Kresoxim pharmacophore

Kresoxim-methyl is based on the same strobilurin A lead compounds in which variations of the methoxyacrylate moiety produced the methoxyiminoacetate pharmacophore. 

From the BASF group, a first review concentrated on the discovery of BAS 490 F (kresoxim-methyl), on pharmacophore variations and on structure-activity relationships at the mitochondrial target level [7]. Another paper was focused more on biokinetic features, and their affect on final biological properties [8j. In 1999 a general review summarized the historical evolution from natural products to commercial strobilurins up to trifloxystrobin, and the international R D competition, including some dramatic patent races [9j. Additionally, strobilurins have been reviewed in Russian, Chinese and Indian journals [10-13]. 

By definition, F = 1 for the enol ether stilbene, and hence the smaller F, the higher the activity. This test has proven to be an extremely useful tool, inter alia in the identification of new pharmacophore variants. To give an impression of resulting structure-activity relationships, Fig. 13.2.5 shows a small selection of such pharmacophore variants together with their corresponding F values. The presented compounds all contain the same side-chain, namely that of kresoxim-methyl. For a more detailed discussion, see Refs. [7, 9]. 

Fig. 13.2.5. Strobilurins with the kresoxim-methyl side chain and variations on the pharmacophore. Their relative activities at the target level are given below the formulas F is inversely proportional to the activity (see text).

---