Insulin derivatives, processes for their preparation and their use, and pharmaceutical agents for the treatment of diabetes mellitus
First Claim
1. An insulin derivative of the formula I ##STR6## in which R1 denotes H or H-PheR30 represents the radical of Ala, Thr or Ser andR31 represents a physiologically acceptable organic group of basic character of the formula Xn -S which has up to 50 carbon atoms, in whichn is 0, 1, 2 or 3,X represents identical or different radicals of naturally occurring neutral or basic α
- -amino acids andS denotes OH or a physiologically acceptable group which blocks the carboxyl group but S being, if n is 0, a positively charged or protonatable basic radical or, if n is greater than 0, S can carry such a radical, or in which, if n is 2 or 3, the C-terminus X-S can also represent the homoserine lactone radical, and which contains or does not contain a terminal carboxyl group or an ester or an amide thereof, and wherein, if R1 represents H-Phe, the C-terminus --R30 --R31 cannot denote --Thr(Arg)m --OH, --Ala(Arg)m --OH or --Ser--(Arg)m --OH, where m is 1 or 2, which has an isoelectric point between 5.8 and 8.5, or a physiologically acceptable salt thereof.
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Accused Products
Abstract
The invention relates to insulin derivatives of the formula I ##STR1## in which R1 denotes H or H--Phe, R30 represents the radical of a neutral L-aminoacid and R31 represents a physiologically acceptable organic group of basic character with up to 50 carbon atoms, these derivatives having an isoelectric point between 5.8 and 8.5, processes for their preparation and their use, and agents containing these derivatives for the treatment of diabetes mellitus.
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Citations
21 Claims
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1. An insulin derivative of the formula I ##STR6## in which R1 denotes H or H-Phe
R30 represents the radical of Ala, Thr or Ser and R31 represents a physiologically acceptable organic group of basic character of the formula Xn -S which has up to 50 carbon atoms, in which n is 0, 1, 2 or 3, X represents identical or different radicals of naturally occurring neutral or basic α - -amino acids and
S denotes OH or a physiologically acceptable group which blocks the carboxyl group but S being, if n is 0, a positively charged or protonatable basic radical or, if n is greater than 0, S can carry such a radical, or in which, if n is 2 or 3, the C-terminus X-S can also represent the homoserine lactone radical, and which contains or does not contain a terminal carboxyl group or an ester or an amide thereof, and wherein, if R1 represents H-Phe, the C-terminus --R30 --R31 cannot denote --Thr(Arg)m --OH, --Ala(Arg)m --OH or --Ser--(Arg)m --OH, where m is 1 or 2, which has an isoelectric point between 5.8 and 8.5, or a physiologically acceptable salt thereof. - View Dependent Claims (2, 8, 9, 10, 11, 12)
- -amino acids and
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3. A pharmaceutical composition comprising an effective amount of an insulin derivative, with an isoelectric point between 5.8 and 8.5, of the formula I, ##STR7## in which R1 denotes H or H--Phe
R30 represents the radical of Ala, Thr or Ser and R31 represents a physiologically acceptable organic group of basic character of the formula Xn --S which has up to 50 carbon atoms, in which n is 0, 1, 2 or 3, X represents identical or different radicals of naturally occurring neutral or basic α - -amino acids and
S denotes OH or a physiologically acceptable group which blocks the carboxyl group but S being, if n is 0, a positively charged or protonatable basic radical or, if n is greater than 0, S can carry such a radical, or in which, if n is 2 or 3, the C-terminus X-S can also represent the homoserine lactone radical, and which contains or does not contain a terminal carboxyl group or an ester or an amide thereof, or one of its physiologically acceptable salts. - View Dependent Claims (5, 13, 14, 15, 16, 17, 18, 19, 20)
- -amino acids and
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4. A pharmaceutical composition comprising an effective amount of an insulin derivative, with an isoelectric point between 5.8 and 8.5, of the formula I. ##STR8## in which R1 denotes H or H--Phe
R30 represents the radical of Ala, Thr or Ser and R31 represents --Arg--OH or --Arg--Arg--OH or an ester or an amide thereof, or one of its physiologically acceptable salts.
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21. An insulin derivative of the formula I ##STR9## in which R1 denotes H or H-Phe,
R30 represents the radical of Ala, Thr or Ser and R31 represents a physiologically acceptable organic group of basic character of the formula Xn -S which has up to 50 carbon atoms, in which n is 0, 1, 2 or 3, X represents identical or different radicals of naturally occurring neutral or basic α - amino acids and
S denotes OH or a physiologically acceptable group which blocks the carboxyl group but S being, if n is 0, a positively charged or protonatable basic radical or, if n is greater than 0, S can carry such a radical, or in which, if n is 2 or 3, the C-terminus X-S can also represent the homoserine lactone radical, and the terminal group is a carboxyl group or an ester or an amide thereof, and wherein, if R1 represents H-Phe, the C-terminus -R30 -R31 cannot denote -Thr(Arg)m OH, -Ala(Arg)m OH or -Ser(Arg)m OH, where m is 1 or 2, or ThrR31 in which R31 is (a) an amino acid, (b) a peptide or (c) an amide or ester of (a) or (b), which has an isoelectric point between 5.8 and 8.5, or a physiologically acceptable salt thereof.
- amino acids and
Specification