Synthesis, Characterization, and Evaluation of the Antibacterial Activity of Some Novel Thiazolo- [1,2,4] Triazolo [1,5-a] Pyridine Derivatives

Indian Journal of Advanced Chemistry (IJAC) ISSN: 2582-8975 (Online), Volume-5 Issue-2, October 2025 1 Published By: Lattice Science Publication (LSP) © Copyright: All rights reserved. Retrieval Number: 100.1/ijac.B203005021025 DOI: 10.54105/ijac.B2030.05021025 Journal Website: www.ijac.latticescipub.com Synthesis, Characterization, and Evaluation of the Antibacterial Activity of Some Novel Thiazolo- [1,2,4] Triazolo [1,5-a] Pyridine Derivatives Pendam Prashanth Babu, Pingili Upendra, Dharanipathi Venkateshwar Rao Abstract: A novel four-step scientific protocol has been reported for the synthesis of thiazolo- [1,2,4] triazolo[1,5-a] pyridine and its derivatives (6a-c) as target moieties in good overall yields by using 1-(2-(Trifluoromethyl)-5-methylthiazol-4yl) ethanone (1) as starting compound. The IR, PMR, Mass spectral data, and elemental analysis validated the chemical structures of all the intermediates and products. Furthermore, the newly synthesised intermediates and final derivatives were screened for their antibacterial activity against different bacterial strains, and it was found that a few of them exhibited noteworthy antibacterial activity with varying degrees of disparity. Keywords: Thiazole, 1,2,4-Triazole, Pyridine Derivatives, Antibacterial Activity Abbreviations: IR: Infrared PMR: Proton Magnetic Resonance NMR: Nuclear Magnetic Resonance H: Hour 0C: Degree Centigrade MM: Millimetre TLC: Thin Layer Chromatography CM: Centimetre FT: Fourier Transform MHz: Mega Hertz PPM: Parts Per Million TMS: Tetra Methyl Silane GC-MS: Gas Chromatography Mass Spectrometry EI: Electron Ionization CE: Capillary Electrophoresis Mol: Mole ML: Millilitre MP: Melting Point M/Z: Mass-To-Charge Ration Manuscript received on 02 May 2025 | First Revised Manuscript received on 19 May 2025 | Second Revised Manuscript received on 16 September 2025 | Manuscript Accepted on 15 October 2025 | Manuscript published on 30 October 2025. *Correspondence Author(s) Dr. Pendam Prashanth Babu*, Professor, Department of Chemistry, Sree Chaitanya College of Engineering, Karimnagar, Hyderabad (Telangana), India. Email ID: [email protected], ORCID ID: 0009-0000-5748-2256 Dr. Pingili Upendra, Assistant Professor, Department of Chemistry, Government Degree College for Women (Autonomous), Nalgonda, Hyderabad (Telangana), India. Email ID: [email protected] Dr. Dharanipathi Venkateshwar Rao, Assistant Professor, Department of Chemistry, Government Degree College, Ibrahimpatnam, Ranga Reddy, Hyderabad (Telangana), India. Email ID: [email protected] © The Authors. Published by Lattice Science Publication (LSP). This is an open access article under the CC-BY-NC-ND license http://creativecommons.org/licenses/by-nc-nd/4.0/ I. INTRODUCTION Heterocyclic chemistry is one of the most complex and intriguing branches of organic chemistry. Many broader aspects of this section are recognised as disciplines of general significance that impact nearly all aspects