35264-09-6Relevant articles and documents
Harnessing the anti-nociceptive potential of nk2 and nk3 ligands in the design of new multifunctional μ/δ-opioid agonist–neurokinin antagonist peptidomimetics
Ballet, Steven,Gadais, Charlène,Janecka, Anna,Martin, Charlotte,Neve, Jolien De,Piekielna-Ciesielska, Justyna
supporting information, (2021/09/13)
Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or-NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharma-cophore Dmt-DALDA (H-Dmt-D-Arg-Phe-Lys-NH2 ) and the dual μ/δ opioid agonist H-Dmt-D-Arg-Aba-βAla-NH2 (KGOP01). Opioid binding assays unequivocally demonstrated that only hybrids SBL-OPNK-5, SBL-OPNK-7 and SBL-OPNK-9, bearing the KGOP01 scaffold, conserved nanomo-lar range μ-opioid receptor (MOR) affinity, and slightly reduced affinity for the δ-opioid receptor (DOR). Moreover, NK binding experiments proved that compounds SBL-OPNK-5, SBL-OPNK-7, and SBL-OPNK-9 exhibited (sub)nanomolar binding affinity for NK2 and NK3, opening promising opportunities for the design of next-generation opioid hybrids.
NOVEL SUBSTITUTED AMIDES OF TRITERPENE DERIVATIVES AS HIV INHIBITORS
-
Page/Page column 29, (2017/02/28)
The present invention relates to compounds of novel substituted amides of triteripene derivatives of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and formula (II) are as defined herein. The present invention also relates to,, and pharmaceutical compositions comprising compounds of formula (I) useful for the treatment of viral diseases and particularly HIV mediated diseases.
New cathepsin inhibitors to explore the fluorophilic properties of the S2 pocket of cathepsin B: Design, synthesis, and biological evaluation
Fustero, Santos,Rodrigo, Vanessa,Sanchez-Rosello, Maria,Del Pozo, Carlos,Timoneda, Joaquin,Frizler, Maxim,Sisay, Mihiret T.,Bajorath, Juergen,Calle, Luis P.,Canada, F. Javier,Jimenez-Barbero, Jesas,Guetschow, Michael
supporting information; scheme or table, p. 5256 - 5260 (2011/06/24)
Fluor-in or out? Based on β,β-difluorinated cycloaliphatic amino acids, a library of new dipeptide nitriles was evaluated as human cathepsin inhibitors. The orientation of the fluorinated face relative to the protein structure of cathepsin B was elucidated by molecular modeling and NMR studies (see figure). For (R)-configured eutomers, the fluorine atoms are directed to the S2 pocket, whereas in (S)-configured distomers, the fluorinated face is solvent-exposed.
