Biphenyl structure-activity relationship

Poland, A. and Glover, E. Chlorinated biphenyl induction of arylhydrocarbon hydroxylase activity A study of the structure-activity relationship. Mol. Pharmacol. (1977) 13 924-938. 

For halogenated aromatic hydrocarbons like polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) the binding to the aryl hydrocarbon (Ah) receptor regulates their toxicity [89]. The Ah receptor controls the induction of one of the cytochrome P450 enzymes in the liver. Toxic responses such as thymic atrophy, iveight loss, immu-notoxicity and acute lethality are associated ivith the relative affinity of PCBs, PCDFs and PCDDs for the Ah receptor [89]. The quantitative structure-activity relationship (QSAR) models predicting the affinity of the halogenated aromatic hydrocarbons ivith the Ah receptor describe the electron acceptor capability as well as the hydrophobicity and polarizability of the chemicals [89[. 

Polybrominated Biphenyls. In air, the two processes that may result in significant degradation or transformation of PBBs are photooxidation by hydroxyl radicals and direct photolysis. The estimated half-life of pentachlorobiphenyl in air due to reaction with hydroxyl radicals is 41.6 83.2 days (Atkinson 1987a). Based on a structure-activity relationship for the estimation of half-lives for the gas-phase reactions of hydroxyl radicals with organic compounds (Atkinson 1987b), the estimated half-lives of hexabromobiphenyl and decabromobiphenyl due to reaction with OH radicals are 182 and 2,448 days, respectively. These half-lives are consistent with the half-life of pentachlorobiphenyl due to reaction with OH radicals. However, the half-lives of brominated biphenyls expected to be present in the particulate phase in the air may be even longer than the estimated half-lives due to gas phase reaction. Therefore, the Iransfonnation of the hexa- and other higher brominated PBBs in the atmosphere due to reaction with OH radicals may not be irrportant. 

Chen LC, Berberian I, Koch B, et al. 1992. Polychlorinated and polybrominated biphenyl congners and retinol levels in rat tissues Structural-activity relationships. Toxicol Appl Pharmacol 114(l) 47-55. 

Goldstein JA, Safe S. 1989. Mechanism of action and structure-activity relationships for the chlorinated dibenzo-p-dioxins and related compounds. In Kimbrough, Jenson, eds. Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products Elsevier Science Publishers, 239-293. 

Mills RA, Minis CD, Dannan GA, et al. 1985. Studies on the structure-activity relationships for the metabolism of polybrominated biphenyls by rat liver microsomes. Toxicol Appl Pharmacol 78 96-104. 

Miigge, I., Podlogary, B.L. 3D Quantitative Structure-Activity Relationships of Biphenyl Carboxylic Acid MMP-3 Inhibitors Exploring Automated Docking as Alignment Method. Quant. Struct.-Act. Relat. 2001, 20, 215-223. 

Krishnan V, Safe S. 1993. Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCFDs) as antiestrogens in MCF-7 human breast cancer cells Quantitative structure-activity relationships. Toxicol Appl Pharmacol 120 55-61. 

Mor, M., Rivara, S., Lodola, A., Plazzi, P. V., Tarzia, G., Duranti, A., Tontini, A., Piersanti, G., Kathuria, S., and Piomelli, D. (2004). Cyclohexylcarbamic acid 3 - or 4 -substituted biphenyl-3-yl esters as fatty add amide hydrolase inhibitors Synthesis, quantitative structure-activity relationships, and molecular modeling studies.. Med. Chem. 47, 4998—5008. 

Ivanciuc T, Ivanciuc O, Klein DJ. Modeling the bioconcentration factors and bioaccumulation factors of polychlorinated biphenyls with posetic quantitative super-structure/activity relationships (QSSAR). Mol Divers 2006 10 133-45. 

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. 

The replacement of the 3-phenoxybenzyl alcohol fragment by 2-methyl[1,1 -biphenyl]-3-yl leads to an increase in initial and residual foliar activity in the alkyl aryl oxime ethers. An unanticipated result was the activity of these oxime ethers as soil insecticides. The corresponding 3-phenoxybenzyl alcohol oxime ethers were inactive as soil insecticides. The results of a structure activity relationship study revealed biological activity is enhanced by electron withdrawing substituents. 

Hirashima, S., Suzuki, T., Ishida, T., Noji, S., Yata, S., Ando, I., Komatsu, M., Ikeda, S., Hashimoto, H. Benzimidazole derivatives bearing substituted biphenyls as hepatitis C virus NS5B RNA-depend-ent RNA polymerase inhibitors structure-activity relationship studies and identification of a potent and highly selective inhibitor JTK-109. J. Med. Chem. 2006, 49, 4721-4736. 

Connor K, Ramamootrhy K, Moore M, et al. 1997. Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens Structure-activity relationships. Toxicol Appl Pharmacol 145 111-123. 

Davis D, Safe S. 1990. Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice Structure-activity relationships as Ah receptor agonists and partial antagonists. Toxicology 63 97-111. 

Denomme MA, Bandiera S, Lambert I, et al. 1983. Polychlorinated biphenyls as phenobarbitone-type inducers of microsomal enzymes Structure-activity relationships for a series of 2,4-dichloro-substituted congeners. Biochem Pharmacol 32 2955-2963. 

Kodavanti PRS, Ward TR, McKinney JD, et al. 1995. Increased [ H]phorbol ester binding in rat cerebellar granule cells by polychlorinated biphenyl mixtures and congeners Structure-activity relationships. Toxicol Appl Pharmacol 130 140-148. 

Leece B, Denomme MA, Towner R, et al. 1985. Polychlorinated biphenyls Correlation between in vivo and in vitro quantitative structure-activity relationships (QSARs). J Toxicol Environ Health 16 379-388. 

Waller, C.L., Minor, D.L. and McKinney, J.D. (1995) Using three-dimensional quantitative structure-activity relationships to examine estrogen receptor binding affinities of polychlorinated hydroxy-biphenyls. Environ. Health Persp., 103, 702-707. 

Zarrinmayeh H, Tromiczak E, Zimmerman DM et al (2006) A novel class of positive allosteric modulators of AMPA receptors design, synthesis, and structure-activity relationships of 3-biphenyl-4-yl-4-cyano-5-ethyl-l-methyl-lH-pyrrole-2-carboxylic acid, LY2059346. Bioorg Med Chem Lett 16 5203-5206... 

Muegge I, Podlogar B. 3D-quantitative structure activity relationship of biphenyl carboxylic acid MMP-3 inhibitors exploring automated docking as alignment tool. Quant Struct-Act Relat 2001 20 215-222. 

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