An Epidemiological and biomolecular survey of cystic echinococcosis in cattle in Sardinia

Although Cystic Echinococcosis (CE) is still a health, economic and social problem of great importance in Sardinia today, not all aspects of it have been studied, and in particular its epidemiology in cattle. This note updates the epidemiological data on Bovine CE in Sardinia, and with the help of advances made in biomolecular taxonomy identifies the strains of Echinococcus granulosus in cattle

Pyrimidinedione derivatives as AMPA glutamatergic receptor agonists and their preparation, pharmaceutical compositions and use in the treatment of CNS diseases

The invention relates to compds. of formula I, to processes for their prepn. and uses thereof. Compds. of formula I wherein E is (CH2)1-2; A is O and S; B and D are independently C and CH; Y, Y and Z are independently S, N, O, C and CH; R1-R4 are independently H, Me, Et, absent, etc.; R5 is H, C1-8 alkyl and C5-6 cycloalkyl; R6 is substituted Me and substituted benzyl; and their salts, tautomers, geometric isomers, enantiomers, diastereomers and racemates thereof, are claimed. Example compd. II was prepd. via heterocyclization of Et 4-oxo-3-tetrahydrothiophenecarboxylate with S-Et isothiouronium bromide; the resulting 2-(ethylthio)thieno[3,4-d]pyrimidin-4(3H,5H,7H)-one underwent hydrolysis to give thiono[3,4-d]pyrimidine-2,4(1H,3H,5H,7H)-dione, which underwent N-alkylation with (S)-3-[(tert-butoxycarbonyl)amino]oxetan-2-one to give (S)-1-[2'-(tert-butoxycarbonyl)amino-2'-carboxyethyl]thieno[3,4-d]pyrimidine-2,4-(1H,3H,5H,7H)-dione, which underwent deprotection to give II. All the invention compds. were evaluated for their glutamatergic receptor binding affinity (some data given)

Process Development and Scale-Up for the Preparation of the 1‑Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461

A practical and scalable route to the Wnt inhibitor SEN461 <b>1</b> is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported

Development of a Scalable Route to the SMO Receptor Antagonist SEN794

A practical and scalable route to the SMO receptor antagonist SEN794 <b>1</b> is described herein. A new and efficient access to the key intermediate <b>7</b> via the Kröhnke reaction was developed, significantly simplifying the synthesis and reducing costs. The optimized route consists of six chemical steps plus a palladium scavenging step. The intermediates are solids and were isolated by filtrations, except for ester <b>9</b>, which was telescoped as the crude oil into the subsequent step. In the final amide formation step, target compound <b>1</b> was conveniently crystallized from the reaction mixture in high purity

Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents

We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties

An efficient approach to chiral C8/C9-Piperazino-Substituted 1,4-Benzodiazepin-2-ones as peptidomimetic scaffolds

A promising way to interfere with biological processes is through the modulation of protein-protein interactions by rneans of small molecules acting as peptidomimetics. The 1,4-benzodiazepine scaffold c has been widely reported as a peptide-mimicking, pharmacogenic system. While several synthetic pathways to C6-8 substituted benzodiazepines have been disclosed, few 1,4-benzodiazepines substituted at C9 have been reported. Herein, we describe a versatile approach to introduce cyclic, protonatable functionality at C8/C9. Introduction of the piperazine system at C8 and C9 gave access to a unique functionalization of the versatile benzodiazepine skeleton, broadening tailoring options on the benzofused side of the molecule, and the possibility of discovering novel peptidomimetics potentially able to modulate protein-protein interactions. Coupling of activated amino acids with poorly reactive anilines under mild conditions, while avoiding racemization, gave easy access to these compounds. Efficient amino acid activation was obtained by exploiting the rapid formation of acid chlorides under low temperature and acid/base free conditions, using triphenylphosphine and hexachloroacetone. This procedure successfully resulted in high reaction yields, did not produce racemization (ee > 98%, as demonstrated by using chiral solvating agents), and was compatible with the acid sensitive protecting groups present in the substrates

Synthesis and Antiplasmodial Activity of Bicyclic Dioxanes as Simplified Dihydroplakortin Analogues

Here we report the synthesis and evaluation of antiplasmodial activity of a novel series of bicyclic peroxides inspired by the marine natural compound dihydroplakortin. We developed a synthetic strategy leading to the dihydroplakortin-related peroxides in only a few steps. The in vitro antiplasmodial potency of the peroxides was similar to, or greater than, that of the reference natural compound, and structure-activity relationship studies revealed several key structural requirements for activity and potency