- Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
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PRMT5 plays important roles in diverse cellular processes and is upregulated in several human malignancies. Besides, PRMT5 has been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments, with a Kd of 0.987 μM. Kinetic experiments indicated that 17 was a SAM competitive inhibitor other than the substrate. In addition, 17 showed selective antiproliferative effects against MV4-11 cells, and further studies indicated that the mechanism of cellular antitumor activity was due to the inhibition of PRMT5 mediated SmD3 methylation. 17 may represent a promising lead compound to understand more about PRMT5 and potentially assist the development of treatments for leukemia indications.
- Mao, Ruifeng,Shao, Jingwei,Zhu, Kongkai,Zhang, Yuanyuan,Ding, Hong,Zhang, Chenhua,Shi, Zhe,Jiang, Hualiang,Sun, Dequn,Duan, Wenhu,Luo, Cheng
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p. 6289 - 6304
(2017/08/02)
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- AMIFAMPRIDINE DIHYDROCHLORIDE
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The present invention relates to novel salt of 3,4-diaminopyridine as 3,4-diaminopyridine dihydrochloride (or Amifampridine dihydrochloride), useful in the preparation of pharmaceutical composition thereof. The present application also relates to an improved process for the preparation of substantially pure Amifampridine dihydrochloride (I) having purity of greater than 99.5% (by HPLC).
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Page/Page column 16
(2017/11/03)
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- Benzo[1,2-b:4,5-b′]dithiophene-Pyrido[3,4-b]pyrazine Small-Molecule Donors for Bulk Heterojunction Solar Cells
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We report on the synthesis, material properties, and bulk heterojunction (BHJ) solar cell characteristics of a set of π-conjugated small-molecule (SM) donors composed of benzo[1,2-b:4,5-b′]dithiophene (BDT) and pyrido[3,4-b]pyrazine (PP) units, examining the perspectives of alkyl-substituted PP acceptor motifs in SM designs. In these systems (SM1-4), both the type of side chains derived from the PP motifs and the presence of ring substituents on BDT critically impact (i) molecular packing, and (ii) thin-film morphologies and charge transport in BHJ solar cells. With the appropriate side-chain pattern, the ring-substituted analogue SM4 stands out, achieving efficiencies of ca. 6.5% with PC71BM, and fine-scale morphologies comparable to those obtained with some of the best-performing polymer donors in BHJ solar cells. 1H-1H DQ-SQ NMR analyses are used to examine the distinct self-assembly pattern of SM4, expected to factor into the development of the BHJ morphology.
- Wolf, Jannic,Babics, Maxime,Wang, Kai,Saleem, Qasim,Liang, Ru-Ze,Hansen, Michael Ryan,Beaujuge, Pierre M.
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p. 2058 - 2066
(2016/05/10)
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- QUINOXALINONES AND DIHYDROQUINOXALINONES AS RESPIRATORY SYNCYTIAL VIRUS ANTIVIRAL AGENTS
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Quinoxalinones and dihydroquinoxalinones having inhibitory activity on RSV replication and having the formula (I) including addition salts, and stereochemically isomeric forms thereof; compositions containing these compounds as active ingredient and processes for preparing these compounds and compositions.
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Page/Page column 25
(2014/08/07)
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- Structure-guided design of substituted aza-benzimidazoles as potent hypoxia inducible factor-1α prolyl hydroxylase-2 inhibitors
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We report the structure-based design and synthesis of a novel series of aza-benzimidazoles as PHD2 inhibitors. These efforts resulted in compound 22, which displayed highly potent inhibition of PHD2 function in vitro.
- Frohn, Mike,Viswanadhan, Vellarkad,Pickrell, Alexander J.,Golden, Jennifer E.,Muller, Kristine M.,Buerli, Roland W.,Biddlecome, Gloria,Yoder, Sean C.,Rogers, Norma,Dao, Jennifer H.,Hungate, Randall,Allen, Jennifer R.
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scheme or table
p. 5023 - 5026
(2009/05/26)
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- Synthesis of 3,4-diaminopyridine and imidazo[4,5-c]pyridines by nitration of 4-acylaminopyridines
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New methods for the preparation of 3,4-diaminopyridine (5) and imidazo[4,5-c]pyridines 7a,7b based on direct nitration of 4- acylaminopyridines 3a, 3b have been explored.
- Bakke,Riha
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p. 1143 - 1145
(2007/10/03)
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- Hair dye compositions and process comprising and utilizing a combination of isatin and aminopyridine derivatives
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The invention relates to a process for dyeing keratinous fibers, comprising the simultaneous or sequential application of a component (A) containing at least one compound of formula (I): STR1 in which: R1 denotes hydrogen, alkyl, acetyl, benzoyl, phenyl or carboxyalyl; R2 and R3 denote a hydrogen, alkyl, hydroxyl, halogen, nitro, alkylphenyl, phenyl or alkoxy; and a component (B) containing at least one compound of formula (II): STR2 in which: R4 denotes a hydrogen atom or a β-hydroxyethyl group; n=0, 1 or 2, and m=0 or 1; as well as its cosmetically acceptable salts; or one compound of formula (III): STR3 in which: R5 denotes a hydrogen atom, a hydroxyl group or a group STR4 R6 denotes a hydroxyl group or a group N STR5 R7 denotes H or NH2, R8 denotes a group STR6 R9 and R10, independently of one another, representing a hydrogen atom, a C1 -C4 alkyl, a group (CH2)p --Z, where p=1 to 4 and Z represents OH, halogen, NH2, NHR' or NHR'R", where R' and R" denote a C1 -C4 alkyl or form a heterocycle with the nitrogen atom to which they are attached; with the proviso that one of R5 to R8 denotes NH2 ; and its cosmetically acceptable salts, as well as to the dyeing agents employed.
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- Diaminopyridine compounds and methods of use
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The present invention relates to compositions and method for inhibiting nonenzymatic cross-linking (protein aging) which contain diaminopyridines and derivates thereof. Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
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