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Novel spirocyclic pyrrolidones as P2/P1 mimetics in potent inhibitors of HIV-1 protease. 2002

Wieslaw M Kazmierski, and Eric Furfine, and Andrew Spaltenstein, and Lois L Wright
GlaxoSmithKline, Research Triangle Park, NC 27709, USA. wieslaw.m.kazmierski@gsk.com

We have developed concise and efficient syntheses of novel spirocyclic pyrrolidones 1-3, which involve the alkylation of pyrrolidone precursor 13 with 1,5-dibromopentane, 16 and 15, followed by an in situ lactamization. Conjugates of 1 and 2 with P1'/P2' hydroxy-indanolamine moiety resulted in novel and potent inhibitors of HIV-1 protease 25 and 26, suggesting that 1 and 2 are novel P2/P1 HIV-PI mimetics.

UI MeSH Term Description Entries
D007769 Lactams Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams. Lactam,Lactim,Lactims
D011760 Pyrrolidinones A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed) Pyrrolidinone,Pyrrolidone,Pyrrolidones
D000478 Alkylation The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. Alkylations
D013141 Spiro Compounds Cyclic compounds that include two rings which share a single atom (usually a carbon). The simplest example of this type of compound is Spiro[2.2]pentane, which looks like a bow tie. Compounds, Spiro
D017320 HIV Protease Inhibitors Inhibitors of HIV PROTEASE, an enzyme required for production of proteins needed for viral assembly. HIV Protease Inhibitor,Inhibitor, HIV Protease,Inhibitors, HIV Protease,Protease Inhibitor, HIV,Protease Inhibitors, HIV
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D040761 Biomimetic Materials Materials fabricated by BIOMIMETICS techniques, i.e., based on natural processes found in biological systems. Bio-Inspired Devices,Bio-Inspired Materials,Bioinspired Devices,Bioinspired Materials,Biomimetic Devices,Biomimicry Devices,Biomimicry Materials,Bio Inspired Devices,Bio Inspired Materials,Bio-Inspired Device,Bio-Inspired Material,Bioinspired Device,Bioinspired Material,Biomimetic Device,Biomimetic Material,Biomimicry Device,Biomimicry Material,Device, Bio-Inspired,Device, Bioinspired,Device, Biomimetic,Device, Biomimicry,Devices, Bio-Inspired,Devices, Bioinspired,Devices, Biomimetic,Devices, Biomimicry,Material, Bio-Inspired,Material, Bioinspired,Material, Biomimetic,Material, Biomimicry,Materials, Bio-Inspired,Materials, Bioinspired,Materials, Biomimetic,Materials, Biomimicry

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