29745-04-8Relevant articles and documents
Structural studies on cycloadducts of furan, 2-methoxyfuran, and 5-trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide
Yit, Wooi Goh,Pool, Brett R.,White, Jonathan M.
, p. 151 - 156 (2008)
(Chemical Equation Presented) The early stages of the retro-Diels-Alder reaction are clearly apparent in the structures of the cycloadducts formed between furan or 5-trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide. The degree of lengthening of the C-C bonds that break in this reaction is clearly related to the known reactivity of these cycloadducts toward this reaction. In the structures of the cycloadducts 21 and 22 derived from 2-methoxyfuran, the early stages of an alternative fragmentation reaction are apparent, consistent with the reactivity of these compounds in solution.
Synthesis and extraction studies with a rationally designed diamide ligand selectIVe to actinide(IV) pertinent to the plutonium uranium redox extraction process
Sharma, Shikha,Panja, Surajit,Bhattacharyya, Arunasis,Dhami, Prem S.,Gandhi, Preetam M.,Ghosh, Sunil K.
, p. 7737 - 7747 (2016)
A new class of conformationally constrained oxa-bridged tricyclo-dicarboxamide (OTDA) ligand was rationally designed for the selective extraction of tetravalent actinides pertinent to the Plutonium Uranium Redox EXtraction (PUREX) process. Two of the designed diamide ligands were synthesized and extraction studies were performed for Pu(iv) from HNO3 medium. The mechanism of extraction was investigated by studying various parameters such as feed HNO3, NaNO3 and OTDA concentrations. The nature of the extracted species was found to be [Pu(NO3)4(OTDA)]. One of the OTDA ligands was elaborately tested and showed the selective extraction of Pu(iv) and Np(iv) over other actinide species, viz., U(vi), Np(v), Am(iii), lanthanides and fission products contained in a nuclear waste from the PUREX process. DFT calculations predicted the charge density on each of the coordinating 'O' atoms of OTDA supporting its high Pu(iv) selectivity over other ions studied and also provided the energy optimized structure of OTDA and its Pu(iv) complex.
Crystal structures of (3R,3aR,4S,7R,7aS)-3-(allyloxy)hexahydro-4,7- epoxyisobenzofuran-1(3H)-one and (3S,3aR,4S,7R,7aS)-3-((E)-but-2-en-1-yloxy) hexahydro-4,7-epoxyisobenzofuran-1(3H)-one: Confirmation of NMR predicted stereocentre geometry
Tarleton, Mark,Bernhardt, Paul V.,McCluskey, Adam
, p. 639 - 644 (2012)
Crystal structures of two isomeric norcantharidin derivatives (3R,3aR,4S,7R,7aS)-3-(allyloxy)hexahydro-4,7-epoxyisobenzofuran-1(3H)-one (7b), and (3S,3aR, 4S,7R,7aS)-3-((E)-but-2-en-1-yloxy)hexahydro-4,7- epoxyisobenzofuran- 1(3H)-one (8a) have been determined. In both instances the equivalent enantiomer was also obtained. The crystal structures of these compounds clarify the stereochemistry inferred only by NMR analysis before. Springer Science+Business Media, LLC 2012.
