Derivatives of aminosulfonic acids, utilization of the same in t

Details Derivatives of aminosulfonic acids, utilization of the same in t Derivatives of aminosulfonic acids, utilization of the same in t

1996-10-30

1999-02-09

Ambrose, Michael G.

Organic compounds -- part of the class 532-570 series

Organic compounds

Silicon containing

558 48, 558 49, 558 50, 560148, 562104, 562105, 562106, 564 82, 564 86, 564 95, C07F 718, C07C31147, C07C31134, C07C30983

Patent

active

058697250

DESCRIPTION:

BRIEF SUMMARY
BACKGROUND OF THE INVENTION

This invention relates to derivatives of aminosulfonic acids and the utilization of the same in the synthesis of pseudopeptides characterized by the presence of at least a sulfonamide type bond, and having a potential pharmacological activity. This invention relates also to a process for the synthesis of said derivatives of aminosulfonic acids as well as their utilization in the synthesis of said pseudopeptides.


STATE OF THE ART

As is known, peptides have been studied for a long time, as they are the transition term in the study of more complex substances such as proteins; besides, peptides as such are already extremely important compounds, being the mediators of biological systems and having proved to be of great importance in the physiological and medical sectors.
Thanks to their characteristics, peptides develop in the nature a basic biological role, and are in many cases drugs to be used in several pathological conditions. In this relation, many studies have been carried out since the fifties to determine the structure of many biologically active peptides; the determination of the structures has allowed to set up the synthesis of the peptides under examination and therefore to study their potential therapeutic effects.
In many cases, such studies have led to satisfactory results, and in the years it was possibile to determine the structure, and consequently, to synthesize many peptides and proteins having a pharmacological activity. One of the more important results achieved in this field was the determination of the whole series of aminoacids and the synthesis of insulin; other studies concerned, for instance, glutathione, a tripeptide which is found in the majority of living cells, alpha-corticotropin, which is composed by 39 aminoacids and is a component of the adrenocorticotrophic hormone ACTH, and oxytocin, a nonapeptide, which is a hormone of the hypophysis involved in the contractions of the uterus; the latter peptide, after long studies, has been isolated, characterized and synthesized, as reported in V. du VIGNEAUD, C.RESSLER, J.M.SWAN, C. W. ROBERTS, P. G. KATSOYANNIS, S. GORDON, J.Am.Chem.Soc. 75,4879 (1953). Thanks to such studies, this substance is today a real drug which is normally used during delivery to induce contractions. Of clinical interest is also an analogous of vasopressin, constituted by eight aminoacids and synthesized by R. HUGUENIN et al., Helv.Chim.Acta 49,695 (1966) and I. VAVRA et al., Lancet 1,948 (1968), which proved to be a powerful and selective antidiuretic to be used in the treatment of diabetes insipidus.
Other peptides analogous of vasopressin have been synthesized, which have also shown an antiduretic activity and have proven useful in promoting an increase in blood pressure.
As is known, the structure of peptides is characterized by the presence of amide bonds which are also indicated by the term of peptide bonds; such bonds have the great drawback of being easily hydrolyzable by hydrolytic enzymes (proteases) which recognize them. The above hydrolytic activity by the enzymes causes the breakdown of the molecule into fragments of different lengths, generally devoided of the pharmacological activity which characterizes the starting peptide.
Hence, it is evident that the utilization of peptides as drugs involves the serious drawback that in the majority of cases the molecule provided with pharmacological activity does not reach the target where said pharmacological activity should be exercized as, as soon as it enters the circle, it is attacked by the hydrolytic enzymes, and because of the hydrolysis of some peptide bonds that has taken place, it is reduced into many fragments almost always devoided of any pharmacological activity. Besides, peptides show generally a low or non-existent oral bioavailability, with the ensuing administration problems.
To obviate the aforementioned drawbacks, many studies have been carried out suitable to identify compounds having structures and characteristics similar to those of peptides, in order to

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