Cyclopropyl-fused pyrrolidine derivatives as dipeptidyl peptidase iv inhibitors

A compound of formula (1):

• wherein
• R1 and R2 are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, heterocyclyl, carbocyclyl, aryl, -alkylaryl, heteroaryl -alkylheteroaryl and an amino acid or a peptide residue;
• R3 represents hydrogen;
• Z is a group of formula I or II:
• wherein X1 and X2 independently represent OR4;
• R4 is selected from the group consisting of hydrogen;
• alkyl, alkenyl, alkynyl, cycloalkyl any of which aforementioned four groups may optionally be substituted by hydroxy;
• heterocyclyl, carbocyclyl, aryl, -alkylaryl, heteroaryl and -alkylheteroaryl;
• Y1 and Y2 are independently selected from hydroxy, alkoxy, cycloalkyloxy, aryloxy and heteroaryloxy;
• or Y1 and Y2 are connected to form one of the following cyclic boronic diester groups:
• wherein
• R9-R18 are independently hydrogen, alkyl, cycloalkyl or aryl;
• and
• each R19 group is independently selected from hydrogen, alkyl, aryl, halo, alkoxy, aryloxy, thioalkyl and thioaryl;
• in addition when Z represents a group of formula (I):
• then R3 may also represent alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, heterocyclyl, carbocyclyl, aryl, -alkylaryl, -alkylheteroaryl, an amino acid or a peptide residue;
• and when Z represents a group of formula (I) R1 and R3 may also optionally be connected to form a ring of the structure
• wherein m is an integer in the range of 2 to 6;
• R2 is as defined above;
• and R1 and R6 are independently selected from hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, cycloalkyl, halo, amino, substituted amino, carbocyclyl, aryl, arylalkyl-, heteroaryl, heteroarylalkyl-, heterocyclyl, alkylcarbonylamino-, arylcarbonylamino-, alkoxycarbonylamino-, aryloxycarbonylamino-, alkoxycarbonyl-, aryloxycarbonyl-, and alkylaminocarbonylamino-;
• including all stereoisomers thereof;
• and pharmaceutically acceptable salts and solvates thereof;
• and prodrugs thereof.