Antonella Ursini

Analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole as potential antibacterial agents

A preliminary exploration of analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole, 1, as novel antibacterial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The presence of two aryl rings, the imidazole NH and either a good electron withdrawing group or an aldehyde or amino group at C-2 were required for good levels of activity against methicillin resistant Staphylococcus aureus (MRSA).

A new method for the resolution of amines and its application to 3-amino-1,5-benzodiazepines

Abstract A new method for the resolution of racemic amines and its application to 3-amino-1,5-benzodiazepines is reported. The method is based upon the reaction of the amines with a chiral auxiliary, namely the tosyl derivative of (S)-(+)-methyl mandelate, followed by the separation of the two diastereomers formed and the subsequent hydrogenation of the separated compounds to give the free chiral amines with good enantiomeric excesses.

1,5-Benzodiazepines as CCK-B antagonists. Effect of halogen substitution at the benzo-fused ring on potency and selectivity

Abstract Some 1,5-benzodiazepines substituted with halogen atoms in the benzo-fused ring were synthesized and evaluated as CCK antagonists at both CCK-A and CCK-B receptors. Details of the binding of these agents to both receptors are reported and discussed briefly.

SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF 4-AMINO TRINEMS

Abstract This article deals with the study carried out on the synthesis of 4-amino substituted trinems 1 starting from the key-intermediate (3S, 4R)-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(1′R, 2′S, 3′R)-1′,2′-epoxycyclohex-3′-yl]azetidin-2-one 2 . In particular, epoxide opening with various amines and subsequent cyclization to the corresponding trinems were explored. Their synthesis and antimicrobial activity are reported.

A CHEMICAL METHOD FOR THE PREPARATION OF NOVEL 1,5-BENZODIAZEPINES ACTING AS CCK-B ANTAGONISTS IN HIGH ENANTIOMERIC PURITY

Abstract A series of new N-(1,5-benzodiazepin-3-yl)-N′-arylureas, 2 , bearing an alkyl substituent at the N5 position of the benzodiazepine nucleus has been studied as potential CCK-B antagonists. The homochiral compounds were obtained by resolving their precursors (amines 4 ) with a new resolution method based on the reaction between the amines and the chiral auxiliary 5 , the subsequent separation of the diastereomers ( 6 and 7 ) and the eventual removal of the auxiliary moiety by hydrogenation. The resolved amines and the corresponding final ureas showed good enantiomeric excesses.

Synthesis and evaluation of novel 1,5-Benzodiazepines as potent and selective CCK-B ligands. Effect of the substitution of the N-5 phenyl with alkyl groups

Abstract The synthesis and biological evaluation of both 3-ureido and 3-carbamate derivatives of 1,5-benzodiazepines bearing bulky alkyl substituents at N-1 and N-5 positions is reported. Their activity as CCK-B receptor antagonists is discussed and compared with the related N-5-phenyl derivatives.

Synthesis and structure-activity relationship of new 1,5-dialkyl-1,5-benzodiazepines as cholecystokinin-2 receptor antagonists.

This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 was replaced with more hydrophilic substituents, like alkyl groups bearing basic functions. In some cases, the resolution of the racemic key intermediates 3-amino-benzodiazepines was also accomplished. Among the compounds synthesized and characterised so far in this class, the 5-morpholinoethyl derivative 54, was selected as potential follow up of GV150013 and submitted for further evaluation.

Diastereomeric separation of 1,5-benzodiazepines due to the presence of a chiral centre on the N-5 alkylic chain

The presence of a chain bearing a stereogenic centre at the N-5 position of 1-(1-adamantylmethyl)-3-arylureido-2,4-dioxo-1,5-benzodiazep ines induces optical resolution. The synthesis of these compounds and their potency as potential CCK-B receptor antagonists is discussed briefly here.

Synthesis and Evaluation of 1,5‐Benzodiazepines with Bridged Cycloalkyl Substituents at the N‐1 Position as Potent and Selective CCK‐B Ligands

The synthesis and biological evaluation of 3‐ureido and 3‐carbamate derivatives of 1,5‐benzodiazepines bearing bridged cycloalkyl substituents at N‐1 are reported. Their activity as CCK‐B receptor ligands is briefly discussed.

Synthesis of 6α-methoxy-6β-hydroxymethylpenems

Abstract The synthesis of 6α-methoxy-6β-hydroxymethyl-2-phenoxy-methylpenem and of 6α-methoxy-6β-hydroxymethyl-2-(1-methyltetrazol-5-yl)thiomethylpenem was accomplished via reaction of pivaloyl 6-diazopenicillanate with methyl orthoformate in the presence of boron trifluoride as a catalyst. The resulting pivaloyl 6α-methoxy-6β-trimethoxymethyl penicillanate was processed to the final penems via the corresponding secopenicillanate by well established procedures.