Vinblastin-23-oyl amino acid derivatives for use as antitumor agents
AssigneeOmnichem
InventorsAndre B. L. Trouet, Jean A. A. J. Hannart, Kandukuri S. B. Rao
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Abstract
Amino acid derivatives of vinblastine, including peptide derivatives, methods of their preparation and pharmaceutical compositions containing such vinblastine derivatives for use as antitumor agents are described.
Claims17
A vinblastine derivative of the formula ##STR8## wherein R.sub.1 is an ester of a .alpha.-aminoacid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, glutamic acid, aspargine, glutamine, arginine, lysine, cysteine, cystine, methionine, phenylalanine, tyrosine, trypthophan, proline, histidine, hydroxy-lysine, hydroxyproline, or of a peptide consisting of 1-6 identical or different such amino-acids, and the ester group, which may be straight or branched, being a carboalkoxy group having 2-9 carbon atoms, and R.sub.2 is hydrogen or a C.sub.2 -C.sub.9 alkanoyl group, and their pharmaceutically acceptable mineral or organic acid addition salts.
A vinblastine derivative of the formula ##STR9## wherein R.sub.2 is a hydrogen atom or C.sub.2 -C.sub.9 alkanoyl group, R.sub.3 is a hydrogen atom, straight or branched C.sub.1 -C.sub.8 alkyl, hydroxy-C.sub.1 -C.sub.8 -alkyl, carboxy-C.sub.1 -C.sub.8 -alkyl, amido-C.sub.1 -C.sub.8 -alkyl, amino- C.sub.1 -C.sub.8 alkyl or hydroxyalkyl, guanadino-C.sub.1 -C.sub.8 -alkyl, thio-C.sub.1 -C.sub.8 alkyl, cysteinyl-methyl, methylthio-ethyl, benzyl, hydroxy-benzyl, or a group:
- ##STR10## or R.sub.3 together with the carbon to which it is attached and the amido nitrogen, forms an azole or an hydroxy-azole ring;
- n is an integer of from 1 to 6, and R.sub.4 is a straight or branched C.sub.1 -C.sub.8 -alkyl, or a benzyl group and their pharmaceutically acceptable mineral and organic acid addition salts.
Ethyl or methyl N-(O-4-deacetyl-vinblastin-23-oyl)-L-tryptophanate and their additions salts with pharmaceutically acceptable acids.
Ethyl or methyl N-(O-4-deacetyl-vinblastin-23-oyl)-isoleucinate and their addition salts with pharmaceutically acceptable acids.
Ethyl N-(O-4-deacetyl-vinblastin-23-oyl)-valinate and its addition salts with pharmaceutically acceptable acids.
Ethyl N-(O-4-deacetyl-vinblastin-23-oyl)-L-valyl-L-tryptophanate and its addition salts with pharmaceutically acceptable acids.
The sulfuric acid addition salt of a compound selected from the group consisting of:
- ethyl or methyl N-(O-4-deacetyl-vinblastin-23-oyl)-L-tryptophanate
- ethyl or methyl N-(O-4-deacetyl-vinblastin-23-oyl)-isoleucinate
- ethyl N-(O-4-deacetyl-vinblastin-23-oyl)-valinate
- ethyl N-(O-4-deacetyl-vinblastin-23-oyl)-L-valyl-L-tryptophanate
- wherein said addition salt is in a ratio of 1:1.
Ethyl N-(O-4-deacetyl-vinblastin-23-oyl)-L-tryptophanate sulphate.
Dependencies are inferred from the claim text.