2. Academic Validation
  3. A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779

A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779

  • J Med Chem. 2012 Jun 14;55(11):5243-54. doi: 10.1021/jm300248q.
Benjamin J Dugan 1,  Diane E Gingrich,  Eugen F Mesaros,  Karen L Milkiewicz,  Matthew A Curry,  Allison L Zulli,  Pawel Dobrzanski,  Cynthia Serdikoff,  Mahfuza Jan,  Thelma S Angeles,  Mark S Albom,  Jennifer L Mason,  Lisa D Aimone,  Sheryl L Meyer,  Zeqi Huang,  Kevin J Wells-Knecht,  Mark A Ator,  Bruce A Ruggeri,  Bruce D Dorsey
Affiliations

Affiliation

  • 1 Worldwide Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, Pennsylvania 19380, United States. bdugan@cephalon.com
PMID: 22594690 DOI: 10.1021/jm300248q
Abstract

Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 Inhibitor. A program to optimize selective JAK2 inhibitors to combat Cancer while reducing the risk of immune suppression associated with JAK3 inhibition was undertaken. The structure-activity relationships and biological evaluation of a novel series of compounds based on a 1,2,4-triazolo[1,5-a]pyridine scaffold are reported. Para substitution on the aryl at the C8 position of the core was optimum for JAK2 potency (17). Substitution at the C2 nitrogen position was required for cell potency (21). Interestingly, meta substitution of C2-NH-aryl moiety provided exceptional selectivity for JAK2 over JAK3 (23). These efforts led to the discovery of CEP-33779 (29), a novel, selective, and orally bioavailable inhibitor of JAK2.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15343
    99.23%, JAK2抑制剂
    JAK
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z