- Highly efficient organocatalysts for the asymmetric aldol reaction
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A new class of bifunctional organocatalysts containing both thiazolidine/pyrrolidine and imidazole cycles was prepared via a readily available synthetic route. The highly efficient five step methodology did not require intermediary purification and provid
- Jacoby,Vontobel,Bach,Schneider
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p. 7416 - 7421
(2018/05/04)
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- A Potent, Selective, and Orally Bioavailable HCV NS5A Inhibitor for Treatment of Hepatitis C Virus: (S)-1-((R)-2-(Cyclopropanecarboxamido)-2-phenylacetyl)-N-(4-phenylthiazol-2-yl)pyrrolidine-2-carboxamide
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Starting from the initial lead 4-phenylthiazole 18, a modest HCV inhibitor (EC50 = 9440 nM), a series of structurally related thiazole derivatives has been identified as a novel chemical class of potent and selective HCV NS5A inhibitors. The introduction of a carboxamide group between the thiazole and pyrrolidine ring (42) of compound 18 resulted in a dramatic increase in activity (EC50 = 0.92 nM). However, 42 showed only moderate pharmacokinetic properties and limited oral bioavalability of 18.7% in rats. Further optimization of the substituents at the 4-position of the thiazole ring and pyrrolidine nitrogen of the lead compound 42 led to the identification of compound 57, a highly potent and selective NS5A inhibitor of HCV (EC50 = 4.6 nM), with greater therapeutic index (CC50/EC50 > 10000). Pharmacokinetic studies revealed that compound 57 had a superior oral exposure and desired bioavailability of 45% after oral administration in rats.
- Kang, Iou-Jiun,Hsu, Sheng-Ju,Yang, Hui-Yun,Yeh, Teng-Kuang,Lee, Chung-Chi,Lee, Yen-Chun,Tian, Ya-Wen,Song, Jen-Shin,Hsu, Tsu-An,Chao, Yu-Sheng,Yueh, Andrew,Chern, Jyh-Haur
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p. 228 - 247
(2017/04/26)
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- NOVEL BETULINIC ACID PROLINE DERIVATIVES AS HIV INHIBITORS
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The invention relates to novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases. These compounds are esterified in position 3 and are substituted in position 17 of the betulinic acid structure, via a linking group W, by a saturated 5-7 membered nitrogen-heterocycle.
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- Synthesis and evaluation of non-dimeric HCV NS5A inhibitors
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Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).
- Amblard, Franck,Zhang, Hongwang,Zhou, Longhu,Shi, Junxing,Bobeck, Drew R.,Nettles, James H.,Chavre, Satish,McBrayer, Tamara R.,Tharnish, Philip,Whitaker, Tony,Coats, Steven J.,Schinazi, Raymond F.
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p. 2031 - 2034
(2013/05/09)
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- PDF INHIBITORS
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The invention relates to novel compounds that are inhibitors of peptidyl deformylase (PDF). The compounds are useful as antimicrobials and antibiotics. The compounds of the invention display selective inhibition of peptidyl deformylase versus other metalloproteinases such as MMPs. Methods of preparation and uses of the compounds are also disclosed.
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Page/Page column 34
(2010/11/28)
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