Synthesis of a 5-Azaindole Phosphonic Acid as a Computationally Designed Inhibitor of the Low Molecular Weight Phosphatase HCPTP

Weitgenant, Jeremy A.; Katsuyama, Isamu; Bigi, Marinus A.; Corden, Steven J.; Zabell, Adam P.R.; Homan, Kristoff T.; Wiest, Olaf; Stauffacher, Cynthia V.; Helquist, Paul

doi:10.3987/com-06-s(w)38

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Cited by 6 publications

(2 citation statements)

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“…1 H NMR (499 MHz, CDCl 3 ): δ 7.18 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 4.39 (s, 2H), 3.81 (s, 2H), 3.25 (t, J = 7.1 Hz, 2H), 2.43(t, J = 8.1 Hz, 2H), 1.98 (quin, J = 7.7 Hz, 2H). The spectral data were consistent with those reported in the literature …”

Section: Methodssupporting

confidence: 91%

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Iridium-Catalyzed Single-Step N-Substituted Lactam Synthesis from Lactones and Amines

Kim

Hong

2015

J. Org. Chem.

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Section: Methodssupporting

confidence: 91%

“…The spectral data were consistent with those reported in the literature. 21 1-[(4-Methylphenyl)methyl]-2-pyrrolidinone (3ac). Brown liquid (62 mg, 65%).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Iridium-Catalyzed Single-Step N-Substituted Lactam Synthesis from Lactones and Amines

Kim

Hong

2015

J. Org. Chem.

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Identification of novel inhibitors for a low molecular weight protein tyrosine phosphatase via virtual screening

Homan

Balasubramaniam

Zabell

et al. 2010

Bioorganic & Medicinal Chemistry

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The human cytoplasmic protein tyrosine phosphatase (HCPTP) has been identified as a potential target for inhibition in order to downregulate metastatic transformation in several human epithelial cancers such as breast, prostate and colon cancer. Docking with two scoring functions on both isoforms of HCPTP was employed as an initial virtual screen to identify potential inhibitors. Compounds identified as potential inhibitors via this in silico screen were subjected to kinetic analysis in order to validate their selection as improved inhibitors. Eleven compounds with IC50’s of less than 100 μM were identified in a single concentration screen. Five of these compounds were determined to have IC50 of less than 10 μM; however, all but one of these compounds inhibited via non-specific aggregation. The validated effective inhibitor, which is based on a naphthyl sulfonic acid, strongly resembles a previously synthesized rationally designed azaindole phosphonic acid. This similarity suggests subsequent inhibitor optimization based on this scaffold may generate effective inhibitors of HCPTP. The structural elements of the computationally identified inhibitors are discussed to analyze the combined use of rationally design and virtual screening to reduce false negatives in the identification of multiple strong inhibitors of HCPTP.

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Synthesis and reactivity of 4-, 5- and 6-azaindoles

2007

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Synthesis of a 5-Azaindole Phosphonic Acid as a Computationally Designed Inhibitor of the Low Molecular Weight Phosphatase HCPTP

Cited by 6 publications

References 24 publications

Iridium-Catalyzed Single-Step N-Substituted Lactam Synthesis from Lactones and Amines

Iridium-Catalyzed Single-Step N-Substituted Lactam Synthesis from Lactones and Amines

Identification of novel inhibitors for a low molecular weight protein tyrosine phosphatase via virtual screening

Synthesis and reactivity of 4-, 5- and 6-azaindoles

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