The 1,3,4-trisubstituted-l,4-benzodiazepin-2-one 2 is a non-peptide mimic of somatostatin 1. It displaces the radioligand [125I-Tyr3]-octreotide with an IC50 of 7 ~tM.Somatostatin (SRIF) is a cyclic peptide occuring in two major physiologically active forms (SRIF-14) 1 and SRIF-28 which are expressed in a tissue specific manner in several organs including small intesting, stomach, pancreas and brain. SRIF inhibits the release of many hormones such as growth hormone, insulin, gastrin, glucagon and it acts as a neurotransmitter in the brain, l Due to the rapid proteolytic degradation of somatostatin in vivo (plasma T1/2< 3min), analogues with increased metabolic stability have been obtained which are highly useful for the treatment of various endocrine and malignant disorders. 2 In an attempt to obtain non-peptide mimetics of SRIF-14 1, compounds utilizing sugars as scaffolding and carrying the side chains of 1 important for biological activity have been reported. 3'4 These compounds have IC50 values of approximately 20 ~Vl for the SRIF-receptor as measured by means of radioligand binding on rat cortex membranes. 4'5 The low affinity of these ligands might be attributed to the high number of degrees of rotational freedom and therefore to the large change in entropy needed to attain the "stacking" association between the indolyl and the aminoalkyl substituents thought to be necessary for binding. 6'7 In this paper, we report the design, synthesis, and receptor binding affinity of a new SRIF-mimetic 2 having restricted conformational freedom (Figure 1).