75468-42-7Relevant academic research and scientific papers
A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS
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, (2019/07/17)
The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.
Cycloaddition of Fluorenone N-Aryl Nitrones with Methylenecyclopropanes and Sequential 1,3-Rearrangement: An Entry to Synthesis of Spirofluorenylpiperidin-4-ones
Ma, Xiao-Pan,Zhu, Jie-Feng,Wu, Si-Yi,Chen, Chun-Hua,Zou, Ning,Liang, Cui,Su, Gui-Fa,Mo, Dong-Liang
, p. 502 - 511 (2017/04/26)
A facile synthesis of various spirofluorenylpiperidin-4-ones has been achieved in good yields from fluorenone N-aryl nitrones and methylenecyclopropanes. This method involved an initial cycloaddition to form a 5-spirocyclopropane-isoxazoline, which underwent a highly selective 1,3-rearrangement to give the desired product. The stereochemistry of the spirofluorenylpiperidin-4-one could be controlled by the cycloaddition and sequential rearrangement strategy. Furthermore, the spirofluorenylpiperidin-4-ones could be not only prepared in one-pot procedure but also converted to useful scaffolds by reduction or oxidation conditions.
Synthesis and Superpotent Anticancer Activity of Tubulysins Carrying Non-hydrolysable N-Substituents on Tubuvaline
Sani, Monica,Lazzari, Paolo,Folini, Marco,Spiga, Marco,Zuco, Valentina,De Cesare, Michelandrea,Manca, Ilaria,Dall'Angelo, Sergio,Frigerio, Massimo,Usai, Igor,Testa, Andrea,Zaffaroni, Nadia,Zanda, Matteo
, p. 5842 - 5850 (2017/04/28)
Synthetic tubulysins 24 a–m, containing non-hydrolysable N-substituents on tubuvaline (Tuv), were obtained in high purity and good overall yields using a multistep synthesis. A key step was the formation of differently N-substituted Ile-Tuv fragments 10 b
Solvent-Controlled Bifurcated Cascade Process for the Selective Preparation of Dihydrocarbazoles or Dihydropyridoindoles
Mo, Dong-Liang,Wink, Donald J.,Anderson, Laura L.
, p. 13217 - 13225 (2016/02/19)
A solvent-controlled cascade process has been identified for the dual purpose of the preparation of either dihydrocarbazoles or dihydropyridoindoles from identical N-aryl-α,β-unsaturated nitrones and electron-deficient allene starting materials. These reactions proceed smoothly under mild metal-free conditions affording a range of two types of skeletally distinct indole-based heterocycles in high yield and diastereoselectivity. These transformations demonstrate the use of a bifurcated cascade process that hinges on the ring-opening event of a benzazepine intermediate for the synthesis of skeletally diverse heterocyclic products and rapid access to biologically-significant, indole-based structures.
Synthesis and structure-activity relationship studies of novel tubulysin U analogues-effect on cytotoxicity of structural variations in the tubuvaline fragment
Shankar, Sreejith P.,Jagodzinska, Monika,Malpezzi, Luciana,Lazzari, Paolo,Manca, Ilaria,Greig, Iain R.,Sani, Monica,Zanda, Matteo
, p. 2273 - 2287 (2013/04/23)
Tubulysins are cytotoxic natural products with promising anti-cancer properties, originally isolated from myxobacterial cultures. Structurally, tubulysins are tetrapeptides, incorporating three unusual (Mep, Tuv and Tup) and one proteinogenic amino acid (Ile). Here we describe the synthesis and structure-activity relationship studies of novel tubulysin U and V analogues, with variations in the central Tuv fragment, which is known to be of paramount importance for tubulysins' potency and hence cytotoxicity, but has seldom been modified in previous studies. Specifically, we replaced the natural iso-propyl and acetoxy functionalities with other structurally related groups. In general, the new analogues showed much lower potency relative to native tubulysin U. However, one of the synthetic analogues (1f) having a MOM function replacing the acetyl group exhibited a 22 nM IC50 on the HT-29 cell line which is comparable to the IC50 displayed by tubulysin U (3.8 nM). Furthermore, the synthetic methodology reported herein was found to be flexible enough to deliver different core-modified tubulysin analogues and hence may be regarded as a scalable and convenient strategy for the chemical generation of novel tubulysin analogues.
Synthesis and cytotoxicity evaluation of diastereoisomers and N-terminal analogues of tubulysin-U
Shankar, P. Sreejith,Bigotti, Serena,Lazzari, Paolo,Manca, Ilaria,Spiga, Marco,Sani, Monica,Zanda, Matteo
, p. 6137 - 6141 (2013/10/22)
Tubulysins are potent anti-mitotic natural compounds and a scalable and efficient synthetic route for generation of its analogues has been developed and extended to the synthesis of diastereoisomers and N-terminal analogues of tubulysin-U. Structure-activ
X = Y - ZH systems as potential 1,3-dipoles part 35. Generation of nitrones from oximes. Class 3 processes. Tandem intramolecular Michael addition (1,3-azaprotio cyclotransfer) - Intermolecular 1,3-dipolar cycloaddition reactions
Grigg, Ronald,Markandu, Jasothara,Perrior, Trevor,Surendrakumar, Sivagnanasundram,Warnock, William J.
, p. 6929 - 6952 (2007/10/02)
Aldoximes and ketoximes possessing γ- or δ-alkenyl substituents undergo thermal conversion to 5-and 6- membered cyclic nitrones via a 1,3-azaprotio cyclotransfer, a 2n + 2oσ + 2π concerted process, rather than a Michael addition. The reactions can be performed as a tandem nitrone formation-cycloaddition sequence or, if required, the intermediate nitrones can be isolated. The cycloadditions usually proceed via an exo-transition state and show both regio- and diastereofacial-specificity. Preliminary attempts at chiral induction via a menthyl auxiliary are reported.
