695:
782:
514:
732:) of the triketones, David Lee saw a potential discrepancy in the existing structure-activity analysis. Other than the 2-chloro-4-nitro substitution pattern, no other triketones with electron-withdrawing substituents in the 4-position had ever been prepared. He hypothesized that the activity of the triketones could be correlated to the electron withdrawing ability of the substituents. The activity of the 2-chloro-4-nitro analog was an outlier, and it was theorized that perhaps the nitro group was being reduced
637:
707:
358:
216:
526:
625:
584:
755:
worked on this project. Within a relatively short time, major progress was made in optimizing certain substitution combinations. SC-0051 (sulcotrione) was synthesized and tested in Sept. – Oct. 1983, and SC-1296 (mesotrione) and SC-0735 (nitisinone) were both synthesized and tested in early 1984. Triketones were in widespread university field trials in 1985. The first of the triketone patents was published in 1986.
58:, is something all living things do. HPPD inhibitors were first brought to market in 1980, although their mechanism of action was not understood until the late 1990s. They were originally used primarily in Japan in rice production, but since the late 1990s have been used in Europe and North America for corn, soybeans, and cereals, and since the 2000s have become more important as weeds have become resistant to
502:
1509:(9) David L. Lee, Christopher G. Knudsen, William J. Michaely, John B Tarr, Hsiao-Ling Chin, Nhan H. Nguyen, Charles g. Carter, Thomas H. Cromartie, Byron H. Lake, John M. Shribbs, Stott Howard, Sean Hauser, D. Dgarin, The Synthesis nd Structure-Activity Relationships of the Triketone HPPD Herbicides, Insect, Weed and Fungal Control, ACS Symposium Series No. 774 2000), p. 8-19
435:
is mutated and does not work, leading to very harmful products building up in the body. Fumarylacetoacetate hydrolase acts on tyrosine after HPPD does, so scientists working on making these inhibitors hypothesized that inhibiting HPPD and controlling tyrosine in the diet could treat this disease. A
340:
there are no crop-rotation restrictions. Pyrasulfotole was also introduced in 2007 for cereals in North
America, and was the first new class of herbicide in cereals in many years, and an important advance against weeds that had become resistant to existing herbicides. It remains active in the soil
1419:
Christopher G. Knudsen, David L. Lee, William J. Michaely, Hsiao-ling Chin, Nhan H. Nguyen, Ronald J. Rusay, Thomas H. Cromartie, Reed Gray, Byron H. Lake, Torquil E. M. Frasier and David
Cartwright , Discovery of the triketone class of HPPD inhibiting herbicides and their relationship to naturally
601:
activity against grass weeds at a very high application rate of 100 pounds per acre (112 kg/ha). He prepared a series of analogs in which the alkanoyl group was modified and a patent was obtained on this series of compounds. These compounds had similar, weak herbicidal activity similar to that
331:
that are problems in rice, that had become resistant to sulfonylurea herbicides. Mesotrione was introduced in 2002 and like sulcotrione is a triketone, so it is effective on the same weeds and crops, but is more potent, making it more useful in mixes with other herbicides - an important factor for
1586:
Ellis, M.K., A.C. Whitfield, L.A. Gowans, T.R. Auton, W.M. Provan, E.A. Lock and L.L. Smith 1995, Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methylsulfonylbenzoyl)-cyclohexane-1,3-dione. Toxicol. Appl
Pharmacol.
754:
At this point a very large effort on the synthesis of analogs was commenced with David Lee coordinating the effort. Key chemists participating in this were
Charles Carter, Bill Michaely, Hsiao-ling Chin, Nhan Nguyen and Chris Knudsen, although at one time almost every synthesis chemist at the WRC
803:
Work on the mode of action and toxicology of the triketones took on a broader range of interactions when
Stauffer Chemical was purchased by ICI in June 1987. ICI then split off the pharmaceutical and agrochemical businesses as Zeneca and then Syngenta was formed in 2000 by the merger of Novartis
456:
weed control of weeds in the back yard of his house. This curiosity led to the discovery and development of the triketone class of herbicides. Investigation of the mode of action of this class of compounds led to the discovery that it could be used to treat patients with tyrosinaemia type 1, a
335:
Topramezone was introduced in 2006 for corn and soy, and is the most potent HPPD inhibitor, but has serious carry-over issues especially for soybean in US, where the minimum time from application to planting is 18 months. Tembotrione was introduced in 2007 for corn, and works against key grass
1518:
Lee, David L., Knudsen, Christopher G.,Michaely, William J., Chin, Hsiao-Ling, Nguyen, Nhan H., Carter, Charles G., Cromartie, Thomas G., Lake, Byron H., Shribbs, John M., Frasier, Torquil E.M.,The
Structure-Activity Relationships of the Triketone Class of HPPD Herbicides, Pesticide Science
322:
herbicides were introduced. In 1990 sulcotrione was introduced for post- emergence weed control in corn. Isoxaflutole opened the market more broadly for HPPD inhibitors when it was introduced in 1996 for corn and sugarcane, and for use as a pre-emergence herbicide that could control
795:
There had been some early toxicological concern about corneal and paw lesions which were observed with rats that had repeatedly dosed with a triketone. Several chemists and toxicologists came upon a paper describing very similar ocular, but not skin, lesions with inhibitors of
679:). Bill Michaely prepared several of these, but the herbicidal activity remained modest and all work in the area was terminated. It was not until David Lee was able to show that these compounds were in equilibrium with the 2-hydroxy triketones(
1071:
Hausman, Nicholas E; Singh, Sukhvinder; Tranel, Patrick J; Riechers, Dean E; Kaundun, Shiv S; Polge, Nicholas D; Thomas, David A; Hager, Aaron G (2011-01-26). "Resistance to HPPD-inhibiting herbicides in a population of waterhemp
1496:(8) David L. Lee, Michael P. Prisbylla, Thomas H. Cromartie, Derek P. Dagarin, Stott W. Howard, W. Mclean Provan, Martin K. Ellis, Torquil Fraser, Linda C. Mutter. The Discovery and Structural Requirements of Inhibitors of
1577:(14) M.P. Prisbylla, B.C. Onisko ,J.M. Shribbs, D.O. Adams, Y. Liu, M.K. Ellis, T.R Hawkes, L.C. Mutter, The Novel Mechanism of Action of the Herbicidal Triketones, Brighton Crop Protection Conference – Weeds (1993.) 731-8
660:
substituent had herbicidal activity but no antidote activity. This observation coupled with the knowledge of the herbicidal activity of the earlier leptospermone analogs was pivotal in formulating an idea of a potential
1564:
Kolzumi, S., Nagatsu, T., Iinuma, H., Ohno, M., Takeuchi,T. and
Umezawa,H. (1982). Inhibition of phenylalanine hydroxylase, a pterin-requiring monooxygenase, by ouudenone and its derivatives, Journal of Antibiotics 35:
800:. Linda Mutter in the WRC Toxicology Section used a spot test for tyrosine on the urine of treated rats and had positive results. Plasma tyrosine analysis further confirmed the buildup of tyrosine in treated rats.
