Derivatives of somatostatin and process therefor

Abstract

Abstract in which R2 is as defined herein with the proviso that when R2 of the second heptapeptide derivative is hydrogen then R3 of the first heptapeptide derivative is hydrogen or Boc-NH and when R2 of the second heptapeptide derivative is carboxyl then R3 of the first heptapeptide derivative is hydrogen. Said first and second heptapeptide derivatives are obtained from smaller peptides by a series of condensations involving the reaction of an appropriately protected peptide unit having an activated carboxylic ester with an appropriately protected peptide having a free amino group. Subsequently the first and second heptapeptide derivatives are condensed according to the azide method to obtain the linear tetradecapeptide derivative of formula in which R2 and R3 are as defined herein; thereafter the linear tetradecapeptide derivative is transformed into the desired tetradecapeptide derivative of formula 1 by oxidizing and deprotecting processes. The linear, reduced form of the tetradecapeptides of this invention (i.e., the compounds of formula 1a) are obtained by deprotection of the aforementioned linear tetradecapeptide derivative or by reduction of the tetradecapeptide derivatives of formula 1. The compounds of formulae 1 and 1a are useful for management of juvenile diabetes and the treatment of acromegaly and methods for their use are disclosed. Compounds of the formula 1 or 1a IN WHICH R1 is hydrogen and R2 is hydrogen or carboxyl, or R1 is amino and R2 is hydrogen are disclosed. The compounds are obtained by a process comprising the preparation of a first heptapeptide derivative of formula IN WHICH R3 is hydrogen or Box-NH- and the preparation of a second heptapeptide derivative of formula

Inventors

• 👤 Hans U Immer
• 👤 Kazimir Sestanj
• 👤 Verner R Nelson
• 👤 Manfred K Gotz

Bibliographic Details