Design of N-Acylprolyltyrosine 'Tripeptoid' Analogues of Neurotensin as Potential Atypical Antipsychotic Agents
| العنوان: | Design of N-Acylprolyltyrosine 'Tripeptoid' Analogues of Neurotensin as Potential Atypical Antipsychotic Agents |
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| المؤلفون: | Grigory G. Rozantsev, Tatiana A Gudasheva, N. A. Bondarenko, Natalya I. Zaitseva, Tatiana A. Voronina, Rita U. Ostrovskaya, Ludmila S. Asmakova, Vera K. Briling, S. B. Seredenin |
| المصدر: | Journal of Medicinal Chemistry. 41:284-290 |
| بيانات النشر: | American Chemical Society (ACS), 1998. |
| سنة النشر: | 1998 |
| مصطلحات موضوعية: | Male, Magnetic Resonance Spectroscopy, Stereochemistry, medicine.drug_class, Liquid phase, Atypical antipsychotic, Peptide, complex mixtures, Chemical synthesis, Mice, Structure-Activity Relationship, chemistry.chemical_compound, In vivo, Drug Discovery, Peptide synthesis, medicine, Animals, Neurotensin, chemistry.chemical_classification, Dipeptide, Behavior, Animal, Chemistry, digestive, oral, and skin physiology, Rats, Mice, Inbred C57BL, Tyrosine, Molecular Medicine, hormones, hormone substitutes, and hormone antagonists, Antipsychotic Agents |
| الوصف: | A series of N-acylprolyltyrosine amides was designed as tripeptoid analogues of neurotensin. The substituted dipeptides were tested in vivo for antidopamine activity by their ability to inhibit the apomorphine-induced climbing in mice and the dopamine-induced extrapolatory behavior impairment in rats. The N-acylprolyltyrosine amides structure-activity relationships have indicated the size of the N-acyl group and the configuration of amino acids that are important for the activity. We found that the bioactivity has been increased dramatically when the n-hydrocarbon chain on the N-acyl group was increased from four to five carbon atoms. The activity seems to reside exclusively in the L-Tyr diastereomers. All of the compounds tested were inactive in the cataleptogenic action and did not exhibit the acute toxicity even at doses 500-1000 times higher than ED50 in climbing test. On this basis, the N-acylprolyltyrosine amides could potentially be a novel class of atypical antipsychotic agents. |
| تدمد: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm970217c |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efb97009dc2c6520b2711c58c64e616d https://doi.org/10.1021/jm970217c |
| رقم الانضمام: | edsair.doi.dedup.....efb97009dc2c6520b2711c58c64e616d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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| DOI: | 10.1021/jm970217c |