150:
that protect it. Plants turn white without deformation due to a complete loss of chlorophyll, which has led compounds of this class to be classified as "bleaching herbicides", as are protox inhibitors.
597:
He approached a chemist, Ron Rusay, at the
Western Research Center who independently synthesized the compound and submitted it for further greenhouse testing. These tests showed that it had modest
545:) as an indicator species at the very high application rate of 100 pounds per acre (112 kg/ha). There was a herbicidal effect from this test, so the extracts were developed on a preparative
1478:
Lee, D.L., Kollman, P.A., Marsh, F.J., Wolff, M.E., Quantitative relationships between steroid structure and binding to putative progesterone receptors, J. Med. Chem. , 20 (1977) pp. 1139-46
109:
The mechanism of action for HPPD inhibitors was misunderstood for the first twenty years that these products were sold, starting in 1980. They were originally thought to be inhibitors of
654:
activity toward other herbicides. When attempting to optimize the antidote activity, several aryl substituted analogs were prepared. What was discovered was that those compounds with an
1248:
Lock, EA; et al. (Aug 1998). "the discovery of the mode of action of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), its toxicology and development as a drug".
388:
Tembotrione has low acute toxicity via the oral, dermal and inhalation routes of exposure (Toxicity category III or IV). It is a dermal sensitizer but not an eye or dermal irritant
576:) which was a known natural product that had been derived from the steam-volatile oils of some Australian plants, but which had never been cited as having any biological activity.
539:
To investigate this effect, he took soil from underneath these plants and extracted and fractionated it. The resulting extracts were applied to soil flats containing watergrass (
1217:
1324:
Beaudegnies, R; et al. (Jun 2009). "Herbicidal 4-hydroxyphenylpyruvate dioxygenase inhibitors--a review of the triketone chemistry story from a
Syngenta perspective".
1308:
1528:(10) Evans, J.O. and Gunnell, R.W. (1986) Evaluation of SC-0774, SC-0051 and SC-5676 in field corn. Research.progress.report. Western Society of Weed Science(USA),130-131
668:
A small task force consisting of David Lee, Bill
Michaely and Don James prepared a number of substituted triketones with chloro-, bromo- and methyl-substituents in the
556:
The area where the herbicidal activity was seen was extracted and he submitted the isolated active ingredient to Ken Cheng at the Western Research Center who, using
1546:
Sandman, Gerhard, Schmidt, Arno, Linden, Harmut, Böger, Peter, (1991) Phytoene Desaturase, the Essential Target for Bleaching Herbicides, Weed Science, 39:474-479
838:
that was inhibited, a fact which was confirmed by S. Lindstedt. Further tests established that HPPD was the enzyme inhibited in plants as well as mammals.
737:
1168:
Extracted from The Pesticide Book, 6th ed*. (2004), Published by MeisterPro Information Resources, A division of Meister Media Worldwide, Willoughby, Ohio
751:
was a good catalyst for the preparation of the o-chloro analogs. Use of this catalyst allowed for the first time production of the o-nitro triketones.
744:) was prepared. The prospect of improving the biological activity with new aromatic substitution patterns totally rejuvenated work on the triketones.
1878:
759:
177:
This class of herbicides represents one of the last discoveries of a new herbicide mode of action in the wave of discovery that ended in late 1990s.
729:
725:
721:
302:
1201:
2197:
292:
270:
1756:
318:
Pyrazolate, pyrazoxyfen and benzofenap were first commercialized in the Japanese rice market starting in 1980, but became less important when
1908:
1817:
1736:
469:
296:
284:
274:
262:
1190:
1956:
266:
258:
89:: pyrazolones, triketones, and diketonitriles. The triketone class is based on a chemical that certain plants make in self-defense called
2362:
2342:
2337:
2239:
1827:
1716:
2352:
1941:
1731:
1537:
Michaely, W.J., Kratz, G.W., Certain 2-(2-substituted benzoyl)-1,3- cyclohexanediones and their use as herbicides, US 4,780,127 (1988)
2413:
2312:
1232:
369:
327:
as did sulcotrione, but also additional grass weeds. Benzobicyclon, was introduced in 2001 for control of broadleaf weeds and some
227:
1460:
Reed A. Gray, Chien K. Tseng, Ronald J. Rusay, 1-Hydroxy-2-(alkylketo)-4,4,6,6-tetramethyl cyclohexen-3,5-diones, US4,202,840(1980)
332:
fully controlling weeds and preventing the development of resistance. It has become the biggest selling member of the HPPD class.
1305:
819:
was not inhibited by the triketones. He furthermore found that the urine of rats treated with III showed elevated levels of both
269:(Yukawide, introduced by Mitsubishi Chemical Corp and RhĂ´ne-Poulenc Agro, 1987, as of 2009 sold by Bayer CropScience as Taipan);
1178:
553:
seeds were placed on this sheet and germinated. The active ingredient was identified by bleaching symptoms on the test species.
