Mannich bases derivatives of 2-Phenyl-5-Benzimidazole sulfonic acid; Synthesis, Characterization, Computational studies and Biological evaluation

Abstract A new series of N-Mannich bases of 2-Phenyl-5-benzimidazole sulfonic acid have been synthesized through amino methylation reaction with secondary amines. The two moieties were held together through a methylene bridge, which comes from formaldehyde (Formalin Solution 37%) used in the reaction. Chemical structures of the newly synthesized compounds have been confirmed using FT-IR, 1HNMR and 13CNMR. Different in vitro assays including Anti-oxidant, Enzyme inhibition, Anti-microbial and Cytotoxicity assay were performed to evaluate the biological potential with reference to the standard drug. Among the synthesized library, compound 3a shows maximum alpha-glucosidase inhibition with an IC50 value of 66.66 µg/ml, compound 3d was found most toxic with LC50 value of 10.17 µg/ml. ADME evaluation studies were performed with the help of Molinspiration online software. Docking calculations were also performed. Given the importance of the nucleus involved, the synthesized compound might find extensive medicinal applications as reported in the literature.

Synthesis and evaluation of mannich bases of benzimidazo [1,2-c] quinazolin- 6[5h]-thione for antimicrobial activity

The intermediate Benzimidazo[1,2-c] quinazolin-6[5H]-thione [1] was obtained by cyclization of 2-[2'- aminophenyl] benzimidazole with carbon disulfide. Mannich base [2a-d] of compound [1] was obtained on treatment with Para formaldehyde and secondary aliphatic amines, similarly treatment of [1] with different ketones afforded respective mannich bases [3 e-h]. All derivatives synthesized were characterized from IR and 1HNMR spectral data's. Moderate anti bacterial activity was exhibited from 2a-d and from 3f, 3h against S. aureus, E. coli, and E. fecalis but very negligent activity were seen from these compounds when screened against P aeruginosa

Synthesis and alpha-glucosidase inhibitory activity of N-(1,5-diaryl-3-pentone-1-yl)-4-aminobenzoic acid / 药学学报

In order to find highly active antidiabetic lead compound, sixteen 4-aminobenzoic acid derivatives were designed and synthesized directly through Mannich reaction in the solution of ethanol at 15-35 degrees C with facile method, mild reaction condition and high yield (45%-90%). Fifteen of them are new compounds. Their structures were confirmed by 1H NMR, 13C NMR, IR, ESI-MS and HR-MS. Alpha-glucosidase inhibitory activity of these compounds indicated that most of these compounds possess the activity with the order: 2c > 2b > 2h > 1a > 1f. The structure-activity relationship of these 4-aminobenzoic acid derivatives was also discussed.

Synthesis and antibacterial activity of imidazothiadiazoles and heterocyclic-amine Mannich-base hydrochloride / 药学学报

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.

Synthesis and antitubercular activity of some mannich bases derived from isatin isonicotinic acid hydrazone

The purpose of this study based on the design and synthesis of a new series of 4-[1-[substitutedaminomethyl]]-2-oxo-2,3-dihydro-1H-3-indolylidene-pyridine- carboxylic acid hydrazones [2a-g] in a trial to overcome the resistance developed with the therapeutic uses of isonicotinic acid hydrazide [isoniazid, INH]. The new compounds were prepared by reacting isatin isonicotinic acid hydrazone with formalin and the appropriate secondary amines. The structures of the newly synthesized compounds were elucidated using different spectral data [IR, 1 HNMR, and 13 CNMR] as well as elemental methods of analyses. The lipophilicity of the synthesized compounds supercedes that of INH as expressed by Clog P.The new compounds [2a-g] as well as INH as a reference drug were tested for their antitubercular activity against bovine Mycobacterium tuberculosis at a dose level of 10 micromol. The tested compounds exhibited comparable inhibitory activity against the tested TB strain comparing to INH a reference drug

Sythesis of new benzopyranone mannich bases

Reaction of 7-hydroxy-5-methoxy-2-methyl-4-oxo-benzopyran-6- carboxaldehyde [1] with formaldehyde and piperidine [or morpholine] to give the corresponding 8-substituted piperidinomethyl or morpholinomethyl derivatives [compounds 2 and 3, respectively]. When formaldehyde and diethylamine were used, bis-[6-formyl-7-hydroxy-5- methoxy-2-methyl-4-oxo-benzopyran-8-yl]-methane [4] was formed. Reaction of 1 with hydroxylamine gave the aldoxime [5], which upon reaction with acetic anhydride gave the corresponding 7-acetyloxy-6- cyano-5-methoxy-2-methyl-4-oxo-benzopyran [6]. Mild hydrolysis of [6] with sodium hydroxide gave 6-cyano-7-hydroxy-5-methoxy-2-methyl- 4-oxo-benzopyran [7]. Reaction of 7 with piperidine and formaldehyde afforded the corresponding Mannich base [8]. Reaction of 1 with urea in ethanol gave the unexpected 5-ethoxy-7-hydroxy-2-methyl-4-oxo- benzopyran [10] which reacted with piperidine and formaldehyde to give the corresponding Mannich base [11]. Reaction of 1 with acetic anhydride gave 3-[7-hydroxy-5-methoxy-2-methyl-4- oxo-benzopyran-6- yl]-acrylic acid [12], while with acetic anhydride in the presence of anhydrous sodium acetate afforded 5-methoxy-8-methyl-2,6- dioxo- [2H,5H]-benzo-[3,2-b:4,5-b']-dipyran [13]. The Mannich bases 3, 14 and the dimer 4 were obtained from compound 12. The dimer 4 could be also obtained by reaction of 1 with formaldehyde. Structures of the compounds prepared were determined by MS, 1H-NMR, IR and elemental analyses. The compounds prepared showed promising antimicrobial activity

Antileishmanial agents: synthesis of allopurinol prodrugs for oral administration

Synthesis of six prodrugs of allopurinol (4-hydroxypyrazolo-(3,4-d)pyrimidine) is described. These compounds were given orally to male and female BALB/C (sensitive) and C57BL/6 (partially resistant) strains of mice, wich had been previously infected with Leishmania mexicana. The results show that at end of the treatment there was weak regression of lesions confirmed through measurement of nodule diameter in the infected animals

Neuropharmacological actions of some newly synthesized Mannich bases.

Benzamido (alkyl) methyl pyrrolidine Mannich bases were synthetized and subjected to certain neuropharmacological studies. All the bases reduced the pentobarbitone sleeping time and rota-rod grip of rats. The Mannich bases II, III and V raised the minimal electro-shock seizure threshold of rats. The TAB-induced pyrexia was not reduced by the bases I and III in rabbits. None of the bases showed any significant analgesic activity.