From Spanish fly to room-temperature ionic liquids (RTILs): Synthesis, thermal stability and inhibition of dynamin 1 GTPase by a novel class of RTILs
Zhang, Jie,Lawrance, Geoffrey A.,Chau, Ngoc,Robinson, Phillip J.,McCluskey, Adam
, p. 28 - 36 (2008)
In a series of simple synthetic manipulations the active component of the aphrodisiac Spanish fly has resulted in the generation of a new family of room-temperature ionic liquids (RTILs). These RTILs are synthesized in high yield from readily attainable starting materials and can be generated in either meso or chiral forms dependant on the starting furan analogue. Substituted furans (2-methyl and 2-ethyl) afford chiral RTILs, furan affords a family of meso RTILs. In all cases the counterion was crucial, with CH3SO 3- consistently displaying the lowest melting points. Of the RTILs synthesized, TGA plots showed most to be stable up to at least 250°C. We had sought to use these RTILs in a series of dynamic combinatorial chemistry (DCC) assembly reactions via solubulisation of dynamin GTPases pleckstrin homology (PH) domain, as such all analogues were screened as potential inhibitors. Screening reveals that these RTILs display varying levels of dynamin GTPase inhibition with a number amongst the most potent inhibitors of dynamin GTPase yet discovered, e.g.13 IC50 = 2.3 ± 0.3 μM (4-(N,N-dimethyl-N-octadecyl-N-ethyl)-4-aza-10-oxatricyclo[5.2.1]decane-3, 5-dione bromide. Accordingly these RTILs have limited utility for DCC assembly with dynamin GTPase, but may be of use with other proteins or in other fields of study. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
Synthesis and anticancer activity of a series of norcantharidin analogues
Tarleton, Mark,Gilbert, Jayne,Sakoff, Jennette A.,McCluskey, Adam
, p. 573 - 581 (2012)
Cantharidin (1) and norcantharidin (2) display high levels of anticancer activity against a broad range of tumour cell lines. Synthetic manipulation of norcantharidin yields (3S,3aR,4S,7R,7aS)-3-hydroxyhexahydro-4,7- epoxyisobenzofuran-1(3H)-one (3), which also displays a high level of anticancer activity against tumour cells but interestingly, shows selectivity towards HT29 (colon; GI50 = 14 μM) and SJ-G2 (glioblastoma; GI50 = 15 μM) cell lines. Substitution at the hydroxyl group of the cyclic lactone within (3) produces a diasteromeric pair of products that have no difference in cytotoxicity over the cell lines tested. Incorporation of an isopropyl tail at this position (16) produced the most promising compound of this series to date, with strong selectivity towards HT29 (colon; GI50 = 19 μM) and SJ-G2 (glioblastoma; GI50 = 21 μM) cell lines but completely void of any activity against the remaining tumour cell lines (GI50 > 100 μM), as per the parent molecule. We also discovered that the introduction of a terminal phosphate moiety (28) at the same position produced a different trend in cytotoxicity with strong activity in BE2-C (neuroblastoma; GI 50 = 9 μM) cells; suggestive of an alternate mode of action.
Synthesis and biological evaluation of norcantharidin analogues: Towards PP1 selectivity
Stewart, Scott G.,Hill, Timothy A.,Gilbert, Jayne,Ackland, Stephen P.,Sakoff, Jennette A.,McCluskey, Adam
, p. 7301 - 7310 (2007)
Simple modifications to the anhydride moiety of norcantharidin have lead to the development of a series of analogues displaying modest PP1 inhibition (low μM IC50s) comparable to that of norcantharidin (PP1 IC50 = 10.3 ± 1.37 μM). However, unlike norcantharidin, which is a potent inhibitor of PP2A (IC50 = 2.69 ± 1.37 μM), these analogues show reduced PP2A inhibitory action resulting in the development of selective PP1 inhibitory compounds. Data indicates that the introduction of two ortho-disposed substituents on an aromatic ring, or para-substituent favours PP1 inhibition over PP2A inhibition. Introduction of a p-morphilinoaniline substituent, 35, affords an inhibitor displaying PP1 IC50 = 6.5 ± 2.3 μM; and PP2A IC50 = 7.9 ± 0.82 μM (PP1/PP2A = 0.82); and a 2,4,6-trimethylaniline, 23, displaying PP1 IC50 = 48 ± 9; and PP2A IC5 85 ± 3 μM (PP1/PP2A = 0.56). The latter shows a 7-fold improvement in PP1 versus PP2A selectivity when compared with norcantharidin. Subsequent analysis of 23 and 35 as potential PP2B inhibitors revealed modest inhibition with IC50s of 89 ± 6 and 42 ± 3 μM, respectively, and returned with PP1/PP2B selectivities of 0.54 and 0.15. Thus, these analogues are the simplest and most selective PP1 inhibitors retaining potency reported to date. Crown Copyright
Cyclohexanedicarboxylic acid derivative with bridge ring and pharmaceutical composition and application thereof
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Paragraph 0081-0083; 0100-0101, (2021/11/10)
The invention discloses a cyclohexane dicarboxylic acid derivative with a bridged ring represented by general formula (I). The application of the stereoisomers and the pharmaceutically acceptable salts in the preparation of antitumor drugs has obvious inhibition effects on leukemia, liver cancer, lung cancer, gastric cancer and ovarian cancer. The compound disclosed by the invention has high anti-tumor activity, wide anti-tumor spectrum and low toxicity, and is suitable for preparing anti-cancer drugs.