134:. Preventing the breakdown of tyrosine has three negative consequences: the excess of tyrosine stunts growth; the plant suffers
1161:
747:
A key discovery in the preparation of these compounds was the finding by Jim Heather in the WRC Process Development group that
758:
With a long history of working with bleaching herbicides which inhibit phytoene desaturase including the commercial herbicide
1658:
893:
van Almsick, Andreas (2009). "New HPPD-Inhibitors - A Proven Mode of Action as a New Hope to Solve Current Weed Problems".
923:
Cole, D.; Pallett, K.E.; Rodgers, M. (2000). "Discovering new Modes of Action for herbicides and the impact of genomics".
1487:
James B. Heather, Pamela D. Milano, Process for the production of acylated 1,3- dicarbonyl compounds, US 4,695,673 (1987)
828:
116:
36:
736:. The 4-methylsulfonyl group was then prepared to test this hypothesis, and what was to become the commercial herbicide
50:
into molecules that are then used by plants to create other molecules that plants need. This process of breakdown, or
1596:
Lindsted, W. and B. Odelhög , 4-Hydroxyphenylpyruvate dioxygenase from human liver (1987) Methods Enzymol. 142;139-142
2556:
2018:
855:
419:
The collaboration to develop the stacked HPPD inhibitor/glyphosate resistant products was first announced in 2007.
336:
species and importantly, kills broadleaf weeds, including glyphosate-, ALS- and dicamba-resistant weeds. Used with
675:
One working hypothesis was that the active ingredient in these triketones was the cyclized tetrahydroxanthenones(
1983:
452:
The origin of the triketone family of HPPD inhibitors had its beginnings in the curiosity of a biologist about
309:(aka IFT) (Balance and Merlin, introduced by RhĂ´ne-Poulenc Agro, 1996 and as of 2009 sold by Bayer CropScience)
995:
602:
found with the lead compound. Because of the weak herbicidal activity, work on other analogs was not pursued.
432:
650:
While this compound did not have any herbicidal activity, it did show activity in a screen designed to show
1141:
1087:
74:, that was originally under development as an herbicide as a member of this class and is used to treat an
766:), there was some considerable interest to find that these compounds do not inhibit phytoene desaturase
2254:
2028:
1860:
656:
401:
110:
63:
1918:
546:
724:(QSAR) after a post-doctoral year with Professors Manfred Wolff and Peter Kollman where he used the
672:
position. Biological activity remained modest and the task force was disbanded after a short while.
2582:
2511:
1855:
1651:
811:
studies, Martin Ellis at the ICI Central Toxicology Laboratory identified triketone inhibition of
404:
resistant to HPPD inhibitors: in one version, the crops are resistant to both HPPD inhibitors and
1078:
488:'s Western Research Center (WRC) in California, that few weeds emerged under bottlebrush plants (
191:
2481:
541:
2433:
1612:"4-Hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides: Past, present, and future"
1291:
561:
1432:"The occurrence of β-triketones in the steam-volatile oils of myrtaceous Australian plants"
1420:
occurring -triketones, Allelopathy in Ecological Agriculture and Forestry (2000), p.101-111
816:
797:
490:
186:
1229:
694:
8:
2491:
2456:
1850:
1644:
748:
67:
1359:
McKieman, P.J. (2006). "Nitisinone in the treatment of hereditary tyrosinaemia type 1".
1218:
Bayer CropScience, Mertec and M.S. Technologies to Co-Develop New Soybean Trait Products
605:
Shortly after this, another WRC chemist, Bill Michaely, synthesized an aroyl triketone (
2451:
1384:
1273:
1119:
428:
79:
1022:
Wolfgang Kramer and Ulrich Schirmer, Modern Crop Protection Compounds (1)197-276(2012)
781:
295:(ShowAce, introduced by SDS Biotech and Sandoz Crop Protection (now Syngenta), 2001);
1966:
1376:
1372:
1341:
1265:
1111:
1103:
1053:
977:
651:
565:
485:
447:
397:
155:
154:
More specifically, inhibition of HPPD prevents the formation of a breakdown product,
98:
1388:
1206:
February 12, 2014. "Seed Companies Pick Up the Pace on Seed Trait-Herbicide Systems"
1158:
1123:
513:
93:; the class was developed by scientists at companies that eventually became part of
2577:
1623:
1443:
1368:
1333:
1277:
1257:
1095:
1091:
1045:
969:
954:
932:
902:
835:
135:
484:) had their common origin in the observation in 1977 by Reed Gray, a biologist at
457:
treatment which has been said to "transform the natural history of tyrosinaemia".
291:(Callisto and Lumax, introduced by Zeneca, 2002 and as of 2009 sold by Syngenta);
2168:
1312:
1236:
1165:
324:
636:
287:(Mikado, introduced by Zeneca, 1990 and as of 2009 sold by Bayer CropScience));
2390:
2357:
2304:
1845:
774:, whereas the triketones do not, further suggested a different mode of action.
75:
1975:
1337:
1261:
973:
66:
are under development that include resistance to HPPD inhibitors. There is a
2571:
2446:
2441:
2263:
2202:
2111:
2085:
2037:
1888:
1751:
1107:
860:
684:
569:
460:
All of the herbicidal and pharmaceutical triketone HPPD inhibitors including
163:
90:
436:
series of small clinical trials were attempted with one of their compounds,
2551:
2546:
2536:
2398:
2181:
1883:
1792:
1784:
1726:
1721:
1679:
1667:
1636:
1380:
1345:
1115:
1057:
981:
453:
319:
306:
159:
55:
1269:
706:
2423:
2418:
2176:
2158:
2138:
2128:
2120:
2045:
1993:
1946:
1781:
1771:
1741:
1706:
441:
440:
and were successful, leading to nitisinone being brought to market as an
413:
254:
171:
167:
147:
143:
139:
1628:
1611:
357:
345:, it does not damage crops and there are no crop-rotation restrictions.
