Human immunodeficiency virus HIV protease inhibitors

A wide variety of simple transformations on chiral pool materials can lead to unnatural amino acid derivatives. This is illustrated by the Pictet-Spengler reaction of L-phenylalanine, followed by amide formation and reduction of the aromatic ring (Scheme 2.18).52 The resultant amide (11) is an intermediate in a number of commercial human immunodeficiency virus (HIV) protease inhibitors. 

One of the few industrial examples of the asymmetric synthesis of halohydrins is in a process to the human immunodeficiency virus (HIV) protease inhibitor, Indinavir.190 The y,8-unsaturated carboxamide 23 is smoothly converted into iodohydrin 24 (92%, 94% de) (Scheme 9.34). (For more on the chemistry of the indanol, see Chapter 24.)191... 

A microbial reduction with a Rhodococcus erythropolis strain was used by BMS scientists to prepare the chiral chlorohydrin from the chloroketone (Scheme 19.15). This intermediate is incorporated into the human immunodeficiency virus (HIV) protease inhibitor Atazanavir (26). This strain was identified through screening and provided >90% yield with a diastereomeric purity of >98% and an ee of >99%.62... 

Dieleman IP, in t Veld B, Borleffs JC, Schreij G. Acute respiratory failure associated with the human immunodeficiency virus (HIV) protease inhibitor indinavir in an HIV-infected patient. Clin Infect Dis I998 26(4) 1012-13. 

Human immunodeficiency virus (HIV) protease inhibitors have provided the pharmaceutical and fine chemical industry with a number of difficult problems... 

An interesting example of polymorphic structure differentiation is that of human immunodeficiency virus (HIV) protease inhibitors. The HIV protease inhibitors pose a serious problem in their bioavailability. Invirase showed only modest market performance, and it was soon superseded by drugs, such as ritonavir (Norvir) and indinavir sulfate (Crixivan ) that had better bioavailability. Three years after initial approval, saquinavir was reintroduced in a formulation with sixfold higher oral bioavailability relative to the original product. Ritonavir was originally launched as a semisolid dosage form, in which the waxy matrix contained the dispersed drug in order to achieve acceptable oral bioavailabiUty. Two years after its introduction, ritonavir... 

This table is intended to hold results of assays testing compounds in reg-istry.structure for activity as human immunodeficiency virus (HIV) protease inhibitors. As new assays are added, the test results can be added to newly created tables with similar definitions. For example, there might be tables for HIV reverse transcriptase inhibitors stored in a table named hiv.rt. Other assay results might be stored in new schemas, for example, fpr.htfc for high-throughput flow cytometry results for the formyl peptide receptor (FPR), or f pr.ca for FPR cell adhesion assay results. Each of these tables would have columns of data named and typed appropriately for each assay. Each table would have a column containing a compound id that references compounds in the registry, structure table. 

The human immunodeficiency virus (HIV) protease inhibitor ritonavir is an inhibitor of both CYP3A4 and P-glycoprotein. Substrates of these two elimination pathways are particularly susceptible to interactions with ritonavir. 

The 1S,2R stereoisomer 17 has been obtained via the Baker s yeast reduction of the unsaturated bromoketone 18 in 99% e.e. and 75% yields at 3 g/L. The reaction occurs presumably through the reduction of the initially formed saturated ketone 19. The fact that racemic bromoketone 20 is also reduced by yeast to the same enantiomer with complete stereoselectivity is evidence that the intermediate bromoketone 19 rapidly racemizes in the reaction medium. The efficiency of the latter biotransformation makes it preferable to the corresponding yeast reduction of the unsaturated compound (Scheme 7). The preparation of such enantiomerically pure compounds found significance in the preparation of optically active l-amino-2-indanol as ligand in the human immunodeficiency virus (HIV) protease inhibitor indinavir [47]. 

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