Synthesis of l-ascorbic acid-amino acid-norcantharidin conjugates and their biological activity evaluation in vitro
Wang, Xianheng,Wu, Caoyuan,Zhang, Jidong,Zhao, Changkuo,Zhou, Yiqi
, (2022/01/06)
Three components of L-ascorbic acid, amino acid and functionalized norcantharidins were constructed together in several steps to form 42 norcantharidin derivatives in a high yield. The structure of these synthesized l-ascorbic acid-amino acid-norcantharidin conjugates are determined by 1HNMR, 13CNMR and MS spectrum. The results showed that compounds 6e, 6g, 6j, 6l, 6m, 6b, 6e, 6i, and 6n showed high cytotoxicity to HepG2 and compounds 6b, 6e-g, 6l, 6n, 7b, 7d, 7h, 7i, 7n, 8g, 8i exhibited high cytotoxicity to SW480; Meanwhile, besides 6b, 6e, 6g, and 6k, the other compounds showed less toxic to LO2 at a concentration of 50 μg/mg after 72 h. Compound 6g can induce Mφ-type macrophages derived from mouse bone marrow to polarize to M1-type macrophages.
Norcantharidin carboxylic acid trifluorobenzyl ester as well as synthesis method and application thereof
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Paragraph 0043-0045, (2020/07/02)
A norcantharidin carboxylic acid trifluorobenzyl ester as well as a synthesis method and application thereof are provided. The specific structure of the norcantharidin carboxylic acid trifluorobenzylester as shown in the formula I is shown in the specification. Activity tests show that the norcantharidin carboxylic acid trifluorobenzyl ester as shown in the formula I is a suitable anti-tumor candidate drug, especially as an anti-liver cancer candidate drug. Compared with positive control drugs norcantharidin and sodium norcantharidate, the water solubility, the stability and the anti-tumor activity are improved. In addition, the synthesis method of the norcantharidin carboxylic acid trifluorobenzyl ester has the advantages that the raw materials are easy to obtain, and the operation and the implementation are very easy.
Synthesis and anti-tumor application of norcantharidin carboxylic acid difluorobenzyl ester
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Paragraph 0038-0039, (2020/07/13)
The invention provides synthesis and anti-tumor application of norcantharidin carboxylic acid difluorobenzyl ester with a structural formula shown as I in the specification. The specific structure ofthe norcantharidin carboxylic acid difluorobenzyl ester as shown in the formula I is shown in the specification, and activity tests show that the norcantharidin carboxylic acid difluorobenzyl ester asshown in the formula I, which is designed and synthesized by the invention, is a suitable anti-tumor candidate drug, especially as a candidate anti-liver-cancer drug. Compared with positive control drugs norcantharidin and sodium norcantharidate, the water solubility, the stability and the anti-tumor activity are improved. In addition, the synthesis method of norcantharidin carboxylic acid difluorobenzyl ester has the advantages that the raw materials are easy to obtain, and the operation and the implementation are very easy.
