TRH mimetics: Differentiation of antiamnesic potency from antidepressant effect

Mazurov, A. A.; Андронаті, С. А.; Korotenko, T. I.; Sokolenko, Nikolai; Dyadenko, A. I.; Shapiro, Yury E.; Gorbatyuk, V. Ya.; Воронина, Т. А.

doi:10.1016/s0968-0896(97)00141-7

Cited by 11 publications

(6 citation statements)

References 60 publications

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“…The known compounds were identified by comparison of spectroscopic data with those reported in the literature as 24 R -ergosta-4,6,8(14),22-tetraen-3-one, stigmasta-7,22-diene-3β,5α,6α-triol, 5α,8α-epidioxyergosta-6,22-diene-3β-ol, 3β-hydroxy-11,12- O -isopropyldrimene ( 14 ), 3β,11,12-trihydroxydrimene, , 11,12,13α-trihydroxydrimene, cyclo( l -Pro- l -Val), cyclo( l -Leu- d -Pro), cyclo( l -Leu- l -Pro), , cyclo(ILe-Pro), cyclo(Ala-Pro), cyclo(Ala-Phe), , cyclo(4-OH-Pro-Phe), , cyclo( l -Phe- d -Pro), ,, cyclo(6-HyP-Phe), cycle(Gln-Pro), cyclo(Gly-Leu), and cyclo(Phe-Ser)…”

Section: Resultsmentioning

confidence: 99%

Homo- and Heptanor-sterols and Tremulane Sesquiterpenes from Cultures of Phellinus igniarius

Lin

Zhu

et al. 2010

J. Nat. Prod.

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Four steroids, a homopregnene (1) and three heptanorergosterane derivatives (2-4), nine tremulane sesquiterpenes (5-13), and 18 known compounds have been isolated from cultures of the fungus Phellinus igniarius. Their structures and absolute configurations were elucidated by spectroscopic data analysis. In preliminary in vitro assays, at 10(-5) M, compounds 8, 9, 13, and 3beta-hydroxy-11,12-O-isopropyldrimene (14) showed significant vascular-relaxing activities against phenylephrine-induced vasoconstriction with relaxing rates of 35.7%, 45.4%, 46.6%, and 32.1%, respectively, as compared with the blank control.

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Section: Resultsmentioning

confidence: 99%

Homo- and Heptanor-sterols and Tremulane Sesquiterpenes from Cultures of Phellinus igniarius

Lin

Zhu

et al. 2010

J. Nat. Prod.

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“…To distinguish between the two azo forms 8C and 8D , the 1 H NMR spectra of the products exhibit one NH and one OH (D 2 O exchangeable) singlet signals near δ 12 ppm and luck the doublet signal at δ 5–6 ppm for C─H of tautomer 8C . Also, the structure of compounds 8 was further evidenced by alternative synthesis via reaction of ketene aminal 3 and methyl ( N ‐(4‐chlorophenyl)hydrazono)chloroacetate Ae under the same reaction conditions to afford a product that proved to be identical in all respects (mp, mixed mp, and IR) with compound 8e (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Site‐ and Regioselectivity of the Reaction of Hydrazonoyl Chlorides with Perimidine Ketene Aminal. Antimicrobial Evaluation of the Products

Farghaly

Mahmoud

2014

Journal of Heterocyclic Chem

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Reaction of hydrazonoyl chlorides with perimidine ketene aminal derivative in dioxane in the presence of triethylamine afforded either pyrrolo[1,2‐a]perimidines or pyrazolyl perimidines depending on the type of hydrazonoyl chloride used. The reaction was found to be site‐ and regioselective according to the suggested mechanism. The structure of the newly synthesized compounds was established on the basis of spectral data and elemental analyses. In addition, the antimicrobial activity of the newly synthesized compounds was evaluated, and the results showed moderate activity of all compounds against the bacterial species.

