- ISOINDOLINONE DERIVATIVES AS IRAK4 MODULATORS
-
Compounds of Formula (0), and stereoisomers and pharmaceutically acceptable salts thereof, as well as methods of use as Interleukin-1 Receptor Associated Kinase (IRAK4) inhibitors are described herein.
- -
-
Page/Page column 71; 72
(2019/01/10)
-
- Potent antimicrobial agents against azole-resistant fungi based on pyridinohydrazide and hydrazomethylpyridine structural motifs
-
Abstract Schiff base derivatives have recently been shown to possess antimicrobial activity, and these derivatives include a limited number of salicylaldehyde hydrazones. To further explore this structure-activity relationship between salicylaldehyde hydrazones and antifungal activity, we previously synthesized and analyzed a large series of salicylaldehyde and formylpyridinetrione hydrazones for their ability to inhibit fungal growth of both azole-susceptible and azole-resistant species of Candida. While many of these analogs showed excellent growth inhibition with low mammalian cell toxicity, their activity did not extend to azole-resistant species of Candida. To further dissect the structural features necessary to inhibit azole-resistant fungal species, we synthesized a new class of modified salicylaldehyde derivatives and subsequently identified a series of modified pyridine-based hydrazones that had potent fungicidal antifungal activity against multiple Candida spp. Here we would like to present our synthetic procedures as well as the results from fungal growth inhibition assays, mammalian cell toxicity assays, time-kill assays and synergy studies of these novel pyridine-based hydrazones on both azole-susceptible and azole-resistant fungal species.
- Backes, Gregory L.,Jursic, Branko S.,Neumann, Donna M.
-
p. 3397 - 3407
(2015/08/03)
-
- Discovery of pyridyl-based inhibitors of Plasmodium falciparum N-myristoyltransferase
-
N-Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative 3, providing a versatile platform to study the effects of substitution on the scaffold, which yielded pyridyl 19. This molecule exhibited improved enzyme and cellular potency, and reduced lipophilicity compared to inhibitor 3. Further structure-based inhibitor design led to the discovery of 30, the most potent inhibitor in this series, which showed single-digit nM enzyme affinity and sub-μM anti-plasmodial activity.
- Yu, Zhiyong,Brannigan, James A.,Rangachari, Kaveri,Heal, William P.,Wilkinson, Anthony J.,Holder, Anthony A.,Leatherbarrow, Robin J.,Tate, Edward W.
-
p. 1767 - 1772
(2015/10/20)
-
- Syntheses, structures and photoluminescent properties of a series of divalent nickel and cadmium complexes based on 3-carboxy-1-(4′-(2″- carboxy)biphenylmethyl)-2-oxidopyridinium and structurally different N-donor ligands
-
Ten new coordination polymers, namely, [Cd(L)(pbib)0.5] (1), [Ni(L)(pbib)]·2H2O (2), [Cd2(L)2(pytp) 2]·H2O (3), [Cd(L)(tbpy)] (4), [Ni(L)(pytp)] (5), [Ni(L)(tbpy)]·0.25H2O (6), [
- Pu, Ai-Ting,Yang, Jin,Kan, Wei-Qiu,Yang, Yan,Ma, Jian-Fang
-
p. 556 - 570
(2013/04/10)
-
- Role of lactam vs. lactim tautomers in 2(1H)-pyridone catalysis of aromatic nucleophilic substitution
-
3-Ethylaminocarbonyl-2(1H)-pyridone 1 and 3-ethoxycarbonyl-2(1H)-pyridone 2 have been synthesised and tested as catalysts for the aromatic nucleophilic substitution of fluoride by piperidine in 2-fluoro-5-nitrobenzonitrile 3. A kinetic model which takes into account the dimerisation of the catalysts has been developed, which allows a quantitative analysis of measured data. 3-Ethylaminocarbonyl-2(1H)-pyridone 1 exists exclusively as a lactam tautomer, either monomeric or dimeric but 3-ethoxycarbonyl-2(1H)-pyridone 2 exists as a lactim monomer, whereas its dimer exists in the lactam form. Despite such differences, these two compounds exhibit similar catalytic efficiencies for the reaction studied, suggesting that lactim and lactam tautomers have comparable efficiencies in tautomeric catalysis.
- Loppinet-Serani, Anne,Charbonnier, Florence,Rolando, Christian,Huc, Ivan
-
p. 937 - 942
(2007/10/03)
-
- Ring Transformation Reactions of 1-Substituted 2(1H)-Pyrimidinones and Related Compounds with Active Methylene Compounds
-
1-Substituted 2(1H)-pyrimidinones (I) underwent ring transformation with malononitrile and ethyl acetoacetate in the presence of sodium ethoxide to give 2-amino-3-pyridinecarbonitriles (II-VII) and N-(substituted)amino-3-pyridinecarboxylic acids (XIV and XV), respectively.Further, I reacted with ethyl cyanoacetate, dialkyl malonate, or ethyl benzoylacetate to give pyridine derivatives (VIII-XIII) bearing various functional groups at the C-3 position.The reaction of 1-substituted 2(1H)-pyrimidinethiones and 4,6-dimethyl-1-phenyl-2-phenylimino-1,2-dihydropyrimidine with active methylene compounds is also discussed.Keywords - ring transformation; 1-substituted 2(1H)-pyrimidinone; 1-substituted 2(1H)-pyrimidinethione; active methylene compound; sodium alkoxide; pyridine derivative.
- Katoh, Akira,Omote, Yoshimori,Kashima, Choji
-
p. 2942 - 2946
(2007/10/02)
-