Analgetics. II. Relation between structure and activity of some .beta.-amino ketones

Ms, Atwal; Bauer, Ludwig; Sn, Dixit; Je, Gearien; Megahy, M.; Morris, Robert; Pokorny, Christopher S

doi:10.1021/jm00306a006

Cited by 19 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the compounds synthesized, compounds 2, 6-8, and 10 were new, while compounds 1, 3-5, and 9 have been previously reported [16,[27][28][29]. The structures of the synthesized compounds were confirmed by 1 H-and 13 C-NMR (Table 1), UV, IR and MS data ( Table 2).…”

Section: Resultsmentioning

confidence: 71%

“…The ratios of ketone, paraformaldehyde amine HCl previously used [16] in the preparation of compound 3 were 1:1.7:1.5, and the paraformaldehyde was added in two portions, which differs from our method. The medium was acidified with HCl after heating for 7 h. First the basic form of compound 3 was obtained using 50% NaOH, and then compound 3 itself was obtained by passing gaseous HCl through a solution of the base in ether.…”

Section: Synthetic Condition Optimizationmentioning

confidence: 97%

See 1 more Smart Citation

Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents

2007

View full text Add to dashboard Cite

1-Aryl-3-phenethylamino-1-propanone hydrochlorides 1-10, which are potential potent cytotoxic agents, were synthesized via Mannich reactions using paraformaldehyde, phenethylamine hydrochloride as the amine component and acetophenone, 4'-methyl-, 4'-methoxy-, 4'-chloro-, 4'-fluoro-, 4'-bromo-, 2',4'-dichloro-, 4'-nitro-, 4'-hydroxyacetophenone or 2-acetylthiophene as the ketone component. Yields were in the 87-98 % range. Of the compounds synthesized, compounds 2, 6-8 and 10 were new. The optimum reaction conditions were investigated by changing the mol ratios of the reactants, the solvents and the acidity levels using 1 and 10 as representative targets. It was observed that the best mol ratio of the ketone, paraformaldehyde and phenethylamine hydrochloride was 1:1.2:1 (compared with a 2:2.1 ratio), and the most suitable reaction medium was ethanol containing concentrated hydrochloric acid (compared with only ethanol or no solvent). This study may serve as a guide for the conditions of the reactions to synthesize compounds having similar chemical structures.

show abstract

Section: Resultsmentioning

confidence: 71%

Section: Synthetic Condition Optimizationmentioning

confidence: 97%

Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents

2007

View full text Add to dashboard Cite

show abstract

“…

…”

mentioning

confidence: 99%

Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Gül

Vepsäläinen

et al. 2003

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Mannich bases have several biological activities such as antimicrobial, [1][2][3][4][5] cytotoxic, [6][7][8][9] anticancer, 10) analgesic, 11) anti-inflammatory, 12,13) diuretic 14,15) and anticonvulsant [16][17][18][19] activities. An amino ketone, Mannich base, containing at least one activated hydrogen atom at the b position to an amino function, can undergo deamination in vivo 20) or under simulated in vitro conditions 1,3,6) to liberate the corressponding a,b-unsaturated ketones. The a,b-unsaturated ketone is an active center for nucleophilic attack. The biological activities of Mannich bases, such as antimicrobial, [1][2][3]21,22) cytotoxic and anticancer 6,9,23) activities, have been attributed to these liberated a,b-unsaturated ketones which can alkylate nucleophiles, especially thiol groups 1,6,24,25) rather than amino and hydroxyl groups, 26) by Michael type addition reactions of nucleophiles to a,b-unsaturated ketones.27) In addition, enzyme-catalyzed alkylation of the thiol group of cystein with a,b-unsaturated carbonyl compounds has been observed. 28)The antimicrobial activity of a,b-unsaturated ketones is due to their reactions with essential thiol groups in bacteria and fungi, resulting in b-ketothioethers.29) Electron densities on b-carbons are lower 30) than on a-carbons in various unsaturated ketones, and thus the attack of the nucleophils should occur at the b-carbon atoms. It was also shown that increased antimicrobial activity was associated with an increased breakdown of the Mannich bases.29) Similarly, a number of a,b-unsaturated ketones have alkylating ability against biologically important nucleophiles to produce cytotoxicity. 21,23) The amino group in Mannich bases would increase the water solubilizing property of the molecule, which may assist in transportation of the compound to the site of action.Production of thiol adducts in the stability studies, 1,3,6) carried out under in vitro physiological conditions (in phosphate buffer with pH 7.4, at 37°C), with 2-mercaptoethanol, various unsaturated ketones or Mannich bases, suggests that a,bunsaturated ketones and Mannich bases producing unsaturated ketones by deamination to exert their antimicrobial activities by thiol alkylation of unsaturated ketones.Clark and co-workers 31) found that the thiol adduct had the greatest fungitoxicity, which was probably due to the same reaction. Dimmock et al. (1994) have shown that Mannich bases of conjugated styryl ketones inhibit one or more of the following enzymes in the glutathione metabolic pathway: namely, glutathione S-transferases, glutathione reductase, gamma-glutamyl transpeptidase and glutathione peroxidase in Candida albicans. 32) They concluded that the antifungal activity of the Mannich bases of conjugated styryl ketones may be due, at least in part, to interference with the GSH metabolic pathway. In one of our previous studies, we observed that mono-Mannich bases and bis Mannich bases decrease the total glutathione level in a dose-dependent manner when Jurkat cells are exposed to the co...