of modern organic, medicinal, and biological chemistry. The heterocyclic compounds constitute the most extensive and most varied family of organic compounds. These offer a high degree of structural diversity and have proven to be broadly and economically useful as therapeutic agents. They are widely found in natural products, including nucleic acids, plant alkaloids, anthocyanins, flavones, hem, chlorophyll, vitamins, proteins, and hormones. Synthetically produced heterocycles have enormous potential as the most promising molecules for lead structures in the design of various agrochemicals, pharmaceuticals, and veterinary products, and thus play a key role in human life. N NN OH N N NF F N NN OH F F N N F N NN O OH OH OH NH2 O I II III N H N N NNH N N N N N IV V N N NN N N N N N NN Cl VI VII NN N F F O NH2 N NN S N O HO O OH O VIII IX The derivatives of the triazole ring have significant application value in various fields, including agrochemistry [1] and material chemistry [2]. Its unique structure facilitates the formation of a variety of enzymes and receptors, inducing broadspectrum biological Synthesis, Characterization, and Evaluation of the Antibacterial Activity of Some Novel Thiazolo- [1,2,4] Triazolo [1,5-a] Pyridine Derivatives 2 Published By: Lattice Science Publication (LSP) © Copyright: All rights reserved. Retrieval Number: 100.1/ijac.B203005021025 DOI: 10.54105/ijac.B2030.05021025 Journal Website: www.ijac.latticescipub.com activities, such as anticancer [3], antituberculosis [4], antibacterial [5], and anti-HIV [6]. Its derivatives have been widely applied in many medicinal scaffolds like, Fluconazole (I) [7], Voriconazole (II) [8], Ribavirin (III) [9], Rizatriptan (IV) [10], Letrozole (V) [11], Anastrozole (VI) [12], Vorozole (VII) [13], Rufinamide (VIII) [14], and Tazobactam (IX) [15]. On the other hand, Pyridine derivatives abundantly exist in nature, and they play a vital role in the field of heterocyclic chemistry [16]. Such compounds are widely used in various applications of medicinal science [17], and their derivatives have been synthesised and studied for their [18] biological and pharmacological significance [19]. Some of them proved to possess antiviral [20], anti-diabetic [21], antimicrobial [22], antitumor [23], antiparasitic [24], and neurotropic activities [25]. II. RESULTS AND DISCUSSION With the increasing interest in triazole compounds as potential therapeutic agents and in continuation of our studies to design and construct some novel heterocycles with this core in the structure, herein we have been interested in reporting the synthesis of a few thiazole-based thiazolo- [1,2,4] triazolo [1,5-a] pyridine and its derivatives (6a-c). The constitution of all the compounds has been identified by their spectral data (IR, PMR, and Mass) and elemental analysis. Finally, the antibacterial activity of compounds (46) was also evaluated against a few bacterial strains. As per the synthetic sequence of the present investigation shown in Scheme 1, the reaction is initiated by the Aldol condensation of starting material, 