Structure-activity relationships carbamates

Woo, Y.-T. (1983) Carcinogenicity, mutagenicity and teratogenicity of carbamates, fhiocarbamates and related compounds an overview of structure-activity relationships and environmental concerns. Environ. Carcinog. Ecotoxicol. Rev., Cl (1), 97-133. 

Drossman, H., H. Johnson, and T. Mill, Structure activity relationships for environmental processes 1 Hydrolysis of esters and carbamates , Chemosphere, 17, 1509-1530 (1988). 

Maxwell, D.M., Lenz, D.E. (1992). Structure-activity relationships and anticholinesterase activity. In Clinical and Experimental Toxicology of Organophosphates and Carbamates (B. Ballantyne, T.C. Marrs, eds), pp. 47-58. Butterworth-Heinemann, Oxford. 

Levesque. L. etai (1991) The interaction of 3.5-pyrazolidinedione drugs with receptors for f-Met-Leu-Phe on human neutrophil leukocytes a study of the structure- activity relationship. Can. J. Physiol. Pharmacol., 69,419-425. Levesque. L. era (1992) Comparison of two classes of non-peptide drugs as antagonists of neutrophil receptors for f-Met-Leu-Phe. Pyrazolons and iodinated radiographic contrast agents. Biochem. Pharmacol., 43. 553-560. Derian. C.K. er at (1996) Selective inhibition of N-formylpeptide-induced neutrophil activation by carbamate-modified peptide analogues. Biochemistry, 35.1265-1269. 

Lin G, Lai CY, Liao WC. Molecular recognition by acetylcholinesterase at the peripheral anionic site Structure-activity relationships for inhibitions by aryl carbamates. Bioorg Med Chem 1999 7 2683-9. 

Although a structure-activity relationship can not be established yet for the whole substitution pattern, some preliminary comments can be made other than those reported for substitution at N-1 1) a meta substituent on the ureidic phenyl, (e.g. dimethyl amino or thiomethyl ) may enhance B receptor affinity (however, this is dependent on the substituent at N-1) 2) introduction of an ortho-T substituent on the N-5 phenyl proved to be beneficial in combination Avith a meta dimethylamino substituent on the ureidic side chain and a branched alkyl at N-1 3) substitution with halogens at the fiised aromatic ring was not as valid as in other series (e.g. carbamates) [30]. 

Various V-methyl and 0-methyl derivatives (4"-, 6-, 11-, and 12-) of 37 were prepared and evaluated for their antibacterial activity. 6-O-Methyl AZM (56a) (Fig. 10) was slightly less active than AZM, while 11-0-methyl AZM (56b) exhibited remarkably increased antibacterial activity [72-74]. (Structure of 6-0 methyl AZM was later revised to 12-O-methyl AZM [73, 74].) 9a-V, 11-Cyclic carbamate azalide (57), 8a-V-azalides (58), and 14-membered azalide (59) (Fig. 10) are interesting in view of their structure-activity relationship compared with 19, although they generally exhibited the same or lower activity compared with AZM (19) [75-78]. 

Su, W. G. (1999). Novel macrolide C-4" carbamate derivative Chemistry and structure activity relationship. Presented at 3rd International Antibacterial Drug Discovery Development (March 8-9, Princeton). 

Only limited carbamate structure-activity relationship studies have been done with regard to comparisons of the inhibitory capacity toward AChE versus BuChE. However, based on structure-activity studies with five Af-methyl carbamates, Loewenstein et aL (1993) concluded that the CM binding site on BuChE is less flexible than the same site on AChE. 

Wolfe et al. (1978) have developed structure-activity relationships for the hydrolysis of a number of TV-substituted and TV,TV-disubstituted carbamates. An excellent correlation was found between the second-order alkaline hydrolysis rate constant (kb) for the carbamates and the pKa of the alcohol formed upon hydrolysis. The linear free energy relationships for the TV-phenyl and TV-methyl-TV-phenyl carbamates are illustrated in Figure 2.10. These data indicate that only the TV-phenyl carbamates will hydrolyze under environmental conditions. The half-life for the hydrolysis of these chemicals will be less than 6 months at pH 8 at 25°C. 

While alkyl substituted piperidines have low levels of SRTD activity, the amides, carbamates, and ureas are much more active compounds (Table 2). The 4-fluorophenylurea, Compound 10, has the highest SRTD activity of any compound in the diaminoquinazoline area. The substitution patterns on the aniline and benzo portions of the molecule were reinvestigated with the more active group in Position 4, but the structure-activity relationships were found to be the same as for the 4-cyclohexylamino compounds as described in Figure 1. 

Structure-Activity Relationship Studies and Development of 5-li iazine and Carbamate Anticytokinins... 

Carbamates - A series of 2-substituted 1,3-propanediol dicarbamates were prepared and the pharmacology of these compounds together with structure-activity relationships were discussed. ... 

Carbamates - Structure activity relationships have been studied with respect to toxicity and anticholinesterase activity. 9 The mechanism of acetylcholinesterase inhibition by the carbamates is not entirely clear. 

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. 

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