165682-90-6Relevant academic research and scientific papers
Solvent-free synthesis of bacillamide analogues as novel cytotoxic and anti-inflammatory agents
Kumar, Sunil,Aggarwal, Ranjana,Kumar, Virender,Sadana, Rachna,Patel, Bhumi,Kaushik, Pawan,Kaushik, Dhirender
, p. 718 - 726 (2016/08/15)
Synthesis of fourteen analogues of bacillamide, a bioactive tryptamide alkaloid of marine origin, has been accomplished through a highly efficient convergent route. The present solvent-free protocol involves the formation of thiazole ring in the initial step followed by amide coupling between substituted ethyl 2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxylates and tryptamine in presence of 2-hydroxy-4,6-dimethylpyrimidine, a solid phase catalyst to yield N-[2-(1H-indol-3-yl)ethyl]-2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxamides as bacillamide analogues having structural variation at position-2 of thiazole ring. Bacillamide and its analogues were evaluated for their cytotoxic activity against three cancer cell lines (HCT-116, MDA-MD-231 and JURKAT cell lines) using colorimetric cell proliferation assay. Compounds 17a and 17b exhibited potent anti-cell proliferation activity with IC50values in the range of ～3.0?μM and ～0.1–0.6?μM, respectively against these cell lines. Preliminary mechanism of action studies indicates that these compounds initiate caspase dependent apoptosis. Also, compounds 16d, 16f, 17a and 17d exhibited excellent anti-inflammatory activity comparable to well-known NSAID indomethacin and better to bacillamide, when evaluated using carrageenan induced rat hind paw oedema method.
The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore
Washburn, David G.,Holt, Dennis A.,Dodson, Jason,McAtee, Jeff J.,Terrell, Lamont R.,Barton, Linda,Manns, Sharada,Waszkiewicz, Anna,Pritchard, Christina,Gillie, Dan J.,Morrow, Dwight M.,Davenport, Elizabeth A.,Lozinskaya, Irina M.,Guss, Jeffrey,Basilla, Jonathan B.,Negron, Lorena Kallal,Klein, Michael,Willette, Robert N.,Fries, Rusty E.,Jensen, Timothy C.,Xu, Xiaoping,Schnackenberg, Christine G.,Marino Jr., Joseph P.
supporting information, p. 4979 - 4984 (2013/09/02)
Lead optimization of piperidine amide HTS hits, based on an anilino-thiazole core, led to the identification of analogs which displayed low nanomolar blocking activity at the canonical transient receptor channels 3 and 6 (TRPC3 & 6) based on FLIPR (carbac
Design, synthesis, and SAR studies of 4-substituted methoxylbenzoyl-aryl- thiazoles analogues as potent and orally bioavailable anticancer agents
Lu, Yan,Li, Chien-Ming,Wang, Zhao,Chen, Jianjun,Mohler, Michael L.,Li, Wei,Dalton, James T.,Miller, Duane D.
supporting information; experimental part, p. 4678 - 4693 (2011/09/14)
In a continued effort to improve upon the previously published 4-substituted methoxybenzoyl-aryl-thiazole (SMART) template, we explored chemodiverse "B" rings and "B" to "C" ring linkage. Further, to overcome the poor aqueous solubility of this series of agents, we introduced polar and ionizable hydrophilic groups to obtain water-soluble compounds. For instance, based on in vivo pharmacokinetic (PK) studies, an orally bioavailable phenyl-amino-thiazole (PAT) template was designed and synthesized in which an amino linkage was inserted between "A" and "B" rings of compound 1. The PAT template maintained nanomolar (nM) range potency against cancer cell lines via inhibiting tubulin polymerization and was not susceptible to P-glycoprotein mediated multidrug resistance in vitro, and markedly improved solubility and bioavailability compared with the SMART template (45a-c (PAT) vs 1 (SMART)).
