Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ

Brahmam Pujala, Anil K. Agarwal, Sandip Middya, Monali Banerjee, Arjun Surya, Anjan K. Nayak, Ashu Gupta, Sweta Khare, Rambabu Guguloth, Nitin A. Randive, Bharat U. Shinde, Anamika Thakur, Dhananjay I. Patel, Mohd Raja, Michael J. Green, Jennifer Alfaro, Patricio Avila, Felipe Pérez de Arce, Ramona G. Almirez, Stacy KannoSebastián Bernales, David T. Hung, Sarvajit Chakravarty, Emma McCullagh, Kevin P. Quinn, Roopa Rai, Son M. Pham

Resultado de la investigación: Article

9 Citas (Scopus)

Resumen

The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3Kδ are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3Kδ as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases.

Idioma originalEnglish
Páginas (desde-hasta)1161-1166
Número de páginas6
PublicaciónACS Medicinal Chemistry Letters
Volumen7
N.º12
DOI
EstadoPublished - 8 dic 2016
Publicado de forma externa

Huella dactilar

Phosphatidylinositol 3-Kinases
B-Lymphocytes
Cells
Derivatives
Signal transduction
Enzyme Inhibitors
Signal Transduction
Lymphoma
Phosphotransferases
Chemical activation
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Citar esto

Pujala, B., Agarwal, A. K., Middya, S., Banerjee, M., Surya, A., Nayak, A. K., ... Pham, S. M. (2016). Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ. ACS Medicinal Chemistry Letters, 7(12), 1161-1166. https://doi.org/10.1021/acsmedchemlett.6b00356
Pujala, Brahmam ; Agarwal, Anil K. ; Middya, Sandip ; Banerjee, Monali ; Surya, Arjun ; Nayak, Anjan K. ; Gupta, Ashu ; Khare, Sweta ; Guguloth, Rambabu ; Randive, Nitin A. ; Shinde, Bharat U. ; Thakur, Anamika ; Patel, Dhananjay I. ; Raja, Mohd ; Green, Michael J. ; Alfaro, Jennifer ; Avila, Patricio ; Pérez de Arce, Felipe ; Almirez, Ramona G. ; Kanno, Stacy ; Bernales, Sebastián ; Hung, David T. ; Chakravarty, Sarvajit ; McCullagh, Emma ; Quinn, Kevin P. ; Rai, Roopa ; Pham, Son M. / Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ. En: ACS Medicinal Chemistry Letters. 2016 ; Vol. 7, N.º 12. pp. 1161-1166.
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abstract = "The aberrant activation of B-cells has been implicated in several types of cancers and hematological disorders. BTK and PI3Kδ are kinases responsible for B-cell signal transduction, and inhibitors of these enzymes have demonstrated clinical benefit in certain types of lymphoma. Simultaneous inhibition of these pathways could result in more robust responses or overcome resistance as observed in single agent use. We report a series of novel compounds that have low nanomolar potency against both BTK and PI3Kδ as well as acceptable PK properties that could be useful in the development of treatments against B-cell related diseases.",
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Pujala, B, Agarwal, AK, Middya, S, Banerjee, M, Surya, A, Nayak, AK, Gupta, A, Khare, S, Guguloth, R, Randive, NA, Shinde, BU, Thakur, A, Patel, DI, Raja, M, Green, MJ, Alfaro, J, Avila, P, Pérez de Arce, F, Almirez, RG, Kanno, S, Bernales, S, Hung, DT, Chakravarty, S, McCullagh, E, Quinn, KP, Rai, R & Pham, SM 2016, 'Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ', ACS Medicinal Chemistry Letters, vol. 7, n.º 12, pp. 1161-1166. https://doi.org/10.1021/acsmedchemlett.6b00356

Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ. / Pujala, Brahmam; Agarwal, Anil K.; Middya, Sandip; Banerjee, Monali; Surya, Arjun; Nayak, Anjan K.; Gupta, Ashu; Khare, Sweta; Guguloth, Rambabu; Randive, Nitin A.; Shinde, Bharat U.; Thakur, Anamika; Patel, Dhananjay I.; Raja, Mohd; Green, Michael J.; Alfaro, Jennifer; Avila, Patricio; Pérez de Arce, Felipe; Almirez, Ramona G.; Kanno, Stacy; Bernales, Sebastián; Hung, David T.; Chakravarty, Sarvajit; McCullagh, Emma; Quinn, Kevin P.; Rai, Roopa; Pham, Son M.

En: ACS Medicinal Chemistry Letters, Vol. 7, N.º 12, 08.12.2016, p. 1161-1166.

Resultado de la investigación: Article

TY - JOUR

T1 - Discovery of Pyrazolopyrimidine Derivatives as Novel Dual Inhibitors of BTK and PI3Kδ

AU - Pujala, Brahmam

AU - Agarwal, Anil K.

AU - Middya, Sandip

AU - Banerjee, Monali

AU - Surya, Arjun

AU - Nayak, Anjan K.

AU - Gupta, Ashu

AU - Khare, Sweta

AU - Guguloth, Rambabu

AU - Randive, Nitin A.

AU - Shinde, Bharat U.

AU - Thakur, Anamika

AU - Patel, Dhananjay I.

AU - Raja, Mohd

AU - Green, Michael J.

AU - Alfaro, Jennifer

AU - Avila, Patricio

AU - Pérez de Arce, Felipe

AU - Almirez, Ramona G.

AU - Kanno, Stacy

AU - Bernales, Sebastián

AU - Hung, David T.

AU - Chakravarty, Sarvajit

AU - McCullagh, Emma

AU - Quinn, Kevin P.

AU - Rai, Roopa

AU - Pham, Son M.

PY - 2016/12/8

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KW - B-cell

KW - BCR

KW - BTK

KW - inhibitor

KW - p110δ

KW - PI3K

KW - pyrazolopyrimidine

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JO - ACS Medicinal Chemistry Letters

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