162174-87-0Relevant articles and documents
Design, synthesis, and biological evaluation of novel 4-hydroxypyrone derivatives as HIV-1 protease inhibitors
Sun, Chun-Lai,Pang, Rui-Fang,Zhang, Hang,Yang, Ming
, p. 3257 - 3262 (2005)
Twenty-four 4-hydroxypyrone derivatives were synthesized with a facile synthetic method to develop novel HIV protease inhibitors. Most of them were shown to display good antiviral activities in SIV-infected CEM cells. The introduction of α-naphthylmethyl group to C-6 of 5,6-dihydropyran-2-ones led to an effective antiviral compound that showed an EC50 value at 1.7 μM with a therapeutic index of 46.
Synthesis and antitumor activity of 4-hydroxycoumarin derivatives
Jung, Jae-Chul,Lee, Ji-Ho,Oh, Seikwan,Lee, Jae-Gon,Park, Oee-Sook
, p. 5527 - 5531 (2007/10/03)
A series of 4-hydroxycoumarin derivatives was prepared and evaluated for antitumor activity against five human tumor cell lines. A series of 4-hydroxycoumarin derivatives was prepared and evaluated for antitumor activity. The key fragments were 2a-c, 5c, 12b, 13b, 17, and 18 which were prepared via dianion ring cyclization, Friedel-Crafts acylation, and Reformatsky reaction. Compound 20b showed the most potent antitumor activity among the total 12 derivatives and compounds 19a and 19b exhibited efficacy comparable to etoposide in vitro antitumor activity.
Continuous process for preparing dihydropyrones
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, (2008/06/13)
The invention relates to a continuous process for preparing dihydropyrones of general formula I, wherein the groups R1 and R2 have the meanings described herein.
Pyran-2-ones and 5,6-dihydropyran-2-ones useful for treating hyperplasia and other diseases
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Page 74, (2010/02/05)
Certain 2H-pyran-2-ones are useful for treating benign prostatic hypertrophy or hyperplasia, prostatic cancer, alopecia, hirsutism, acne vulgaris and seborrhea.
Tipranavir (PNU-140690): A potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class
Turner, Steve R.,Strohbach, Joseph W.,Tommasi, Ruben A.,Aristoff, Paul A.,Johnson, Paul D.,Skulnick, Harvey I.,Dolak, Lester A.,Seest, Eric P.,Tomich, Paul K.,Bohanon, Michael J.,Horng, Miao-Miao,Lynn, Janet C.,Chong, Kong-Teck,Hinshaw, Roger R.,Watenpaugh, Keith D.,Janakiraman, Musiri N.,Thaisrivongs, Suvit
, p. 3467 - 3476 (2007/10/03)
A broad screening program previously identified phenprocoumon (1) as a small molecule template for inhibition of HIV protease. Subsequent modification of this lead through iterative cycles of structure-based design led to the activity enhancements of pyrone and dihydropyrone ring systems (II and V) and amide-based substitution (III). Incorporation of sulfonamide substitution within the dihydropyrone template provided a series of highly potent HIV protease inhibitors, with structure-activity relationships described in this paper. Crystallographic studies provided further information on important binding interactions responsible for high enzymatic binding. These studies culminated in compound VI, which inhibits HIV protease with a K(i) value of 8 pM and shows an IC90 value of 100 nM in antiviral cell culture. Clinical trials of this compound (PNU-140690, Tipranavir) for treatment of HIV infection are currently underway.
Structure-based design of HIV protease inhibitors: 5,6-dihydro-4- hydroxy-2-pyrones as effective, nonpeptidic inhibitors
Thaisrivongs, Suvit,Romero, Donna L.,Tommasi, Ruben A.,Janakiraman, Musiri N.,Strohbach, Joseph W.,Turner, Steve R.,Biles, Carolyn,Morge, Raymond R.,Johnson, Paul D.,Aristoff, Paul A.,Tomich, Paul K.,Lynn, Janet C.,Horng, Miao-Miao,Chong, Kong-Teck,Hinshaw, Roger R.,Howe, W. Jeffrey,Finzel, Barry C.,Watenpaugh, Keith D.
, p. 4630 - 4642 (2007/10/03)
From a broad screening program, the 4-hydroxycoumarin phenprocoumon (I) was previously identified as a lead template with HIV protease inhibitory activity. The crystal structure of phenprocoumon/HIV protease complex initiated a structure-based design effort that initially identified the 4- hydroxy-2-pyrone U-96988 (II) as a first-generation clinical candidate for the potential treatment of HIV infection. Based upon the crystal structure of the 4-hydroxy-2-pyrone III/HIV protease complex, a series of analogues incorporating a 5,6-dihydro-4-hydroxy-2-pyrone template were studied. It was recognized that in addition to having the required pharmacophore (the 4- hydroxy group with hydrogen-bonding interaction with the two catalytic aspartic acid residues and the lactone moiety replacing the ubiquitous water molecule in the active site), these 5,6-dihydro-4-hydroxy-2-pyrones incorporated side chains at the C-6 position that appropriately extended into the S1' and S2' subsites of the enzyme active site. The crystal structures of a number of representative 5,6-dihydro-4-hydroxy-2-pyrones complexed with the HIV protease were also determined to provide better understanding of the interaction between the enzyme and these inhibitors to aid the structure- based drug design effort. The crystal structures of the ligands in the enzyme active site did not always agree with the conformations expected from experience with previous pyrone inhibitors. This is likely due to the increased flexibility of the dihydropyrone ring. From this study, compound XIX exhibited reasonably high enzyme inhibitory activity (K(i) = 15 nM) and showed antiviral activity (IC50 = 5 μM) in the cell-culture assay. This result provided a research direction which led to the discovery of active 5,6-dihydro-4-hydroxy-2-pyrones as potential agents for the treatment of HIV infection.
