The title compound (E)-3-(3-methylthiophen-2-yl)-1-(pyrazin-2-yl)prop-2-en-1-one was synthesized and the product obtained was characterized by spectroscopic techniques and finally the structure was confirmed by X-ray diffraction technique. The compound crystallizes in the monoclinic crystal syst...

A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles whe...

The application of the intramolecular Pauson-Khand reaction of 1,n-enynes provides a convenient method for the construction of polycyclic frameworks but this process has largely been limited to the formation of 5,5- and 5,6-fused ring systems. In this report, we describe the application of the P...

The effectiveness of Sc(OTf)3 as a Lewis acid catalyst for the 1,4-addition reaction of carbamates to appropriate 2-acetyl-2-pentenoic esters is herein reported. In particular, N-benzyl-(tert-butyldimethylsilyloxy)carbamate added efficiently to the title substrates to afford a new class of polyf...

Upon treatment with homochiral lithium (R)-N-benzyl-N-(α-methylbenzyl)amide, γ-benzyloxy but-2-enoates undergo competitive conjugate addition and γ-deprotonation, while γ-tert-butyldimethylsilyloxy but-2-enoates undergo exclusive conjugate addition. Treatment of γ-benzyloxy or γ-tert-butyl...

3-(3-(tert-Butyldimethylsilyloxy)buta-1,3-dienyl)oxazolidin-2-one was reacted with several electrophilic 2H-azirines to give the expected cycloadducts in moderate to good yields. Treatment of the cycloadducts under acidic conditions gave six-membered ring aminoenones and aziridine derivatives. I...

A remarkable Lewis acid tuning has been observed in the nucleophilic addition of Grignard reagent to BIGN, the N-benzyl nitrone derived from 1,2-O-isopropylidene-D-glyceraldehyde. The obtained α,β-dialkoxy hydroxyl-amines can serve as starting points for the synthesis of both aminodiols and α...

(2S,5S)-N-Boc-5-tert-butylproline (1) was synthesized by an improved procedure featuring the conversion of (2S)-1-tert-butyldimethylsiloxy-2-N-(PhF)amino-5-oxo-6,6-dimethylheptane (16) into its corresponding imino alcohol followed by directed hydride delivery to reduce the imine functionality wi...

Analogs of salinosporamide A with variations of the C2 and C5 substituents are prepared in 8–10 steps using as the first and key transformation a diastereoselective Mukaiyama aldol reaction between the chiral 5-tert-butyldimethylsiloxy-3-methyl-1H-pyrrole-2-carboxylic ester depicted and various...

N-tert-Butylbenzenesulfenamide (1)-catalyzed oxidation of various primary and secondary alcohols to the corresponding aldehydes and ketones was efficiently carried out by using N-chlorosuccinimide (NCS) in the coexistence of potassium carbonate and molecular sieves 4 Å at easy-to-control tempera...

In this chapter, chemistry and structural aspects along with medicinal importance of four-membered saturated and unsaturated mono N, O, and S heterocycles such as azetidine, azetidin-2-ones, azetines, azete oxetane, oxetanone, oxetene, and thietane are discussed. Besides monoheteroatom heterocyc...

Three angiotensin II receptor antagonists—losartan, candesartan, and zolarsartan—were investigated. All the compounds, which are structural analogues, are metabolized via conjugation to glucuronic acid. Interestingly, both O- and N-glucuronidation take place, so that regioisomers are formed. O...

The role of galanin in memory paradigms has been largely evaluated. The galanin-antagonist galantide, a chimeric peptide obtained from amino acids 1–13 of galanin attached to the C-terminal fragment of bradykinin, has been found to improve social memory in ‘social recognition' test when i...

While intracerebroventricular injection of galanin (5 μg/rat) inhibited sexual behavior in experienced male rats - without producing any other locomotor or behavioral deficit -, injection of the galanin antagonist, galantide, by the same route (1 or 2 μg/rat) stimulated sexual behavior (improv...

The effect of the chimeric ligand galantide on the galanin-induced activation of membrane K+ conductance and inhibition of voltage-dependent Ca2+ conductance has been studied using voltage-clamped dissociated mudpuppy parasympathetic neurons. Galantide did not activate the K+ conductance but pro...

We have previously shown that galantide ameliorates mild acute pancreatitis (AP), and the salivary tripeptide analogue, feG, ameliorates severe AP in mice. In this study, we compared the efficacy of combining galantide and feG with that of the individual agents in treating mild AP induced in mic...

BackgroundWe have previously shown that galantide, a non-specific galanin receptor antagonist, ameliorates acute pancreatitis (AP) induced in mice. Octreotide, a somatostatin analogue, has been used in the treatment of AP with inconsistent outcomes. This study set out to compare the efficacy of ...

Chemical properties of 1,2,4-thiadiazole have been reviewed in the last few years. However, the usefulness of 1,2,4-thiadiazole as a privileged system in medicinal chemistry has prompted the advances on the therapeutic potential of this system. This review provides a brief summary of the medicin...

(6′R)- and (6′S-6′-C-methyl-3-deazaneplanocin A's were synthesized from D-ribose as anti-RNA virus agents. Of these compounds, (6′R)-6′-C-methyl-3-deazaneplanocin A (4b) showed the greatest anti-RNA virus activity in vitro. It was found that the 6′R-configuration was essential for the...

3-[6-(2-Dimethylamino-1-imidazol-1-yl-butyl)-naphthalen-2-yloxy]-2,2-dimethyl-propionic acid and analogs were designed and synthesized as highly potent and selective CYP26 inhibitors, serving as retinoic acid metabolic blocking agents (RAMBAs), with demonstrated in vivo efficacy to increase the ...