1-(2-(Trifluoromethyl)-5methylthiazol-4-yl)ethanone (1) with substituted benzald ehyde (2a-c) to produce the corresponding, (E)-3-(2phenyl)-1-(2-(trifluoromethyl)-5-methylthiazol-4-yl)prop-2en-1-one (3a-c) by using NaOH as a base in boiling ethanol for 8-10 h with steady stirring. The latter intermediate, 2Amino-4-(phenyl)-6-(2(trifluoromethyl)-5-methylthiazol-4yl) pyridine-3-carbonitrile (4a-c) has been prepared via cyclisation by refluxing the mixture of 3a-c with malononitrile using ammonium acetate as a base in absolute ethanol under constant stirring for 6-7 h. In the further conversion at refluxing temperature (140150 0C) for 7-9 h, the intermediate 4a-c with acetonitrile using AlCl3 as a catalyst produced the corresponding N-(4- (2-phenyl)-3-cyano-6-(2-trifluoromethyl)-5-methylthiazol-4yl) pyridine-2-yl) acetamide (5a-c) in good yields. To achieve the target derivatives, 7-(phenyl)-5-(2- (trifluoromethyl)-5-methylthiazol-4-yl)-2-methyl-[1,2,4]- triazolo[1,5-a] pyridine-8-carbonitrile (6a-c) through cyclisation, the final intermediate, 5a-c is reacted with MnO2 in benzene under reflux for 10-12 h and yield of the obtained products ranged within 74-79 %. III. ANTIBACTERIAL ACTIVITY The newly synthesized compounds 4a-c, 5a-c, and 6a-c have been evaluated in vitro for their antibacterial activity against various bacterial strains such as Pseudomonas aeruginosa, Bacillus subtilis, Salmonella paratyphi, Staphylococcus aureus, Shigella flexneri, and Escherichia coli by cup-plate method [26] and the zone of inhibition was determined in mm. The activity of the tested compounds was compared with that of the known antibacterial agent Ampicillin, and the results are disclosed in Table 1. According to the screening output, it is observed that derivatives 4a-c, 5a-c, and 6a-c exhibited low to good activity, with a degree of disparity. Products 6a and 6c disclosed the highest activity with a 27 mm zone of inhibition each, and compound 4a exhibited the lowest activity with 12 mm against P. aeruginosa. The evaluation of the antibacterial activity against B. subtilis revealed that the most active appeared to be derivative 6b, with an inhibition of 21 mm, while 4c had the least activity. Similarly, compound 6b showed very high activity with a 24 mm zone of inhibition against S. paratyphi. The most active derivatives were 6b against S. aureus, 6c towards S. flexneri, and 6a in the direction of E. coli, with zone of inhibition of 27 mm, 24 mm, and 28 mm, respectively. It is interesting to note that none of the compounds in the present investigation is inactive towards any bacterial strain. IV. EXPERIMENTAL SECTION Melting points were determined with a B-540 Melting point Analyzer and are uncorrected. TLC was performed with Merck Silica gel 60 F254 silica gel plates. The IR spectra (ν cm-1) were recorded on a Perkin Elmer Spectrum Bx FT-IR spectrometer using KBr tablet pellets. The 1H NMR was recorded in CDCl3 or DMSO-d6 as a solvent on the Varian Gemini NMR spectrometer at 300 MHz. Chemical shifts were expressed as δ, ppm relative to TMS. Mass spectra were measured with a Shimadzu GC-MS-QP-1000 