Process for the preparation of tetrapeptide ligands of type B CCK receptors, and of pharmaceutical compositions that contain them

摘要

The present invention relates to the process for preparation of a compound of formula: A-B-C-D in which A is a functionalized acetyl or R9-C(O)-, in which R9 is a heterotricyclic or a carbotricyclic; B is a functionalized 2-aminopropionyl residue; or A-B taken together are functionalized piperazinadionyl or functionalized 5-amino-3-aza-4-keto-hexanoyl; C is in which R20 is hydrogen or lower alkyl and R21 is carboxy or tetrazolyl; or B-C taken together are a bridged Ala-Asp residue or a bridged Ala-(tetrazolyl)Ala residue; and D is a functionalized ethylamine, functionalized tetra-hydro- isoquinolyl, functionalized piperazinon-1-yl, dehydro-Phe- amide or a dehydro-Phe analogue; or C-D taken together are functionalized succinimidyl, or of a pharmaceutically acceptable salt thereof, characterized by comprising: a) the step-by-step coupling of the adequately protected amino acids or of amino acid analogues represented by A, A-B, B, C, C-D or D, as here defined, followed by removal of the protecting groups; or b) coupling of the adequately protected fragments of dipeptide or greater length, comprising said fragments, the amino acids or amino acid analogues, represented by the formulae A, A-B, B, C, C-D and D, as here defined, followed by removal of the protecting groups. The invention also relates to the process for preparation of pharmaceutical compositions containing those compounds, which are useful in the treatment of disorders of the central nervous system, in substance abuse, in gastrointestinal disorders, endocrine disorders and nutritional disorders, and in the treatment of shock and of respiratory and cardiovascular insufficiencies.