HIV therapeutics

HIV-1 integrase strand transfer inhibitors, 45, 263 HIV prevention strategies, 40, 277 HIV protease inhibitors, 26,141 29, 123 HIV reverse transcriptase inhibitors, 29,123 HIV therapeutics, 40, 291 HIV vaccine, 27, 255... 

There is a great need to advance novel strategies for anti-HIV therapeutics. Small organic molecules that target unique viral RNA sites and that can prevent the... 

Mechanism of Action Inhibits the activity of HIV-1 protease, the enzyme necessary for the formation of infectious HIV. Therapeutic Effect Formation of immature noninfec-tious viral particles rather than HIV replication. 

While over 33 million people are living with HIV/AIDS, the impact of HIV therapies has been shown by a nationwide decline in AIDS-related deaths. The vast majority of anti-HIV therapeutic agents have been limited to reverse transcriptase and protease inhibitors.5,6 However, the development of resistance to these inhibitors7 and the toxic side effects associated with these compounds8 indicate a major need for further discovery and development of alternative strategies such as those targeting other stages... 

Wliich anti-HIV therapeutics specifically target the infecting agent ... 

Bauman JD, Patel D, Arnold E (2011) Fragment screening and HIV therapeutics. Top Curr Chem doi 128 2011 232... 

Bisamide 56 is prepared by coupling of the diacid 55 with 1 -(S)-2-(R)-1 -amino-2-indanol (54) using DEPC as an activating agent.22 The binding data for 56 compare very favorably with the established HIV therapeutic agent indinavir 2... 

Virtual screening and HIV-1 repHcation assays have been used to identify the oxadiazole 84 as a novel and potent lead compound (2013CMC426 Figure 31). Compound 84 is able to reduce virus replication as a consequence of direct interaction with the (4,5)-bisphosphate (PI(4,5)P2) binding pocket of the HFV-l matrix (MA) protein. Compound 84 inhibits several HFV-l MDR strains, with IC50 values of 7.5—15.6 pM for tested isolates. This new chemical entity seems promising for the discovery of a new class of anti-HIV therapeutics. 

The triterpene sapogenins betulinic acid, oleanolic acid and ursolic acid show cytotoxic and anti-inflammatory effects, and based on their structures novel chemopreventive and anticancer agents are being developed (Liby et al., 2007). A derivative of betulinic acid, beviri-mat, is the first member of a new class of anti HIV therapeutics, maturase inhibitors. These... 

Pumfery, A., de la Fuente, C.R. Berro, Nekhai, S.F. Kashanchi and Chao., S.H. Potential use of pharmacological cychn dependent kinase inhibitors as anti HIV therapeutics. Curr. Pharm. 

Magnus NA, Confalone PN, Storace L, Patel M, Wood CC, Davis WP, Parsons RL Jr (2003) General scope of 1,4-diastereoselective additions to a 2(3H)-quinazolinone practical preparation of HIV therapeutics. J Org Chem 68 754-761... 

Jiang B, Si YG (2004) Highly enantioselective construction of a chiral tertiary carbon center by alkynylation of a cycUc N-acyl ketimine an efficient preparation of HIV therapeutics. Angew Chem Int Ed 43 216—218... 

Just like palladium, the molybdenum-catalyzed reaction has been extended to an asymmetric variant. Following development of the reaction by Trost and co-workers,they reported a concise and efficient synthesis of the HIV therapeutic tipranavir (119). While the key tetrasubstituted centre in compound 115 was constructed by a palladium-boron co-catalyzed DYKAT reaction, the stereogenic centre in nitroaromatic 117 was installed in a molybdenum-catalyzed DYKAT reaction. Both compounds were subsequently elaborated to tipranavir (119). While it has been determined that the molybdenum-catalyzed reaction proceeds with overall retention, the stereochemistry of each step has not been extensively studied. Recent studies have suggested a retention-retention pathway may be in operation. ... 

CM with the Hindered Olefin 1,1-Disubstituted and trisub stituted olefins do not usually dimerize even in the presence of [Ru]-II, and these olefins are categorized as type Iff or type fV. The sterically crowded olefin such as 2-methyl-2-butene, however, was found to be available as a CM partner by Grubbs and co-workers. Porco and Qi employed this CM partner for the synthesis of clusianone 105, which is a potential anti-HIV therapeutic agent isolated from the floral resin of clusia species (Scheme 24.25). The isopropenyl moiety was smoothly incorporated into the side chain of clusianone precursor 104 by CM reaction of 102 with 103 as a solvent. 

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