136465-90-2Relevant academic research and scientific papers
PROCESS FOR SYNTHESIS OF SYN AZIDO EPOXIDE AND ITS USE AS INTERMEDIATE FOR THE SYNTHESIS OF AMPRENAVIR and SAQUINAVIR
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Paragraph 0086, (2015/02/18)
Disclosed herein is a novel route of synthesis of syn azide epoxide of formula 5, which is used as a common intermediate for asymmetric synthesis of HIV protease inhibitors such as Amprenavir, Fosamprenavir, Saquinavir and formal synthesis of Darunavir an
A PROCESS FOR SYNTHESIS OF SYN AZIDO EPOXIDE AND ITS USE AS INTERMEDIATE THE SYNTHESIS OF AMPRENAVIR and SAQUINAVIR
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Page/Page column 26, (2013/07/25)
Disclosed herein is a novel route of synthesis of syn azide epoxide of formu 5, which is used as a common intermdeiate for asymmetric synthesis of HIV protease inhibitors such as Amprenavir, Fosamprenavir, Saquinavir and formal synthesis of Darunavir and
Enantioselective synthesis of HIV protease inhibitor amprenavir via Co-catalyzed HKR of 2-(1-azido-2-phenylethyl)oxirane
Gadakh, Sunita K.,Santhosh Reddy,Sudalai, Arumugam
experimental part, p. 898 - 903 (2012/09/22)
A short and efficient enantioselective synthesis of the HIV protease inhibitor amprenavir 1 (99% ee) as well as a formal synthesis of saquinavir 3 have been achieved in high enantiomeric purity starting from commercially available materials. Our strategy mainly comprises a Co-catalyzed two-stereocentred hydrolytic kinetic resolution (HKR) of racemic 2-(1-azido-2-phenylethyl)oxirane as the chirality inducing step. Also presented is a concise synthesis of (S)-3-hydroxytetrahydrofuran 4, the key structural feature, in high enantiomeric purity (98% ee).
Studies toward the Large-Scale Synthesis of the HIV Proteinase Inhibitor Ro 31-8959
Parkes, Kevin E. B.,Bushnell, David J.,Crackett, Peter H.,Dunsdon, Stephen J.,Freeman, Andrew C.,et al.
, p. 3656 - 3664 (2007/10/02)
Ro 31-8959 (1), a potent and selective inhibitor of HIV proteinase, is currently in phase III clinical trials.Six approaches for the large-scale synthesis of this compound have been studied.All routes employ an initial disconnection to an electrophilic L-phenylalanine homologue equivalent 13 and the decahydroisoquinoline derivative 5.They differ in adopting either an epoxide, a cyclic sulfate, or an aldehyde as the electrophilic entity and develop chirality from L-phenylalanine, dimethyl D-tartrate, or a Sharpless epoxidation.The preferred route starts from N-phthaloyl-L-phenylalaninyl chloride and uses tris((trimethylsilyl)oxy)ethene to effect homologation to hydroxy ketone 30, which is elaborated in a five-step two-pot procedure to N-phthaloyl epoxide 33 and hence 1.Kilogram quantities of Ro 31-8959 have been prepared using this route.
The Development of Cyclic Sulfolanes as Novel and High-Affinity P2 Ligands for HIV-1 Protease Inhibitors
Ghosh, Arun K.,Lee, Hee Yoon,Thompson, Wayne J.,Culberson, Chris,Holloway, M. Katharine,et al.
, p. 1177 - 1188 (2007/10/02)
Design and synthesis of a novel series of protease inhibitors incorporating conformationally constrained cyclic ligands for the S2-substrate binding site of HIV-1 protease is described. We recently reported urethanes of 3-tetrahydrofuranyl as P2 ligands for HIV-1 protease inhibitors. Subsequently, we have found that the urethane of 3(S)-hydroxysulfolane further increased the in vitro potency of these inhibitors. Furthermore, introduction of a small 2-alkyl group cis to the 3-hydroxyl group of either heterocyclic system further enhanced enzyme affinity. The cis-2-isopropyl group thus far offered optimum enhancement of the inhibitory properties. This led to the discovery of inhibitor 43 (IC50 3.5 nM, CIC95 50+/-14 nM) of comparable in vitro antiviral potency to the current clinical candidate 1 (Ro 31-8959) but of reduced molecular weight due to the exclusion of the P3 quinoline ligand. Also, it has been demonstrated that the octahydropyrindene derivative 34 is an effective replacement of the P1' decahydroisoquinoline derivative.
Potent HIV Protease Inhibitors: The Development of Tetrahydrofuranylglycines as Novel P2 Ligands and Pyrazine Amides as P3-Ligands
Ghosh, Arun K.,Thompson, Wayne J.,Holloway, M. Katharine,McKee, Sean P.,Duong, Tien T.,et al.
, p. 2300 - 2310 (2007/10/02)
A series of protease inhibitors bearing constrained unnaturel amino acids at the P2-position and novel heterocycles at the P3-position of compound 1 (Ro 31-8959) were synthesized, and their in vitro enzyme inhibitory and antiviral ac
