- The efficient synthesis of 3-[6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl]-1H-indazole
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This study presents an efficient synthesis of 3-[6-(substituted-phenyl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazol-3-yl]-1H-indazole via dehydrative condensation with cyclization of 4-amino-5-(1H-indazol-3-yl)-4H-[1,2,4]triazole-3-thiol and fluorinated or nonfluorinated carboxylic acids in presence of phosphorous oxychloride. The multistep reaction pathway proceeds through different compounds. Present synthesis has the advantages of easily accessible starting materials, convenient synthesis, simple reaction condition, wider substrate scope, and higher yield (75% to 90% isolated).
- Raut, Santosh,Hadi, Abdul,Pathan, Mohd Arif
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p. 1291 - 1305
(2020/02/04)
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- HETEROARYL-SUBSTITUTED TRIAZOLES AS APJ RECEPTOR AGONISTS
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Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.
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Paragraph 0756
(2018/06/12)
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- Suprafenacine, an Indazole-hydrazide agent, target Cancer cells through microtubule destabilization
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Microtubules are a highly validated target in cancer therapy. However, the clinical development of tubulin binding agents (TBA) has been hampered by toxicity and chemoresistance issues and has necessitated the search for new TBAs. Here, we report the identification of a novel cell permeable, tubulin-destabilizing molecule - 4,5,6,7-tetrahydro-1H-indazole-3- carboxylic acid [1p-tolyl-meth-(E)-ylidene]-hydrazide (termed as Suprafenacine, SRF). SRF, identified by in silico screening of annotated chemical libraries, was shown to bind microtubules at the colchicine-binding site and inhibit polymerization. This led to G2/M cell cycle arrest and cell death via a mitochondria-mediated apoptotic pathway. Cell death was preceded by loss of mitochondrial membrane potential, JNK - mediated phosphorylation of Bcl-2 and Bad, and activation of caspase-3.Intriguingly, SRF was found to selectively inhibit cancer cell proliferation and was effective against drug-resistant cancer cells by virtue of its ability to bypass the multidrug resistance transporter P-glycoprotein. Taken together, our resultssuggest that SRF has potential as a chemotherapeutic agent for cancer treatment and provides an alternate scaffold for the development of improved anti-cancer agents.
- Choi, Bo-Hwa,Chattopadhaya, Souvik,Thanh, Le Nguyen,Feng, Lin,Nguyen, Quoc Toan,Lim, Chuan Bian,Harikishore, Amaravadhi,Reddy, Ravi Prakash,Bharatham, Nagakumar,Zhao, Yan,Liu, Xuewei,Yoon, Ho Sup
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supporting information
(2015/02/18)
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- TUBULIN INHIBITORS
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The present invention relates to a compound of Formula (I) for use as a medicament, wherein: m is 0, 1, 2, 3, 4, or 5; R1 and R2 together form a five-membered, six-membered, or seven-membered ring, wherein R1 and R2 together as a group is -(CH2)3-, -(CH2)4 -, or -(CH2)5-; R3 at each occurrence is independently selected from the group consisting of H, halogen, hydroxyl, alkoxy, and a substituted or unsubstituted C1-C5 alkyl; and R4 is H, halogen, or a substituted or unsubstituted C1-C5 alkyl
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Paragraph 00220; 00221; 00232
(2013/11/18)
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