An efficient eco-friendly synthesis of 4-aryl tetrazolo[1,5-a][1,8]naphthyridine derivatives have been successfully prepared through microwave method in short reaction time. The microwave method has unique advantages, short reaction time, easy workup procedure, and simple purification of the products. Synthesized the entire molecule evaluated for their antimicrobial activity among them compounds 6g and 6a demonstrated highest anti-microbial activity. Moreover, in silico molecular modeling evaluation has done by considering docking scores, hydrogen bond interactions, affinity, and the short distance between ligand and receptor. All the molecules good docking results have shown that binding interactions with the target protein and obtained results were well complemented to the antimicrobial activity.
Research Article
Eco-friendly green construction of 4-Aryl-tetrazolo-[1,5-a][1,8]naphthyridine scaffolds and their in vitro anti-microbial and molecular modeling studies
https://doi.org/10.21203/rs.3.rs-2453479/v1
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Tetrazolo[1
5-a][1
8]naphthyridines
antimicrobial activity
molecular docking studies
In the current research, the treatment and cure of bacterial infections still remainder as an essential and very challenging therapeutic problem, because of the emergence of bacteria resistant to present therapeutic agents. Nitrogen contains substituted heterocyclic compounds play utmost function in medicinal chemistry and they have broad range of natural products and synthetic molecules with most important biological activities1-2. Among these, 1,8-naphthyridine nuclei are contains targets because of their beneficial pharmacological properties, including that anti-inflammatory,3 anti-malarial,4 antioxidant,5 anti-HIV,6 anti-proliferative,7 anti-tumor activity,8 antagonism or agonism of receptors,9 anti-tuberculosis activity10 and gastric anti-secretary activities.11 Some of the biologically active 1,8-naphthyridine derivatives are shown in Figure 1.
Nowadays, the advantages and benefits of microwave condition reactions have become very attractive and powerful technology in the field of pharmaceutical chemistry. Moreover, Microwave heating is expansively used as a convenient source of heating in organic synthesis reactions. The heating is instantaneous and extremely specific. The profit of microwave-supported organic synthesis is widely established and this technique is a simple, faster, and an efficient technology, It is used to drop off the duration of time to carry diverse organic transformations along with high yield, lowest by-products, and minimum energy utilization with maximum selectivity.12-16 In prolongation, of our foregoing studies on the development of green methodologies and biologically active compounds.17-21 We report here in a facile and convenient synthetic strategy for the preparation of 4-aryl tetrazolo[1,5-a][1,8]naphthyridine derivatives in the presence of simple glacial acetic acid formed high yield and these compounds showed interesting antimicrobial activity.
Required chemicals were procured from Merck and all these reagents and chemicals used for reaction without need further purification. The reaction progress was monitored by using thin layer chromatography using solvent hexane and ethyl acetate (7:3) ratio. NMR spectrum recorded by using the model Bruker 400 MHz spectrometer in DMSO-d6. Mass spectrums were recorded by using ESI mass spectrometer and IR was recorded with model Bruker Tensor 27 series FT-IR. The melting points were confirmed by Buchi melting point apparatus. Microanalyses by Carlo-Erba model
Construction procedure of 3-(2-chloro-4-fluorophenyl)-1,8-naphthyridin-2-amine (3)
A mixture of 2-aminonicotinaldehyde 1 (1 m mol, 122.12 mg) active methylene compound 2-(2-chloro-4-fluorophenyl) acetonitrile 2 (1 m mol, 237.21 mg) and piperidine (10%) catalyst used in the reaction interestingly formed desired compound 3 with good yield.
General procedure for the synthesis of 3-(2-chloro-4-fluorophenyl)-1,8-naphthyridin-2(1H)-one (4)
3-(2-chloro-4-fluorophenyl)-1,8-naphthyridin-2-amine 3 (1 m mol, 273.70 mg) which was converted into the desired 3-(2-chloro-4-fluorophenyl)-1,8-naphthyridin-2(1H)-one 4 with an excess of HNO2 formed desired product 4.
Preparation of 2-chloro-3-phenyl-1,8-naphthyridine (5)
A mixture of reaction intermediate 3-aryl-1,8-naphthyridin-2(1H)-one 4 (0.1 mmoL) and POCl3 (15 mL) was added after (5-6 h) under conventional method and under microwave method (2-3 m) obtained good yields.
