years. The herbicidal activity of urea derivatives containing a heterocyclic radical, such as benzthiazole, thiazole, thiadiazole, oxadiazole and pyridine, is favourable if one or two methyl groups are substituted at the N -nitrogen. The carrier of total or selective action in these derivatives is presumably the heterocyclic part of the molecule. More recently several new groups of compounds have become known, mainly in the patent literature, for which the structure-activity on relationships are still to be elucidated. 

A large number of new tropanyl esters and other related compounds have been prepared, with the purpose of contributing further structure-pharmacological activity relationships. Inter alia, para-substituted tropanyl benzoates (for studies of the substrate specificity of atropine esterase), benzazocines (narcotic antagonists) from 6-hydroxytropinone, 5-aryl-furan-2-carboxylic esters of pseudotropine (local anaesthetics), 2,4,5-trimethylpyrrole-3-carboxylic acid... 

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