TH98389A - New analogue of intestinal peptides that act on blood vessels. - Google Patents

Abstract

DC60 (25/09/50) VPAC-2 receptor agonist, formula [X-(SEQ ID NO : 2)-Y], for the treatment of pulmonary dysfunction disorders, such as COPD, administered as a medication, for example, by inhalation. VPAC-2 receptor agonist, formula [X-(SEQ) ID NO : 2)-Y], for the treatment of pulmonary dysfunction disorders, such as COPD, administered as a medication, for example, by inhalation.

Claims (7)

1. An analog of the intestinal peptide acting on the annular vascular system is given by the formula I X-His-R2-Asp-Ala-R5-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-R16-Nle-R18- Ala-Lys-Lys21-Tyr-Leu-Asn-Asp25-Leu-R27-R28-Gly-Gly-Thr-Y [X-(SEQ ID NO: 2)-Y], where X is the amino hydrogen of the N-terminus of histidine, which may be selectively replaced by a hydrolyzable amino shielding group, most notably the acetyl group; and Y is the carboxyhydroxy of the C-terminus of threonine, which may be selectively replaced by a hydrolyzable carboxy shielding group. The most special proposal is to use the NH2 unit, with the underlined unit indicating a covalent bond connection between the side chain of the first amino acid (Lys21) and the last amino acid (Asp25) within that segment. R2 is Ser or Ala; R5 is Thr, Ser, Asp, Gln, Pro, or CocMe Val; R16 is Gln, Ala, or Arg; R18 is Ala, Lys, or Glu; R21 is Lys or Leu, except R27 must be Lys when R5 is CocMe Val and R16 is Arg; R28 is Lys or Asn, or the pharmaceutically applicable salt of this substance. 2. An analog of the intestinal peptide acting on the annular vascular network of claim 1, where R5 is Ser or CocMe Val. 3. The compound of claim 2, where R27 is Lys. 4. Selected compounds from the group containing His-Ser-Asp-Ala-Thr-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala-Lys-Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 3), His-Ser-Asp-Ala-Ser-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala-Lys-Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 4). His-Ser-Asp-Ala-MeVal-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala- Lys-Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 8), His-Ser-Asp-Ala-Ser-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala-Lys- Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 11), His-Ser-Asp-Ala-Ser-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala-Lys- Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 19), His-Ser-Asp-Ala-MeVal-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala- Lys-Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 23), and His-Ser-Asp-Ala-MeVal-Phe-Thr-Glu-Asn-Tyr-Thr-Lys-Leu-Arg-Lys-Gln-Nle-Ale-Ala- Lys-Lys-Tyr-Leu-Asn-Asp-Leu-Lys-Lys-Gly-Gly-Thr (SEQ ID NO: 25), 5. An analog of the intestinal peptide acting on the annular vascular system of claim 1, which is X-(SEQ ID NO : 8)-Y. 6. A pharmaceutical composition containing an analog of the enteric peptide that acts on the annular vascular stent of Patent 1 and at least one pharmaceutically applicable carrier or excipient. 7. Use of analogs of intestinal peptides acting on the annular blood vessels of claim 1 for the preparation of medications for the treatment of pulmonary dysfunction disorders.