Synthesis and specific nootropic activity of (–)-cytisine derivatives with carbamide and thiocarbamide moieties in their structure

Tsypysheva, I. P.; Koval’skaya, A. V.; Makara, N. S.; Лобов, А. Н.; Petrenko, I. A.; Galkin, E. G.; Sapozhnikova, T. A.; Zarudii, F. S.; Yunusov, M. S.

doi:10.1007/s10600-012-0329-7

Cited by 32 publications

(16 citation statements)

References 17 publications

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“…Two-dimensional 1 H-1 H COSY, 1 H-13 C HSQC, 1 H-13 C HMBC, and 1 H-1 H NOESY spectra were recorded using standard multi-pulse sequences of the instrument software. Physicochemical constants of 2, 3, 6, and 10-23 agreed with the published values [9,10,[12][13][14][15][16][17][18].…”

Section: Methodssupporting

confidence: 86%

“…[9]; b. PhCHO, THF, 64qC, NaBH 4 ; c. AllNCS, C 6 H 6 , 80 °Ñ; d. [11]; e. RNCO, C 6 H 6 , 80qÑ; f. CH 2 (C 6 H 4 NCO) 2 , C 6 H 6 , 80qÑ Scheme 1…”

mentioning

confidence: 99%

“…We synthesized N-benzyl-(12-N-methylcytisine)-3-amine (4), N-(12-methylcytisin-3-yl)-Nc-allylthiourea (5), N-(cytisino-1-carbonothioyl)benzamide (6), N- (12-methylcytisin-5-yl)-Nc-allylurea (7), N- (12-methylcytisin-5-yl)-Ncphenylurea (8), and N,Nc-[methylene-bis(4,1-phenylene)]dicytisinecarboxamide (9) in order to discover (-)-cytisine derivatives that were modulators of this TF activity (Scheme 1). These supplemented the library of (-)-cytisine (1) derivatives with variously shaped thio-and carboxamide groups that were prepared by us earlier [9,10].…”

mentioning

confidence: 99%

“…These supplemented the library of (-)-cytisine (1) derivatives with variously shaped thio-and carboxamide groups that were prepared by us earlier [9,10].…”

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confidence: 99%

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Amines, Amides, and Thio- and Carboxamides of (–)-Cytisine as Nfat Transcription Factor Modulators

et al. 2014

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A library of derivatives of the quinolizidine alkaloid (-)-cytisine with amine, amide, and thio-and carboxamides in the 3-, 5-, and 12-positions were synthesized. Their activity with respect to NFAT transcription factor was studied. It was shown that NFAT modulation activity was a function of the nature of the substituent.The discovery of compounds that modulate transcription factor (TF) activity is currently used to select potential targeting drug candidates. Numerous studies showed that activation of NFAT (nuclear factor of activated T-cells) TF plays an important role in the normal functioning of the immune system. However, excessive activation of this TF causes the development of immunopathological reactions such as autoimmune processes, inflammation, transplant rejection, carcinogenesis, and metastasis. Thus, the search for new NFAT modulators is extremely critical [1][2][3].A sufficient number of NFAT inhibitors/activators of natural and synthetic origin have now been identified [4][5][6]. However, such studies of the quinolizidine alkaloid (-)-cytisine and its derivatives have not been conducted.This TF was chosen as the screening target because the anti-inflammatory and immunomodulating activities of several quinolizidine alkaloids were reported [7,8].

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Section: Methodssupporting

confidence: 86%

“…[9]; b. PhCHO, THF, 64qC, NaBH 4 ; c. AllNCS, C 6 H 6 , 80 °Ñ; d. [11]; e. RNCO, C 6 H 6 , 80qÑ; f. CH 2 (C 6 H 4 NCO) 2 , C 6 H 6 , 80qÑ Scheme 1…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…These supplemented the library of (-)-cytisine (1) derivatives with variously shaped thio-and carboxamide groups that were prepared by us earlier [9,10].…”

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confidence: 99%

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Amines, Amides, and Thio- and Carboxamides of (–)-Cytisine as Nfat Transcription Factor Modulators

et al. 2014

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“…The syntheses of thio-and carboxamides 4 and 5, substituted ureas 6 and 7, nitro derivatives 9 and 10, carbamide 12, and dibromo derivative 8 were described by us previously [10,11]. Dinitro derivative 11 was synthesized by repeated nitration of 9.…”

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confidence: 99%

Search for compounds with antiviral activity among synthetic (-)-cytisine derivatives

et al. 2013

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The antiviral activity of several amides and thio-and carboxamides of ()-cytisine in addition to bromination and nitration products of its 2-pyridone core was studied. Compounds with a selectivity index close to 10 were found.Keywords: ()-cytisine, H1N1 flu virus.Some plants that exhibit antiviral properties are known to bear alkaloids. Thus, several genera of the family Fabaceae, e.g., Sophora, Acacia, and Caragana, yield extracts that are highly active against hepatitis C (HCV), hepatitis B (HBV), Herpes simplex 1 (HSV-1), and several other viruses [1][2][3][4][5].The search for new antiviral agents should be conducted among representatives of the most common structural groups of quinolizidine alkaloids, including ()-cytisine, because plants of the family Fabaceae are the principal producers of them [6] and the aforementioned antiviral properties may be associated with them.The pharmacological profiles of ()-cytisine itself and its derivatives are very broad. Neuropharmacological, antiinflammatory, analeptic, and antidiabetic activity was established for them [7]. An example of a study of the antiviral properties of ()-cytisine itself and several of its synthetic derivatives was published [8].We synthesized two groups of derivatives of ()-cytisine and N-methylcytisine that contained substituents on the secondary N atom and in the 2-pyridone core in order to discover compounds with antiviral activity and to establish the structure-activity relationship.The transformation products of the ()-cytisine secondary amine were amides of m-fluoro-, m-bromo-, and p-chlorobenzoic acids (1-3) that were prepared by the hydroxysuccinimide method as before [9]. The syntheses of thio-and carboxamides 4 and 5, substituted ureas 6 and 7, nitro derivatives 9 and 10, carbamide 12, and dibromo derivative 8 were described by us previously [10,11]. Dinitro derivative 11 was synthesized by repeated nitration of 9. Table 1 summarizes results from the study of the toxicity and antiviral activity of cytisine derivatives 1-12. According to the results, starting alkaloid ()-cytisine had low toxicity and antiviral activity. Transformation products of the ()-cytisine secondary amine, i.e., amides of m-fluoro-, m-bromo-, and p-chlorobenzoic acids 1-3, differed in toxicity and activity. This indicated that the nature of the corresponding acid and the halogen atom and its position on the aromatic ring affected the antiviral properties.

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Synthesis and Molecular Structure of N-{(1R,5S)-3-Methyl-8-Oxo-1,3,4,5,6,8-Hexahydro-2H-1,5-Methanopyrido[1,2-α] [1,5]Diazocin-9-yl}Acetamide

2014

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Synthesis and specific nootropic activity of (–)-cytisine derivatives with carbamide and thiocarbamide moieties in their structure

Cited by 32 publications

References 17 publications

Amines, Amides, and Thio- and Carboxamides of (–)-Cytisine as Nfat Transcription Factor Modulators

Amines, Amides, and Thio- and Carboxamides of (–)-Cytisine as Nfat Transcription Factor Modulators

Search for compounds with antiviral activity among synthetic (-)-cytisine derivatives

Synthesis and Molecular Structure of N-{(1R,5S)-3-Methyl-8-Oxo-1,3,4,5,6,8-Hexahydro-2H-1,5-Methanopyrido[1,2-α] [1,5]Diazocin-9-yl}Acetamide

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