Kappa receptor opioid peptides

Details Kappa receptor opioid peptides Kappa receptor opioid peptides

C - Chemistry, Metallurgy

07

K

C07K 5/107 (2006.01) A61K 38/07 (2006.01) C07K 5/10 (2006.01) C07K 5/117 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2315878

Peptides which exhibit high selectivity for the kappa opioid receptor (KOR) and long duration of peripheral action without significant entry into the brain are created which are sequences of four D-isomer amino acid residues having a C-terminus which is a mono- or di-substituted amide. Representative compounds, which have an affinity for the KOR at least 1,000 times their affinity for the mu opioid receptor and an ED50 of not greater than about 0.5 mg/kg, include H-D-Phe-D-Phe-D-Nle-D-Arg-NHEt, H-D-Phe-D-Phe-D-Nle-D-Arg-morpholinyl, H-D-Phe- D-Phe-D-Nle-D-Arg-NH-4-picolyl, H-D-Phe-D-Pho-D-Nle-D-Arg-NHPr, H-D-Phe-D-Phe-D-Nle-D-Arg-thiomorpholinyl, H-D-Phe-D-Phe-D-Nle-D-Arg-NEt2, H-D-Phe-D-Phe-D-Nle-D-Arg-NHMe, H-D-Phe-D-Phe- D-Leu-D-Orn-morpholinyl, H-D-4Fpa-D-Phe-D-Nle-D-Arg-NH-4-picolyl, H-D-Phe-D-Phe-D-Nle-D-Arg-NH- cyclopropyl, H-D-Ala-(2Thi)-.D-3, 4Cpa-D-Leu-D-Arg-morpholinyl, H-D-Phe-D-Phe-D-Nle-D-Gmf-morpholinyl, H-D-Phe-D- Phe-D-Leu-D-Orn-NH(Aeb), H-D-Phe-D-Phe-D-Leu-D-Lys-morpholinyl, H-D-Phe-D-Phe-D-Nle-D-Arg-piperazinyl, and H-D-Phe-D-Phe-D-Nle-D-Arg-NH(Hoh).

L'invention porte sur la création de peptides présentant une forte sélectivité pour le récepteur opioïde kappa (KOR) et une action périphérique de longue durée sans pénétration significative dans le cerveau. Il s'agit de séquences de quatre isomères D de résidus d'acides aminés présentant une extrémité C consistant en un amide mono ou di-substitué. Lesdits composés représentatifs dont l'affinité pour le KOR est au moins mille fois supérieure à leur affinité pour le récepteur mu de l'opioïde, et qui présentent une ED¿50? ne dépassant pas environ 0,5 mg/kg comprennent: le H-D-Phe-D-Phe-D-Nle-D-Arg- NHEt, le H-D-Phe-D-Phe-D-Nle-D-Arg-morpholinyle, le H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-picolyle, le H-D-Phe-D-Phe-D-Nle-D-Arg-NHPr, le H-D-Phe-D-Phe-D-Nle-D-Arg-thiomorpholinyle, le H-D-Phe-D-Phe-D-Nle-D-Arg-NEt¿2?, le H-D-Phe-D-Phe-D-Nle-D-Arg-NHMe, le H-D-Phe-D-Phe-D-Leu-D-Orn-morpholinyle, le H-D-4Fpa-D-Phe-D-Nle-D-Arg-NH-4-picolyle, le H-D-Phe-D-Phe-D-Nle-D-Arg-NH-cyclopropyle, le H-D-Ala(2Thi)-D-3,4Cpa-D-Leu-D-Arg-morpholinyle, le H-D-Phe-D-Phe-D-Nle-D-Gmf-morpholinyle, le H-D-Phe-D-Phe-D-Leu-D-Orn-NH (Aeb), le H-D-Phe-D-Phe-D-Nle-D-LYS- morpholinyle, le H-D-Phe-D-Phe-D-Nle-D-Arg-pipérazinyle, et le H-D-Phe-D-Phe-D-Nle-D-Arg-NH(Hoh).

Affiliated with

Also associated with

Rating

Kappa receptor opioid peptides does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Kappa receptor opioid peptides, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Kappa receptor opioid peptides will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFCA-PAI-O-2007941