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

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)3706-3712
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number14
DOIs
StatePublished - Jul 15 2006

Fingerprint

Thiazoles
Structure-Activity Relationship
Interleukin-2
Allergies
Jurkat Cells
T-cells
Ovalbumin
Anti-Idiotypic Antibodies
Assays
Pneumonia
Hypersensitivity
Asthma
T-Lymphocytes
Molecules
Antibodies

All Science Journal Classification (ASJC) codes

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

Cite this

Das, J., Furch, J. A., Liu, C., Moquin, R. V., Lin, J., Spergel, S. H., ... 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
Das, Jagabandhu ; Furch, Joseph A. ; Liu, Chunjian ; Moquin, Robert V. ; Lin, James ; Spergel, Steven H. ; McIntyre, Kim W. ; Shuster, David J. ; O'Day, Kathleen D. ; Penhallow, Becky ; Hung, Chen Yi ; Doweyko, Arthur M. ; Kamath, Amrita ; Zhang, Hongjian ; Marathe, Punit ; Kanner, Steven B. ; Lin, Tai An ; Dodd, John H. ; Barrish, Joel C. ; Wityak, John. / Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors. In: Bioorganic and Medicinal Chemistry Letters. 2006 ; Vol. 16, No. 14. pp. 3706-3712.
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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.",
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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

Discovery and SAR of 2-amino-5-(thioaryl)thiazoles as potent and selective Itk inhibitors. / Das, Jagabandhu; Furch, Joseph A.; Liu, Chunjian; Moquin, Robert V.; Lin, James; Spergel, Steven H.; McIntyre, Kim W.; Shuster, David J.; O'Day, Kathleen D.; Penhallow, Becky; Hung, Chen Yi; Doweyko, Arthur M.; Kamath, Amrita; Zhang, Hongjian; Marathe, Punit; Kanner, Steven B.; Lin, Tai An; Dodd, John H.; Barrish, Joel C.; Wityak, John.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 14, 15.07.2006, p. 3706-3712.

Research output: Contribution to journalArticle

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

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SN - 0960-894X

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