Long-acting k-opioid receptor agonist

A long acting K-opioid receptor agonist having a structure of structural formula I:

• AA1 in structural formula I is D-Tyr(Me), or D-Tyr(Et), or D-Tyr(Ipr), or D-Phe(2-F), or D-Phe(4-F), or D-Phe(2-Cl), or D-Phe(4-Cl), or D-Phe(2-Br), or D-Phe(4-Br), or D-Phe(2-I), or D-Phe(4-I), or D-Phe(4-Me), or D-Phe(4-Et), or D-Phe(4-Ipr), or D-Phe(4-NH2), or D-Phe(4-NHCH3), or D-Phe(4-NHCH2CH3), or D-Phe(4-NHCH(CH3)2), or D-Phe(4-N(CH3)2), or D-Phe(4-N(CH3)CH2CH3);
• AA2 in structural formula I is D-Leu, or D-cyclopropylalanine;
• AA3 in structural formula I is (PEGm1(CH2)m2CO)m3—, or (AA6)m1, or is absent, wherein:
• m1 is an integer ranging from 1 to 10;
• m2 is an integer ranging from 1 to 5;
• m3 is an integer ranging from 1 to 5;
• and
• AA6 is Gly, or D-Ala, or L-Ala, or D-Leu, or L-Leu, or D-Phe, or L-Phe, or D-Ser, or L-Ser, or D-Thr, or L-Thr, or D-Tyr, or L-Tyr, or D-Asp, or L-Asp, or D-Glu, or L-Glu, or D-Gln, or L-Gln, or D-Lys, or L-Lys, or D-Arg, or L-Arg, or D-His, or L-His;
• AA4 in structural formula I is (AA7)n, or is absent, wherein:
• n is an integer ranging from 1 to 10;
• and
• AA7 is D-Lys, or L-Lys, or D-Dap, or L-Dap, or D-Dab, or L-Dab, or D-Orn, or L-Orn, or D-Dah, or L-Dah, or D-Dao, or L-Dao;
• AA5 in structural formula I is OH, or NH2;
• and
• R in structural formula I is HO2C(CH2)n1CO-(AA8)n2-(PEGn3(CH2)n4CO)n5—, or HO2C(CH2)n1CO-(AA8)n2-(AA9)n6-, wherein:
• n1 is an integer ranging from 10 to 20;
• n2 is an integer ranging from 1 to 5;
• n3 is an integer ranging from 1 to 30;
• n4 is an integer ranging from 1 to 5;
• n5 is an integer ranging from 1 to 5;
• n6 is an integer ranging from 1 to 10;
• AA8 is γGlu, or εLys, or β-Ala, or γ-aminobutyric acid, or 5-Ava;
• and
• AA9 is Ala, or Gly, or Leu, or Phe, or Ser, or Thr, or Tyr, or Asp, or Glu, or Gln, or Lys, or D-Lys, or Arg, or His.