1408064-96-9Relevant academic research and scientific papers
Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3Kδ inhibitors
Qin, Lan-Ying,Ruan, Zheming,Cherney, Robert J.,Dhar, T.G. Murali,Neels, James,Weigelt, Carolyn A.,Sack, John S.,Srivastava, Anurag S.,Cornelius, Lyndon A.M.,Tino, Joseph A.,Stefanski, Kevin,Gu, Xiaomei,Xie, Jenny,Susulic, Vojkan,Yang, Xiaoxia,Yarde-Chinn, Melissa,Skala, Stacey,Bosnius, Ruth,Goldstein, Christine,Davies, Paul,Ruepp, Stefan,Salter-Cid, Luisa,Bhide, Rajeev S.,Poss, Michael A.
, p. 855 - 861 (2017/02/10)
As demonstrated in preclinical animal models, the disruption of PI3Kδ expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3Kδ may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3Kδ inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model.
Development of a practical synthesis of a functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus
Zheng, Bin,Conlon, David A.,Corbett, R. Michael,Chau, Melissa,Hsieh, Dau-Ming,Yeboah, Agnes,Hsieh, Daniel,Mueslehiddinoglu, Jale,Gallagher, William P.,Simon, Jeffrey N.,Burt, Justin
, p. 1846 - 1853 (2013/01/15)
Functionalized pyrrolotriazine 1b is a key heterocyclic building block in the synthesis of BMS-690514, a potent anticancer agent. Described herein are our development activities that led to the efficient preparation of 1b on a large scale. The key transformations include a selective C-alkylation of an oxalacetate salt with a hydrazonyl bromide to form a 2-hydrazonoethyl-3- oxosuccinate, followed by cyclodehydration to an aminopyrrole. Subsequent deprotection and condensation with formamidine afforded the pyrrolotriazine scaffold. Further elaboration of this core provided the desired pyrrolotriazinyl amine.
