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Synthesis and Biological Evalution of Some Novel Derivatives of Imidazole
Synthesis and Biological Evalution of Some Novel Derivatives of Imidazole
Chemistry Department, St. Xavier’s College (Autonomous), Navarangpura, Ahmedabad-380009, Gujarat, India
1
E-mail: makwana_atul@yahoo.com
2
E-mail: ali_malani@yahoo.com
Received 3 July 2018, Accepted; 3 October 2018
Abstract: Imidazole is an important heterocyclic moiety in the field of medicinal chemistry and drug dis-
covery. Imidazole is a five member ring having three carbon atoms and two nitrogen atoms out of which
both the nitrogens are at first and third positions. Imidazole has wide range of therapeutic importance.
Looking to the pharmacological importance of the Imidazole moiety here we have synthesized some novel
derivatives of Imidazole. The newly synthesize compounds were analyzed by infrared spectroscopy, nucle-
ar magnetic resonance and mass spectrometry techniques. The entire series of synthesized compounds was
evaluated for biological activities by broth dilution method.
R
R
H DMF
120°C to 130°C
O O
O
O N
O HN
N N
O H2 N N H
I (a-p)
Keywords: Imidazole, Biological Activity, Medicinal Chemistry, Drug Discovery, Therapeutic importance
Chemistry & Biology Interface 323 Vol. 8 (6), November – December 2018
Chemistry & Biology Interface, 2018, 8, 6, 323-328
Chemistry & Biology Interface 324 Vol. 8 (6), November – December 2018
Chemistry & Biology Interface, 2018, 8, 6, 323-328
Allyl 4-(4-flourophenyl)-2-methyl-1,4- (1H, m), 6.32 (1H, s), 7.45 (1H, t,J=9.2), 7.53
dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine- (2H, d, J=10.3), 7.22 (2H, t, J=8.4), 7.59 (2H, d,
3-carboxylate (Ic) J=4.5), 10.99 (1H, s), Mass (m/z): 415.
IR (cm-1): 741 (Ar C-H bending), 1686 (Ar
C=C bending), 1761 (COOR), 3051 (Ar C-H Allyl 4-(3-bromophenyl)-2-methyl-1,4-
Stretching), NMR(DMSO, 400MHz) (δ ppm): dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-
3-carboxylate (Ig)
2.50 (3H, s), 4.47 (2H, m), 5.12 (1H, d, d, J=1.9,
8.2), 5.22 (1H, d, d, J=1.9, 8.2), 5.66 (1H, s), IR (cm-1): 741 (Ar C-H bending), 1686 (Ar
6.32 (1H, s), 7.11 (2H, d, J=7.9), 7.22 (4H, m), C=C bending), 1761 (COOR), 3051 (Ar C-H
7.60 (2H, d, J=10.3), 11.00 (1H, s), Mass (m/z): Stretching), NMR(DMSO, 400MHz) (δ ppm):
364. 2.29 (3H, s), 4.57 (2H, d), 5.28 (1H, d), 5.42
(1H, d), 5.66 (1H, s), 6.06 (1H, d), 7.22 (4H, m),
Allyl 4-(4-nitrophenyl)-2-methyl-1,4- 7.40 (2H, d), 7.59 (2H, d), 12.49 (1H, s), Mass
dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine- (m/z): 325.
3-carboxylate (Id)
IR (cm-1): 741 (Ar C-H bending), 1686 (Ar Allyl 4-(2-nitrophenyl)-2-methyl-1,4-
C=C bending), 1761 (COOR), 3051 (Ar C-H dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-
Stretching), NMR(DMSO, 400MHz) (δ ppm): 3-carboxylate (Ih)
2.51 (3H, s), 4.46 (2H, m), 5.11 (1H, d, d, IR (cm-1): 741 (Ar C-H bending), 1686 (Ar
J=1.64, 8.4), 5.22 (1H, d, d, J=1.64, 8.4), 5.66 C=C bending), 1761 (COOR), 3051 (Ar C-H
(1H, m), 6.36 (1H, s), 7.22 (2H, t, J=9.2), 7.49 Stretching), NMR(DMSO, 400MHz) (δ ppm):
(2H, d, J=7.9), 7.60 (2H, d, J=10.2), 8.14 (2H, 2.51 (3H, s), 4.47 (2H, m), 5.12 (1H, d, d, J=1.9,
d, J=8.4), 10.88 (1H, s), Mass (m/z): 390. 8.4), 5.22 (1H, d, d, J=1.9, 8.4), 5.60 (1H, m),
6.30 (1H, s), 7.22 (2H, t, J=10.3), 7.48 (1H, d,
Allyl 4-(3,4-dimethoxyphenyl)-2-methyl-1,4- J=7.9), 7.52 (1H, t,J=8.4), 7.60 (2H, d, J=8.4),
dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine- 7.72 (1H, t, J=9.2), 8.00 (1H, d, J=4.9), 10.92
3-carboxylate (Ie) (1H, s), Mass: (m+1) 391.