General procedure for the synthesis of 4-phenyl tetrazolo[1,5-a][1,8]naphthyridine derivatives (6a-h)
2-chloro-3-phenyl-1,8-naphthyridine 5 (0.1 mmoL) and sodium azide (0. 2 mmoL) in the presence of catalytic amount of acetic acid and methanol (10 mL) under conventional method (6-8 h) microwave conditions (3-4 m) for the specified time indicated in (Table I). By the TLC the progress of the reaction was monitored. After that confirmed by TLC, the separated solid crude product was filtered, washed with ethanol, dried and recrystallized from acetic acid obtained analytically pure products (6a-h).
4-phenyltetrazolo [1,5-a][1,8]naphthyridine (6a)
Light yellow solid; mp 211–213 OC; IR (KBr, υmax, cm-1): 3085, 1638, 1478, 736; 1H NMR (400 MHz, DMSO-d6); δ(ppm)9.02 (s, 1H), 8.29-8.07 (d, 2H, J = 7.2 Hz), 7.67-7.52 (d, 2H, J = 7.2 Hz, aromatic CH), 7.53-7.31 (m, 4H, aromatic CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 148.3, 145.2, 139.4, 136.8, 132.8, 129.7, 124.9, 118.2; Mass (ESI) m/z: 247.07; Anal. Calcd. ForC14H9N5: C, 68.01; H, 3.67; N, 28.32 Found: C, 68.08; H, 3.73; N, 28.37%.
4-(4-bromophenyl)tetrazolo[1,5-a][1,8]naphthyridine (6b)
Yellow solid; mp 197-198 OC; IR (KBr, υmax, cm-1):3019, 1634, 1459, 847; 1H NMR (400 MHz, DMSO-d6); δ(ppm) 9.49 (s, 1H), 7.96-7.85 (d, 2H, J = 7.2 Hz), 7.68-7.58 (d, 2H, J = 7.2 Hz, aromatic CH), 7.41-7.48 (m, 2H, aromatic CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 148.7, 140.5, 138.6, 136.8, 134.6, 129.7, 128.4, 120.6; Mass (ESI) m/z: 327.19; Anal. Calcd. ForC14H8BrN5: C, 51.56; H, 2.47; N, 21.47; Found: C, 51.68; H, 2.57; N, 21.71%.
4-(3-chlorophenyl)tetrazolo[1,5-a][1,8]naphthyridine (6c)
Pale yellow solid; mp 221-222 OC; IR (KBr, υmax, cm-1): 1651, 1604, 836 (C-Cl); 1H NMR (400 MHz, DMSO-d6); δ(ppm) 8.96 (s, 1H), 8.07 (s, 1H), 7.76-7.68 (m, 3H, aromatic CH), 7.43 (s, 1H), 7.34 (d, 2H, J = 7.2 Hz, aromatic CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 151.0, 147.8, 139.9, 138.6, 133.7, 132.4, 130.1, 129.3, 125.3, 122.2, 120.0; Mass (ESI) m/z: 281.05; Anal. Calcd. ForC14H8ClN5: C, 59.69; H, 2.86; N, 24.86 Found: C, 59.74; H, 2.89; N, 24.91%.
4-(4-nitrophenyl)tetrazolo[1,5-a][1,8]naphthyridine (6d)
Block solid; mp 168-169 OC; IR (KBr, υmax, cm-1):1659, 1614, 847 (C=N); 1H NMR (400 MHz, DMSO-d6); δ(ppm) 9.46 (s, 1H), 8.17-8.02 (m, 4H, aromatic CH), 7.39 (d, 2H, J = 7.2 Hz), 7.01(s, 1H); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 149.2, 146.2, 139.5, 136.7, 131.6, 129.2, 128.6, 119.7; Mass (ESI) m/z: 292.07; Anal. Calcd. For C14H8N6O2 (292.07): C, 57.54; H, 2.76; N, 28.76; Found: C, 57.59; H, 2.84; N, 28.79%.
4-(3-nitrophenyl)tetrazolo[1,5-a][1,8]naphthyridine (6e)
Light green solid; mp 192-193OC; IR (KBr, υmax, cm-1): 1652, 1602, 854; 1H NMR (400 MHz, DMSO-d6); δ(ppm) 9.69 (s, 1H), 7.48 (d, 2H, J = 7.2 Hz), 7.38-7.45 (m, 5H, aromatic CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 150.0, 148.2, 141.4, 139.0, 137.2, 133.3, 131.4, 129.5, 128.0, 121.3, 117.0; Mass (ESI) m/z:292.07; Anal. Calcd. ForC14H8N6O2: C, 57.54; H, 2.76; N, 28.76; Found: C, 57.58; H, 2.82; N, 28.80%.
