Synthesis and SAR of new 5-phenyl-3-ureido-1,5-benzodiazepines as cholecystokinin-B receptor antagonists.

A series of 5-phenyl-3-ureidobenzodiazepine-2,4-diones was synthesized and evaluated as cholecystokinin-B (CCK-B) receptor antagonists. Structure-activity relationship (SAR) studies revealed the importance of the N-1 substituent for potent and selective CCK-B affinity. Addition of substituents at the urea side chain provided in some cases more potent compounds. Moreover the introduction of bulky substituents such as adamantylmethyl at N-1 and resolution of the racemic ureas resulted in our lead compound GV150013.

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 of 5-membered ring-type compounds as potential cholecystokinin receptor ligands.

Imidazolidine-2,4-diones and 1,5-diphenyl tetramic acid derivatives were selected in order to evaluate some 5-membered heterocyclic ring compounds as potential templates for the synthesis of CCK receptor ligands. All the compounds were evaluated in vitro towards both CCK-B and CCK-A receptors.

Synthesis and receptor binding affinity of cholecystokinin receptor ligands: 2-and 1-indolyl derivatives of PD134308.

The synthesis of two "dipeptoids" structurally related to the CCK-B antagonist CI-988 (PD134308) is described. The 2- and 1-indolyl derivatives 4a, b were prepared in order to define the role of the tryptophan moiety in this series of "dipeptoids". They were evaluated as competitors in the binding of [3H]-CCK8S on guinea pig brain CCK-B receptors.

[Agricultural work: noise exposure and cardiovascular effects]. / Lavoro agricolo: esposizione a rumore ed effetti cardiovascolari.

Aim of the study was to assess cardiovascular effects in the farmers exposed to noise. We assessed two samples of 143 farmers using tactor (mean age 51.0 +/- 10.5 years, length of service 33.0 +/- 10.5 years) and 193 farmers not exposed to noise (controls) (mean age 48.3 +/- 13.7 years, length of service 30.6 +/- 14.7 years). After the phonometric measurements all farmers were undergone to a medical examination, measurements of blood pressure, a audiometric test and a electrocardiogram. The collected data show an increased prevalence of hypertension and electrocardiographic anomalies in farmers exposed to noise (systolic hypertension n. 53, 37.1%; diastolic hypertension n. 60, 42.0%; electrocardiographic anomalies n. 44; 30.8%) compared to the control group (systolic hypertension n. 23, 16.1%; diastolic hypertension n. 26, 18.2%; electrocardiographic anomalies n. 5; 3.5%) (systolic hypertension p = 0.002; diastolic hypertension p = 0.003; electrocardiographic anomalies p = 0.030). Our results could be taken to mean that there are effects of chronic exposure to noise on cardiovascular apparatus; this would stimulate the screening programmes for farmers.

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).

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.