Synthesis and Tuberculostatic Activity of Some Substituted Amino Acid Methyl Esters with Sym-Tetrazine Moieties

Русинов, Г. Л.; Latosh, N. I.; Ишметова, Р. И.; Кравченко, М. А.; Ганебных, И. Н.; Соколов, В. А.; Чупахин, О. Н.

doi:10.1007/s11094-005-0068-1

Cited by 12 publications

(4 citation statements)

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“…8 Both s-tetrazine and 1,3,4-thiadiazole also exhibit a broad spectrum of biological activity. Consequently, their derivatives can be used in medicine [9][10][11][12][13][14][15][16][17][18][19] and 1,3,4-thiadiazole-containing systems serve as plantprotection products. 20,21 In addition, an extremely interesting potential application of s-tetrazine derivatives is in medical diagnostics.…”

Section: Introductionmentioning

confidence: 99%

1,3,4-Thiadiazol-2-ylphenyl-1,2,4,5-tetrazines: efficient synthesis via Pinner reaction and their luminescent properties

Maj¹,

Kudelko²,

Świątkowski³

2021

Arkivoc

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Due to the interest in, and diverse applications of, 1,2,4,5-tetrazines and 1,3,4-thiadiazoles, individually and, more recently, in combination, a series of novel 1,2,4,5-tetrazine derivatives conjugated directly or via a 1,4phenylene linker with a 1,3,4-thiadiazole core, were synthesized. A six-step reaction sequence, involving the Pinner reaction and oxidation under mild conditions, was used. This approach worked well for both symmetrical and unsymmetrical arrangements. Their luminescence properties were examined and are reported. The obtained compounds may have a number of great applications potential.

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Section: Introductionmentioning

confidence: 99%

1,3,4-Thiadiazol-2-ylphenyl-1,2,4,5-tetrazines: efficient synthesis via Pinner reaction and their luminescent properties

Maj¹,

Kudelko²,

Świątkowski³

2021

Arkivoc

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“…Such a search is now in progress in large pharmaceutical companies, including Johnson & Johnson (http://www.jnjru.ru/), Novartis (http://www.novartis.ru/), Eli Lilly (http://www.lilly.ru/Nitro/), etc. A number of new compounds, including those affecting new targets and having new mechanisms of action, have already been put to clinical trials (for a review, see [104][105][106][107][113][114][115][116][117][118][119][120][121]; Table 3). It seems promising for this purpose to study protein kinases, which are numerous enzymes that are involved in the bacterial response to environ mental changes, including phosphorylation reactions.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations of the rv0407, rv3547, rv3261, and rv3262 genes OPS 67683 (ínitroimidazoox azines) [116] Inhibition of cell wall lipid and mycolic acid syntheses Nitrate reductase Mutation of the rv3547 gene TMC 207 (R207910) (dia rylquinolynes) [117] Inhibition of ATP synthesis F 0 F 1 ATP synthase Mutation of the atpE gene SQ 109 (diethiamines) [118] Inhibition of cell wall synthesis ND ND LL3858 (pyrroles) [ 1 1 9 ] N D N D N D Linezolid (oxazolidones) [120] Inhibition of protein synthesis Ribosomes ND BTZ043 (nitrobenzothiazino nes) [121] Inhibition of arabinane synthesis DprE1 subunit of decaprenyl phosphoryl β O ribose 2' epi merase Mutation of the rv3790 gene Tritrazin N (azolotetrazines) [113,114] Inhibition of serine/threonine protein kinases Protein kinases PknA and PknB ND Note: ND, no data.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

2012

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The review summarizes the data on the Mycobacterium tuberculosis mutations that lead to multi drug resistance (MDR) to various antibiotics. MDR strains arose over the past 30 years as a variety of antitu berculosis drugs were introduced in medicine, and they largely discount the results of chemotherapy for tuberculosis. The most dangerous of them are strains with extensive drug resistance (XDR), which are resis tant to four or five different drugs on average. The molecular mechanisms that make a strain resistant are con sidered. XDR and MDR strains result from successive and usually independent resistance mutations, which arise in various regions of the mycobacterial genome. In addition, the formation of resistant strains is affected by the phenomenon of tolerance and mycobacterial latency in infected tissues.

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“…Polynitrogen containing heterocycles are promising compounds for the design of new effective drugs due to their high affinity for biological targets and wide possibilities of chemical modifications making it possible to modulate such biological properties as activity, toxicity, lipophilicity, and cumulativity. 1,2 Tuberculostatic activity of imidazo [1,2 b] and [1,2,4]triazolo [4,3 b] [1,2,4,5]tetr azines, 3 as well as of 3 (3,5 dimethylpyrazol 1 yl) 1,2,4,5 tetrazines containing hydrazone 4 or aminoacid ester 5 moi eties in С(6) position has been recently found and reported.…”

