1531-18-6Relevant articles and documents
Rational Design of Novel Highly Potent and Selective Phosphatidylinositol 4-Kinase IIIβ (PI4KB) Inhibitors as Broad-Spectrum Antiviral Agents and Tools for Chemical Biology
Mejdrová, Ivana,Chalupská, Dominika,Pla?ková, Pavla,Müller, Christin,?ála, Michal,Klíma, Martin,Baumlová, Adriana,H?ebabecky, Hubert,Procházková, Eli?ka,Dejmek, Milan,Strunin, Dmytro,Weber, Jan,Lee, Gary,Matou?ová, Marika,Mertlíková-Kaiserová, Helena,Ziebuhr, John,Birkus, Gabriel,Boura, Evzen,Nencka, Radim
, p. 100 - 118 (2017)
Phosphatidylinositol 4-kinase IIIβ (PI4KB) is indispensable for the replication of various positive-sense single stranded RNA viruses, which hijack this cellular enzyme to remodel intracellular membranes of infected cells to set up the functional replication machinery. Therefore, the inhibition of this PI4K isoform leads to the arrest of viral replication. Here, we report on the synthesis of novel PI4KB inhibitors, which were rationally designed based on two distinct structural types of inhibitors that bind in the ATP binding side of PI4KB. These “hybrids” not only excel in outstanding inhibitory activity but also show high selectivity to PI4KB compared to other kinases. Thus, these compounds exert selective nanomolar or even subnanomolar activity against PI4KB as well as profound antiviral effect against hepatitis C virus, human rhinovirus, and coxsackievirus B3. Our crystallographic analysis unveiled the exact position of the side chains and explains their extensive contribution to the inhibitory activity.
SUBSTITUTION OF ALKYL AND HYDROXYALKYL GROUP FOR RING HYDROGEN AND OF HYDROXYALKYL GROUP FOR CYANO GROUP IN GAMMA-IRRADIATION OF PYRIDINECARBONITRILES IN ALCOHOL
Sugimori, Akira,Mori, Shoji,Maeda, Kazuo,Nishijima, Masayuki
, p. 769 - 772 (1984)
Gamma-irradiation of pyridinecarbonitriles in alcohol in the presence of sulfuric acid brings about the substitution of the alkyl group derived from alcohol for,the ring hydrogen, while that in the absence of sulfuric acid causes the substitution of hydroxyalkyl group for CN at the 2- and 4-positions.Hydroxyalkyl radicals and solvated electrons play important role in the substitution.
Preparation method of 2-ethyl-4-cyanopyridine
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Paragraph 0017; 0024; 0026; 0028; 0031-0032, (2021/01/20)
The invention provides a preparation method of 2-ethyl-4-cyanopyridine. According to the preparation method, 1-(4-bromopyridin-2-yl)ethanone is used as an initial raw material, 2-ethyl-4-bromopyridineis prepared through reduction of a catalyst and a reducing agent, and 2-ethyl-4-cyanopyridine is obtained through cyanation. The total yield is 85% or more, and the product purity is 99% or more. Theroute is simple and convenient, auxiliary materials are common compounds, and the solvent can be recycled. The product is a single compound. Compared with a traditional synthesis method, the synthesis method has the advantages that isomer 3-ethyl-4-cyanopyridine is not generated, and the requirement for post-treatment of synthesis of ethylthio isonicotinamide is low. The synthetic route is safe,simple and convenient to operate, environment-friendly, capable of relaxing the bowels and suitable for industrial production.
Diarylthiazole: An antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system
Bellale, Eknath,Naik, Maruti,Vb, Varun,Ambady, Anisha,Narayan, Ashwini,Ravishankar, Sudha,Ramachandran, Vasanthi,Kaur, Parvinder,McLaughlin, Robert,Whiteaker, James,Morayya, Sapna,Guptha, Supreeth,Sharma, Sreevalli,Raichurkar, Anandkumar,Awasthy, Disha,Achar, Vijayshree,Vachaspati, Prakash,Bandodkar, Balachandra,Panda, Manoranjan,Chatterji, Monalisa
supporting information, p. 6572 - 6582 (2014/10/15)
Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE) >0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.
