914348-94-0Relevant academic research and scientific papers
Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids
He, Ling,Jiang, Yan,Qiao, Zhen,Qiu, Hanyue,Su, Xiaojiao,Tan, Qiuyuan,Yang, Jiaojiao,Yang, Zhao,Zhang, Min,Zhou, Wenqiang
, p. 13105 - 13111 (2021/05/10)
We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L-tryptophan as the starting material. Two key bridged skeleton-forming reactions, namely tandem sequential oxidative cyclopropanol ring-opening cyclization and ketone α-allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, Na-methyl-16-epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N-demethylkoumine) with more complex cage scaffolds has been accomplished.
Structure-guided design, synthesis, and biological evaluation of (2-(1 H-Indol-3-yl)-1 H-imidazol-4-yl)(3,4,5-trimethoxyphenyl) methanone (ABI-231) analogues targeting the colchicine binding site in Tubulin
Wang, Qinghui,Arnst, Kinsie E.,Wang, Yuxi,Kumar, Gyanendra,Ma, Dejian,White, Stephen W.,Miller, Duane D.,Li, Wei,Li, Weimin
, p. 6734 - 6750 (2019/08/20)
ABI-231 is a potent, orally bioavailable tubulin inhibitor that interacts with the colchicine binding site and is currently undergoing clinical trials for prostate cancer. Guided by the crystal structure of ABI-231 in complex with tubulin, we performed structure-activity relationship studies around the 3-indole moiety that led to the discovery of several potent ABI-231 analogues, most notably 10ab and 10bb. The crystal structures of 10ab and 10bb in complex with tubulin confirmed their improved molecular interactions to the colchicine site. In vitro, biological studies showed that new ABI-231 analogues disrupt tubulin polymerization, promote microtubule fragmentation, and inhibit cancer cell migration. In vivo, analogue 10bb not only significantly inhibits primary tumor growth and decreases tumor metastasis in melanoma xenograft models but also shows a significant ability to overcome paclitaxel resistance in a taxane-resistant PC-3/TxR model. In addition, pharmacological screening suggested that 10bb has a low risk of potential off-target function.
Indole-substituted hydrazide derivatives and uses thereof
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Paragraph 0166; 0216-0219, (2018/11/03)
The invention discloses indole-substituted hydrazide derivatives and a use thereof, concretely relates to novel indole-substituted hydrazide derivatives and a medicinal composition including the abovecompounds, a use of the derivatives and the medicinal composition in the protection of nerve cells, and also relates to a method for preparing the compounds and the medicinal composition, and a use of the compounds and the medicinal composition in the preparation of drugs for treating diseases associated with glutamate excitotoxicity and oxidative stress damage or free radicals, or neurodegenerative diseases, especially the Alzheimer disease.
Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents
Pedada, Srinivasa Rao,Yarla, Nagendra Sastry,Tambade, Pawan J.,Dhananjaya, Bhadrapura Lakkappa,Bishayee, Anupam,Arunasree, Kalle M.,Philip, Gundala Harold,Dharmapuri, Gangappa,Aliev, Gjumrach,Putta, Swathi,Rangaiah, Gururaja
, p. 289 - 297 (2018/04/19)
Secretory phospholipase A2 (sPLA2) is an important enzyme that plays a key role in various inflammatory diseases including cancer and its inhibitors have been developed as preventive or therapeutic agents. In the present study, a series of new indole containing isoxazole derivatives (10a–10o) is synthesized and evaluated for their sPLA2 inhibitory activities. All compounds (10a–10o) showed significant sPLA2 inhibition activities both in vitro and in vivo studies which is substantiated in in silico studies. Among all the tested compounds, 10o showed potent sPLA2 inhibition activity, that is comparable or more to ursolic acid (positive control). Further studies demonstrated that 10o showed in vitro antiproliferative activity when tested against MCF-7 breast and DU145 prostate cancer cells. Furthermore, compounds 10a–10o obeyed lipinsky's rule of 5 and suggesting druggable properties. The in vitro, in vivo and in silico results are encouraging and warrant pre-clinical studies to develop sPLA2-inhibitory compound 10o as novel therapeutic agent for various inflammatory disorders and several malignancies.
VIRAL REPLICATION INHIBITORS
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Page/Page column 129; 182, (2013/04/13)
The present invention relates to a series of novel compounds, methods to prevent or treat viral infections in animals by using the novel compounds and to said novel compounds for use as a medicine, more preferably for use as a medicine to treat or prevent viral infections, particularly infections with RNA viruses, more particularly infections with viruses belonging to the family of the Flaviviridae, and yet more particularly infections with the Dengue virus. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the novel compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of viral infections. The invention also relates to processes for preparation of the compounds.