4-(4-chlorophenyl)tetrazolo[1,5-a][1,8]naphthyridine (6f)
Light Brown solid; mp 234-235OC; IR (KBr, υmax, cm-1):1647, 1601, 833; 1H NMR (400 MHz, DMSO-d6); δ(ppm) 8.58 (m, 2H), 7.69 (s, 1H), 7.48 (d, 2H, J = 7.2 Hz, aromatic CH), 7.19 (m, 3H, aromatic CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 153.6, 148.3, 139.4, 136.8, 134.6, 132.8, 130.1, 129.3, 128.0, 124.4,121.4,118.7; Mass (ESI) m/z: 281.05; Anal. Calcd. ForC14H8ClN5: C, 59.69; H, 2.86; N, 24.86 Found: C, 59.77; H, 2.81; N, 24.93%.
4-(3-bromophenyl)tetrazolo[1,5-a][1,8]naphthyridine (6g)
Light yellow solid; mp 183-184 OC; IR (KBr, υmax, cm-1): 1657, 1609, 847; 1H NMR (400 MHz, DMSO-d6); δ(ppm) 8.83 (s, 1H), 7.68 (m, 3H), 7.47 (d, 2H, J = 7.2 Hz, aromatic CH), 7.29 (d, 2H, J = 7.2 Hz, aromatic, CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 149.4, 148.2, 139.7, 137.3, 132.4, 129.5, 128.8, 120.3; Mass (ESI) m/z: 325.00; Anal. Calcd. ForC14H8BrN5: C, 51.56; H, 2.47; N, 21.47 Found: C, 51.49; H, 2.52; N, 21.56%.
4-(4-methoxyphenyl)tetrazolo[1,5-a][1,8]naphthyridine (6h)
Yellow solid; mp 162-163 OC; IR (KBr, υmax, cm-1):1652, 1606, 875; 1H NMR (400 MHz, DMSO-d6); δ(ppm)9.18 (s, 1H), 8.27-8.19 (m, 4H, aromatic CH), 7.69-7.62 (m, 3H, aromatic CH); 13C NMR (400 MHz; DMSO-d6);δ(ppm) 157.6, 151.4, 148.3, 143.9, 139.0, 138.1, 132.4, 131.5, 128.0, 122.6, 118.2, 55.9; Mass (ESI) m/z: 277.10; Anal. Calcd. For C15H11N5O: C, 64.97; H, 4.00; N, 25.26; Found: C, 64.85; H, 4.11; N, 25.29%.
Biology
Antimicrobial activity
All the prepared molecules (6a-h) were tested antibacterial and anti-fungal activity by reported literature Agar disk-diffusion method [18]. For the antibacterial activity taken gram positive and gram negative pathogenic bacteria at three different concentration checked zone of inhibition and we have taken reference drug Penicillin. Tested all the molecules shown good activity, for fungal studies took two strains and checked at three different concentrations compared with reference drug Clotrimazole, tested all compounds displayed excellent fungal activity. Particularly, 6g and 6a molecules exhibited utmost activity shown in table 2.