215:
2541:
2521:
2501:
2461:
2367:
2327:
2229:
2093:
2075:
2060:
1951:
1903:
1898:
1893:
1822:
1802:
1797:
1761:
1691:
1431:
808:
610:
557:
525:
477:
461:
437:
405:
288:
280:
166:. Plastoquinone is, in turn, a critical co-factor in the formation of
128:
124:
71:
59:
51:
44:
32:
1447:
624:
2531:
2506:
2486:
2322:
2244:
2224:
2143:
2070:
2065:
2050:
1931:
1926:
1711:
1671:
936:
770:. The fact that phytoene desaturase inhibitors typically have a high
662:
598:
247:
86:
1610:
Jhala, Amit J.; Kumar, Vipan; Yadav, Ramawatar; et al. (2023).
1099:
1049:
1033:
906:
2496:
2347:
2332:
2317:
2295:
2281:
2234:
2216:
2153:
2148:
2055:
2013:
1998:
1936:
1812:
1766:
1746:
1696:
1292:"Nitisinone (Oral Route) Description and Brand Names - Mayo Clinic"
1137:
812:
409:
342:
337:
200:
131:
94:
47:
448:
History of the discovery of the triketone class of HPPD inhibitors
273:(Huskie and Infinity, introduced by Bayer CropScience, 2007); and
2526:
2516:
2408:
2133:
1837:
1807:
1683:
1500:-hydroxyphenylpyruvate Dioxygenase. Weed Science,45(5),p.601-609
1034:"Why there are no new herbicide modes of action in recent years"
583:
2276:
1988:
1701:
328:
120:
40:
2271:
771:
609:) as an unexpected byproduct when attempting to synthesize a
501:
687:
that the reason for the biological activity was understood.
431:, a different enzyme involved in the breakdown of tyrosine,
2403:
2381:
2008:
2003:
196:
1070:
85:
HPPD inhibitors can be classified into three fundamental
2303:
996:"Inhibition of Pigment Synthesis (Bleaching Herbicides)"
827:-hydoxyphenyllactic acids. These results suggested that
101:
has also been active in developing new HPPD inhibitors.
2262:
396:
To deal with rising resistance to existing herbicides,
123:
found in both plants and animals, which catalyzes the
1216:
Bayer CropScience press release. November 26, 2007
856:"HPPD herbicide-tolerant soybeans: new type of GMO"
1609:
922:
412:, crops that are resistant to HPPD inhibitors and
246:As of 2009, HPPD inhibitors had three fundamental
1064:
348:
2569:
1555:MeisterPro Crop Protection Handbook 2011, p. 428
1469:MeisterPro Crop Protection Handbook 2011, p. 618
1410:MeisterPro Crop Protection Handbook 2011, p. 632
848:
54:, and making new molecules from the results, or
1401:MeisterPro Crop Protection Handbook 2011, p.502
1189:Gil Gullickson for Crops.com December 5, 2012
299:(Laudis introduced by Bayer CropScience, 2007)
1652:
1130:
730:quantitative structure–activity relationships
722:quantitative structure–activity relationships
391:
341:during the growing season and when used with
1666:
1573:
1571:
1191:Something old, something new with herbicides
174:in plants from being destroyed by sunlight.
1323:
1142:"Know the Facts about HPPD Weed Resistance"
892:
277:(Clio and Impact, introduced by BASF, 2006)
158:, which in turn is a key precursor for the
1659:
1645:
1228:National Organization for Rare Disorders.
1159:An Introduction to Herbicides (2ndEdition)
568:identified the structure as being that of
35:that prevent growth in plants by blocking
1627:
1568:
888:
886:
884:
882:
880:
878:
206:
1358:
1136:
780:
705:
693:
635:
623:
582:
524:
512:
500:
265:(Paicer, introduced by Ishihara, 1985);
1429:
1317:
1230:Physician's Guide to Tyrosinemia Type 1
948:
946:
804:Agribusiness and Zeneca Agrochemicals.
261:(Sanbird, introduced by Sankyo, 1980);
2570:
1157:George W. Ware and David M. Whitacre.
918:
916:
875:
180:
104:
1640:
955:"4-Hydroxyphenylpyruvate dioxygenase"
952:
720:David Lee had a strong background in
1247:
1222:
1031:
943:
683:) by trapping the intermediate with
352:
210:
913:
313:
117:4-Hydroxyphenylpyruvate dioxygenase
37:4-Hydroxyphenylpyruvate dioxygenase
17:4-Hydroxyphenylpyruvate dioxygenase
13:
1603:
832:-hydroxyphenylpyruvate dioxygenase
14:
2594:
1179:Pesticide Fact Sheet: Tembotrione
1076:) from Illinois, United States".
815:in rat liver and also found that
494:) in the back yard of his house.
1373:10.2165/00003495-200666060-00002
356:
214:
1590:
1580:
1558:
1549:
1540:
1531:
1522:
1512:
1503:
1490:
1481:
1472:
1463:
1454:
1423:
1413:
1404:
1395:
1352:
1298:
1284:
1241:
1210:
1195:
1183:
1171:
1151:
195:) in two different locations -
43:in plants that breaks down the
1025:
1016:
988:
665:for this class of herbicides.
422:
349:Herbicide risks and toxicities
189:was known: In 2010 Waterhemp (
1:
841:
433:fumarylacetoacetate hydrolase
1088:Society of Chemical Industry
408:, and in collaboration with
400:has been developing various
146:is destroyed due to lack of
7:
895:Outlooks on Pest Management
823:-hydroxyphenylpyruvate and
10:
2599:
547:thin layer chromatographic
402:genetically modified crops
392:Genetically modified crops
111:protoporphyrinogen oxidase
64:Genetically modified crops
2474:
2432:
2391:Photosystem II inhibitors
2389:
2380:
2305:Photosystem II inhibitors
2294:
2253:
2215:
2190:
2167:
2119:
2110:
2084:
2036:
2027:
1974:
1965:
1917:
1869:
1836:
1780:
1678:
1338:10.1016/j.bmc.2009.03.015
974:10.1016/j.abb.2004.08.015
728:. Looking over the QSAR (
2264:Photosystem I inhibitors
203:- developed resistance.
