Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I

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

doi:10.1016/j.bmcl.2008.08.104

Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I

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

KU-KIST Graduate School of Converging Science and Technology

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

33 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 kinase family. Highly efficient parallel syntheses were devised to prepare analogues for SAR studies. A number of these 4-amino-6-benzimidazole-pyrimidines exhibited single-digit nanomolar IC₅₀s against Lck in biochemical and cellular assays. These 4-amino-6-benzimidazole-pyrimidines represent a new class of tyrosine kinase inhibitors.

Original language	English
Pages (from-to)	5618-5621
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	20
DOIs	https://doi.org/10.1016/j.bmcl.2008.08.104
Publication status	Published - 2008 Oct 15

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.2008.08.104

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Zhang, G., Ren, P., Gray, N. S., Sim, T., Liu, Y., Wang, X., Che, J., Tian, S. S., Sandberg, M. L., Spalding, T. A., Romeo, R., Iskandar, M., Chow, D., Martin Seidel, H., Karanewsky, D. S., & He, Y. (2008). Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I. Bioorganic and Medicinal Chemistry Letters, 18(20), 5618-5621. https://doi.org/10.1016/j.bmcl.2008.08.104

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title = "Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I",

abstract = "A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src kinase family. Highly efficient parallel syntheses were devised to prepare analogues for SAR studies. A number of these 4-amino-6-benzimidazole-pyrimidines exhibited single-digit nanomolar IC50s against Lck in biochemical and cellular assays. These 4-amino-6-benzimidazole-pyrimidines represent a new class of tyrosine kinase inhibitors.",

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 Yi Liu and Xia Wang and Jianwei Che and Tian, {Shin Shay} and Sandberg, {Mark L.} and Spalding, {Tracy A.} and Russell Romeo and Maya Iskandar and Donald Chow and {Martin Seidel}, H. and Karanewsky, {Donald S.} and Yun He",

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day = "15",

doi = "10.1016/j.bmcl.2008.08.104",

language = "English",

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TY - JOUR

T1 - Discovery of pyrimidine benzimidazoles as Lck inhibitors

T2 - Part I

AU - Zhang, Guobao

AU - Ren, Pingda

AU - Gray, Nathanael S.

AU - Sim, Taebo

AU - Liu, Yi

AU - Wang, Xia

AU - Che, Jianwei

AU - Tian, Shin Shay

AU - Sandberg, Mark L.

AU - Spalding, Tracy A.

AU - Romeo, Russell

AU - Iskandar, Maya

AU - Chow, Donald

AU - Martin Seidel, H.

AU - Karanewsky, Donald S.

AU - He, Yun

PY - 2008/10/15

Y1 - 2008/10/15

N2 - A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src kinase family. Highly efficient parallel syntheses were devised to prepare analogues for SAR studies. A number of these 4-amino-6-benzimidazole-pyrimidines exhibited single-digit nanomolar IC50s against Lck in biochemical and cellular assays. These 4-amino-6-benzimidazole-pyrimidines represent a new class of tyrosine kinase inhibitors.

AB - A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src kinase family. Highly efficient parallel syntheses were devised to prepare analogues for SAR studies. A number of these 4-amino-6-benzimidazole-pyrimidines exhibited single-digit nanomolar IC50s against Lck in biochemical and cellular assays. These 4-amino-6-benzimidazole-pyrimidines represent a new class of tyrosine kinase inhibitors.

KW - Autoimmune disease

KW - Kinase inhibitor

KW - Lck inhibitor

KW - Pyrimidine benzimidazoles

KW - Transplantation rejection

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M3 - Article

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AN - SCOPUS:53449083913

SN - 0960-894X

VL - 18

SP - 5618

EP - 5621

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 20

ER -

Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I

Abstract

Keywords

ASJC Scopus subject areas

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