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A series of salicylate-based compounds were designed and synthesized based on the simple function group replacement from our previously reported catechol-containing inhibitors of methionine aminopeptidase (MetAP).
Though group replacement is wasteful, labour cost of replacements is greater when done singly; for example, the light bulbs in a large subway system may be replaced in groups to save labour.
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Several furyl group replacements were explored (blue region of 3, Figure 1); however, none proved superior to the parent 5-nitrofuryl moiety (21– 21).
This means that structural modifications that only change a few atoms (e.g. changing a carbon to a nitrogen, an R-group replacement, or moving an R-group around a ring) will only have a small effect on the value.
Intra-group replacements were considered as conservative and inter-group ones as radical replacements.
This categorization makes it possible, for example, to distinguish activity cliffs that are caused by R-group replacements, small chemical changes in core structures, or chiral centers.
The methyl at R could be replaced by a small alkyl group; however, replacement with larger alkyl groups led to a decrease in activity.
Now the 2013 draft class would have a long way to go to match the ineptitude the class of 2000, which produced 17.3 wins fewer than a group of replacement players would, but second place is still well within reach.
Methylation of the phenolic hydroxy group and replacement of the 4-methyl group of phentolamine with varying lipophilic substituents yielded bioisosteric analogs selective for the α2- versus α1-adrenoceptors.
Official Airlines Guides of Oakbrook, Ill., uses a group leader replacement system.
This is no motley group of replacement players; this is major league execution of showy fluff.
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