Table 1 Inhibition (mm) values of compounds (6a–h) at 100μg/disk against at three different concentrations
|
(ZOI; in mm) |
||||||||||||
|
Products |
B.S |
F.S |
||||||||||
|
S.A |
E.C |
C.A |
A.N |
|||||||||
|
10 |
20 |
30 |
10 |
20 |
30 |
10 |
20 |
30 |
10 |
20 |
30 |
|
|
6a |
7 |
17 |
26 |
8 |
16 |
25 |
7 |
15 |
26 |
8 |
16 |
25 |
|
6b |
5 |
10 |
19 |
4 |
11 |
21 |
6 |
11 |
20 |
6 |
12 |
21 |
|
6c |
6 |
11 |
22 |
5 |
12 |
22 |
7 |
12 |
21 |
6 |
13 |
22 |
|
6d |
6 |
16 |
25 |
7 |
15 |
23 |
6 |
14 |
25 |
7 |
14 |
24 |
|
6e |
5 |
12 |
19 |
4 |
12 |
19 |
5 |
13 |
20 |
7 |
13 |
18 |
|
6f |
4 |
11 |
21 |
5 |
10 |
18 |
6 |
12 |
19 |
6 |
12 |
16 |
|
6g |
9 |
18 |
28 |
8 |
19 |
27 |
8 |
18 |
26 |
8 |
17 |
27 |
|
6h |
7 |
14 |
23 |
6 |
13 |
22 |
5 |
14 |
22 |
4 |
12 |
21 |
|
P |
10 |
18 |
30 |
10 |
19 |
29 |
- |
- |
- |
- |
- |
- |
|
C |
- |
- |
- |
- |
- |
- |
9 |
19 |
30 |
10 |
19 |
29 |
(ZOI= Zone of Inhibition, B.S= Bacterial Strains, (S.A= Staphylococus Aureus, E.C= Escherichia Coli), F.S=Fungal Strains (C.A= Candida Albicans, A.N= Aspergillus Niger) and P= Penicillin, C= Clotrimazole)
Molecular Modeling Studies
Prepared compounds molecular structure was was prepared in chem draw software drawn structures were minimized energy using the energy minimization module of discovery studio version 4.1 (DS 4.1 Accelrys Inc., San Diego, CA, USA) and applied CHARMM force field. The three-dimensional structure of TNF-alpha inducing protein was retrieved from Protein Data Bank database with PDB: 3GIO Jang et al, 200918. The molecules structure preparation and correction of protein were performed using Discovery Studio 4.1 suite. The target protein file was make by eliminating the structural water molecule, hetero atoms and co-factors by leaving only the residues associated with protein by using ADS tool was used to prepare target protein file addition of polar hydrogen’s to the macromolecule. The molecular docking was performed using ligand fit module and obtained results were scrutinized based on number of H-bonds and highest dock score by SS Viewer Shyam et al. 201319. The molecular modeling results showed that all molecules exhibited very good binding energies towards the receptor active sites. Molecular docking results are identified based on the best interacted ligands, lowest binding energy, high docking score and the number of H-bonding, hydrophobic interactions at receptor site. The Table.2 represents the docking score and binding energies of compounds (6a-h). We performed docking with 8 ligands and identified the best interacted ligands with receptors on the basis of interactions and H-Bond distances as shown in Table 2 and (Figs. 2, 3). We performed for the all the molecules ADMET properties shown in Table 3 Compounds 6g, and 6a has shown good interactions with the receptor.
Table 2 Molecular docking interactions and energy scores of compounds (6a-h).
|
Analog |
Receptor 3GIO (Interacting atoms) |
Ligand (atoms) |
H-bond Distance (Ao) |
Docking energy (Kcal/mol) |
|
6a |
PRO567O |
NH |
2.60 |
-89.6985 |
|
PRO568O |
NH |
2.65 |
||
|
TYR610O |
NH |
3.11 |
||
|
6b |
ASP532OD2 |
NH |
2.74 |
-73.6618 |
|
6c |
PRO567O |
NH |
2.68 |
-77.8808 |
|
TYR610O |
NH |
3.17 |
||
|
6d |
ALA533NH |
O |
2.61 |
-79.8844 |
|
PRO567O |
NH |
2.77 |
||
|
PRO567O |
NH |
2.78 |
||
|
6e |
GLN574N |
O |
2.85 |
-86.2321 |
|
LYS600NH |
O |
3.35 |
||
|
6f |
PRO567NH |
O |
2.70 |
-77.8808 |
|
PRO567NH |
O |
2.79 |
||
|
TYR610O |
NH |
3.07 |
||
|
6g |
PRO567O |
NH |
2.55 |
-84.4763 |
|
PRO567O |
NH |
2.64 |
||
|
TYR610O |
NH |
3.13 |
||
|
6h |
PRO567O |
NH |
2.71 |
-75.6359 |
|
ALA533NH |
O |
3.07 |
Table 3 ADMET properties of the synthesized molecules (6a-h).