162:of both tocopherols and
1262:10.1023/A:1005458703363
1079:Pest Management Science
1074:Amaranthus tuberculatus
1038:Pest Management Science
1032:Duke, S.O. (Apr 2012).
192:Amaranthus tuberculatus
185:As of 2011 very little
62:and other herbicides.
1430:Hellyer, R.O. (1968).
953:Moran, GR (Jan 2005).
788:
713:
701:
643:
631:
590:
551:Echinochloa crus-galli
542:Echinochloa crus-galli
532:
520:
508:
207:Products and economics
784:
709:
697:
639:
627:
586:
528:
516:
504:
1306:Orfadin (nitisinone)
962:Arch Biochem Biophys
817:tyrosine hydroxylase
798:tyrosine hydroxylase
491:Callistemon citrinus
2492:aminocyclopyrachlor
2457:sulfometuron methyl
1629:10.1017/wet.2022.79
1250:J Inherit Metab Dis
813:tyrosine catabolism
749:acetone cyanohydrin
248:chemical frameworks
181:Resistance in weeds
105:Mechanism of action
87:chemical frameworks
68:pharmaceutical drug
2452:metsulfuron-methyl
2121:Nitrophenyl ethers
1311:2014-05-04 at the
1235:2014-02-11 at the
1202:Rhonda Brooks for
1164:2014-05-05 at the
789:
714:
702:
644:
632:
591:
533:
521:
509:
429:Type I tyrosinemia
368:. You can help by
226:. You can help by
142:(vitamin E); and
80:type I tyrosinemia
2565:
2564:
2470:
2469:
2376:
2375:
2290:
2289:
2211:
2210:
2112:Protox inhibitors
2106:
2105:
2102:
2101:
2029:ACCase inhibitors
1519:54:377-384 (1998)
1448:10.1071/CH9682825
1442:(11): 2825–2828.
925:Pesticide Outlook
793:
792:
718:
717:
648:
647:
595:
594:
566:mass spectrometry
537:
536:
486:Stauffer Chemical
398:Bayer CropScience
386:
385:
244:
243:
156:homogentisic acid
99:Bayer CropScience
31:) are a class of
2590:
2387:
2386:
2301:
2300:
2260:
2259:
2169:Pyrimidinediones
2117:
2116:
2034:
2033:
1972:
1971:
1919:Organophosphorus
1661:
1654:
1647:
1638:
1637:
1633:
1631:
1597:
1594:
1588:
1584:
1578:
1575:
1566:
1562:
1556:
1553:
1547:
1544:
1538:
1535:
1529:
1526:
1520:
1516:
1510:
1507:
1501:
1494:
1488:
1485:
1479:
1476:
1470:
1467:
1461:
1458:
1452:
1451:
1427:
1421:
1417:
1411:
1408:
1402:
1399:
1393:
1392:
1356:
1350:
1349:
1321:
1315:
1302:
1296:
1295:
1288:
1282:
1281:
1245:
1239:
1226:
1220:
1214:
1208:
1199:
1193:
1187:
1181:
1175:
1169:
1155:
1149:
1148:
1146:
1134:
1128:
1127:
1068:
1062:
1061:
1029:
1023:
1020:
1014:
1013:
1011:
1009:
1000:
992:
986:
985:
959:
950:
941:
940:
937:10.1039/B009272J
920:
911:
910:
890:
873:
872:
870:
869:
852:
777:
776:
690:
689:
620:
619:
579:
578:
549:sheet. The same
497:
496:
381:
378:
360:
353:
314:Agricultural use
239:
236:
218:
211:
170:, which protect
136:oxidative damage
2598:
2597:
2593:
2592:
2591:
2589:
2588:
2587:
2583:HPPD herbicides
2568:
2567:
2566:
2561:
2466:
2428:
2372:
2286:
2249:
2207:
2186:
2163:
2098:
2080:
2023:
1961:
1913:
1879:flurochloridone
1865:
1851:copper arsenate
1832:
1776:
1674:
1665:
1616:Weed Technology
1606:
1604:Further reading
1601:
1600:
1595:
1591:
1585:
1581:
1576:
1569:
1563:
1559:
1554:
1550:
1545:
1541:
1536:
1532:
1527:
1523:
1517:
1513:
1508:
1504:
1495:
1491:
1486:
1482:
1477:
1473:
1468:
1464:
1459:
1455:
1428:
1424:
1418:
1414:
1409:
1405:
1400:
1396:
1357:
1353:
1332:(12): 4134–52.
