Sumitomo New Fungicide Candidate – Inpyrfluxam approved by USEPA 2020

 

The development story of Inpyrfluxam fungicide, which belongs to SDHI chemistry started in 1985 by Monsanto Co. and followed by Sumitomo for detail refer below IP Information section.  

Inpyrfluxam is a novel fungicide active ingredient discovered by Sumitomo Chemical, belongs to a class of compounds known as succinate dehydrogenase inhibitors (SDHI) that have a mode of action inhibiting energy production process in pathogenic fungi.

The inpyrfluxam active ingredient will be known as INDIFLINTM, and brands based on INDIFLINTM technology will be marketed.

CAS RN: 1352994-67-2

IUPAC: 3-(difluoromethyl)-1-methyl-N-[(3R)-1,1,3-trimethyl-2,3-dihydroinden-4-yl]pyrazole-4-carboxamide

Chemical Class: Pyrazolecarboxamide fungicide

Fungicide Class: Succinate dehydrogenase Inhibitor (SDHI)

FRAC: Code 7 (FRAC, 2018)

Inpyrfluxam belongs to pyrazolecarboxamide fungicide class. It proposed for foliar and seed treatment agricultural uses. The chemical provides protection against Rhizoctonia species causing seed decay, seedling damping‐off, and root rot.

Valent U.S.A. Corp., a fully owned U.S. subsidiary of Sumitomo Chemical. Valent, U.S.A., LLC (Walnut Creek, CA 94596) applied for the USEPA registration of inpyrfluxam fungicide for controlling fungal diseases on many crops, including: apples, cereal grains, corn, peanut, rice, sorghum, sugar beet and many legume vegetables within crop group 6.

Inpyrfluxam is a succinate dehydrogenase inhibitor (SDHI) fungicide belonging to FRAC code 7 (FRAC, 2018). It belongs to subgroup pyrazole-4-carboxamide and there is medium to high risk of fungi developing resistance against to fungicides in Code 7 (FRAC, 2018).

Inpyrfluxam use rates on labeled crops, are generally lower (0.044 – 0.089 lbs. a.i./A/Application) than other fungicides (such as azoxystrobin, benzovindiflupyr, fluxapyroxad, penthiopyrad with use rate ranging from 0.036 – 0.391 lbs. ai/A/Application on these crops. The registrant claims that inpyrfluxam does not have cross resistance with other fungicides having different mode of action and therefore benefiting growers in fungicide resistance management.

Biological and Economic Analysis Division (BEAD) finds that inpyrfluxam’s benefits are obvious on soybean and sugarbeet crops only. On soybean, inpyrfluxam provides a new mode of action to control aerial blight disease and therefore it is likely to play a role in resistance management. Similarly, on sugarbeet inpyrfluxam provides a new mode of action for controlling RRCR and it is likely to play a role in disease control and resistance management. On other crops, inpryfluxam appears to be at par with registered fungicides in controlling various diseases and increasing crop yields.

The uses proposed for inpyrfluxam are:

• Seed treatment of crop group 6 (legume vegetables), crop group 15 (cereal grains), crop subgroup 20A (rapeseed), dry seeded rice, and sugar beet;
• Foliar application to apple, peanut, soybean, and sugar beet; and
• In-furrow soil application at planting to corn (field, sweet, and pop).

Inpyrfluxam adds a new mode of action against key fungal pests that can cause high yield losses to soybean and sugarbeet crops. It is also likely to play a role in fungicide resistance management on those crops. On other crops (apple, corn, peanut and rice), inpyrfluxam appears to be comparable to currently available alternative fungicides.

Human health risk estimates for inpyrfluxam are not of concern for all potential routes of exposure, including dietary, occupational and aggregate. The proposed registration contains several measures to mitigate ecological risks associated with the proposed uses.

EPA reviewed inpyrfluxam jointly with Canada’s Pest Management Regulatory Agency (PMRA), with Mexico as an observing member. U.S. tolerances and Canadian MRLs are being harmonized as part of the joint review process. PMRA has not yet published its proposed decision document.

The proposed registration includes four products: one technical grade and three end-use products.

EPA Registration Number: 59639– EGE. Docket ID number: EPA–HQ–OPP– 2018–0038.

Applicant: Valent U.S.A. LLC, 1600 Riviera Avenue, Suite 200, Walnut Creek, CA 94596.

Product name: V–10417 FS Fungicide. A

Active ingredient: Fungicide— Inpyrfluxam at 97.4%.

IP information:

The compound was originally disclosed in WO1992012970 assigned to Monsanto Co., which has legal status Expired and it’s patent family equivalents are US5093347; JP3050405; EP569505;

Subsequently, Sumitomo filed another patent (WO2011162397) on the enantiomer ratio R form/S form of the carboxamide compound is 80/20 or more. The estimated expiry is 20 June 2031

Equivalents:

JP2012025735; CN102958367; BR 112012033013; US8580836; IN2013CN00492; JP6246768;

Plant disease control carboxamide compound composition and method of controlling plant disease;

Sumitomo’s Patent US4742074 filed in 1985, where the Applicant claims the basic moiety, however, does not claim difluoromethyl substituent as one of the possible alternatives (Inpyrfluxam has difluoromethyl substituent on the pyrazole ring).

Monsanto filed their Patent US5093347 in 1991, where they specifically claim the compound with difluoromethyl substituent on the pyrazole ring. Patent Specifically claims the compound under discussion (3-Difluoromethyl-1-methyl-N-(1,1,3-trimethylindane-4-yl)pyrazole-4-carboxamide), without any mention of the optical activity of the said molecule.

Sumitomo identified a predominantly R enantiomeric mixture (R form/S form ratio in the range of 90/10 to 10,000/1) at which Monsantos pyrazolecarboxamide fungicide exhibited excellent fungicidal activity and filed a patent application (WO2011162397) globally. Sumitomo product was named Inpyrfluxam.

Sumitomo patent is granted in Australia, China, Canada, Europe, Japan, Korea, New Zealand, Russia, Taiwan, Ukraine, US, South Africa, Israel, Mexico; while patent applications are pending in other countries like Argentina, Brazil, Chile, Indonesia, Malaysia, Thailand, Vietnam & India. Patent Application is refused in Colombia.

Source: USEPA

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