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2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: modification of target structure to minimize reactive metabolite formation.

Abstract：

:The JAK2/STAT pathway has important roles in hematopoiesis. With the discovery of the JAK2 V617F mutation and its presence in many patients with myeloproliferative neoplasms, research in the JAK2 inhibitor arena has dramatically increased. We report a novel series of potent JAK2 inhibitors containing a 2,7-pyrrolotriazine core. To minimize potential drug-induced toxicity, targets were analyzed for the ability to form a glutathione adduct. Glutathione adduct formation was decreased by modification of the aniline substituent at C2.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Weinberg LR,Albom MS,Angeles TS,Breslin HJ,Gingrich DE,Huang Z,Lisko JG,Mason JL,Milkiewicz KL,Thieu TV,Underiner TL,Wells GJ,Wells-Knecht KJ,Dorsey BD

doi

10.1016/j.bmcl.2011.10.032

subject

Has Abstract

pub_date

2011-12-15 00:00:00

pages

7325-30

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)01420-X

journal_volume

21

pub_type

杂志文章

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