- Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines
-
A series of N-substituted tetrahydro-β-carbolines were synthesized and screened for antileishmanial activity through an in vitro assay that involves promastigotes and axenic amastigotes of Leishmania donovani, the causative agent for visceral leishmaniasis. The thiophen-2-yl analogs 9b and 11f and naphthyl analog 11h were found to show significant activity against promastigotes with IC50 values of 12.7, 9.1 and 22.1 μM, respectively. Analogs 9b and 11h were also effective against axenic amastigotes with IC50 values of 62.8 and 87.6 μM, respectively. The antileishmanial activity of analogs was then tested in human macrophage cell line infected with L. donovani amastigotes and 2-naphthyl linked analog 11h was found to be effective with IC50 value of 28.3 μM. Several analogs also displayed antitrypanosomal activity against Trypanosoma brucei, the causative agent for human African trypanosomiasis. Compounds 11e, 11f and 11h were more effective than others with IC50 values of 1.0, 8.9 and 10.2 μM, respectively. All synthesized analogs were not cytotoxic towards mammalian cell lines including Vero (monkey kidney fibroblasts), HEPG2 (human hepatoma cells), LLC-PK1 (pig kidney epithelial cells) and THP-1 (human macrophages).
- Manda, Sudhakar,Khan, Shabana I.,Jain, Surendra K.,Mohammed, Shabber,Tekwani, Babu L.,Khan, Ikhlas A.,Vishwakarma, Ram A.,Bharate, Sandip B.
-
supporting information
p. 3247 - 3250
(2014/07/22)
-
- The preparation of 3-substituted 1-chlorocarbonyl-imidazolidin-2-ones using bis(trichloromethyl) carbonate
-
A novel synthesis of 3-substituted 1-chlorocarbonyl-imidazolidin-2-ones using bis(trichloromethyl) carbonate is reported. The bis(trichloromethyl)carbonate is used to generate phosgene in situ in stoichiometric amounts. The yields and purity of the products obtained are better than those obtained by a conventional way using phosgene.
- Su,Zhang
-
p. 440 - 441
(2007/10/03)
-
- Azlocillin. Ein neues Penicillin aus der Acylureidoreihe. Synthese und chemische Eigenschaften
-
Azlocillin, 6--penicillanic acid is a new semi synthetic acylureido-penicillin presenting a broad antibacterial spectrum, especially against Pseudomonas.Synthesis from ampicillin and 6-aminopenicillanic acid as well as physicochemical properties of free acid and sodium salt are described.Azlocillin is cleaved by penicillinase to penicilloate which is further degraded by acid to peniollate.Keywords: Azlocillin. - Acylureidopenicillin. - Antibacterial activity.
- Koenig, Hans-Bodo,Metzer, Karl-Georg,Offe, Hans-Albert,Schroeck, Wilfried
-
-
- Nitroimidazoles: Part IV - 1-Sulphonyl(carbamoyl/thiocarbamoyl)-3-(1-methyl-5-nitroimidazol-2-yl)-2-imidazolidinones
-
Sulphone (5) is condensed with sodium salts of a variety of 1-suplphonyl (7), 1-thiocarbamoyl (9) and 1-carbonyl (10)-2-imidazolidinones to give 3-(2-imidazolyl)imidazolidinones (12), (13) and (14) respectively, out of which 1-methylsulphonyl-3-(1-methyl-5-nitro-imidazol-2-yl)-2-imidazolidinone (12a) is undergoing clinical trials as an antiamoebic-antitrichomonal agent. 15 and 16 are analougous imidazolidinones, while 17 and 18 are benzimidazolone derivatives.The reaction of 5 with the sodium salt of 2-imidazolidinone gives rise to the mono and bis-condensation products 21 and 22 respectively.Several other minor byproducts, 23-27 have been identified. 23, 26 and 27 arise from 21. 