EP0454302A2
Expired / Lapsed
EP
⏱️ 0.0 years remaining
Tuftsin derivatives
Assignee: MSD KK
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Filing: 1991-03-22
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Granted: —
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Expires: 2011-03-22
Abstract
Abstract Linear or circular tetra peptides which activate immunocompetent cells, i.e., macrophages and polymorphonuclear leukocyte, provide a host-mediated inhibition of the growth of tumors, provide protective effects for infectious diseases such as viral, bacterial and fungal diseases, and exhibit therapeutic effects on autoimmune diseases such as lupus erythematosus, rheumatoid and the like, and therefore, are useful for production of pharmaceutical preparations for the treatment of these diseases.
Inventors
- 👤 Hiroyuki C/O Banya Pharmaceutical Co. Ltd. Suda
- 👤 Junko Harada
- 👤 Seiichi C/O Banyu Pharmaceutical Co. Ltd Tanaka
- 👤 Yutaka C/O Banyu Pharmaceutical Co. Ltd. Koike
- 👤 Akira C/O Banyu Pharmaceutical Co. Ltd. Okura
- 👤 Hiroharu C/O Banyu Pharmaceutical Co.Ltd Arakawa
- 👤 Takayoshi C/O Banyu Pharmaceutical Co.Ltd Okabe
- 👤 Masanori C/O Banyu Pharmaceutical Co.Ltd Okanishi
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-30 15:15
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/02; C07K5/0215; C07K5/0202; A; A61; A61K; A61K38/00
Claims Analysis
Total Claims: 7
Claim 1
Independent Claim
234 words
A peptide derivative represented by the formula (I): wherein V represents a hydroxyl group; W represents a hydrogen atom, lower alkyl, cycloalkyl having three to seven carbon atoms, phenyl, amino, mono- or di-lower alkylamino, amidino, or guanidino group; or W and V together form a group of the formula: X represents a hydrogen atom, or hydroxy or mercapto group; R¹ represents a hydrogen atom, or a phenyl, p-hydroxyphenyl or lower alkyl group, which lower alkyl group is optionally substituted with one to three of the same or different substituents selected from the group consisting of amino, hydroxy, lower alkoxy, mercapto, lower alkylthio, lower alkylfulfinyl, lower alkylsulfonyl, carboxyl, aryl, heteroaryl, cycloalkyl having three to seven carbon atoms and of bicycloalkyl having eight to ten carbon atoms, wherein the aryl, heteroaryl, cycloalkyl or bicycloalkyl group is optionally substituted with hydroxy, lower alkyloxy, lower alkyl, nitro, amino, mono- or di-loweralkylamino, mercapto, lower alkylthio, lower alkylfulfinyl or with lower alkylsulfonyl; R² and R³ are the same and represent a hydrogen atom or a lower alkyl group; or one of R² and R³ represents a hydrogen atom, and the other represents a hydroxy, lower alkoxy or lower alkyl group; or both R² and R³ together form a single bond; A represents an amino, mono- or di- lower alkylamino, amidino, or guanidino group; and m and n independently represent an integer of 0 to 4; and pharmaceutically acceptable salts thereof
Claim 2
Dependent Claim
218 words
A peptide derivative represented by the formula (II): wherein X represents a hydrogen atom, or hydroxy or mercapto group; W¹ represents a hydrogen atom, lower alkyl, cycloalkyl having three to seven carbon atoms, phenyl, amino, mono- or di-lower alkylamino, amidino, or guanidino group; R¹ represents a hydrogen atom, or a phenyl, p-hydroxyphenyl or lower alkyl group, which lower alkyl group is optionally substituted with one to three of the same or different substituents selected from the group consisting of amino, hydroxy, lower alkoxy, mercapto, lower alkylthio, lower alkylfulfinyl, lower alkylsulfonyl, carboxyl, aryl, heteroaryl, cycloalkyl having three to seven carbon atoms and of bicycloalkyl having eight to ten carbon atoms, wherein the aryl, heteroaryl, cycloalkyl or bicycloalkyl group is optionally substituted with hydroxy, lower alkyloxy, lower alkyl, nitro, amino, mono- or di-loweralkylamino, mercapto, lower alkylthio, lower alkylfulfinyl or with lower alkylsulfonyl; R² and R³ are the same and represent a hydrogen atom or a lower alkyl group; or one of R² and R³ represents a hydrogen atom, and the other represents a hydroxy, lower alkoxy or lower alkyl group; or both R² and R³ together form a single bond; A represents an amino, mono- or di- lower alkylamino, amidino, or guanidino group; and m and n independently represent an integer of 0 to 4; and pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim
