Analgesic dipeptide derivatives. Part 8. 3-Amino-2-hydroxy-4-[2-(o-nitrophenylthio)indol-3-yl]butanoic acid [AH(Nps)IBA]-containing dipeptide analogues of the analgesic compound H-Trp(Nps)-Lys-OMe

  title={Analgesic dipeptide derivatives. Part 8. 3-Amino-2-hydroxy-4-[2-(o-nitrophenylthio)indol-3-yl]butanoic acid [AH(Nps)IBA]-containing dipeptide analogues of the analgesic compound H-Trp(Nps)-Lys-OMe},
  author={Rosario Herranz and Soledad Vinuesa and Concepci{\'o}n P{\'e}rez and Ma Teresa Garc{\'i}a-L{\'o}pez and Marı́a L de Ceballos and Joaquı́n Del Rı́o},
  journal={Journal of The Chemical Society-perkin Transactions 1},
A series of diastereoisomeric dipeptides, analogues of the analgesic compound H-Trp(Nps)Lys-OMe, containing 3-amino-2-hydroxy-4-(2-(o-nitrophenylthio)indol-3-yl]butanoic acid [AH(Nps)IBA) and Lys or Leu has been synthesized. These compounds were tested as aminopeptidase-M and -B (AP-M and AP-B) inhibitors and as analgesics. The AH(Nps)IBA-Leu dipeptides, independently of their stereochemistry, were poor inhibitors of AP-M and AP-B, with IC50-values in the 10–4 mol dm–3 range, while the AH(Nps… 
1 Citations
Pyrazine alkaloids via dimerization of amino acid-derived α-amino aldehydes: biomimetic synthesis of 2,5-diisopropylpyrazine, 2,5-bis(3-indolylmethyl)pyrazine and actinopolymorphol C.
This methodology demonstrates the viability of a recently proposed, alternative biosynthetic route to 2,5-disubstituted pyrazine natural products in nature and describes a novel, concise approach to pyrazines from α-amino aldehydes derived from readily available, cheap amino acids.


Analgesic dipeptide derivatives. 4. Linear and cyclic analogues of the analgesic compounds arginyl-2-[(o-nitrophenyl)sulfenyl]tryptophan and lysyl-2-[(o-nitrophenyl)sulfenyl]tryptophan.
The most active compounds, 15 and 19, were found to exhibit a naloxone-reversible antinociceptive effect similar to those of 1b and 2b and approximately 50 and 12.5 times higher than those of Kyotorphin and its D isomer, respectively.
Analgesic dipeptide derivatives. 3. Synthesis and structure-activity relationships of o-nitrophenyl-modified analogues of the analgesic compound H-Lys-Trp(NPS)-OMe.
Structural-activity studies indicate that the role of the NPS and CmPS moieties could be related to the adoption of a preferential active conformation.
Analgesic dipeptide derivatives. II. Synthetic dipeptides containing a C-terminal 2-(2-nitrophenylsulfenyl) tryptophan residue.
The analgesic activities of Gpr- and Har-containing dipeptides have been evaluated and the influence of the side chain length of the basic amino acid on the analgesic effect is studied.
Synthesis of sulfur-containing analogues of bestatin. Inhibition of aminopeptidases by alpha-thiolbestatin analogues.
The results suggest that the sulfur atoms in 2-thiolbestatin and bestatin thioamide do not interact strongly with the active-site zinc atom of these aminopeptidases when the inhibitors are bound to the enzyme.
A new method to synthesize .ALPHA.-aminoaldehydes.
Benzyloxycarbonyl (Cbz)-amino acid esters were reduced to the corresponding α-aminoaldehydes with diisobutylaluminum hydride. Comparison of specific rotation of the Cbz-aminoalcohols, which were
Characterization of aminopeptidases responsible for inactivating endogenous (Met5)enkephalin in brain slices using peptidase inhibitors and anti-aminopeptidase M antibodies.
Analysis of the concentration-protection curves of the three agents for recovery of the (Met5)enkephalin released from pallidal slices in the presence of the "enkePHalinase" inhibitor, thiorphan, indicated that both aminopeptidases participated in enkphalin degradation but that the role of aminopesptidase M was largely predominant, in contrast with its low relative activity in the preparation.
Inhibition of arginine aminopeptidase by bestatin and arphamenine analogues. Evidence for a new mode of binding to aminopeptidases.
Analysis of the synthesis and inhibition kinetics of a new, potent inhibitor of arginine aminopeptidase and structure-activity data for a series of ketomethylene dipeptide isosteres show that the S1 and S1' subsites preferentially bind basic and aromatic side chains, respectively.
Design of novel inhibitors of aminopeptidases. Synthesis of peptide-derived diamino thiols and sulfur replacement analogues of bestatin.
The design rationale and synthesis of novel peptidyl diamino thiol inhibitors of rat brain aminopeptidase are presented, along with accompanying structure-activity analysis, and speculations on the possible mode of enzyme-inhibitor binding of bestatin are offered.