Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Chemical aftertreatment – e.g. – acylation – methylation – etc.
Patent
1991-05-15
1993-10-12
Russel, Jeffrey E.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Chemical aftertreatment, e.g., acylation, methylation, etc.
530409, 530410, 560 53, 560116, 560118, 560155, 560169, 560170, A61K 3702, C07F 9117, C07K 1702, C12N 900
Patent
active
052527077
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
The present invention relates to a novel inositol derivative, particularly an inositol-1,4,5-triphosphoric acid (hereinafter referred to as "IP.sub.3 ") derivative, an inositol-1,3,4-triphosphoric acid (hereinafter referred to as "1,3,4-IP.sub.3 ") derivative, an inositol-1,3,4,5-tetraphosphoric acid (hereinafter referred to as "IP.sub.4 ") derivative, their pharmaceutically acceptable salts, and a novel therapeutic medicine for various diseases of animals containing any of the above-mentioned compounds as an effective component, the aforesaid therapeutic medicine being capable of controlling the metabolic process of an organism concerned with calcium ions or controlling proteins to be bonded to or for recognizing IP.sub.3, 1,3,4-IP.sub.3, IP.sub.4 or the like so as to thereby exert a medicinal virtue. Furthermore, the present invention relates to a method for preparing the above-mentioned novel inositol derivatives, particularly the P.sub.3 derivative, the 1,3,4-IP.sub.3 derivative, the IP.sub.4 derivative or their pharmaceutically acceptable salts, a solid phase carrier which is bonded to the above-mentioned inositol derivative, particularly the IP.sub.3 derivative, the 1,3,4-IP.sub.3 derivative or the IP.sub.4 derivative having affinity for proteins to be bonded to or for recognizing IP.sub.3, 1,3,4-IP.sub.3, IP.sub.4 or the like, and a process for preparing the solid phase carrier.
SUMMARY OF THE INVENTION
Disclosed are novel inositol derivatives represented by the formula (I) ##STR1## where A is (CH.sub.2).sub.n CH(R')NH.sub.2, ##STR2## R' is a hydrogen atom, a lower alkyl group having 1 to 5 carbon atoms, a lower hydroxyalkyl group, a lower aminoalkyl group, a phenyl group, a p-hydroxyphenyl group, a benzyl group, a p-hydroxybenzyl group, a 3-methylindole group, or a 5-methylimidazole group; n is from 0 to 5; each of R.sup.1 to R.sup.5 is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a phenyl group, a phenyl group mono- or tetra-substituted by an alkyl group having 1 to 4 carbon atoms or a halogen atom, a cyclohexyl group or a cyclohexyl group mono- or tetra-substituted by an alkyl group having 1 to 4 carbon atoms or a halogen atom; B is a hydrogen atom, NH.sub.2 or NHCOCF.sub.3 ; and P is a phosphoric acid group which is free or protected by a protective group or a pharmaceutically acceptable salt of the inositol derivative. These inositol derivatives may be bonded to a solid phase carrier or conjugated to a protein or polypeptide.
Also described are procedures for preparing salts represented by formula (I) of claim 9 which comprises the steps of previously protecting the hydroxyl group at the 1 position of an inositol-4,5-diphosphoric acid derivative with a silanizing agent, reacting said derivative with a carboxylic acid, preferably on having an amino group or a nitro group, removing the silyl group, phosphorylating the 1 position to produce an inositol-1,4,5-triphosphoric acid derivative in which the 2 position is substituted by a carboxylic ester, reacting this derivative with a reducing agent to produce a salt of an inositol-1,4,5-triphosphoric acid in which the 2 position is substituted by a carboxylic acid substituted by an amino group, and then reducing by reaction of a nitrite and an azido compound, reaction of a nitrite, p-aminoethyl-phenol and an acid, reaction with an aldehyde, reaction with a ketone, reaction with an isocyanate, reaction with chlorocarbonic ester or reaction with a carboxylic acid.
A preferred aspect of the invention includes novel inositol derivatives represented by formula (II) or (III) ##STR3## where A is (CH.sub.2).sub.n CH(R')NH.sub.2 ##STR4## R' is a hydrogen atom, a lower alkyl group having 1 to 5 carbon atoms, a lower hydroxyalkyl group, a lower aminoalkyl group, a phenyl group, a p-hydroxyphenyl group, a benzyl group, a p-hydroxybenzyl group, a 3-methylindole group, or a 5-methylimidazole group; n is from 0 to 5; each of R.sup.1 to R.sup.5 is a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl
REFERENCES:
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Awaya Akira
Hirata Masato
Ozaki Shoichiro
Watanabe Yutaka
Mitsui Toatsu Chemicals Incorporated
Russel Jeffrey E.
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