Hall, Sara M.’s team published research in ACS Chemical Neuroscience in 7 | CAS: 77128-73-5

ACS Chemical Neuroscience published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Product Details of C25H23NO4.

Hall, Sara M. published the artcileDiscovery of Stable Non-opioid Dynorphin A Analogues Interacting at the Bradykinin Receptors for the Treatment of Neuropathic Pain, Product Details of C25H23NO4, the publication is ACS Chemical Neuroscience (2016), 7(12), 1746-1752, database is CAplus and MEDLINE.

Dynorphin A (Dyn A) is a unique endogenous ligand that possesses well-known neuroinhibitory effects via opioid receptors with a preference for the kappa receptor but also neuroexcitatory effects, which cause hyperalgesia. We have shown that the neuroexcitatory effects are mediated through bradykinin (BK) receptors and that intrathecal (i.th.) administration of our lead ligand 1, [des-Arg7]-Dyn A-(4-11), which shows good binding affinity (IC50 = 150 nM) at the BK receptors, blocks Dyn A-induced hyperalgesia in naïve animals and reverses thermal and tactile hypersensitivities in a dose-dependent manner in nerve-injured animals. However, 1 has a serious drawback as a potential drug candidate for the treatment of neuropathic pain because of its susceptibility to enzymic degradation In an effort to increase its stability, we modified ligand 1 using non-natural amino acids and found that analogs substituted at or near the N-terminus with a D-isomer retain binding at the receptor and provide a large increase in stability. In particular when Leu5 was modified, with either the D-isomer or N-methylation, there was a large increase in stability (t1/2 = 0.7-160 h in rat plasma) observed From these studies, we have developed a very stable Dyn A analog 16, [D-Leu5,des-Arg7]-Dyn A-(4-11), that binds to BK receptors (IC50 = 130 nM) in the same range as ligand 1 and shows good antihyperalgesic effects in both naïve rats and L5/L6 spinal nerve ligation rats.

ACS Chemical Neuroscience published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem