1190379-86-2Relevant articles and documents
The discovery of novel N-(2-pyrimidinylamino) benzamide derivatives as potent hedgehog signaling pathway inhibitors
Xin, Minhang,Wen, Jun,Tang, Feng,Tu, Chongxing,Shen, Han,Zhao, Xinge
, p. 6777 - 6783 (2013)
Hedgehog signaling pathway inhibitors are emerging as new therapeutic intervention against cancer. A novel series of N-(2-pyrimidinylamino) benzamide derivatives as hedgehog signaling pathway inhibitors were designed and synthesized. Most compounds presented significant inhibitory effect on hedgehog signaling pathway, among which 21 compounds exhibited more potent than vismodegib. Furthermore, compound 6a showed moderate pharmacokinetic properties in vivo, representing a promising lead compound for further exploration.
Discovery of novel 4-(2-pyrimidinylamino)benzamide derivatives as highly potent and orally available hedgehog signaling pathway inhibitors
Xin, Minhang,Zhang, Liandi,Jin, Qiu,Tang, Feng,Wen, Jun,Gu, Liyun,Cheng, Lingfei,Zhao, Yong
, p. 115 - 125 (2016)
A series of novel hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2-pyrimidinylamino)benzamide. The SAR for this series was described and many derivatives showed potent inhibitory activity. Among these compounds, compounds 12af and 12bf were identified to have high potency and optimal PK profiles. Although both of compounds 12af and 12bf did not show strong antitumor efficacy in LS-174T nude mice model, they were promising candidates as Hh signaling inhibitors due to great potency against Hh signaling pathway and outstanding PK properties, deserving further evaluation in other Hh signaling operative tumor models.
As Hedgehog signal transduction pyrimidine amines and pyridine amine inhibitors
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Paragraph 0951; 0953; 0961; 0962, (2019/06/26)
The invention relates to pyrimidinamine and pyridinamine Hedgehog signal conduction inhibitors. The inhibitors are compounds with the structure represented by formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to a medicinal use of the above compounds as hedgehog signal conduction inhibitors.
Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKε kinases
McIver, Edward G.,Bryans, Justin,Birchall, Kristian,Chugh, Jasveen,Drake, Thomas,Lewis, Stephen J.,Osborne, Joanne,Smiljanic-Hurley, Ela,Tsang, William,Kamal, Ahmad,Levy, Alison,Newman, Michelle,Taylor, Debra,Arthur, J. Simon C.,Clark, Kristopher,Cohen, Philip
, p. 7169 - 7173,5 (2012/12/12)
The design, synthesis and structure-activity relationships of a novel series of 2,4-diamino-5-cyclopropyl pyrimidines is described. Starting from BX795, originally reported to be a potent inhibitor of PDK1, we have developed compounds with improved selectivity and drug-like properties. These compounds have been evaluated in a range of cellular and in vivo assays, enabling us to probe the putative role of the TBK1/IKKε pathway in inflammatory diseases.
Design, synthesis, and biological evaluation of a series of novel AXL kinase inhibitors
Mollard, Alexis,Warner, Steven L.,Call, Lee T.,Wade, Mark L.,Bearss, Jared J.,Verma, Anupam,Sharma, Sunil,Vankayalapati, Hariprasad,Bearss, David J.
supporting information; experimental part, p. 907 - 912 (2012/01/19)
The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its overexpression in several types of cancers coupled with its ability to promote tumor growth and metastasis. To identify small molecule inhibitors of AXL, we built a homology model of its catalytic domain to virtually screen and identify scaffolds displaying an affinity for AXL. Further computational and structure-based design resulted in the synthesis of a series of 2,4,5-trisubstitued pyrimidines, which demonstrated potent inhibition of AXL in vitro (IC50 = 19 nM) and strongly inhibited the growth of several pancreatic cell lines.
PYRIMIDINE DERIVATIVES CAPABLE OF INHIBITING ONE OR MORE KINASES
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Page/Page column 61-62, (2009/10/30)
A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, formula (I): wherein: R1 is C3-8-cycloalkyl; X is O, NR7 or C3-6-heterocycloalkyl; R2 is aryl, heteroaryl, fused or unfused aryl-C3-6-heterocycloalkyl or fused or unfused heteroaryl-C3-6-heterocycIoalkyl, each of which is optionally substituted by one or more substitutents selected from aryl, heteroaryl, C1-6-alkyl, C3-7-cycloalkyl and a group A, wherein said C1-6-alkyl group is optionally substituted by one or more substituents selected from aryl, heteroaryl, R10 and a group A, said heteroaryl group is optionally substituted by one or more R10 groups; and wherein said C3-6-heterocycloalkyl group optionally contains one or more groups selected from oxygen, sulfur, nitrogen and CO; R3 is C1-6-alkyl optionally substituted by one or more substituents selected from aryl, heteroaryl, -NR4R5, -OR6, -NR7(CO)R6, -NR7(CO)NR4R5, -NR7SO2R6, -NR7COOR7, -CONR4R5, C3-6-heterocycloalkyl and formula (a, b, c): wherein R4-7 and A are as defined in the claims. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of one or more kinases.
