The discovery of thiamethoxam: a second-generation neonicotinoid.
Neonicotinoids represent a novel and distinct chemical class of insecticides with remarkable chemical and biological properties. In 1985, a research programme was started in this field, in which novel nitroimino heterocycles were designed, prepared and assayed for insecticidal activity. The methodology for the synthesis of 2-nitroimino-hexahydro-1,3,5-triazines, 4-nitroimino-1,3,5-oxadiazinanes and 4-nitroimino-1,3,5-thiadiazinanes is outlined. Bioassays demonstrated that 3-(6-chloropyridin-3-ylmethyl)-4-nitroimino-1,3,5-oxadiazinane exhibited better insecticidal activity than the corresponding 2-nitroimino-hexahydro-1,3,5-triazine and 4-nitroimino-1,3,5-thiadiazinane. In most tests, this compound was equally or only slightly less active than imidacloprid. A series of structural modifications on this lead structure revealed that replacement of the 6-chloro-3-pyridyl group by a 2-chloro-5-thiazolyl moiety resulted in a strong increase of activity against chewing insects, whereas the introduction of a methyl group as pharmacophore substituent increased activity against sucking pests. The combination of these two favourable modifications led to thiamethoxam (CGA 293 343). Thiamethoxam is the first commercially available second-generation neonicotinoid and belongs to the thianicotinyl sub-class. It is marketed under the trademarks Actara for foliar and soil treatment and Cruiser for seed treatment. The compound has broad-spectrum insecticidal activity and offers excellent control of a wide variety of commercially important pests in many crops. Low use rates, flexible application methods, excellent efficacy and the favourable safety profile make this new insecticide well-suited for modern integrated pest management programmes in many cropping systems.
Maienfisch
P
P
Novartis Crop Protection AG, Research Department, WRO-1060.1.14, CH-4002 Basel, Switzerland. peter.maienfisch@cp.novartis.com
Huerlimann
H
H
Rindlisbacher
A
A
Gsell
L
L
Dettwiler
H
H
Haettenschwiler
J
J
Sieger
E
E
Walti
M
M
D000691:Anabasine / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D002622:Chemistry, Agricultural / Q000379:methods; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007300:Insect Control; D007306:Insecticides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010078:Oxazines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D010573:Pesticide Residues / Q000032:analysis; D010944:Plants / Q000378:metabolism; D012987:Soil / Q000032:analysis; D013329:Structure-Activity Relationship; D000077922:Thiamethoxam; D013844:Thiazoles; D014867:Water / Q000737:chemistry
D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D010078:Oxazines; D010573:Pesticide Residues; D012987:Soil; D013844:Thiazoles; D014867:Water; C082359:imidacloprid; D000077922:Thiamethoxam; D000691:Anabasine