Compounds and their use in treatment of tachykinin receptor mediated disorders

The NK2R agonist according to any one of the preceding claims, wherein X2 is arginine (R).

The NK2R agonist according to any one of the preceding claims, wherein X3 is tyrosine (Y).

The NK2R agonist according to any one of the preceding claims, wherein X4 is threonine (T).

The NK2R agonist according to any one of the preceding claims, wherein X5 is selected from the group consisting of:

• 2-aminoisobutyric acid (Aib) and serine (S).

The NK2R agonist according to any one of the preceding claims, wherein X6 is N-methyl-leucine (Me-Leu).

The NK2R agonist according to any one of the preceding claims, wherein X7 is methoxinine (Mox).

The NK2R agonist according to any one of the preceding claims, wherein n is 15 and wherein X is —OH.

The NK2R agonist according to any one of the preceding claims, wherein Lg of the conjugated moiety does not comprise functional groups that are positively charged at pH=7.4.

The NK2R agonist according to any one of the preceding claims, wherein Lg of the conjugated moiety has a net neutral charge or −1 at pH=7.4.

The NK2R agonist according to any one of the preceding claims, wherein the conjugated moiety is of formula (B1);

The NK2R agonist according to any one of the preceding claims, wherein the conjugated moiety (B) is covalently attached to the N-terminus of (A), optionally via an amide bond.

The NK2R agonist according to any one of the preceding claims, wherein the conjugated moiety (B) is covalently attached to the N-terminus of (A) via an amide bond with the N-terminal α-NH2 group.

The NK2R agonist according to any one of the preceding claims, wherein the peptide (A) is amidated on the C-terminus.

The NK2R agonist according to any one of the preceding claims, wherein the peptide (A) comprises from 7 to 15 amino acids, such as from 7 to 14 amino acids, such as from 7 to 13 amino acids, such as from 7 to 12 amino acids, such as from 7 to 11 amino acids, such as from 7 to 11 amino acids, such as from 7 to 10 amino acids, such as from 7 to 9 amino acids, such as from 7 to 8 amino acids, preferably wherein the peptide comprises 7 amino acids.

The NK2R agonist according to any one of the preceding claims, wherein the peptide (A) comprises no more than 15 amino acids, such as no more than 14 amino acids, such as no more than 13 amino acids, such as no more than 12 amino acids, such as no more than 11 amino acids, such as no more than 10 amino acids, such as no more than 9 amino acids, such as no more than 8 amino acids, such as no more than 7 amino acids.

The NK2R agonist according to any one of the preceding claims, wherein the peptide (A) consists of 7 amino acids of the general formula X1X2X3X4X5X6X7.

The NK2R agonist according to any one of the preceding claims, wherein

• (A) is:
• Asp;Lys;Phe;Val;Gly;NmLeu;Nle;NH2 (compound 305), and
• (B) is of formula (B1) covalently attached to the N-terminal aspartate of (A).

The NK2R agonist according to any one of the preceding claims, wherein the NK2R agonist is a selective neurokinin receptor 2 (NK2R) agonist.

The NK2R agonist according to any one of the preceding claims, wherein the NK2R agonist has an EC50 towards human NK2R of 300 nM or less, such as 250 nm or less, such as 200 nm or less, such as 150 nM or less, such as 100 nM or less, such as 90 nM or less, such as 80 nM or less, such as 70 nM or less, such as 60 nM or less, such as 50 nM or less.

The NK2R agonist according to any one of the preceding claims, wherein the NK2R agonist has an EC50 towards human NK2R of 50 nM or less, such as 40 nm or less, such as 30 nm or less, such as 20 nM or less, such as 15 nM or less, such as 14 nM or less, such as 13 nM or less, such as 12 nM or less, such as 11 nM or less, such as 10 nM or less.

The NK2R agonist according to any one of the preceding claims, wherein the NK2R agonist has an EC50 towards human NK1R of at least 100 nM, such as at least 200 nM, such as at least 300 nM, such as at least 400 nM, such as at least 500 nM.

The NK2R agonist according to any one of the preceding claims, wherein the NK2R agonist has an EC50 towards human NK3R of at least 100 nM, such as at least 200 nM, such as at least 300 nM, such as at least 400 nM, such as at least 500 nM.

A pharmaceutical composition comprising the neurokinin receptor 2 (NK2R) agonist as defined in any one of the preceding claims, and one or more pharmaceutically acceptable adjuvants, excipients, carriers, buffers and/or diluents.