show abstract

“…The most suitable reaction medium was ethanol with added concentrated hydrochloric acid (compared to the medium without solvent and only ethanol) [50]. As reported in the literature, compound 3a, is a mono-Mannich base with methoxy substitution [31], and compound 4a, is a mono-Mannich base with a chloride substitution [51].…”

Section: Synthesis Of the Compoundsmentioning

confidence: 99%

“…The process whereby these compounds are formed is known as the Mannich reaction [1]. Mannich bases have several biological activities such as antimicrobial [2][3][4][5][6][7][8][9][10][11], cytotoxic [4,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26], anticancer [1,[27][28][29][30], analgesic [31], anti-inflammatory [4,[32][33][34][35], diuretic [36], and anticonvulsant activities [37][38][39][40]. It has been reported that they have an inhibiting effect on DNA topoisomerase I [12,13] and II [41].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antifungal Activity of 1‐Aryl‐3‐phenethylamino‐1‐propanone Hydrochlorides and 3‐Aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols

Mete

Ozelgul

Kazaz

et al. 2010

Archiv der Pharmazie

View full text Add to dashboard Cite

Mono-Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides, 1a, 2a, 3a, 4a, 5a, 6a, 7a, 8a, 9a, and semi-cyclic mono-Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols, 1b, 2b, 3b, 4b, 5b, 6b, 7b, 8b, 9b, were synthesized by a non-classical Mannich reaction. The aryl part was: C(6)H(5 )for 1a, 1b; 4-CH(3)C(6)H(4) for 2a, 2b; 4-CH(3)OC(6)H(4 )for 3a, 3b; 4-ClC(6)H(4 )for 4a, 4b; 4-FC(6)H(4) for 5a, 5b; 4-BrC(6)H(4) for 6a, 6b; 2,4-(Cl)(2)C(6)H(3) for 7a, 7b; 4-NO(2)C(6)H(4 )for 8a, 8b; and C(4)H(3)S(2-yl) i. e., 2-thienyl for 9a, 9b. Piperidinol compounds 2b, 3b, 4b, 5b, 7b, 8b, and 9b are reported here for the first time. The synthesized compounds were tested against seven types of plant pathogenic fungi and three types of human pathogenic fungi using the agar dilution assay. Itraconazole was tested against Candida parapsilosis as the reference compound, while Nystatin was tested as the reference compound against the other fungi. Compounds 1a, 1b, 2a, 4a, 4b, 5a, 5b, 6a, 7a, 8a, 9a, and 9b can be selected as model compounds to develop new antifungal agents against the human pathogen Microsporum canis. Compounds 8a and 8b, which had a similar antifungal activity compared with the reference compound Nystatin against the plant pathogen Aspergillus flavus, can serve as model compounds to develop new antifungal agents to solve agricultural problems.

show abstract

Analgetics. II. Relation between structure and activity of some .beta.-amino ketones

Cited by 19 publications

References 0 publications

Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents

Synthesis of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides as Possible Potent Cytotoxic Agents

Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Synthesis and Antifungal Activity of 1‐Aryl‐3‐phenethylamino‐1‐propanone Hydrochlorides and 3‐Aroyl‐4‐aryl‐1‐phenethyl‐4‐piperidinols

Contact Info

Product

Resources

About