1326:Bioorg Med Chem
1322:
1318:
1313:Wayback Machine
1303:
1299:
1290:
1289:
1285:
1246:
1242:
1237:Wayback Machine
1227:
1223:
1215:
1211:
1200:
1196:
1188:
1184:
1176:
1172:
1166:Wayback Machine
1156:
1152:
1144:
1135:
1131:
1100:10.1002/ps.2100
1069:
1065:
1050:10.1002/ps.2333
1030:
1026:
1021:
1017:
1007:
1005:
1003:LSUAgCenter.com
998:
994:
993:
989:
957:
951:
944:
921:
914:
907:10.1564/20feb09
891:
876:
867:
865:
854:
853:
849:
844:
834:(HPPD) was the
760:flurochloridone
450:
425:
394:
382:
376:
373:
366:needs expansion
351:
325:broadleaf weeds
316:
240:
234:
231:
224:needs expansion
209:
183:
138:due to lack of
107:
70:on the market,
29:HPPD inhibitors
12:
11:
5:
2596:
2586:
2585:
2580:
2563:
2562:
2560:
2559:
2554:
2549:
2544:
2539:
2534:
2529:
2524:
2519:
2514:
2509:
2504:
2499:
2494:
2489:
2484:
2478:
2476:
2472:
2471:
2468:
2467:
2465:
2464:
2459:
2454:
2449:
2444:
2438:
2436:
2434:ALS inhibitors
2430:
2429:
2427:
2426:
2421:
2416:
2411:
2406:
2401:
2395:
2393:
2384:
2378:
2377:
2374:
2373:
2371:
2370:
2365:
2360:
2358:terbuthylazine
2355:
2350:
2345:
2340:
2335:
2330:
2325:
2320:
2315:
2309:
2307:
2298:
2292:
2291:
2288:
2287:
2285:
2284:
2279:
2274:
2268:
2266:
2257:
2251:
2250:
2248:
2247:
2242:
2237:
2232:
2227:
2221:
2219:
2213:
2212:
2209:
2208:
2206:
2205:
2200:
2194:
2192:
2188:
2187:
2185:
2184:
2179:
2173:
2171:
2165:
2164:
2162:
2161:
2156:
2151:
2146:
2141:
2136:
2131:
2125:
2123:
2114:
2108:
2107:
2104:
2103:
2100:
2099:
2097:
2096:
2090:
2088:
2086:DIM herbicides
2082:
2081:
2079:
2078:
2073:
2068:
2063:
2058:
2053:
2048:
2042:
2040:
2038:FOP herbicides
2031:
2025:
2024:
2022:
2021:
2016:
2011:
2006:
2001:
1996:
1991:
1986:
1980:
1978:
1969:
1963:
1962:
1960:
1959:
1954:
1949:
1944:
1939:
1934:
1929:
1923:
1921:
1915:
1914:
1912:
1911:
1906:
1901:
1896:
1891:
1886:
1881:
1875:
1873:
1871:HPPD inhbitors
1867:
1866:
1864:
1863:
1858:
1853:
1848:
1846:cacodylic acid
1842:
1840:
1834:
1833:
1831:
1830:
1825:
1820:
1815:
1810:
1805:
1800:
1795:
1789:
1787:
1778:
1777:
1775:
1774:
1769:
1764:
1759:
1754:
1749:
1744:
1739:
1734:
1729:
1724:
1719:
1714:
1709:
1704:
1699:
1694:
1688:
1686:
1676:
1675:
1664:
1663:
1656:
1649:
1641:
1635:
1634:
1605:
1602:
1599:
1598:
1589:
1579:
1567:
1557:
1548:
1539:
1530:
1521:
1511:
1502:
1489:
1480:
1471:
1462:
1453:
1422:
1412:
1403:
1394:
1351:
1316:
1297:
1283:
1256:(5): 498–506.
1240:
1221:
1209:
1194:
1182:
1170:
1150:
1129:
1063:
1024:
1015:
987:
942:
912:
874:
846:
845:
843:
840:
791:
790:
726:Prophet system
716:
715:
703:
646:
645:
633:
593:
592:
535:
534:
522:
510:
449:
446:
424:
421:
393:
390:
384:
383:
363:
361:
350:
347:
315:
312:
311:
310:
303:diketonitriles
300:
278:
242:
241:
221:
219:
208:
205:
182:
179:
106:
103:
76:orphan disease
9:
6:
4:
3:
2:
2595:
2584:
2581:
2579:
2576:
2575:
2573:
2558:
2555:
2553:
2550:
2548:
2545:
2543:
2540:
2538:
2535:
2533:
2530:
2528:
2525:
2523:
2520:
2518:
2515:
2513:
2510:
2508:
2505:
2503:
2500:
2498:
2495:
2493:
2490:
2488:
2485:
2483:
2480:
2479:
2477:
2473:
2463:
2460:
2458:
2455:
2453:
2450:
2448:
2447:flazasulfuron
2445:
2443:
2442:chlorsulfuron
2440:
2439:
2437:
2435:
2431:
2425:
2422:
2420:
2417:
2415:
2412:
2410:
2407:
2405:
2402:
2400:
2397:
2396:
2394:
2392:
2388:
2385:
2383:
2379:
2369:
2366:
2364:
2361:
2359:
2356:
2354:
2351:
2349:
2346:
2344:
2341:
2339:
2336:
2334:
2331:
2329:
2326:
2324:
2321:
2319:
2316:
2314:
2311:
2310:
2308:
2306:
2302:
2299:
2297:
2293:
2283:
2280:
2278:
2275:
2273:
2270:
2269:
2267:
2265:
2261:
2258:
2256:
2252:
2246:
2243:
2241:
2238:
2236:
2233:
2231:
2228:
2226:
2223:
2222:
2220:
2218:
2214:
2204:
2203:sulfentrazone
2201:
2199:
2198:carfentrazone
2196:
2195:
2193:
2191:Triazolinones
2189:
2183:
2180:
2178:
2175:
2174:
2172:
2170:
2166:
2160:
2157:
2155:
2152:
2150:
2147:
2145:
2142:
2140:
2137:
2135:
2132:
2130:
2127:
2126:
2124:
2122:
2118:
2115:
2113:
2109:
2095:
2092:
2091:
2089:
2087:
2083:
2077:
2074:
2072:
2069:
2067:
2064:
2062:
2059:
2057:
2054:
2052:
2049:
2047:
2044:
2043:
2041:
2039:
2035:
2032:
2030:
2026:
2020:
2017:
2015:
2012:
2010:
2007:
2005:
2002:
2000:
1997:
1995:
1992:
1990:
1987:
1985:
1982:
1981:
1979:
1977:
1973:
1970:
1968:
1964:
1958:
1955:
1953:
1950:
1948:
1945:
1943:
1940:
1938:
1935:
1933:
1930:
1928:
1925:
1924:
1922:
1920:
1916:
1910:
1907:
1905:
1902:
1900:
1897:
1895:
1892:
1890:
1889:leptospermone
1887:
1885:
1882:
1880:
1877:
1876:
1874:
1872:
1868:
1862:
1859:
1857:
1854:
1852:
1849:
1847:
1844:
1843:
1841:
1839:
1835:
1829:
1826:
1824:
1821:
1819:
1816:
1814:
1811:
1809:
1806:
1804:
1801:
1799:
1796:
1794:
1791:
1790:
1788:
1786:
1783:
1779:
1773:
1770:
1768:
1765:
1763:
1760:
1758:
1755:
1753:
1752:pendimethalin
1750:
1748:
1745:
1743:
1740:
1738:
1735:
1733:
1730:
1728:
1725:
1723:
1720:
1718:
1715:
1713:
1710:
1708:
1705:
1703:
1700:
1698:
1695:
1693:
1690:
1689:
1687:
1685:
1681:
1677:
1673:
1669:
1662:
1657:
1655:
1650:
1648:
1643:
1642:
1639:
1630:
1625:
1621:
1617:
1613:
1608:
1607:
1593:
1583:
1574:
1572:
1561:
1552:
1543:
1534:
1525:
1515:
1506:
1499:
1493:
1484:
1475:
1466:
1457:
1449:
1445:
1441:
1437:
1436:Aust. J. Chem
1433:
1426:
1416:
1407:
1398:
1390:
1386:
1382:
1378:
1374:
1370:
1367:(6): 743–50.
