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China achieving great breakthrough in pyrimidinamine fungicides development

A great breakthrough in pyrimidinamine fungicides development was recently achieved by the research team led by Liu Changling of the Pesticide Research Section of Shenyang Research Institute of Chemical Industry (now, Shenyang Sinochem Agrochemical R&D Co. Ltd.). The achievement was made by the research team for the first time in over 20 years after nearly over 10 years of research into the three generations of chemical compounds covering some 20 varieties of different structures. This achievement has successfully solved the challenge of toxicity, which was an obstacle existing in the industry sector for half a century. The application of the Intermediate Derivatization Method to derive pyrimidinamine compounds complies well with the expectations of prime R&D firms and the direction of industry development such as low toxicity, novel structure, better performance and high price performance ratio.

Pyrimidinamine fungicides act effectively against downy mildew and powdery mildew, covering a worldwide $1.5 billion downy mildew market and $2 billion powdery mildew market, which provide great business potentials.

Prime pesticide companies like Syngenta, Dow Chemical, Bayer, DuPont, BASF and several Japanese companies have been conducting researches on the report on pyrimidinamine compounds, which date back to 1968. These researches have lasted for nearly 50 years, and the patent was filed in 2015.

In 1995 and 1997, the miticide pyrimidifen (with 20 times higher toxicity than salt) and the fungicide diflumetorim (with 5 times higher toxicity than salt) were commercialized in Japan, but their applications were limited to certain degree due to high toxicity and high cost. In 2001, there was a reported insecticide in this field, which was however not commercialized till date. Since then, there has been no further achievement in the research in this field because of the high toxicity of compound.

Liu Changling’s research team experienced three iterated upgrades in their pyrimidinamine compounds research process.

The features of the first-generation compound (inclusive of six-class sub-structure) were good biological activity, difficult synthesis, high cost and high toxicity, which is 500 times higher than salt. This is the first-generation structure developed by most of the global research companies.

The features of the second-generation compound (inclusive of four-class sub-structure) were good biological activity, difficult synthesis, high cost and low toxicity. There have been no reports on this generation. Intermediates were all new, as synthesized by the research institutes on their own.

The features of the third-generation compound (inclusive of six-class sub-structure) were simpler structure, good biological activity, easy synthesis, low cost and very low toxicity (rat acute toxicity LD₅₀), which is above 4000mg/kg, lower than 3000mg/kg of salt. It is very promising for commercialization, and its important intermediate has been commercialized so far. The activity of the third-generation compound, such as the SYP-4773, is three to five times that of the fungicide flumorph as developed by Liu Changling’s team, which is even of lower cost than flumorph.

“The Intermediate Derivatization Method has helped a lot in the efficient development and screening of relevant compounds without which it would have not been possible for our team to develop the third-generation compound in such a short time, Professor Liu told AgroPages.

The Intermediate Derivatization Method is a high-efficient pesticide creation technology developed by Liu Changling’s research team based on their long-year practices. The essence of the technology is to utilize the features of organic intermediates, which can enable various chemical reactions, to chemically simplify the complicated process of discovery of the lead compound of the pesticides. Compared to other creation theory or method, this method can achieve an optimized and improved timing, investment and efficiency, resulting in higher probability of success. This novel pesticide creative tactics are not only applicable to the discovery of the lead compound but also more contributive to the invention of new product with independent intellectual property rights.

Pyrimidinamine compounds will possibly be another important fungicide category following triazole fungicide, strobilurin fungicide and SDHI. This new compound is expected to be proven worthy by the market in the next 3 to 5 years.