Kisspeptide-pentasaccharide conjugates

摘要

The invention relates to kisspeptide-pentasaccharide conjugates having the general formula (I) wherein Z1 is Tyr or D-Tyr; Z3 is Trp, Hyp, Phe or Lys(R2); Z5 is Thr, Aib or Ala; Z7 is Gly or azaGly; Z8 is Leu; or Z7 and Z8 together represent; Z10 is Phe or Trp; n is 0 or 1; or R2, when present, represents a pentasaccharide derivative having the formula (II) wherein R is methyl or SO3X; X is a positively charged counterion; with the proviso that when R2 is present, R1 is H or (C1-6) alkylcarbonyl; R3 is H or (C1-3)alkyl; and L represents a pharmacologically inactive linker moiety having 10-50 atoms; or a pharmaceutically acceptable salt thereof; to pharmaceutical compositions comprising the same as well as to the use of said kisspeptide-pentasaccharide conjugates in the treatment of female infertility.;

主权项

1. A kisspeptide-pentasaccharide conjugate having the formula (I)
R1—Z1-(Asn)n-Z3-Asn-Z5-Phe-Z7—Z8-Arg(R3)—Z10—NH2  Formula (I) wherein Z1 is Tyr or D-Tyr; Z3 is Trp, Hyp, Phe or Lys(R2); Z5 is Thr, Aib or Ala; Z7 is Gly or azaGly; Z8 is Leu; or Z7 and Z8 together represent Z10 is Phe or Trp; n is 0 or 1; R1 or R2 represents a pentasaccharide derivative having the formula (II) wherein R is methyl or SO3X; X is a positively charged counterion; with the proviso that when R2 is present, R1 is H or (C1-6) alkylcarbonyl; R3 is H or (C1-3)alkyl; and L represents a pharmacologically inactive linker moiety having 10-50 atoms; or a pharmaceutically acceptable salt thereof; wherein said compound or pharmaceutically acceptable salt is further characterized by least one of the following: (a) Z5 is Thr; (b) R3 is methyl; (c) n is 0; Z1 is D-Tyr; Z3 is Hyp and Z10 is Trp; or (d) R is methyl.