EX mass spectrometer in the EI (70 eV) mode. Elemental analyses have been executed with a CE-440 elemental analyser. Preparation of (E)-3-(2-substituedphenyl)-1-(2-(trifluoro methyl)-5-methylthiazol-4-yl) prop-2-en-1-ones (3a-c) A solution of 1-(2-(Trifluoromethyl)-5-methylthiazol-4-yl) ethanone (1) (0.01 mol) and substituted benzaldehyde (2a-c) (0.01 mol), sodium hydroxide solution (2%, 3 mL) in absolute ethanol (30 mL) was refluxed for 8-10 h. After completion of the reaction, the reaction mixture was poured onto ice-cold water (50 mL). The formed precipitate was filtered off, washed with water, and dried. Purification was carried out by dissolving in ethanol to give pure (E)-3-(2substitutedphenyl)-1-(2-(trifluoromethyl)-5-methylthiazol-4yl) prop-2-en-1-ones (3a-c). Preparation of 2-Amino-4-(2-substituedphenyl)-6- (2(trifluo romethyl)-5-methylthiazol-4-yl) pyridine-3carbonitriles (4a-c) A mixture of compound 3a-c (0.01 mol), malonitrile (0.01 mol), and ammonium acetate (0.07 mol) was dissolved in absolute ethanol (20 mL). The resulting solution was refluxed on a water bath with uniform stirring for 6-7 h. After achieving the reaction, Indian Journal of Advanced Chemistry (IJAC) ISSN: 2582-8975 (Online), Volume-5 Issue-2, October 2025 3 Published By: Lattice Science Publication (LSP) © Copyright: All rights reserved. Retrieval Number: 100.1/ijac.B203005021025 DOI: 10.54105/ijac.B2030.05021025 Journal Website: www.ijac.latticescipub.com N S CF3 O +H O R (i) N S CF3 OR (ii) N S CF3 NCN NH2 R (iii) N S CF3 NCN NH NH R N S CF3 CN N N N R (iv) 13a-c 4a-c 5a-c 6a-c 2a-c Scheme 1: Preparation of Thiazolo- [1,2,4] Triazolo[1,5-a] Pyridines (6a-c) Reagents and conditions: (i) Ethanol, NaOH, reflux, 8-10h; (ii) Malononitrile, CH3COONH4, ethanol, reflux, 6-7h; (iii) AlCl3, acetonitrile, 140-150 0C, 7-9h; (iv) MnO2, benzene, reflux, 10-12h; 2-6 (a) R = Br, (b) R = NO2, (c) R = OCH3 Table-I: Antibacterial Activity of Compounds 4a-c, 5a-c and 6a-c Entry P. auregenosa B. subtilis S. paratyphi S. aureus S. flexneri E. coli 4a 12 10 13 14 11 12 4b 18 15 16 16 14 16 4c 16 09 10 17 10 14 5a 21 18 12 14 16 17 5b 22 16 17 20 21 21 5c 25 20 15 24 20 23 6a 27 17 20 21 23 28 6b 22 21 24 27 21 25 6c 27 20 18 25 24 27 Standard 30 24 26 33 30 33 The residue was dropped into ice-cold water, and neutralised with dilute HCl to yield the crude product, which later was recrystallised from ethanol to obtain pure 2Amino-4-(2-substitutedphenyl)-6-(2(trifluoromethyl)-5methylthiazol-4-yl) pyridine-3-carbonitriles (4a-c). Preparation of N-(4-(2-Substited phenyl)-3-cyano-6-(2trifluoromethyl)-5-methylthiazol-4-yl) pyridine-2-yl) acetamides (5a-c) A mixture of compound 4a-c (0.01 mol), dry AlCl3 (0.02 mol), and acetonitrile (2 mL) was heated in an oil bath at 140-150 0C for 7-9 h with constant stirring. After fulfilment of the reaction, the residue was cooled and dropped in icecold water to precipitate the crude product which was later filtered off, washed with water, and crystallised from ethanol to offer N-(4-(2-Substited phenyl)-3-cyano-6-(2trifluoromethyl)-5-methylthiazol-4-yl) pyridine-2-yl) acetamides (5a-c) in pure form. Preparation of 7-(2-Substitutedphenyl)-5-(2-(trifluoro methyl)-5-methylthiazol-4-yl)-2-methyl-[1,2,4]- triazolo[1,5-a] pyridine-8-carbonitriles (6a-c) The solution of compound 5a-c (0.01) and MnO2 (0.01 mol) in benzene (25 mL) was heated at reflux temperature for 10-12 h. After the realisation of the reaction, the reaction mixture was filtered hot. Solvent was evaporated to collect crude product which was filtered, washed, and recrystallized from ethanol to offer pure 7-(2-Substitutedphenyl)-5-(2- (trifluoromethyl)-5-methylthiazol-4-yl)-2-methyl-[1,2,4]- triazolo[1,5-a] pyridine-8-carbonitriles (6a-c). V. PHYSICAL AND SPECTRAL DATA (E)-3-(2-Bromophenyl)-1-(2-(trifluoromethyl)-5methylthiazol-4-yl)prop-2-en-1-one (3a): Colour: Brown, Yield: 74%, Mp: 125-127 0C, IR (KBr, ν, cm-1): 3045 (C-H, Ar), 2974 (C-H, CH3), 1648 (C=O), 1625 (=C-H), 1584 (C=C, Ar), 1465 (C=N); PMR (CDCl3, δ, ppm): 7.79-7.52 (m, 4H, Ar-H), 7.12 (d, 1H, J = 14.5 Hz, COCH=), 6.48 (d, 1H, J = 14.5 Hz, Ar CH), 2.85 (s, 3H, CH3); Mass (EI, m/z): 375; Elemental analysis: Calculated for C14H9BrF3NOS: C44.70, H-2.41, Br-21.24, F-15.15, N-3.72, O-4.25, S-8.52. Found: C-44.65, H-2.41, Br-21.22, F-15.13, N-3.72, O-4.25, S-8.52. (E)-3-(2-Nitrophenyl)-1-(2-(trifluoromethyl)-5methylthiazol-4-yl)prop-2-en-1-one (3b): Colour: Yellow, Yield: 79%, Mp: 114-116 0C, IR (KBr, ν, cm-1): 3038 (C-H, Ar), 2969 (C-H, CH3), 1645 (C=O), 1632 (=C-H), 1592 (C=C, Ar), 1472 (C=N); PMR (DMSO-d6, δ, ppm): 7.727.49 (m, 4H, Ar-H), 7.21 (d, 1H, J = 15.2 Hz, COCH=), 6.58 (d, 1H, J = 15.2 Hz, ArCH=), 2.79 (s, 3H, CH3); Mass (EI, m/z): 342; Elemental analysis: Calculated for C14H9F3N2O3S: C-48.98, H-2.94, F-16.60, N-8.16, O-13.98, S-9.34. Found: C-48.84, H-2.94, F-16.58, N-8.16, O-13.96, S-9.33. (E)-3-(2-Methoxyphenyl)-1-(2-(trifluoromethyl)-5methylthiazol-4-yl)prop-2en-1-one (3c): Colour: Pale yellow, Yield: 71%, Mp: 130-132 0C, IR (KBr, ν, cm- Synthesis, Characterization, and Evaluation of the Antibacterial Activity of Some Novel Thiazolo- [1,2,4] Triazolo [1,5-a] Pyridine Derivatives 4 Published By: Lattice Science Publication (LSP) © Copyright: All rights reserved. Retrieval Number: 100.1/ijac.B203005021025 DOI: 10.54105/ijac.B2030.05021025 Journal Website: www.ijac.latticescipub.com 1): 3044 (C-H, Ar), 2975 (C-H, CH3), 1652 (C=O), 1640 (=C-H), 1588 (C=C, Ar), 1462 (C=N); PMR (CDCl3, δ, ppm): 7.69-7.40 (m, 4H, Ar-H), 7.25 (d, 1H, J = 16.0 Hz, COCH=), 6.51 (d, 1H, J = 16.0 Hz, ArCH=), 3.25 (s, 3H, OCH3), 2.81 (s, 3H, CH3); Mass (EI, m/z): 327; Elemental analysis: Calculated for C15H12F3NO2S: C-55.04, H-3.70, F17.41, N-4.28, O-9.78, S-9.80. Found: C-54.95, H-3.70, F17.39, N-4.28, O-9.77, S-9.79. 2-Amino-4-(2-Bromophenyl)-6-(2(trifluoromethyl)-5methylthiazol-4-yl)pyridine-3-carbonitrile (4a): Colour: Gray, Yield: 75%, Mp: 121-123 0C, IR (KBr, ν, cm-1): 3235 (N-H, NH2), 3062 (C-H, Ar), 2962 (C-H, CH3), 2236 (C≡N), 1594 (C=C, Ar), 1455 (C=N); PMR (DMSO-d6, δ, ppm): 8.35 (s, 2H, NH2), 7.58-7.32 (m, 5H, Ar-H), 2.74 (s, 3H, CH3); Mass (EI, m/z): 438; Elemental analysis: Calculated for C17H10BrF3N4S: C-46.48, H-2.29, Br-18.19, F-12.98, N-12.76, S-7.30. Found: C-46.45, H-2.29, Br18.17, F-12.97, N-12.75, S-7.30. 