3392-07-2Relevant articles and documents
Peptide Derivatives of Some Physiologically Active Substances
Shevchenko,Andreeva,Nagaev, I. Yu.,Myasoedov
, p. 173 - 176 (2019)
Abstract: The synthesis of Boc-Gly-Pro-Dox, Boc-Gly-Pro-DOPA, and Boc-Gly-Pro-Srt and their deuterated analogues was carried out. The condensation is accompanied by side reactions, which could be minimized by optimizing the reaction conditions. The most versatile approach to the synthesis of Boc-Gly-Pro-Dox, Boc-Gly-Pro-DOPA, and Boc-Gly-Pro-Srt and their deuterated analogues is condensation of Boc-Gly-Pro or Boc-Gly-[2H]Pro with the amino groups of dopamine, serotonin, and doxorubicin. For the introduction of hydrogen isotopes into ΔPro, hydrogenation of its aqueous solution followed by condensation of the reduced proline with Boc-GlyOSu is recommended. Mass spectrometry was used to determine the content of isotopomers in the deuterated products.
Argininamide-type neuropeptide y Y1 receptor antagonists: The nature of: N Ω-carbamoyl substituents determines Y1R binding mode and affinity
Buschmann, Jonas,Keller, Max,Seiler, Theresa,Wifling, David,Bernhardt, Günther
supporting information, p. 274 - 282 (2020/04/17)
The recently resolved crystal structure of the neuropeptide Y Y1 receptor (Y1R), co-crystallized with the high-affinity (pKi: 10.11), argininamide-type Y1R antagonist UR-MK299 (2), revealed that the NΩ-carbamoyl substituent (van der Waals volume: 139 ?3) is deeply buried in the receptor, occupying a hydrophobic pocket. We synthesized and characterized a series of argininamides, structurally related to 2. Y1R affinity decreased with increasing size of the carbamoyl residue (minimal pKi: 5.67). Exceeding a critical size of the substituent (van der Waals volume: 212 ?3), the ligands bound in an inverted mode with the carbamoyl side chain located at the surface of the receptor, as suggested by induced-fit docking and MD simulations.
Design, synthesis and anxiolytic activity evaluation of N-Acyltryptophanyl- containing dipeptides, potential TSPO ligands
Deeva, Olga A.,Dyabina, Alina S.,Gudasheva, Tatiana A.,Mokrov, Grigory V.,Seredenin, Sergey B.,Yarkova, Milada A.
, p. 383 - 399 (2019/07/12)
Background: The 18 kDa translocator protein (TSPO), previously known as the peripheral- type benzodiazepine receptor, plays a key role for the synthesis of neurosteroids by promoting transport of cholesterol from the outer to the inner mitochondrial membrane, which is the ratelimiting step in neurosteroid biosynthesis. Neurosteroids interact with nonbenzodiazepine site of GABAa receptor causing an anxiolytic effect without the side effects. Methods: Using the original peptide drug-based design strategy, the first putative dipeptide ligand of the TSPO N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23) was obtained. Molecular docking of GD-23 in the active pocket of the TSPO receptor using Glide software was carried out. The lead compounds GD-23 and its analogues were synthesized using activated succinimide esters coupling method. The anxiolytic activity of GD-23 and its analogues was investigated in vivo, using two validated behavioral tests, illuminated open field and elevated plus-maze. Results: The in vivo studies revealed that the following parameters are necessary for the manifestation of anxiolytic activity of new compounds: the L-configuration of tryptophan, the presence of an amide group at the C-terminus, the specific size of the N-acyl substituent at the Nterminus. Compound GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide) demonstrated a high anxiolytic-like effect in the doses of 0.05-1.0 mg/kg i.p. comparable with that of diazepam. Compound GD-23 was also active in the open field test when was administered orally in the doses of 0.1-5.0 mg/kg. The involvement of TSPO receptor in the mechanism of anxiolytic-like activity of new compounds was proved by the antagonism of compound GD-23 with TSPO selective inhibitor PK11195 as well as with inhibitors of enzymes which are involved in the biosynthesis of neurosteroids, trilostane and finasteride. Conclusion: A series of N-acyl-tryptophanyl-containing dipeptides were designed and synthesized as 18 kDa translocator protein (TSPO) ligands. Using a drug-based peptide design method a series of the first dipeptide TSPO ligands have been designed and synthesized and their anxiolytic activity has been evaluated. In general, some of the compounds displayed a high level of anxiolytic efficacy comparable with that of diazepam. The involvement of TSPO receptor in the mechanism of anxiolytic activity of new compounds was proved using two methods. On this basis, the N-acyl-Ltryptophanyl- isoleucine amides could potentially be a novel class of TSPO ligands with anxiolytic activity.
Organoarsenic compound and use thereof
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Paragraph 0098-0102, (2019/03/06)
The invention discloses an organoarsenic compound. The organoarsenic compound has the following structural formula as shown in the specification, wherein n is 1 or 2; R, R1, R2, R3, R4 and R5 are respectively and independently amino, R6-CO-NH, R7-CO-O, alkyl, aryl, a heterocyclic substituent, alkoxyl, alkylamino, a halogen atom, nitro, hydroxyl or a hydrogen atom; R6 is alkyl, aminoalkyl or aryl;R7 is alkyl, aminoaryl or aryl. The organoarsenic compound has good inhibitory activity for thioredoxin reductase, has strong cytotoxicity for tumor cell HL-60, and can be used for preparing a thioredoxin reductase inhibitor or an antitumor drug with thioredoxin reductase as a target spot.