24, a transformation product of 5 leads to the ether 25 by a displacement reaction.A second synthesis of 12a involves the nitration of imidazolylimidazolidinone (30) in the terminal step, with 30 becoming available from 1-methyl-2-aminoimidazole (28) and chloroethyl isocyanate, and subsequent reaction of resultant 29 with methanesulphonyl chloride.The higher ring homologue, 33 of 12a is synthesised in poor yield from 5 and 1-methylsulphonylhexahydropyrimidinone.Treatment of 12a and 13a with KI in DMF leads to the isomeric 4-nitro derivatives 38a, b and desmethyl derivates 37a, b.Treatment of 12a with triethyloxonium fluoroborate affords the quaternary isothiourea (35) which is hydrolysed to 36.Treatment of 12a and 13a with aqeous alkali leads to cleavage of imidazolidinone ring to form the ethylenediamines 31a and b.Position isomers 41 and 43 of 12a are respetcively obtained by the reaction of 1-methyl-4-nitro-5-chloro-(40)-, and 1-methyl-5-nitro-4-chloro-(42)-imidazoles with 1-methylsulphonyl-ethylene urea.Treatment of the last compound with various reactive halides, e.g. 2-chlorobenzothiazole, yields several analogues 44a-i of 12a while niridazole (45) and methylsulphonyl chloride affords nitrothiazole analogue 46.
- Nagarajan, K.,Arya, V. P.,George, T.,Sudarsanam, V.,Shah, R. K.,et al.
-
p. 928 - 940
(2007/10/02)
-
- 7-Ureido acetamido substituted cephalosporin antibiotics
-
Cephalosporin antibiotics of the formula STR1 wherein R is STR2 and R" is H, C1 -C3 alkyl, allyl, propargyl, C3 -C6 cycloalkyl, phenyl, benzyl or furfuryl; R' is H or methyl; or R is a cyclic urea group for example, R is STR3 R1 is phenyl, thienyl, or furyl; R3 is a lower alkyl substituted 1H-tetrazole-5-thio or 1,3,4-thiadiazole-5-thio group and R4 is hydrogen or an active ester group, e.g., an acetoxymethyl group; are highly active broad spectrum antibiotics especially useful in the treatment of infections attributable to the gram-negative microorganisms.
- -
-
-
- Cephalosporins and their production
-
Cephalosporins of the formula STR1 their pharmaceutically-acceptable, nontoxic salts, and hydrates thereof are produced, wherein A is hydrogen; unsubstituted or substituted alkyl; aryl; or R1 --X--, wherein X is --CO-- or --SO2 --, and R1 is hydrogen, unsubstituted or substituted alkyl; aryl; thienyl; furyl; amino; alkylamino; dialkylamino; pyrrolidyl; or piperidyl; Or when X is --CO--, R1 can also be alkoxy; B is phenyl, methylphenyl, chlorophenyl, hydroxyphenyl or the moiety STR2 E is hydrogen, hydroxyl or acetoxy; and C is a center of chirality. These compounds are particularly useful for their antimicrobial and, particularly, antibacterial effects.
- -
-
-
- Oxo-imidazolidine substituted cephalosporins and antibacterial compositions and methods of combatting bacteria employing them
-
Cephalosporins of the formula STR1 their pharmaceutically-acceptable, nontoxic salts, and hydrates thereof are produced, wherein A is hydrogen; unsubstituted or substituted alkyl; aryl; or R1 --X--, wherein X is --CO-- or --SO2 --, and R1 is hydrogen, unsubstituted or substituted alkyl; aryl; thienyl; furyl; amino; alkylamino; dialkylamino; pyrrolidyl; or piperidyl; Or when X is --CO--, R1 can also be alkoxy; B is phenyl, methylphenyl, chlorophenyl, hydroxyphenyl or the moiety STR2 E is hydrogen, hydroxyl or acetoxy; and C is a center of chirality. These compounds are particularly useful for their antimicrobial and, particularly, antibacterial effects.
- -
-
-
