217176-33-5Relevant academic research and scientific papers
INHIBITORS OF VIRAL REPLICATION, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES
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Page/Page column 83-84, (2012/11/06)
The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
Novel aldosterone synthase inhibitors with extended carbocyclic skeleton by a combined ligand-based and structure-based drug design approach
Lucas, Simon,Heim, Ralf,Negri, Matthias,Antes, Iris,Ries, Christina,Schewe, Katarzyna E.,Bisi, Alessandra,Gobbi, Silvia,Hartmann, Rolf W.
supporting information; experimental part, p. 6138 - 6149 (2009/10/01)
Pharmacophore modeling of a series of aldosterone synthase (CYP11B2) inhibitors triggered the design of compounds 11 and 12 by extending a previously established naphthalene molecular scaffold (e.g., present in molecules 1 and 2) via introduction of a phenyl or benzyl residue in 3-position. These additional aromatic moieties have been hypothesized to fit into the newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies in our refined CYP11B2 protein model have been performed prior to synthesis to estimate the inhibitory properties of the proposed molecules. While phenyl-substituted compound 11 (IC50 > 500 nM) did not dock under the given pharmacophore constraint (i.e., the Fe(heme)-N(ligand) interaction), benzyl-substituted compound 12 (IC50 = 154 nM) was found to exploit a previously unexplored subpocket of the inhibitor binding site. By structural optimization based on the pharmacophore hypothesis, 25 novel compounds were synthesized, among them highly potent CYP11B2 inhibitors (e.g., 17, IC 50 = 2.7 nM) with pronounced selectivity toward the most important steroidogenic and hepatic CYP enzymes.
Synthesis and PTP1B inhibition of 1,2-naphthoquinone derivatives as potent anti-diabetic agents.
Ahn, Jin Hee,Cho, Sung Yun,Ha, Jae Du,Chu, So Young,Jung, Sun Ho,Jung, Yoon Sung,Baek, Ji Yoen,Choi, In Kyung,Shin, Eun Young,Kang, Seung Kyu,Kim, Sung Soo,Cheon, Hyae Gyeong,Yang, Sung-Don,Choi, Joong-Kwon
, p. 1941 - 1946 (2007/10/03)
A new series of 1,2-naphthoquinone derivatives was synthesized by various synthetic methods and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B). 1,2-Naphthoquinone derivatives with substituent at R(4) position showed submicromolar inhibitory activity, and compound 24 demonstrated 10- to 60-fold selectivity against the tested phosphatases. Also, several 4-aryl-1,2-naphthoquinone derivatives with substituents at R(3), R(6), R(7), or/and R(8) showed submicromolar inhibitory activity and good plasma stability.
