Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors

Jagabandhu Das; Joseph A. Furch; Chunjian Liu; Robert V. Moquin; James Lin; Steven H. Spergel; Kim W. McIntyre; David J. Shuster; Kathleen D. O'Day; Becky Penhallow; Chen Yi Hung; Arthur M. Doweyko; Amrita Kamath; Hongjian Zhang; Punit Marathe; Steven B. Kanner; Tai An Lin; John H. Dodd; Joel C. Barrish; John Wityak

doi:10.1016/j.bmcl.2006.04.060

Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors

Jagabandhu Das
, Joseph A. Furch
, Chunjian Liu
, Robert V. Moquin
, James Lin
, Steven H. Spergel
, Kim W. McIntyre
, David J. Shuster
, Kathleen D. O'Day
, Becky Penhallow
, Chen Yi Hung
, Arthur M. Doweyko
, Amrita Kamath
, Hongjian Zhang
, Punit Marathe
, Steven B. Kanner
, Tai An Lin
, John H. Dodd
, Joel C. Barrish
, John Wityak

Chemistry

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

65 Scopus citations

Abstract

A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.

Original language	English (US)
Pages (from-to)	3706-3712
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2006.04.060
State	Published - Jul 15 2006

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmcl.2006.04.060

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Das, J., Furch, J. A., Liu, C., Moquin, R. V., Lin, J., Spergel, S. H., McIntyre, K. W., Shuster, D. J., O'Day, K. D., Penhallow, B., Hung, C. Y., Doweyko, A. M., Kamath, A., Zhang, H., Marathe, P., Kanner, S. B., Lin, T. A., Dodd, J. H., Barrish, J. C., & Wityak, J. (2006). Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors. Bioorganic and Medicinal Chemistry Letters, 16(14), 3706-3712. https://doi.org/10.1016/j.bmcl.2006.04.060

@article{11132747374849d6904bd81a0d103a2d,

title = "Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors",

abstract = "A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.",

author = "Jagabandhu Das and Furch, \{Joseph A.\} and Chunjian Liu and Moquin, \{Robert V.\} and James Lin and Spergel, \{Steven H.\} and McIntyre, \{Kim W.\} and Shuster, \{David J.\} and O'Day, \{Kathleen D.\} and Becky Penhallow and Hung, \{Chen Yi\} and Doweyko, \{Arthur M.\} and Amrita Kamath and Hongjian Zhang and Punit Marathe and Kanner, \{Steven B.\} and Lin, \{Tai An\} and Dodd, \{John H.\} and Barrish, \{Joel C.\} and John Wityak",

year = "2006",

month = jul,

day = "15",

doi = "10.1016/j.bmcl.2006.04.060",

language = "English (US)",

volume = "16",

pages = "3706--3712",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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Das, J, Furch, JA, Liu, C, Moquin, RV, Lin, J, Spergel, SH, McIntyre, KW, Shuster, DJ, O'Day, KD, Penhallow, B, Hung, CY, Doweyko, AM, Kamath, A, Zhang, H, Marathe, P, Kanner, SB, Lin, TA, Dodd, JH, Barrish, JC & Wityak, J 2006, 'Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 16, no. 14, pp. 3706-3712. https://doi.org/10.1016/j.bmcl.2006.04.060

TY - JOUR

T1 - Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors

AU - Das, Jagabandhu

AU - Furch, Joseph A.

AU - Liu, Chunjian

AU - Moquin, Robert V.

AU - Lin, James

AU - Spergel, Steven H.

AU - McIntyre, Kim W.

AU - Shuster, David J.

AU - O'Day, Kathleen D.

AU - Penhallow, Becky

AU - Hung, Chen Yi

AU - Doweyko, Arthur M.

AU - Kamath, Amrita

AU - Zhang, Hongjian

AU - Marathe, Punit

AU - Kanner, Steven B.

AU - Lin, Tai An

AU - Dodd, John H.

AU - Barrish, Joel C.

AU - Wityak, John

PY - 2006/7/15

Y1 - 2006/7/15

N2 - A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.

AB - A series of structurally novel aminothiazole based small molecule inhibitors of Itk were prepared to elucidate their structure-activity relationships (SARs), selectivity, and cell activity in inhibiting IL-2 secretion in a Jurkat T-cell assay. Compound 3 is identified as a potent and selective Itk inhibitor which inhibits anti-TCR antibody induced IL-2 production in mice in vivo and was previously reported to reduce lung inflammation in a mouse model of ovalbumin induced allergy/asthma.

UR - https://www.scopus.com/pages/publications/33746517432

UR - https://www.scopus.com/pages/publications/33746517432#tab=citedBy

U2 - 10.1016/j.bmcl.2006.04.060

DO - 10.1016/j.bmcl.2006.04.060

M3 - Article

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SN - 0960-894X

VL - 16

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EP - 3712

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 14

ER -

Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors

Abstract

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