1366:
1362:
1355:
1347:
1343:
1339:
1335:
1331:
1327:
1320:
1314:
1310:
1307:
1301:
1293:
1287:
1279:
1275:
1271:
1267:
1263:
1259:
1255:
1251:
1244:
1238:
1234:
1231:
1225:
1219:
1213:
1207:
1205:
1198:
1192:
1186:
1180:
1174:
1167:
1163:
1160:
1154:
1143:
1139:
1133:
1125:
1121:
1117:
1113:
1109:
1105:
1101:
1097:
1093:
1089:
1085:
1081:
1080:
1075:
1067:
1059:
1055:
1051:
1047:
1044:(4): 505–12.
1043:
1039:
1035:
1028:
1019:
1004:
997:
991:
983:
979:
975:
971:
968:(1): 117–28.
967:
963:
956:
949:
947:
938:
934:
930:
926:
919:
917:
908:
904:
900:
896:
889:
887:
885:
883:
881:
879:
863:
862:
861:Farm Progress
857:
851:
847:
839:
837:
833:
831:
826:
822:
818:
814:
810:
805:
801:
799:
787:
783:
779:
778:
775:
773:
769:
765:
761:
756:
752:
750:
745:
743:
739:
735:
731:
727:
723:
712:
708:
704:
700:
696:
692:
691:
688:
686:
685:methyl iodide
682:
678:
673:
671:
666:
664:
659:
658:
653:
642:
638:
634:
630:
626:
622:
621:
618:
616:
612:
608:
603:
600:
589:
585:
581:
580:
577:
575:
571:
570:Leptospermone
567:
563:
559:
554:
552:
548:
544:
543:
531:
527:
523:
519:
515:
511:
507:
503:
499:
498:
495:
493:
492:
487:
483:
479:
475:
471:
467:
463:
458:
455:
445:
443:
439:
434:
430:
420:
417:
415:
411:
407:
403:
399:
389:
380:
371:
367:
364:This section
362:
359:
355:
354:
346:
344:
339:
333:
330:
326:
321:
308:
304:
301:
298:
294:
293:benzobicyclon
290:
286:
282:
279:
276:
272:
271:pyrasulfotole
268:
264:
260:
256:
253:
252:
251:
249:
238:
229:
225:
222:This section
220:
217:
213:
212:
204:
202:
198:
194:
193:
188:
178:
175:
173:
169:
165:
164:plastoquinone
161:
157:
152:
149:
145:
141:
137:
133:
130:
126:
122:
119:(HPPD) is an
118:
114:
112:
102:
100:
96:
92:
91:leptospermone
88:
83:
81:
77:
73:
69:
65:
61:
57:
53:
49:
46:
42:
38:
34:
30:
26:
22:
18:
2552:pyribenzoxim
2547:prosulfocarb
2537:metam sodium
2399:chlortoluron
2182:saflufenacil
1884:isoxaflutole
1870:
1793:aminopyralid
1757:pretilachlor
1727:dimethenamid
1722:diflufenican
1668:Pest control
1619:
1615:
1592:
1582:
1560:
1551:
1542:
1533:
1524:
1514:
1505:
1497:
1492:
1483:
1474:
1465:
1456:
1439:
1435:
1425:
1415:
1406:
1397:
1364:
1360:
1354:
1329:
1325:
1319:
1300:
1286:
1253:
1249:
1243:
1224:
1212:
1204:Farm Journal
1203:
1197:
1185:
1173:
1153:
1132:
1094:): 258–261.
1083:
1077:
1073:
1066:
1041:
1037:
1027:
1018:
1006:. Retrieved
1002:
990:
965:
961:
931:(6): 223–9.
928:
924:
901:(1): 27–30.
898:
894:
866:. Retrieved
864:. 2014-10-08
859:
850:
829:
824:
820:
806:
802:
794:
785:
767:
763:
757:
753:
746:
741:
733:
719:
710:
698:
680:
676:
674:
669:
667:
655:
649:
640:
628:
614:
606:
604:
596:
587:
573:
555:
550:
540:
538:
529:
517:
505:
489:
481:
473:
465:
459:
454:allelopathic
451:
426:
418:
395:
387:
374:
370:adding to it
365:
334:
320:sulfonylurea
317:
307:isoxaflutole
245:
232:
228:adding to it
223:
190:
184:
176:
160:biosynthesis
153:
115:
108:
84:
56:biosynthesis
28:
24:
20:
16:
15:
2424:tebuthiuron
2419:monolinuron
2177:butafenacil
2159:oxyfluorfen
2139:fluorodifen
2129:acifluorfen
2046:chlorazifop
1994:dichlorprop
1947:glufosinate
1909:sulcotrione
1818:pyrithiobac
1772:trifluralin
1742:metolachlor
1737:metazachlor
1707:benfluralin
1008:8 September
807:As part of
617:) analog.
