A Unified Synthesis of Electron-Deficient 1,4- and 1,1,4-Substituted 1,3-Dienes through a Base-Promoted Allylation Followed by -Michael Vinylogous Dehydrosulfinylation.

We disclose a general 2-step synthesis of electron-poor 1,4- and 1,1,4-substituted buta-1,3-dienes bearing electron-withdrawing substituents at both termini of the conjugated system. The method relies on a base-promoted C-allylation of primary or secondary alkylsulfones with γ-bromocrotonate or related amide, nitrile, or sulfone and subsequent vinylogous -Michael dehydrosulfinylation. The geometry of the resulting dienes is substrate-dependent, and predominantly ,-dienes are formed from -electrophiles.

Benzyl-para-di-[5-methyl-4-(n-octylamino) pyrimidin-2(1H)one] as an interferon beta (IFN-β) modulator.

IFN-β is a cytokine that plays a significant role in the immune system. Inhibition of IFN-β might be used as a therapeutic approach to treat septic shock. A peptidomimetic previously developed by our research team, 1-benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one (LT87), was used as an cardioprotective agent in a myocardial ischemia (MI) mouse model.

Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.

More than two decades have elapsed since the publication of the first genome sequence of () which, shortly thereafter, enabled methods to determine gene essentiality in the pathogen. Despite this, target-based approaches have not yielded drugs that have progressed to clinical testing. Whole-cell screening followed by elucidation of mechanism of action has to date been the most fruitful approach to progressing inhibitors into the tuberculosis drug discovery pipeline although target-based approaches are gaining momentum.

Structurally Simple, Readily Available Peptidomimetic 1-Benzyl-5-methyl-4-( n-octylamino)pyrimidin-2(1 H)-one Exhibited Efficient Cardioprotection in a Myocardial Ischemia (MI) Mouse Model.

TLR4, a member of the Toll-like receptor (TLR) family, serves as a pattern recognition receptor in the innate immune response to microbial pathogens. TLR4 also regulates the inflammatory reaction to ischemic injury in the heart. The TRIF-related adaptor molecule (TRAM) is an adapter that recruits the Toll/interleukin 1 receptor (TIR) domain, which contains adapter-inducing IFN-β (TRIF), to activate TLR4, following TRIF-dependent cytokine gene transcription.