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“…7 Among the compounds studied, cyclodipeptide 2 exhibits maximum antidepressant properties. The pronounced effect of this compound and the short time of its achievement (10 rain), which is 3--5 times faster (by this test) than the corresponding value for antidepressants used in clinical practice, indicate that the further Table 3.…”

Section: Methodsmentioning

confidence: 99%

Effect of obligatory replacement and conformational restriction on psychotropic activity of thyroliberin analogs

Mazurov¹,

Korotenko²,

Gorbatyuk³

et al. 1998

Russ Chem Bull

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Easy lactamization of Gln(Asn)--Pro--NH 2 with the formation of cyclic dipeptides with the dikctopiperazine structure (mimetics of the cortformational fragments of linear tripeptides with the X--Pro trans-bond) was observed in the synthesis of tripeptide GIp--GIn--Pro--NH 2 modified by the replacement of histidine with obligatory similar glutamine in thyroliberin (GIp--His--Pro--NH 2, TRH) and in the synthesis of its structural analog [Asn2]TRH. Ion peaks corresponding to the Glp and Pro amino acid residues were revealed in the mass spectra of the peptides synthesized. The biological properties of the compounds obtained were determined indicating that the obligatory replacement resulted in an increased physiological specificity of [GIn2ITRH. The enhanced activity of conformationally restricted cyclic peptides compared to linear ones suggests that the biologically active conformation responsible for the antidepressant activity of linear TRH analogs is the conformation with X--Pro transbond.Key words: thyroliberin, structural modification, obligatory replacement; glutaminyl(asparaginyl)prolylarnide, tactamization; cyclodipeptides, antidepressant activity, biologically active conformation.The use of natural peptides in medicine is associated with several difficulties due to such disadvantages as fast metabolism, restricted penetration into brain, and biological multifunetionality. Therefore, the majority of commercially available drugs of peptide nature are modified analogs of natural peptides.The results of clinical and pharmacological studies indicate that the action of the natural hormone thyroliberin Glp--His--Pro--NH 2 (TRH) on the central nervous system is multi functional, i,2 To study the possibility of narrowing the spectrum of neurotropic activity of TRH, we modified its structure and studied the influence of the latter on the biological activity of the analogs obtained. 3-5 In this work, of numerous different variants of modification of natural peptides, we used the method proposed previously: replacement of obligatory similar amino acids in peptide. 6,7 Therefore, histidine in thyroliberin was replaced by obligatory, similar glutamine and asparagine structurally similar to the latter.The condensation of prolylamide with p-nitrophenyl N-tert-butyloxycarbonylglutaminate in the presence of N-hydroxybenzotriazole (HOBt) gave dipeptide, which after acidolytic deprotection reacted with pentafluorophenyl pyroglutaminate (Scheme 1, n = 2). In addition to the pyroglutaminylprolylamide (1) expected, the reaction mixture contained 3-(l,4-dioxooctahydropyrrolo[ 1,2-a]pyrazin-3-yl)propanamide (2) and pyroglutamylprolylamide (3), whose compositions and structures indicate that their formation is most likely related to intramolecular cyelization ofglutaminylprolylamide after deprotonation of its primary amino group (Scheme 2).It can be assumed that mild conditions of secondary reactions forming diketopiperazine (2) and pyrrolidone (3) structures are the result of the intramolecular activation of carboxamide groups of g...

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TRH mimetics: Differentiation of antiamnesic potency from antidepressant effect

Cited by 11 publications

References 60 publications

Homo- and Heptanor-sterols and Tremulane Sesquiterpenes from Cultures of Phellinus igniarius

Homo- and Heptanor-sterols and Tremulane Sesquiterpenes from Cultures of Phellinus igniarius

Site‐ and Regioselectivity of the Reaction of Hydrazonoyl Chlorides with Perimidine Ketene Aminal. Antimicrobial Evaluation of the Products

Effect of obligatory replacement and conformational restriction on psychotropic activity of thyroliberin analogs

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