470:sulcotrione
464:(Callisto)(
442:orphan drug
423:Medical use
414:glufosinate
297:tembotrione
285:sulcotrione
275:topramezone
263:pyrazoxyfen
255:pyrazolones
172:chlorophyll
168:carotenoids
148:carotenoids
144:chlorophyll
140:tocopherols
2572:Categories
2542:metribuzin
2522:indaziflam
2502:bromoxynil
2462:tribenuron
2368:metamitron
2328:hexazinone
2255:Quaternary
2230:fluroxypyr
2094:sethoxydim
2076:quizalofop
2061:fenoxaprop
1957:piperophos
1952:glyphosate
1904:sethoxydim
1899:nitisinone
1894:mesotrione
1838:Arsenicals
1823:quinclorac
1803:clopyralid
1798:chloramben
1762:propachlor
1692:acetochlor
1672:herbicides
868:2021-03-15
842:References
809:toxicology
611:sethoxydim
599:herbicidal
558:proton NMR
480:(Orfadin)(
478:nitisinone
462:mesotrione
438:nitisinone
406:glyphosate
289:mesotrione
281:triketones
267:benzofenap
259:pyrazolate
187:resistance
129:amino acid
125:catabolism
113:(protox).
72:nitisinone
60:glyphosate
52:catabolism
45:amino acid
33:herbicides
25:inhibitors
2532:methazole
2507:clomazone
2487:aclonifen
2363:terbutryn
2343:propazine
2338:prometryn
2323:cyanazine
2296:Triazines
2272:cyperquat
2245:triclopyr
2240:thiazopyr
2225:dithiopyr
2217:Pyridines
2144:fomesafen
2071:haloxyfop
2066:fluazifop
2051:cyhalofop
1932:bialaphos
1927:bensulide
1828:quinmerac
1717:diethatyl
1712:butachlor
1587:133:12-19
1108:1526-498X
663:toxophore
652:antidotal
472:(Mikado)(
2497:Bentazon
2353:simetryn
2348:simazine
2333:prometon
2318:atrazine
2282:paraquat
2235:imazapyr
2154:nitrofen
2149:lactofen
2056:diclofop
2014:mecoprop
1999:fenoprop
1942:fosamine
1937:ethephon
1813:picloram
1782:Aromatic
1767:propanil
1747:oryzalin
1732:flamprop
1697:alachlor
1684:anilines
1680:Anilides
1622:: 1–14.
1389:24239547
1381:16706549
1346:19349184
1309:Archived
1233:Archived
1162:Archived
1140:(2011).
1138:Syngenta
1124:31756104
1116:21308951
1058:22190296
982:15581571
768:in vitro
410:Syngenta
377:May 2014
343:safeners
338:safeners
235:May 2014
201:Illinois
132:tyrosine
95:Syngenta
48:tyrosine
2578:Enzymes
2527:juglone
2517:dinoseb
2414:monuron
2409:linuron
2313:ametryn
2134:bifenox
2019:2,4,5-T
1967:Phenoxy
1808:dicamba
1278:6717818
1270:9728330
1177:US EPA
734:in vivo
127:of the
2475:Others
2277:diquat
1989:2,4-DB
1976:Auxins
1702:asulam
1387:
1379:
1344:
1276:
1268:
1122:
1114:
1106:
1056:
980:
836:enzyme
738:Mikado
476:) and
329:sedges
121:enzyme
41:enzyme
2557:Ziram
2382:Ureas
1984:2,4-D
1785:acids
1385:S2CID
1361:Drugs
1304:Sobi
1274:S2CID
1145:(PDF)
1120:S2CID
1092:Wiley
1086:(3).
999:(PDF)
958:(PDF)
772:log P
670:ortho
657:ortho
39:, an
2512:DCBN
2482:3-AT
2404:DCMU
2009:MCPB
2004:MCPA
1861:MSMA
1856:DSMA
1565:458.
1377:PMID
1342:PMID
1266:PMID
1112:PMID
1104:ISSN
1054:PMID
1010:2017
978:PMID
711:VIII
681:VIII
564:and
199:and
197:Iowa
21:HPPD
1624:doi
1444:doi
1369:doi
1334:doi
1258:doi
1096:doi
1046:doi
970:doi
966:433
933:doi
903:doi
699:VII
677:VII
530:III
482:III
468:),
427:In
372:.
230:.
97:.
2574::
1670::
1620:37
1618:.
1614:.
1570:^
1440:21
1438:.
1434:.
1383:.
1375:.
1365:66
1363:.
1340:.
1330:17
1328:.
1272:.
1264:.
1254:21
1252:.
1118:.
1110:.
1102:.
1084:67
1082:.
1052:.
1042:68
1040:.
1036:.
1001:.
976:.
964:.
960:.
945:^
929:12
927:.
915:^
899:20
897:.
877:^
858:.
786:IX
764:IX
742:II
641:VI
615:VI
588:IV
574:IV
562:IR
560:,
518:II
474:II
444:.
416:.
305::
283::
257::
250::
82:.
78:,
23:)
1682:/
1660:e
1653:t
1646:v
1632:.
1626::
1498:p
1450:.
1446::
1391:.
1371::
1348:.
1336::
1294:.
1280:.
1260::
1147:.
1126:.
1098::
1090:(
1072:(
1060:.
1048::
1012:.
984:.
972::
939:.
935::
909:.
905::
871:.
830:p
825:p
821:p
762:(
740:(
629:V
613:(
607:V
572:(
506:I
466:I
379:)
375:(
237:)
233:(
27:(
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