2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

Hong Lin; Dennis S. Yamashita; Jin Zeng; Ren Xie; Sharad Verma; Juan I. Luengo; Nelson Rhodes; Shuyun Zhang; Kimberly A. Robell; Anthony E. Choudhry; Zhihong Lai; Rakesh Kumar; Elisabeth A. Minthorn; Kristin K. Brown; Dirk A. Heerding

doi:10.1016/j.bmcl.2009.11.060

2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

Hong Lin, Dennis S. Yamashita, Jin Zeng, Ren Xie, Sharad Verma, Juan I. Luengo, Nelson Rhodes, Shuyun Zhang, Kimberly A. Robell, Anthony E. Choudhry, Zhihong Lai, Rakesh Kumar, Elisabeth A. Minthorn, Kristin K. Brown, Dirk A. Heerding

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3β phosphorylation in a BT474 tumor xenograft model in mice.

Original language	English (US)
Pages (from-to)	679-683
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2009.11.060
State	Published - Jan 15 2010
Externally published	Yes

Keywords

AKT kinase inhibitors
Azaindazole
Selectivity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2009.11.060

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Lin, H., Yamashita, D. S., Zeng, J., Xie, R., Verma, S., Luengo, J. I., Rhodes, N., Zhang, S., Robell, K. A., Choudhry, A. E., Lai, Z., Kumar, R., Minthorn, E. A., Brown, K. K., & Heerding, D. A. (2010). 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorganic and Medicinal Chemistry Letters, 20(2), 679-683. https://doi.org/10.1016/j.bmcl.2009.11.060

Lin, H, Yamashita, DS, Zeng, J, Xie, R, Verma, S, Luengo, JI, Rhodes, N, Zhang, S, Robell, KA, Choudhry, AE, Lai, Z, Kumar, R, Minthorn, EA, Brown, KK & Heerding, DA 2010, '2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 2, pp. 679-683. https://doi.org/10.1016/j.bmcl.2009.11.060

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abstract = "A novel series of AKT inhibitors containing 2,3,5-trisubstituted pyridines with novel azaindazoles as hinge binding elements are described. Among these, the 4,7-diazaindazole compound 2c has improved drug-like properties and kinase selectivity than those of indazole 1, and displays greater than 80% inhibition of GSK3β phosphorylation in a BT474 tumor xenograft model in mice.",

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AU - Lin, Hong

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AU - Zeng, Jin

AU - Xie, Ren

AU - Verma, Sharad

AU - Luengo, Juan I.

AU - Rhodes, Nelson

AU - Zhang, Shuyun

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AU - Choudhry, Anthony E.

AU - Lai, Zhihong

AU - Kumar, Rakesh

AU - Minthorn, Elisabeth A.

AU - Brown, Kristin K.

AU - Heerding, Dirk A.

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2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles

Abstract

Keywords

ASJC Scopus subject areas

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