Substituted pyridazinones

Wheat roots Wheat shoots Barley shoots 

Herbicide Pigment synthesis (% inhib.) transport (cone, for I50) MGDG 18 2/18 3 DGDG 18 2/18 3 

Other laboratories have also carried out simultaneous measurements of the lipid or lipid metabolism changes associated with pyridazinone-induced in plastid morphology. Davies and Harwood examined the effects of Sandoz 6706 and Sandoz 9785 on lipid metabolism and membrane structure in greening barley. Changes seen in chloroplast structures included a slowing of normal differentiation on greening and the appearance of large 

A15-desaturation. Experiments were carried out with [l- C]linoleate and [l- C]linolenate in order to eliminate the possibility that linoleate was desaturated as part of a different substrate and that the labeled linoleate and a-linolenate were merely transferred preferentially to MGDG. The results showed clearly that radiolabeled oleate, linoleate, and linolenate were incorporated in a similar manner, with PC being the most labeled lipid class there was no evidence for a preferential transfer of a-linolenate to MGDG. All the evidence pointed to MGDG being involved in linoleate desaturation and to this process being inhibited by Sandoz 9785. 

Later experiments by Willemot and co-workers confirmed these conclusions. In addition, these authors noticed that spinach leaves were relatively unaffected by Sandoz 9785. By contrast, disks from spinach leaves were sensitive, perhaps because in leaves there was a detoxification process. Isolated spinach chloroplasts were insensitive to Sandoz 9785, and it was suggested that this might be due to a need for Sandoz 9785 to be activated before it could inhibit A15-desaturation.  

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From a variety of basic substituted pyridazinones investigated in Germany [176], ridazolol (59) (CAS 83395-21-5) has been selected for further evaluation as a cardioselective y9-blocker, since in vivo studies (anaesthetized dogs) had revealed that (59) is characterized by a high degree of cardioselectivity. The haemodynamic effects of ridazolol have been studied [177,178], Doses of 20-80 mg of ridazolol have been reported to cause dose-related decrease in exercise-induced tachycardia (for 8 h) and in systolic blood pressure (for 4h)[179],... 

Substituted Pyridazinone Herbicides Structural Requirements for Action on Membrane Lipids... 

Table I. Means and Standard Deviations of the Data for 23 Differentially Substituted Pyridazinones Before and After Analysis by Ward s Method.

Pyrimidines (237) react to give monoadducts but in the case of pyrazines (238) the monoadducts proved to be highly reactive to further cycloaddition (134). The 5-substituted pyridazinones (239) (X=EtS02, I, pyrrolidino. Cl) undergo cycloaddition to the C=C bond as shown followed by elimination of HX to give fused pyrazoles (135). 

Two thieno[3,4-4jpyridazines were prepared via reaction of suitably substituted pyridazinones under microwave conditions <2006PS1755>. 

St John, J.B., Christiansen, M.N., Ashworth, E.N. Gentner, W.A. (1979). Effect of BASF 13-338, a substituted pyridazinone, on iinolenic acid levels and winterhardiness of cereals. Crop Science 19, 65-9. 

Phenylmagnesium bromide has been used to introduce a phenyl group in various substituted pyridazinones [80M1I2 811JC(B)502, 8IM112]. 

Substituted pyridazinones induce a specific decrease in the linolenic acid content accompanied by an increase in the linoleic acid content of plant membranes. The most distinct effect among many 5-substituted pyridazinones (78MI7 83M15 86MI21 87MI17) was shown by 4-chloro-5-... 

Substituted pyridazinone herbicides directly inhibit photosystem II, chloroplast pigment biosynthesis, and membrane lipid biosynthesis. Depending on the substitution, pyridazinones can specifically inhibit the synthesis of linolenic acid in galacto-lipids and phospholipids preferentially alter the fatty acid composition of monogalactosyl diglycerides compared with digalactosyl diglycerides and cause a build-up of saturated fatty acids in the chloroplast membranes. 

The differential responses of plant species and tissues to substituted pyridazinones suggest that control of linolenic acid biosynthesis may vary depending on plant species and even tissue. An interaction between triazine herbicides and the lipid composition of chloroplast membranes may influence sensitivity of weed biotypes to the triazine herbicides. 

Substituted pyridazinone herbicides may have a multifunctional mode of action. Inhibitory action by the substituted pyridazinones has been demonstrated at three separate sites (1, 3). The first site involves interference with photo-... 

The chlorophylls and carotenoids are the pigmented lipids associated with chloroplast membranes. Substituted pyridazinones reduce the accumulation of these pigments (Table II). 

Effect of substituted pyridazinones on chloroplast pigment accumulation in 4-day-old wheat shoots (2). 

Chloroplast membranes differ from most other membranes in that the major portion of the non-pigmented lipids of the chloroplast are the linolenic acid-rich galactolipids, with sulfo-lipids and phospholipids present as the minor lipid constituents. The third site of action affected by pyridazinones in wheat shoots is the formation of galactolipids (, 3 ). The data in Table III summarize the effects of substituted pyridazinones on the relative fatty acid composition of wheat shoots. 

Pyrazon inhibited PS II (Table I) but did not interfere with the accumulation of chloroplast pigments (Table II) or influence the composition of glycerolipids (Table III). Therefore, even though the other substituted pyridazinones also inhibit PS II, their actions on chloroplast pigments and/or glycerolipids are not likely to result from PS II inhibitions. Further evidence that inhibition of PS II does not result in membrane lipid changes is presented in Table IV. 

Murphy, D.J., Harwood, J.L., Lee, K.A., Roberto, F., Stumpf, P.K. and St. John, J.B. (1985) Differential responses of a range of photosynthetic tissues to a substituted pyridazinone, Sandoz 9785. Specific effects on fatty acid desaturation. Phytochemistry 24, 1923-1929. 

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