|
Analog |
ADMET-BBB |
ADMET Solubility |
ADMET Hepatotoxicity Probability |
ADMET CYP2D6 Probability |
ADMET ALOGP98 |
ADMET PSA 2D |
|
6a |
0.127 |
-5.314 |
0.947 |
0.663 |
3.490 |
50.392 |
|
6b |
0.101 |
-5.235 |
0.927 |
0.643 |
3.406 |
50.392 |
|
6c |
-0.814 |
-4.615 |
0.953 |
0.376 |
2.636 |
93.215 |
|
6d |
-0.814 |
-4.621 |
0.960 |
0.623 |
2.636 |
93.215 |
|
6e |
0.101 |
-5.232 |
0.933 |
0.722 |
3.406 |
50.392 |
|
6f |
0.127 |
-5.319 |
0.953 |
0.653 |
3.490 |
50.392 |
|
6g |
-0.508 |
-4.107 |
0.947 |
0.663 |
2.499 |
71.207 |
|
6h |
0.109 |
-5.285 |
0.931 |
0.652 |
3.412 |
50.398 |
BBB = blood-brain barrier (BBB) permeability, ADMET PSA 2D (polar surface area) ADMET AlogP98
Table 4 Molecular Interactions between Ligands and Nicotinic Acetylcholine Receptors
|
Compounds |
Energy |
VDW |
H-bond |
Electrostatic interactions |
|
6a |
-133.453 |
-116.39 |
-17.0631 |
38.60 |
|
6b |
-132.25 |
-119.34 |
-12.9101 |
38.23 |
|
6c |
-138.077 |
-121.254 |
-16.8226 |
37.62 |
|
6d |
-156.26 |
-128.209 |
-27.1998 |
33.01 |
|
6e |
-136.417 |
-111.735 |
-24.6818 |
29.86 |
|
6f |
-138.93 |
-121.968 |
-16.9616 |
37.05 |
|
6g |
-137.149 |
-121.289 |
-15.8596 |
38.15 |
|
6h |
-141.388 |
-120.936 |
-20.4516 |
37.8 |
A illustration for the formation of 4-Aryl tetrazolo[1,5-a][1,8]naphthyridine derivatives (6a–h) were successfully synthesized by the involving of 2-chloro-3-phenyl-1,8-naphthyridine with sodium azide an easily available cheap material and catalyzed by glacial acetic acid under conventional and microwave method is shown in Scheme IV. The reaction intermediate 3-(2-chloro-4-fluorophenyl)-1,8-naphthyridin-2-amine 3 obtained from the reaction of 2-aminonicotinaldehyde 1 with appropriate active methylene compounds 2 in the presence of KOH gave the corresponding compounds (3a-h). Then HNO2 reacted with 3-(2-chloro-4-fluorophenyl)-1,8-naphthyridin-2-amine 3 furnished 3-phenyl-1,8-naphthyridin-2(1H)-ones 4 reacted with POCl3 under microwave heating yielded 2-chloro-3-phenyl-1,8-naphthyridine 5 compounds with good yields. Compound 5 was prepared by according to the following published literature procedure 20. The title compounds 4-phenyl tetrazolo[1,5-a][1,8]naphthyridine derivatives (6a-h) were prepared by reacting the intermediate 2-chloro-3-phenyl-1,8-naphthyridines with sodium azide in the presence of catalytic amount of glacial acetic acid furnished corresponding compounds (6a-h) with good yields under microwave condition were summarized in Table 5.
The reaction is rapid and very clean reaction and experimental procedure for these reactions is remarkably simple. Moreover, the compounds were furnished with a high degree of purity by this procedure and obtained analytically pure products. All the newly synthesized compounds were confirmed by IR, 1H NMR, 13C NMR and mass spectral data as well as elemental analyses studies.
we reported the green method for synthesis of title compounds 4-aryl-tetrazolo [1,5-a][1,8]naphthyridine by the reaction of 2-chloro-3-phenyl-1,8-naphthyridine with cheap and an easily available sodium azide and catalyzed by simple glacial acetic acid furnished good yields under microwave method in short reaction time compare to the conventional method. Activity of the prepared molecules has shown good results specially 6g and 6a displayed highest activity. In silico modeling well complemented to the biological applications.
Acknowledgement
The authors are thankful to the Head of the Department of Chemistry, Osmania University and Indian Institute of Technology, Jodhpur, India for Providing Research facilities.
Declaration
Ethical approval
This article does not encompass any studies with human participants or animals performed by any of the authors.
Competing Interest
The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper.
Author’s contributions
BS=Design and synthesis and drafted the manuscript’s first author, DR= Wrote the manuscript, PS= Microbial activity and docking studies, KK= Analysis data, AA= prepared figures, BS= reviewed the manuscript
Funding
Not applicable.
Availability of data and materials
We attached a supporting file
Conflict of interest
There are no conflicts of interest to declare.
