2. Academic Validation
  3. An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice

An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice

  • Bioorg Med Chem Lett. 2018 Aug 1;28(14):2446-2450. doi: 10.1016/j.bmcl.2018.06.009.
Anna Skogh 1,  Anna Lesniak 2,  Christian Sköld 1,  Maria Karlgren 3,  Fabienne Z Gaugaz 3,  Richard Svensson 3,  Shanti Diwakarla 2,  Anna Jonsson 2,  Rebecca Fransson 1,  Fred Nyberg 2,  Mathias Hallberg 2,  Anja Sandström 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, SE-751 23 Uppsala, Sweden.
  • 2 The Beijer Laboratory, Department of Pharmaceutical Bioscience, Uppsala University, BMC, Box 591, SE-751 24 Uppsala, Sweden.
  • 3 Uppsala Drug Optimization and Pharmaceutical Profiling Platform (UDOPP), Science for Life Laboratory Drug Discovery and Development Platform, Department of Pharmacy, Uppsala University, BMC, Box 580, SE-751 23 Uppsala, Sweden.
  • 4 Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, SE-751 23 Uppsala, Sweden; The Beijer Laboratory, Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, SE-751 23 Uppsala, Sweden. Electronic address: anja.sandstrom@ilk.uu.se.
PMID: 29929882 DOI: 10.1016/j.bmcl.2018.06.009
Abstract

The dipeptide amide H-Phe-Phe-NH2 (1) that previously was identified as a ligand for the substance P 1-7 (SP1-7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1-7 and the tetrapeptide endomorphin-2 that is also binding to the SP1-7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED50) of 4 was superior as compared to gabapentin and morphine that are used in clinic.

Keywords

Neuropathic pain; Peptidomimetics; Phenylalanine bioisostere; SNI mice; Substance P 1–7.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z