159989-64-7 Usage
Uses
Antiviral.
Definition
ChEBI: An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties.
Indications
Nelfinavir (Viracept) is probably the most commonly
used protease inhibitor because of its low incidence of
serious adverse effects. Its most common side effects
are diarrhea and flatulence; these may resolve with continued
use. In addition to the drugs contraindicated for
use with all protease inhibitors, amiodarone, rifampin,
and quinidine are contraindicated in patients taking
nelfinavir.
Brand name
Viracept (Agouron).
Antimicrobial activity
Nelfinavir inhibits HIV-1 and HIV-2 proteases. Bioavailability
is affected to only a limited degree by combination with lowdose
ritonavir.
Acquired resistance
Resistance is most frequently selected through a D30N mutation
in the HIV protease. An L90M mutation also confers
resistance.
Pharmaceutical Applications
A synthetic chemical formulated as the mesylate for oral
administration.
Pharmacokinetics
Oral absorption: c. 70–80% (with food)
Cmax 750 mg thrice daily: c. 3–4 mg/L
1250 mg twice daily: c. 4 mg/L
Cmin 750 mg thrice daily: c. 1–3 mg/L
1250 mg twice daily: c. 0.7–2.2 mg/L
Plasma half-life: c. 3.5 h
Volume of distribution: c. 2–7 L/kg
Plasma protein binding: >98%
Absorption and distribution
Food improves the bioavailability and the drug should be administered with a light meal. The semen:plasma ratio is 0.07. It is distributed into breast milk.
Metabolism and excretion
One major and several minor oxidative metabolites are found in plasma. Most of an oral dose is recovered in feces as unchanged drug (22%) and metabolites (78%). The remainder is recovered in urine, mainly unchanged.
An increase in the area under the time–concentration curve (AUC) has been observed in patients with hepatic impairment, but specific dose recommendations have not been made.
Clinical Use
Treatment of HIV infection (in combination with other antiretroviral drugs)
Side effects
The most common adverse effect is diarrhea of mild
to moderate severity. Other side effects include nausea,
fatigue, vomiting and headache. It is associated with less
dyslipidemia in comparison with ritonavir-boosted protease
inhibitors.
Metabolism
Following oral administration, nelfinavir peak levels in plasma ranged from 0.34 mg/mL (10 mg/kg in the dog) to 1.7 mg/mL (50 mg/kg in the rat). In the dog, nelfinavir was slowly absorbed, and bioavailability was 47%. The drug appeared to be metabolized in the liver, and the major excretory route was in feces.
Check Digit Verification of cas no
The CAS Registry Mumber 159989-64-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,9,9,8 and 9 respectively; the second part has 2 digits, 6 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 159989-64:
(8*1)+(7*5)+(6*9)+(5*9)+(4*8)+(3*9)+(2*6)+(1*4)=217
217 % 10 = 7
So 159989-64-7 is a valid CAS Registry Number.
InChI:InChI=1/C32H45N3O4S/c1-21-25(15-10-16-28(21)36)30(38)33-26(20-40-24-13-6-5-7-14-24)29(37)19-35-18-23-12-9-8-11-22(23)17-27(35)31(39)34-32(2,3)4/h5-7,10,13-16,22-23,26-27,29,36-37H,8-9,11-12,17-20H2,1-4H3,(H,33,38)(H,34,39)/t22-,23+,26-,27-,29+/m0/s1
159989-64-7Relevant articles and documents
A concise synthesis of the HIV-protease inhibitor nelfinavir via an unusual tetrahydrofuran rearrangement
Zook,Busse,Borer
, p. 7017 - 7021 (2000)
An efficient synthesis of nelfinavir 1 was developed. The synthesis features an unusual rearrangement of a 3-amidotetrahydrofuran into a functionalized oxazoline. (C) 2000 Elsevier Science Ltd.
Optimization of an electrolyte system for the simultaneous separation of nelfinavir mesylate and two impurities by micellar electrokinetic chromatography
Bastos, Carina A.,Gomes, Cláudia R. B.,De Souza, Marcus V. N.,De Oliveira, Marcone A. L.
, p. 887 - 898 (2015/05/20)
A methodology for the simultaneous determination of nelfinavir mesylate and the impurities 3-hydroxy-2-methylbenzoic acid and (2R,3R)-4-((3S,4aS,8aS)-3-(tert-butylcarbamoyl) octahydroisoquinolin-2(1H)-yl)-3-hydroxy-1-(phenylthio)butan-2-aminium benzoate by micellar electrokinetic chromatography, with an analysis time of 25 min, was proposed. An electrolyte composed of sodium tetraborate buffer (pH 9.24; 25 mmol L-1), sodium dodecyl sulphate (9 mmol L-1) and methanol (10percent, v/v) was optimized using a mixed-level factorial design, with direct detection at 200 nm. After evaluating some figures of merit, such as selectivity, linearity, precision, limit of detection, limit of quantification, accuracy and robustness (using Youden's test), the method was successfully applied to the analysis of nelfinavir mesylate and its impurities in a pharmaceutical formulation. The optimized methodology is demonstrated to be useful in the determination of these analytes in a synthesis monitoring process, in raw materials and in pharmaceutical formulations, while offering low solvent consumption, requiring a small sample and using non-specific columns as advantages.
Asymmetric synthesis of the potent HIV-protease inhibitor, nelfinavir
Raghavan, Sadagopan,Krishnaiah,Sridhar
supporting information; experimental part, p. 498 - 501 (2010/03/30)
(Chemical Equation Presented) An asymmetric synthesis of nelfinavir is described starting from acrolein and (S)-methyl phenyl sulfoxide. The key features include (a) stereoselective preparation of a β-protected amino-γ,δ-unsaturated sulfoxide by the reaction of an α-sulfinyl carbanion with an unsaturated t-butyl sulfinylimine, (b) stereoselective bromohydrin formation using the pendant sulfoxide group as an intramolecular nucleophile, and (c) use of commercially or readily prepared inexpensive starting materials.
