- A concise synthesis of the HIV-protease inhibitor nelfinavir via an unusual tetrahydrofuran rearrangement
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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.
- Zook,Busse,Borer
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Read Online
- Enantioselective Synthesis of Nelfinavir via Asymmetric Bromocyclization of Bisallylic Amide
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We describe a concise enantioselective synthesis of the HIV-protease inhibitor nelfinavir (1) via a new route in which the key step is construction of the central optically active 1,2-amino alcohol framework via asymmetric bromocyclization of bisallylic amide with N-bromosuccinimide in the presence of a catalytic amount of (S)-BINAP or (S)-BINAP monoxide. The remaining alkene and bromo functionalities were used to install the requisite thioether and chiral perhydroisoquinoline units, respectively.
- Nagao, Yoshihiro,Hisanaga, Tatsunari,Utsumi, Takahiro,Egami, Hiromichi,Kawato, Yuji,Hamashima, Yoshitaka
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p. 7290 - 7295
(2018/07/15)
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- Optimization of an electrolyte system for the simultaneous separation of nelfinavir mesylate and two impurities by micellar electrokinetic chromatography
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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.
- Bastos, Carina A.,Gomes, Cláudia R. B.,De Souza, Marcus V. N.,De Oliveira, Marcone A. L.
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p. 887 - 898
(2015/05/20)
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- Methods for predicting the response to statins
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The invention provides methods for optimizing therapeutic efficacy for treating hypercholesterolemia in a subject having a cardiovascular disease (CVD), comprising (a) determining subject characteristics that affect the likelihood of reaching a goal level of low density lipoprotein (LDL); and (b) obtaining success probabilities of a variety of statin treatments for reaching said goal level of LDL using said subject characteristics and a multivariate model; and (c) administrating the optimal statin treatment with the highest success probability of step (b) to said subject thereby optimizing therapeutic efficacy for treating hypercholesterolemia in said subject.
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- Asymmetric synthesis of the potent HIV-protease inhibitor, nelfinavir
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(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.
- Raghavan, Sadagopan,Krishnaiah,Sridhar
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supporting information; experimental part
p. 498 - 501
(2010/03/30)
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- INTERMEDIATES USEFUL IN THE SYNTHESIS OF HIV-PROTEASE INHIBITORS AND METHODS FOR PREPARING THE SAME
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Optically active 3-amino-butene and 1,2-dihydroxy-3-amino-butane intermediate compounds, useful in the synthesis of HIV-protease inhibitors and methods of preparing these intermediate compounds are disclosed (Formula I).
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- Method of making a HIV-Protease inhibitor
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The present invention is directed to a method of making the HIV-protease inhibitor nelfinavir mesylate.
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Page/Page column 24; 26-27
(2010/11/30)
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- A short synthesis of the HIV-protease inhibitor nelfinavir via a diastereoselective addition of ammonia to the α,β-unsaturated sulfoxide derived from (R)-glyceraldehyde acetonide
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Diastereoselective Michael addition of ammonia to sulfoxide 3a derived from (R)-glyceraldehyde acetonide provides amine 4a, which is converted into Nelfinavir using BF3·Et2O/NaI reduction and subsequent coupling reactions as key steps.
- Ma, Dawei,Zou, Bin,Zhu, Wei,Xu, Huadong
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p. 8511 - 8513
(2007/10/03)
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- A synthesis of the HIV-protease inhibitor nelfinavir from D-tartaric acid
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This letter describes a new synthesis of the HIV-protease inhibitor nelfinavir. The synthesis features a selective opening of a D-tartaric acid-derived cyclic sulfate with nitrogen nucleophiles.
- Albizati, Kim F.,Babu, Srinivasan,Birchler, Angela,Busse, Juliette K.,Fugett, Michelle,Grubbs, Alan,Haddach, Aubrey,Pagan, Miguel,Potts, Barbara,Remarchuk, Travis,Rieger, Dale,Rodriguez, Rick,Shanley, Jim,Szendroi, Robert,Tibbetts, Tony,Whitten, Kathleen,Borer, Bennett C.
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p. 6481 - 6485
(2007/10/03)
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- Process for producing amide derivatives and intermediates therefor
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PCT No. PCT/JP96/02756 Sec. 371 Date Apr. 14, 1998 Sec. 102(e) Date Apr. 14, 1998 PCT Filed Sep. 24, 1996 PCT Pub. No. WO97/11937 PCT Pub. Date Apr. 3, 1997A method for producing an amide derivative of the formula [XV] wherein each symbol is as defined in the specification, and an enantiomer thereof, a novel intermediate useful for producing said compound and a production method thereof. The production method of the present invention is extremely easy and simple as compared to the conventional methods, and enables effective production of compound [XV] at high yields, which includes compound [XVI] having an HIV protease inhibitory action. In addition, the novel intermediates of the present invention are extremely useful as intermediates for producing not only the aforementioned compound [XVI] but also compounds useful as X-ray contrast media.
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- Production of amide derivatives and intermediate compounds therefor
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A method for producing an amide derivative of the formula ?XV! STR1 wherein each symbol is as defined in the specification, and an enantiomer thereof, a novel intermediate useful for producing said compound and a production method thereof. The production method of the present invention is extremely easy and simple as compared to the conventional methods, and enables effective production of compound ?XV! at high yields, which includes compound ?XVI! having an HIV protease inhibitory action. In addition, the novel intermediates of the present invention are extremely useful as intermediates for producing not only the aforementioned compound ?XVI! but also compounds useful as X-ray contrast media.
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