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IN THIS THESIS, THE SYNTHESIS AND PHARMACOLOGICAL PROPERTIES OF SEVERAL NEW LINEAR AND CYCLIC AMIDE-LINKED ANGIOTENSIN II ANALOQUES, WITH MODIFICATIONS AT POSITION 1, 4 AND 8 ARE REPORTED. THIS STUDY WAS PERFORMED IN ORDER TO   FURTHER EVALUATE THE IMPORTANCE AND THE INFLUENCE OF THE AROMATIC AMINO  ACIDS IN POSITIONS 4 AND 8 OF THE MOLECULE AND TO TEST THE RING CLUSTERING  AND THE CHARGE RELAY BIOACTIVE CONFORMATION, WHICH HAS BEEN RECENTLY  SUGGESTED. ALL THE ANALOGUES WERE TESTED ON RAT ISOLATED UTERUS (IN VITRO)  AND THE RESULTS ILLUSTRATE THEIMPORTANCE OF AN AROMATIC RING QUADRUPOLE  AT POSITION 4 AND 8, FOR RECEPTOR BINDING, AND AGONIST ACTIVITY. IN  CONTRAST, OUR FINDINGS SUGGEST THAT THE AROMATIC RING AT POSITION 8 OF ANG  II DOES NOT EXERT A DIRECT EFFECT ON THE RECEPTOR TO ELICIT THE BIOLOGICAL  RESPONSE. USE OF THE NOVEL 2-CHLORO-TRITYL RESIN AND APPLICATION OF THE  FMOC-METHODOLOGY ALLOWED AN EFFICIENT STEPWISE SYNTHESIS OF CYCLIC  AMIDE-LINKED ANG II ANALOQUES. THE ABSENCE OF BIOACTIVITY FOR THE THUS  SYNTHESIZED CYCLIC ANALOGUES, CONFIRM THE CHARGE RELAY BIOACTIVE CONFORMATION.

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ΣΧΕΣΕΙΣ ΧΗΜΙΚΗΣ ΔΟΜΗΣ ΚΑΙ ΒΙΟΛΟΓΙΚΗΣ ΔΡΑΣΗΣ ΓΡΑΜΜΙΚΩΝ ΚΑΙ ΚΥΚΛΙΚΩΝ ΑΝΑΛΟΓΩΝ ΤΗΣΑΓΓΕΙΟΤΕΝΣΙΝΗΣ ΙΙ ΜΕ ΤΡΟΠΟΠΟΙΗΣΕΙΣ ΣΤΙΣ ΘΕΣΕΙΣ 1 4 ΚΑΙ 8. ΜΙΑ ΑΞΙΟΛΟΓΙΚΗ ΔΙΑΜΟΡΦΩΤΙΚΗ ΘΕΩΡΗΣΗ