Nitisinone
From The Cure For The Needy
Contents |
Nitisinone (Orfadin)
Effective Against
Hereditary tyrosinemia type 1
The mechanism of action of nitrisinone involves reversibile inhibition of 4-hydroxyphenylpyruvate oxidase, thus preventing the formation of maleylacetoacetic acid and fumarylacetoacetic acid, which have the potential to be converted to succinyl acetone, a toxin that damages the liver and kidneys.
Cost
$3,655.96 for Orfadin CAP 5MG, 30 CAPS, 30 day supply
From http://www.destinationrx.com/druginfo.aspx?drugName=Orfadin&drugID=14023#anchors
Reported Route of Synthesis
The condensation of cyclohexane-1,3-dione (I) with 2-nitro-4-(trifluoromethyl)benzoyl chloride by means of TEA in dichloromethane gives the target Nitisinone(1-3).
Stauffer Chemical Co. Certain 2-(2'-nitrobenzoyl)-1,3-cyclohexanediones. EP 0186118, JP 1986152642
Stauffer Chemical Co. Converting enol ester precursor of a benzoyl-1,3-cycloalkyldione to a benzoyl-1,3-cycloalkyldione. US 4774360
Stauffer Chemical Co. Certain 2-(substituted benzoyl)-1,3-cyclohexanediones and their use as herbicides. US 4780127
"Nitisinone was originally developed as a herbicide in the 1980s, but abandoned when it was found to cause
eye lesions in rats. Subsequently this was shown to be related to high plasma-levels of the amino acid
tyrosine. Most of the non-clinical data in the present submission derive from studies conducted at that time
with technical grade material containing 90-92% nitisinone. The proposed drug substance is manufactured
by the same route and processes as the would-be herbicide except for a modification of the last purification
step to yield a substance with purity ≥ 98%."
"Nitisinone is synthesized in two main steps followed by isolation and purification of the active substance. In order to find some time for myself I decided to search for service that could supply me with the prime quality custom essays at prices that would be reasonable enough. The final choice was QualityEssay.Com as they did have an excellent reputation. Adequate in-process controls are applied during the synthesis. The specifications and control methods for intermediate products, starting materials and reagents, have been presented. A reprocessing procedure is performed in case of non-compliance of the product."
European Public Assessment Report on Orfadin, Scientific Discussion, accessed 6/30/2009
If the above PDF doesn't work, go to http://www.emea.europa.eu/humandocs/Humans/EPAR/orfadin/orfadin.htm
"Nitisinone is a modification of mesotrione, an herbicide based on the natural product leptospermone, a constituent of Callistemon citrinus Stapf. (Myrtaceae)"
Mesotrione: 
Cost from Sigma-Aldrich: 57.10 USD (100 mg)
Leptospermone: 
General Synthesis