6570. Nitisinone

Nomenclature

CAS number: 104206-65-7
2-[2-Nitro-4-(trifluoromethyl)benzoyl]-1,3-cyclohexanedione; NTBC; Orfadin (Swedish Orphan ).
C14H10F3NO5; mol wt 329.23.
C 51.07%, H 3.06%, F 17.31%, N 4.25%, O 24.30%.

Description and references

Herbicidal triketone that inhibits 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme involved in plastoquinone biosynthesis in plants and in tyrosine catabolism in mammals. Prepn: C. G. Carter, EP 186118 (1986 to Stauffer); idem, US 5006158 (1991 to ICI). Inhibition of HPPD in plants: M. P. Prisbylla et al., Brighton Crop Prot. Conf. - Weeds 1993, 731; in rats: M. K. Ellis et al., Toxicol. Appl. Pharmacol. 133, 12 (1995). LC determn in plasma: M. Bielenstein et al., J. Chromatogr. B 730, 177 (1999). Clinical evaluation in hereditary tyrosinemia type I: S. Lindstedt et al., Lancet 340, 813 (1992). Review of toxicology and therapeutic development: E. A. Lock et al, J. Inherit. Metab. Dis. 21, 498-506 (1998); of clinical experience: E. Holme, S. Lindstedt, ibid. 507-517.

Chemical structure

Properties

Solid, mp 88-94°.

Therapeutic Category

In treatment of inherited tyrosinemia type I.