1233142-16-9Relevant academic research and scientific papers
Piperidine-3,4-diol and piperidine-3-ol derivatives of pyrrolo[2,1-f][1,2,4]triazine as inhibitors of anaplastic lymphoma kinase
Mesaros, Eugen F.,Angeles, Thelma S.,Albom, Mark S.,Wagner, Jason C.,Aimone, Lisa D.,Wan, Weihua,Lu, Lihui,Huang, Zeqi,Olsen, Mark,Kordwitz, Emily,Haltiwanger, R. Curtis,Landis, Amy J.,Cheng, Mangeng,Ruggeri, Bruce A.,Ator, Mark A.,Dorsey, Bruce D.,Ott, Gregory R.
, p. 1053 - 1058 (2015)
The diastereoselective synthesis and biological activity of piperidine-3,4-diol and piperidine-3-ol-derived pyrrolotriazine inhibitors of anaplastic lymphoma kinase (ALK) are described. Although piperidine-3,4-diol and piperidine-3-ol derivatives showed comparable in vitro ALK activity, the latter subset of inhibitors demonstrated improved physiochemical and pharmacokinetic properties. Furthermore, the stereochemistry of the C3 and C4 centers had a marked impact on the in vivo inhibition of ALK autophosphorylation. Thus, trans-4-aryl-piperidine-3-ols (22) were more potent than the cis diastereomers (20).
Optimization of a novel kinase inhibitor scaffold for the dual inhibition of JAK2 and FAK kinases
Zificsak, Craig A.,Gingrich, Diane E.,Breslin, Henry J.,Dunn, Derek D.,Milkiewicz, Karen L.,Theroff, Jay P.,Thieu, Tho V.,Underiner, Ted L.,Weinberg, Linda R.,Aimone, Lisa D.,Albom, Mark S.,Mason, Jennifer L.,Saville, Lisa,Husten, Jean,Angeles, Thelma S.,Finn, James P.,Jan, Mahfuza,O'Kane, Teresa M.,Dobrzanski, Pawel,Dorsey, Bruce D.
scheme or table, p. 133 - 137 (2012/02/15)
The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression.
Strategies to mitigate the bioactivation of 2-anilino-7-aryl-pyrrolo[2,1-f ][1,2,4]triazines: Identification of orally bioavailable, efficacious ALK inhibitors
Mesaros, Eugen F.,Thieu, Tho V.,Wells, Gregory J.,Zificsak, Craig A.,Wagner, Jason C.,Breslin, Henry J.,Tripathy, Rabindranath,Diebold, James L.,McHugh, Robert J.,Wohler, Ashley T.,Quail, Matthew R.,Wan, Weihua,Lu, Lihui,Huang, Zeqi,Albom, Mark S.,Angeles, Thelma S.,Wells-Knecht, Kevin J.,Aimone, Lisa D.,Cheng, Mangeng,Ator, Mark A.,Ott, Gregory R.,Dorsey, Bruce D.
experimental part, p. 115 - 125 (2012/03/11)
Chemical strategies to mitigate cytochrome P450-mediated bioactivation of novel 2,7-disubstituted pyrrolo[2,1-f][1,2,4]triazine ALK inhibitors are described along with synthesis and biological activity. Piperidine-derived analogues showing minimal microsomal reactive metabolite formation were discovered. Potent, selective, and metabolically stable ALK inhibitors from this class were identified, and an orally bioavailable compound (32) with antitumor efficacy in ALK-driven xenografts in mouse models was extensively characterized.
2,7-Pyrrolo[2,1-f][1,2,4]triazines as JAK2 inhibitors: Modification of target structure to minimize reactive metabolite formation
Weinberg, Linda R.,Albom, Mark S.,Angeles, Thelma S.,Breslin, Henry J.,Gingrich, Diane E.,Huang, Zeqi,Lisko, Joseph G.,Mason, Jennifer L.,Milkiewicz, Karen L.,Thieu, Tho V.,Underiner, Ted L.,Wells, Gregory J.,Wells-Knecht, Kevin J.,Dorsey, Bruce D.
, p. 7325 - 7330 (2012/02/04)
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 nov