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confidence: 99%

Synthesis and tuberculostatic activity of amine-substituted 1,2,4,5-tetrazines and pyridazines

et al. 2014

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A series of novel 3,6 disubstituted 1,2,4,5 tetrazines and pyridazines bearing aminopyridyl, hydrazono, or aminoalkyl substituents were synthesized. Ten of these compounds showed marked tuberculostatic activity (MIC  12.5 mkg mL -1 ). . tetrazin 3 amine (4f). The yield was 219 mg (78%), m.p. 235-237 C. Found (%): C, 64.03; H, 5.81; N, 29.88. C 15 H 16 N 6 . Calculated (%): C, 64.27; H, 5.75; N, 29.98. 1 (3,5 Dimethylpyrazol 1 yl) 4 hydrazino 4а morpholino 5,6,7,7а tetrahydro 4аН cyclopenta[d]pyridazine (5h). 1 Mor pholinocyclopentene (306 mg, 2 mmol) was added dropwise to a solution of tetrazine 2h (206 mg, 1 mmol) in MeOH (10 mL) with magnetic stirring. After 15 min the resulting colorless pre cipitate was filtered off, and washed with methanol on filter. The yield was 202 mg (61%), m.p. 210-213 С (decomp.). Found (%): С, 57.88; H, 7.79; N, 29.78. C 16 H 25 N 7 O. Calculated (%): C, 57.98; H, 7.60; N, 29.58. 4 Amino 1 (3,5 dimethylpyrazol 1 yl) 4а (pyrrolidin 1 yl) 5,6,7,7а tetrahydro 4аН cyclopenta[d]pyridazine (5i). 1 Pyrro lidinocyclopentene (274 mg, 2 mmol) was added to a solution of tetrazine 2i (191 mg, 1 mmol) in MeCN (15 mL). The reaction mixture was kept for 10 min at 70 С until red color disappeared and cooled to ~20 С. The precipitate was filtered off and recrys tallized from acetonitrile. The yield was 216 mg (72%), m.p. 159 С (decomp.). Found (%): С, 63.96; Н, 8.33; N, 27.91. C 16 H 24 N 6 . Calculated (%): C, 63.97; H, 8.05; N, 27.98. 6 {2 [1 (4 Chlorophenyl)ethyliden]hydrazino} 3 (3,5 di methylpyrazol 1 yl) 1,2,4,5 tetrazine (6d). A solution of tetr azine 2h (206 mg, 1 mmol) and 4 chloroacetophenone (155 mg, 1 mmol) in MeCN (5 mL) was exposed to microwave radiation for 15 min at 55 С (TLC control). The solvent was evaporated, and the residue was washed with MeCN. The yield was 309 mg (90%), m.p. 184 C. Found (%): С, 52.29; Н, 4.33; N, 32.55. C 15 H 15 ClN 8 . Calculated (%): C, 52.56; H, 4.41; N, 32.69. 6 {2 [1 (4 Chlorophenyl)ethyliden]hydrazino} 3 methoxy 1,2,4,5 tetrazine (7d). The yield was 181 mg (65%), m.p. 104-106 C. Found (%): С, 47.49; Н, 4.10; N, 29.96. C 11 H 11 ClN 6 O. Calculated (%): С, 47.41; Н, 3.98; N, 30.15.Synthesis of 3 amino 6 [2 (1 R ethyliden)hydrazino] 1,2,4,5 tetrazines (8b,c,e, 9b-e) (general procedure). An amine (5 mmol) was added to a solution of hydrazone 6 (1 mmol) in MeCN (10 mL). The reaction mixture was kept for 3-5 h (TLC control) with stirring and heating (70-80 С) and cooled to ~20 C. The precipitate was filtered off and recrystallized from acetonitrile. 6 [2 (1 Phenylethyliden)hydrazino] 3 (4 pyridylethylami no) 1,2,4,5 tetrazine (8b). The yield was 200 mg (60%), m.p. 210 C. Found (%): С, 61.16; Н, 5.37; N, 33.79. C 17 H 18 N 8 . Calculated (%): C, 61.06; H, 5.43; N, 33.51. 3 {2 [1 (4 Methoxyphenyl)ethyliden]hydrazino} 6 (4 pyrid ylethylamino) 1,2,4,5 tetrazine (8c). The yield was 179 mg (49%), m.p. 195 C. Found (%): С, 59.41; Н, 5.50; N, 30.84. C 18 H 20 N 8 O. Calculated (%): C, 59.33; H, 5.53; N, 30.75. 3 {2 [1 (4 Bromophenyl)ethyliden]hydrazin...

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Synthesis and Tuberculostatic Activity of Some Substituted Amino Acid Methyl Esters with Sym-Tetrazine Moieties

Cited by 12 publications

References 4 publications

1,3,4-Thiadiazol-2-ylphenyl-1,2,4,5-tetrazines: efficient synthesis via Pinner reaction and their luminescent properties

1,3,4-Thiadiazol-2-ylphenyl-1,2,4,5-tetrazines: efficient synthesis via Pinner reaction and their luminescent properties

Mycobacterium tuberculosis mutants with multidrug resistance: History of origin, genetic and molecular mechanisms of resistance, and emerging challenges

Synthesis and tuberculostatic activity of amine-substituted 1,2,4,5-tetrazines and pyridazines

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