59698-20-3Relevant articles and documents
As Hedgehog signal transduction pyrimidine amines and pyridine amine inhibitors
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Paragraph 0951; 0953; 0958-0960, (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.
MercuryII-mediated base pairs in DNA: unexpected behavior in metal ion binding and duplex stability induced by 2′-deoxyuridine 5-substituents
Guo, Xiurong,Ingale, Sachin A.,Yang, Haozhe,He, Yang,Seela, Frank
, p. 870 - 883 (2017/02/05)
The stability of the mercury ion mediated dU-HgII-dU pair depends on substituents introduced at the 5-position of the pyrimidine moiety. To this end, a series of oligonucleotides were synthesized with dU modification in central position. Common and new phosphoramidites were utilized. Hybridization experiments provided 12-mer duplexes with non-canonical “dU-dU” pairs. In most cases Hg2+ stabilizes duplexes by metal ion mediated base pair formation identified by higher duplex melting. Among the three types of dU derivatives incorporated in duplex DNA those with small aliphatic side chains have only a minor impact on the stability of the mercury-mediated base pair, while those with a triple bond in the side chain show hysteresis during duplex heating and cooling cycle implying triple bond interaction with mercury ions. Formation of metal ion mediated base pairs is blocked by space occupying aromatic side chains by side chain-helix stacking interactions. These interactions are too strong to permit mercury ion mediated base pair formation and drive the uridine N(3) acceptor atoms in an unfavorable pairing position.
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 (2016/02/05)
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.
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
supporting information, p. 6777 - 6783 (2014/01/06)
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.
The synthesis of some 5-substituted and 5,6-disubstituted 2'- deoxyuridines
Basnak,Balkan,Coe,Walker
, p. 177 - 196 (2007/10/02)
5-Alkyl(cycloalkyl)-2'-deoxyuridines VIa-VIf were synthesised in high yields by condensation of the corresponding silylated bases with 2-deoxy- 3,5-di-O-p-toluoyl-D-erythro-pentosyl chloride in chloroform and subsequent deblocking with sodium methoxide in
Free Radical Rearrangements in Uracil Derivatives
Fenick, David J.,Falvey, Daniel E.
, p. 4791 - 4799 (2007/10/02)
As part of an effort to develop general probes for radical reactions involving DNA bases, several uracil derivatives were synthesized.The rates of the cyclopropyl carbinyl rearrangement in these systems were evaluated by means of competition experiments.The results indicate that when a cyclopropyl group is substituted in the 5-position of uracil, the rearrangement occurs very slowly - with a rate constant of -1.On the other hand, the analog of the 5-hexenyl radical cyclization onto the 5,6-double bond of uracil derivatives occurs with rates which were similar to the parent process: (4.0-8.9)E4 s-1.The experimental results along with semiempirical calculations show that radicals 23 and 25 are unusually stable species.These results explain why no rearrangements are observed when a cyclopropyl-substituted thymine dimer is cleaved by reductive single electron transfer.
