[Synthesis and antibacterial activity of imidazothiadiazoles and heterocyclic-amine Mannich-base hydrochloride].
To optimize the synthetic method and antibacterial activity of fused heterocyclic thiadiazole compounds, cyclocondensation of 2-(4-methoxyphenyl)-5-amino-1,3,4-thiadiazole (2) with alpha-chloro-4-chloro acetophenone (3) resulted in a key intermediate (4), 6 -(4-chlorophenyl)-2-(4-methoxyphenyl)-imidazo-[2,1-b][1,3,4]thiadiazole, which was carried out an nucleophilic substitution with substituted piperazine to give the corresponding free bases of piperazine (5a-5c), then followed by Mannich reaction with heterocyclicamines and formaldehyde to yield the corresponding Mannich bases, (1a-11) as respective hydrochloride salts. The structures were confirmed by IR, 1H NMR, MS and elemental analysis and the antibacterial activities in vitro of fifteen newly synthesized compounds were also tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. The antibacterial results showed that the introduction of a polar group resulted in the enhancement of antibacterial activity in vitro. Thus, the structures of these fused compounds could further be investigated.
Hu
Guo-qiang
GQ
Institute of Pharmacy, Henan University, Kaifeng 475001, China. hgqxy@sina.com.cn
Hou
Li-li
LL
Xie
Song-qiang
SQ
Huang
Wen-long
WL
Zhang
Hui-bin
HB
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008352:Mannich Bases / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D007093:Imidazoles; D008352:Mannich Bases; D013830:Thiadiazoles