Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II

Guobao Zhang; Pingda Ren; Nathanael S. Gray; Taebo Sim; Xia Wang; Yi Liu; Jianwei Che; Weitong Dong; Shin Shay Tian; Mark L. Sandberg; Tracy A. Spalding; Russell Romeo; Maya Iskandar; Zhiliang Wang; H. Martin Seidel; Donald S. Karanewsky; Yun He

doi:10.1016/j.bmcl.2009.09.123

Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II

Guobao Zhang, Pingda Ren, Nathanael S. Gray, Taebo Sim, Xia Wang, Yi Liu, Jianwei Che, Weitong Dong, Shin Shay Tian, Mark L. Sandberg, Tracy A. Spalding, Russell Romeo, Maya Iskandar, Zhiliang Wang, H. Martin Seidel, Donald S. Karanewsky, Yun He

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

9 Citations (Scopus)

Abstract

A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs.

Original language	English
Pages (from-to)	6691-6695
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2009.09.123
Publication status	Published - 2009 Dec 1

Keywords

Autoimmune disease
Kinase inhibitor
Lck inhibitor
Pyrimidine benzimidazoles
Transplantation rejection

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.2009.09.123

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Zhang, G., Ren, P., Gray, N. S., Sim, T., Wang, X., Liu, Y., Che, J., Dong, W., Tian, S. S., Sandberg, M. L., Spalding, T. A., Romeo, R., Iskandar, M., Wang, Z., Seidel, H. M., Karanewsky, D. S., & He, Y. (2009). Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II. Bioorganic and Medicinal Chemistry Letters, 19(23), 6691-6695. https://doi.org/10.1016/j.bmcl.2009.09.123

Zhang, G, Ren, P, Gray, NS, Sim, T, Wang, X, Liu, Y, Che, J, Dong, W, Tian, SS, Sandberg, ML, Spalding, TA, Romeo, R, Iskandar, M, Wang, Z, Seidel, HM, Karanewsky, DS & He, Y 2009, 'Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II', Bioorganic and Medicinal Chemistry Letters, vol. 19, no. 23, pp. 6691-6695. https://doi.org/10.1016/j.bmcl.2009.09.123

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abstract = "A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs.",

keywords = "Autoimmune disease, Kinase inhibitor, Lck inhibitor, Pyrimidine benzimidazoles, Transplantation rejection",

author = "Guobao Zhang and Pingda Ren and Gray, {Nathanael S.} and Taebo Sim and Xia Wang and Yi Liu and Jianwei Che and Weitong Dong and Tian, {Shin Shay} and Sandberg, {Mark L.} and Spalding, {Tracy A.} and Russell Romeo and Maya Iskandar and Zhiliang Wang and Seidel, {H. Martin} and Karanewsky, {Donald S.} and Yun He",

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AU - Zhang, Guobao

AU - Ren, Pingda

AU - Gray, Nathanael S.

AU - Sim, Taebo

AU - Wang, Xia

AU - Liu, Yi

AU - Che, Jianwei

AU - Dong, Weitong

AU - Tian, Shin Shay

AU - Sandberg, Mark L.

AU - Spalding, Tracy A.

AU - Romeo, Russell

AU - Iskandar, Maya

AU - Wang, Zhiliang

AU - Seidel, H. Martin

AU - Karanewsky, Donald S.

AU - He, Yun

PY - 2009/12/1

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KW - Autoimmune disease

KW - Kinase inhibitor

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KW - Pyrimidine benzimidazoles

KW - Transplantation rejection

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Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II

Abstract

Keywords

ASJC Scopus subject areas

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