161192-30-9Relevant articles and documents
Amide derivatives and their medical use
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Paragraph 0035; 0039; 0040, (2018/04/21)
The invention relates to novel amide derivatives shown in a structural formula I in the specification or a pharmaceutically acceptable salt thereof, a medicine composition which takes the compounds as active components, and an application of the derivatives or the pharmaceutically acceptable salt of the derivatives to preparation of analgesia medicines. In the structural formula I, R1 and R2 are a hydrogen atom and a C1-C3 alkyl; R3 is hydrogen atom, C1-C3 alkyl, phenyl or a hydroxyl-substituted alkyl.
Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non-nucleoside inhibitors by means of ligand-based and structure-based approaches
Sabatino, Manuela,Rotili, Dante,Patsilinakos, Alexandros,Forgione, Mariantonietta,Tomaselli, Daniela,Alby, Fréderic,Arimondo, Paola B.,Mai, Antonello,Ragno, Rino
, p. 435 - 458 (2018/02/09)
Abstract: Chemical inhibition of chromatin-mediated signaling involved proteins is an established strategy to drive expression networks and alter disease progression. Protein methyltransferases are among the most studied proteins in epigenetics and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine methyltransferase plays a key role in MLL-rearranged acute leukemia Selective inhibition of DOT1L is an established attractive strategy to breakdown aberrant H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis. Although numerous DOT1L inhibitors have been several structural data published no pronounced computational efforts have been yet reported. In these studies a first tentative of multi-stage and LB/SB combined approach is reported in order to maximize the use of available data. Using co-crystallized ligand/DOT1L complexes, predictive 3-D QSAR and COMBINE models were built through a python implementation of previously reported methodologies. The models, validated by either modeled or experimental external test sets, proved to have good predictive abilities. The application of these models to an internal library led to the selection of two unreported compounds that were found able to inhibit DOT1L at micromolar level. To the best of our knowledge this is the first report of quantitative LB and SB DOT1L inhibitors models and their application to disclose new potential epigenetic modulators. Graphical Abstract: [Figure not available: see fulltext.].
NOVEL THIAZOLIDINEDIONE DERIVATIVE AND USE THEREOF
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Page/Page column 14-15, (2011/11/12)
The present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and the uses thereof. More specifically, the present invention relates to novel thiazolidinedione derivatives expressed by the following formula (I) and a pharmaceutical composition comprising the same. The novel thiazolidinedione derivatives of formula (I) according to the present invention can be effectively used for the prevention or treatment of cardiovascular disease, gastrointestinal disease and renal disease by inhibiting the activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that decomposes prostaglandins as well as useful for the prevention of hair loss and the stimulation of hair growth, and osteogenic stimulation and wound healing.
Synthesis and SAR of thiazolidinedione derivatives as 15-PGDH inhibitors
Wu, Ying,Tai, Hsin-Hsiung,Cho, Hoon
experimental part, p. 1428 - 1433 (2010/05/02)
Prostaglandins have a short life in vivo because they are metabolized rapidly by oxidation to 15-ketoprostaglandins catalyzed by a cytosolic enzyme known as NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Previously, CT-8, a thiazolidinedione analogue, was found to be a potent inhibitor of 15-PGDH. Structure-activity analysis indicated that the N-methylation of thiazolidine-2,4-dione, CT-8, abolished the inhibitory activity, whereas the introduction of an ethyl hydroxyl group at amine in CT-8 still had a good inhibitory effect. Based on the structures of the thiazolidinediones analogues and inhibitory activity, a range of benzylidene thiazolidinedione derivatives were synthesized with different substituents on the phenyl ring and their inhibitory activity was evaluated. Replacement of the cyclohexylethyl group of CT-8 with the hetero five-member ring increased the inhibitory potency. However, replacement of the cyclohexylethyl group with a hetero six-member ring decreased the inhibitory potency significantly. It was found that compound 2 (5-(4-(2-(thiophen-2-yl)ethoxy)benzylidene)thiazolidine-2,4-dione) was the most potent inhibitor that was effective in the nanomolar range.