- C. T. Barrett, J. F. Barrett, Curr. Opin. Biotechnol, 14, 621 (2003).
- M. Shivani, N. Adinarayana, M. Sankaranarayanan, G.C.S.K. Venkata, Future Medicinal Chem. 13, 18 (2021).
- G. Roma, M.Di Braccio, G. Grossi, D.Piras, V.Ballabeni, M.Tognolini, S. Bertoni, E.Barocelli, Eur. J. Med. Chem, 45, 352 (2010).
- O.Srinivas, S. Praveen Kumar, K. Rivas, K. Yokoyama.L. Christophe, M.J. Verlinde, D. Debopamchakrabarti, C. Wesley, b.Vanvoorhis, H.Michael, C.Gelba, BioMed Chem Lett.18, 494, (2008).
- I.N. Bardasov, A.Y. Alekseeva, O.V. Ershov, M. A. Mar’yasov, Pharm. Chem. J. 54, 459–461, (2020).
- V. Massari, D, Daelemans, M.L. Barreca, J. Med. Chem. 53, 641, (2010).
- M.H. Sherlock, J.J.Kaminski, W.C.Tom, J.F.Lee, S.C.Wong, W. Kreutner, R.W. Bryant, A.T. McPhail, J. Med. Chem. 31, 2108, (1988).
- M.S. Behaloa, Giuseppe Mele, J. Heterocyclic Chem. 54, 295, (2017).
- P. Raboisson, R.L. Desjarlais, R. Reed, J. Lattanze, M. Chaikin, C.L. Manthey, B. Tomczuk, J.J, Marugan, Eur. J. Med. Chem. 42, 334, (2007).
- D. Sriram, P. Senthilkumar, M. Dinakaran, P. Yogeeswari, A. China, V. Nagaraja, J. MedChem. 50, 6232, (2007).
- A. Santilli, A.C. Scotese, R.F. Bauer, S.C. Bell, J. Med. Chem. 30, 2270, (1987).
- M.S. Kamel, A. Belal, M.O. Aboelez, E.K. Shokr, H. Abdel-Ghany, H.S. Mansour, A.M. Shawky, M.A.E.A.A.A. El-Remaily, Molecules 27, 2061, (2022).
- M. Lancaster. Principles of sustainable and green chemistry, Handbook of green chemistry and technology, pp.10-27, (2002)
- L.A. Martinho, C.K.Z. Andrade, J. Heterocycl. Chem., 1-13, (2022).
- S.P. Musthafa, J. Antony, R. Natarajan, J.P. Rappai, New J. Chem. 46, 9825, (2022).
- A. Loupy, Microwaves in Organic Synthesis, Wiley-VCH: Weinheim, p 68, 2002.
- Dharavath Ravi, Banoth Sonyanaik, Boda Sakram, Results in Chemistry, 4, 100611, (2022).
- B. Sakram, B. Sonyanaik, K. Ashok, S.Rambabu, S.K Johnmiya, Res ChemIntermed. 42, 1699, (2016).
- B. Sakram, B. Sonyanaik, K. Ashok, S. RambabuRes ChemIntermed.42, 7651, (2016).
- B. Sakram, B. Sonyanaik, K. Ashok, S. Rambabu, D. Ravi, A. Kurumanna, P. Shyam, Res ChemIntermed. 43, 1881, (2017).
- B. Sonyanaik, P. Shyam, B. Sakram, J. H. Chem, 55, 709, (2018).
- A. W.Bauer, M. M.Kirby, J. C.Sherris, M.Truck, Am J ClinPathol. 45, 493, (1966).
- J.Y. Jang, H.J.Yoon, J.Y. Yoon, H.S.Kim, S.J.Lee, K.H.Kim, D.J.Kim, S. Jang, B.G.Han,B.I. Lee,S.W.Suh, J. Mol. Biol. 392, 191 (2009).
- P. Shyam, J. Harika, B. Manjula, International Journal of Innovative Technology and Exploring Engineering. 3, 2278, (2013).
- K. Mogilaiah, H. Ramesh Babu, N. Vasudeva Reddy. Synthetic Communications32, 2377, (2006).
Scheme 4 is available in Supplementary Files section.
No competing interests reported.
- SUPPORTINGFILE11.docx
- Scheme4.png
Scheme IVSynthesis of novel 4-phenyl tetrazolo[1,5-a][1,8]naphthyridine derivatives.
