Bradykinin antagonist pseudopeptide derivatives of aminoalkanoic acids and related olefins
AssigneeScios, Inc.
InventorsDonald James Kyle, Babu Joseph Mavunkel
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Abstract
Pseudopeptide compounds based on a modified bradykinin sequence are potent bradykinin receptor antagonist. All or a portion of the amino acids at positions 2 through 5 of the bradykinin sequence are replaced by 2-pyrrolidinyl and/or amino-alkanoic acid or related olefinic derivatives to reduce the peptidic nature of the compounds. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.
Claims2
A pseudopeptide which has an affinity for the bradykinin B.sub.1 receptor having the formula:
- A--B--C--D--E--F--G--H--I--K
- wherein
- A is selected from the group consisting of the L- and D-isomers of Arg and Lys;
- B is selected from the group consisting of the L- and D-isomers of Arg and Lys;
- C is a direct bond or is selected from the group consisting of Pro, 4Hyp and Oic;
- D is selected from the group consisting of 2-pyrrolidinyl, Pro, 4Hyp and Oic;
- E has the following formula:
- ##STR23## wherein X is selected from the group consisting of a direct bond and an imino (--NH--) group;
- Z.sub.1 is a C.sub.2 to C.sub.18 monoolefin;
- Z.sub.2 is a direct bond;
- Y is selected from the group consisting of hydrogen, hydroxymethyl, C.sub.1 to C.sub.6 alkyl, benzyl, thiophenylmethyl and furanylmethyl;
- m, n and o are independently 0 to 6;
- F is a direct bond or is selected from the group consisting of Phe and N-benzyl-Gly;
- G is selected from the group consisting of Ser, Thr, Gly and Val;
- H is selected from the group consisting of a D-Phe, D-Tic and a D-trans-Hype in which an aryl group, if present, is selected from the group consisting of benzyl, phenyl and naphthyl;
- I is selected from the group consisting of Oic, Aoc, Tic, Phe, and a Hype in which an aryl group, if present, is selected from the group consisting of benzyl, phenyl and naphthyl;
- K is selected from the group consisting of a hydroxyl moiety, an amino moiety and an alkoxy moiety;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.