193 words
A peptide derivative represented by the formula (III): wherein X represents a hydrogen atom, or hydroxy or mercapto group; R¹ represents a hydrogen atom, or a phenyl, p-hydroxyphenyl or lower alkyl group, which lower alkyl group is optionally substituted with one to three of the same or different substituents selected from the group consisting of amino, hydroxy, lower alkoxy, mercapto, lower alkylthio, lower alkylfulfinyl, lower alkylsulfonyl, carboxyl, aryl, heteroaryl, cycloalkyl having three to seven carbon atoms and of bicycloalkyl having eight to ten carbon atoms, wherein the aryl, heteroaryl, cycloalkyl or bicycloalkyl group is optionally substituted with hydroxy, lower alkyloxy, lower alkyl, nitro, amino, mono- or di-loweralkylamino, mercapto, lower alkylthio, lower alkylfulfinyl or with lower alkylsulfonyl; R² and R³ are the same and represent a hydrogen atom or a lower alkyl group; or one of R² and R³ represents a hydrogen atom, and the other represents a hydroxy, lower alkoxy or lower alkyl group; or both R² and R³ together form a single bond; A represents an amino, mono- or di-lower alkylamino, amidino, or guanidino group; and m and n independently represent an integer of 0 to 4; and pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim
52 words
A peptide derivative selected from the group consisting of: AHPA-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); AHCA-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); 3-amino-2-hydroxy-4-(4-hydroxy-phenyl)butanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); 3-amino-2-hydroxybutanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); AHPA-cyclo(-N δ -(S)-ornithyl-(S)-prolyl(S)-arginyl-); 3-amino-2-hydroxy-4-(4-methoxyphenyl)butanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); 3-amino-2,4-dihydroxypentanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); N α -AHCA-(S)-lysyl-(S)-proyl-(S)-arginine; N α -(3-amino-2-hydroxy-4-(4-methoxyphenyl)butanoyl)-(S)-lysyl-(S)-prolyl-(S)-arginine; N α -(3-amino-2-hydroxybutanoyl)-(S)-lysyl-(S)-prolyl-(S)-arginine; N α -AHCA-(S)-leucyl-(S)-prolyl-(S)-arginine; and N α -AHCA-(S)-β-cyclohexylalanyl-(S)-prolyl-(S)-arginine; and a pharmaceutically acceptable salt thereof.
Claim 5
Dependent Claim
52 words
A peptide derivative selected from the group consisting of: (2S,3R)-AHPA-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); (2S,3R)-AHCA-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); (2S,3R)-3-amino-2-hydroxy-4-(4-hydroxyphenyl)butanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); (2S,3R)-3-amino-2-hydroxybutanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); (2S,3R)-AHPA-cyclo(-N δ -(S)-ornithyl-(S)-prolyl-(S)-arginyl-); (2S,3R)-3-amino-2-hydroxy-4-(4-methoxyphenyl)butanoyl-cyclo(-N ε -(S)-lysyl-(S)-prolyl-(S)-arginyl-); (2S,3R,4S)-3-amino-2,4-dihydroxypentanoyl-cyclo(-N ε -(S)-lysyl-(s)-prolyl-(s)-arginyl-); N α -((2S,3R)-AHCA)-(S)-lysyl-(S)-prolyl-(S)-arginine; N α -((2S,3R)-3-amino-2-hydroxy-4-(4-methoxyphenyl)butanoyl)-(S)-lysyl-(S)-prolyl-(S)-arginine; N α -((2S,3R)-3-amino-2-hydroxybutanoyl)-(S)-lysyl-(S)-prolyl-(S)-arginine; N α -((2S,3R)-AHCA)-(S)-leucyl-(S)-prolyl-(S)-arginine; and N α -((2S,3R)-AHCA)-(S)-β-cyclohexylalanyl-(S)-prolyl-(S)-arginine; and a pharmaceutically active salt thereof.
Claim 6
Dependent Claim
143 words
A process for the production of a compound represented by the formula (I) according to claim 1, comprising the steps of: (1) reacting a compound represented by the following formula (IV): wherein R¹ and X have the same meanings as defined in claim 1, or a corresponding compound wherein a amino group, a functional group if present in the R¹, and/or a mercapto or hydroxy group if X is a mercapto or hydroxy group, are protected, with a compound represented by the following formula (V): wherein V, W, R², R³, A, m and n have the same meaning as defined in claim 1, or with a corresponding compound-B-(V) wherein one or more functional groups in the formula (V) are protected, in the presence of a condensation agent, and if necessary in the presence of a base; and optionally, (2) eliminating the protective groups.
Claim 7
Dependent Claim
16 words
A pharmaceutical preparation comprising a peptide derivative according to claim 1 and a pharmaceutically acceptable carrier.
References Cited (Backward Citations)
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