IR (cm ): 739 (Ar C-H bending), 1684 (Ar
-1
Chemistry & Biology Interface 325 Vol. 8 (6), November – December 2018
Chemistry & Biology Interface, 2018, 8, 6, 323-328
Chemistry & Biology Interface 326 Vol. 8 (6), November – December 2018
Chemistry & Biology Interface, 2018, 8, 6, 323-328
The compound Ia showed singlet at 2.52 δ ppm Table 1.Physical properties of the synthesized
corresponds to three protons of methyl group compounds.
and singlet at 6.34 ppmfor proton bonded to ipso Sr. Compound -R Molecular Molecular
No. Id. Formula Weight
carbon of pyrimidine ring.The mass spectrum 1 Ia 4-Cl C21H18ClN3O2 379.84
of compound Ic showed the molecular ion peak 2 Ib 4-Br C21H18BrN3O2 424.29
3 Ic 4-F C21H18FN3O2 363.38
at m/z = 363 corresponding to the molecular 4 Id 4-NO2 C21H18N4O4 390.39
formula C21H18FN3O2. 5
6
Ie
If
3,4-di-OCH3 C23H23N3O4
2,6-di-Cl
405.45
C H Cl N O 414.28 21 17 2 3 2
7 Ig 3-Br C21H18BrN3O2 424.29
8 Ih 2-NO2 C21H18N4O4
390.39
All the synthesized compounds have been 9 Ii 3-NO2 C21H18N4O4
390.39
screened for antibacterial and antifungal 10 Ij 2-Cl C21H18ClN3O2
379.84
11 Ik 3-OH C21H19N3O3
361.39
activities by broth dilution method. From the 12 Il 4-OH C21H19N3O3
361.39
study of the biological activity data in reference 13
14
Im
In
4-CN
4-OCH3
C22H18N4O2
370.40
C22H21N3O3
375.42
to standard drug Gentamycin for antibacterial 15 Io 3-OCH3 C22H21N3O3
375.42
16 Ip 4-CH3 C22H21N3O2
359.42
activity and Nystatin for antifungal activity
(Table-2), we found that compound Ia showed
moderate activity against S. aureus and P. Table 2. Biological activities in the terms of
aeruginosa while compound Ic showed very MIC of the synthesized compounds.
Sr. Compound Minimum inhibitory concentration Minimum
good activity against S. aureus and moderate No. id (MIC) (µ/ml) inhibitory
activity against S. pyogenes. Compound concentration
(µ/ml)
Ig exhibited good activity S. aureus while Gram positive Gram negative Fungus
compound Ih showed moderate activity against bacteria bacteria
S.aureus S.pyogenes E.coli P.aeruginosa C.albicans
S. aureus and good activity against S. pyogenes. MTCC- MTCC- MTCC- MTCC- MTCC-
Compound Il found to posses moderate activity 1 Ia 96
125
442
250
443
500
1688
125
227
250
against S. pyogenes. 2 Ib 250 250 250 500 250
3 Ic 31.25 125 250 250 1000
4 Id 250 1000 125 500 250
In the present study it was observed that most 5 Ie 250 500 500 1000 500
6 If 500 500 250 250 250
of the newly synthesized compounds do not 7 Ig 62.5 1000 500 500 500
posses remarkable anti-fungal activity against 8
9
Ih
Ii
125
1000
62.5
1000
500
1000
500
1000
500
1000
C.albicans 10 Ij 500 250 250 500 1000
11 Ik 1000 250 500 250 250
12 Il 1000 125 250 500 500
R
13 Im 500 500 500 1000 250
R 14 In 500 500 500 1000 500
H DMF
120°C to 130°C
O
15 Io 250 250 1000 500 500
O
O 16 Ip 500 250 250 250 1000
O N
O HN 17 Gentamycin 0.25 0.50 0.05 1.0 -
N
N N 18 Nystatin - - - - 100
O H2 N H
S. aureus=Staphyloccocus aureus, S.
Scheme 1: Reaction scheme for the synthesis pyogenes=Streptococcus pyogenes, E. coli=
of the compoundsI (a-p). Escherichiacoli, P. aeruginosa= Pseudomonas
aeruginosa, C. albicans = Candida albicans.
MIC= Minimum inhibitory concentration.
Conclusions:
Chemistry & Biology Interface 327 Vol. 8 (6), November – December 2018
Chemistry & Biology Interface, 2018, 8, 6, 323-328
Acknowledgements:
References:
Chemistry & Biology Interface 328 Vol. 8 (6), November – December 2018