2-Amino-4-(2-Nitrophenyl)-6-(2(trifluoromethyl)-5methylthiazol-4-yl)pyridine-3-carbonitrile (4b): Colour: Brown, Yield: 71%, Mp: 141-143 0C, IR (KBr, ν, cm-1): 3241 (N-H, NH2), 3055 (C-H, Ar), 2972 (C-H, CH3), 2242 (C≡N), 1584 (C=C, Ar), 1464 (C=N); PMR (CDCl3, δ, ppm): 8.31 (s, 2H, NH2), 7.62-7.38 (m, 5H, Ar-H), 2.78 (s, 3H, CH3); Mass (EI, m/z): 405; Elemental analysis: Calculated for C17H10F3N5O2S: C-50.37, H-2.49, F-14.06, N-17.28, O-7.89, S-7.91. Found: C-50.32, H-2.49, F-14.05, N-17.26, O-7.89, S-7.91. 2-Amino-4-(2-Methoxyphenyl)-6-(2(trifluoromethyl)-5methylthiazol-4-yl) pyridine-3-carbonitrile (4c): Colour: Light brown, Yield: 77%, Mp: 109-111 0C, IR (KBr, ν, cm-1): 3262 (N-H, NH2), 3060 (C-H, Ar), 2977 (C-H, CH3), 2252 (C≡N), 1578 (C=C, Ar), 1469 (C=N); PMR (CDCl3, δ, ppm): 8.39 (s, 2H, NH2), 7.68-7.42 (m, 5H, Ar-H), 3.19 (s, 3H, OCH3), 2.80 (s, 3H, CH3); Mass (EI, m/z): 390; Elemental analysis: Calculated for C18H13F3N4OS: C-55.38, H-3.36, F-14.60, N-14.35, O-4.10, S-8.21. Found: C-55.31, H-3.36, F-14.58, N-14.33, O-4.10, S-8.20. N-(4-(2-Bromophenyl)-3-cyano-6-(2-trifluoromethyl)-5methylthiazol-4-yl)pyridine-2-yl)acetamide (5a): Colour: Gray, Yield: 81%, Mp: 144-146 0C, IR (KBr, ν, cm-1): 3254 (N-H, NH2), 3051 (C-H, Ar), 2962 (C-H, CH3), 2241 (C≡N), 1565 (C=C, Ar), 1478 (C=N); PMR (DMSO-d6, δ, ppm): 7.71-7.49 (m, 5H, Ar-H), 7.21 (s, 1H, =NH), 4.52 (s, 1H, NH), 2.62 (s, 3H, CH3), 2.48 (s, 3H, NH=CCH3); Mass (EI, m/z): 479; Elemental analysis: Calculated for C19H13BrF3N5S: C-47.51, H-2.79, Br-16.64, F-11.87, N14.58, S-6.68. Found: C-47.40, H-2.79, Br-16.62, F-11.85, N-14.56, S-6.68. N-(4-(2-Nitrophenyl)-3-cyano-6-(2-trifluoromethyl)-5methylthiazol-4-yl)pyridine-2-yl)acetamide (5b): Colour: Ash, Yield: 85%, Mp: 139-141 0C, IR (KBr, ν, cm-1): 3264 (N-H, NH2), 3048 (C-H, Ar), 2958 (C-H, CH3), 2260 (C≡N), 1574 (C=C, Ar), 1472 (C=N); PMR (CDCl3, δ, ppm): 7.69-7.29 (m, 5H, Ar-H), 7.30 (s, 1H, =NH), 4.50 (s, 1H, NH), 2.67 (s, 3H, CH3), 2.52 (s, 3H, NH=CCH3); Mass (EI, m/z): 446; Elemental analysis: Calculated for C19H13F3N6O2S: C-51.12, H-2.94, F-12.77, N-18.83, O-7.17, S-7.18. Found: C-51.01, H-2.94, F-12.76, N-18.81, O-7.17, S-7.18. N-(4-(2-Methoxyphenyl)-3-cyano-6-(2-trifluoromethyl)- 5-methylthiazol-4-yl)pyridine-2-yl)acetamide (5c): Colour: Gray, Yield: 82%, Mp: 114-116 0C, IR (KBr, ν, cm1): 3248 (N-H, NH2), 3067 (C-H, Ar), 2948 (C-H, CH3), 2258 (C≡N), 1582 (C=C, Ar), 1463 (C=N); PMR (CDCl3, δ, ppm): 7.65-7.34 (m, 5H, Ar-H), 7.35 (s, 1H, =NH), 4.54 (s, 1H, NH), 3.12 (s, 3H, OCH3), 2.64 (s, 3H, CH3), 2.49 (s, 3H, NH=CCH3); Mass (EI, m/z): 431; Elemental analysis: Calculated for C20H16F3N5OS: C-55.68, H-3.74, F-13.21, N16.23, O-3.71, S-7.43. Found: C-55.59, H-3.74, F-13.20, N16.21, O-3.71, S-7.43. Indian Journal of Advanced Chemistry (IJAC) ISSN: 2582-8975 (Online), Volume-5 Issue-2, October 2025 5 Published By: Lattice Science Publication (LSP) © Copyright: All rights reserved. Retrieval Number: 100.1/ijac.B203005021025 DOI: 10.54105/ijac.B2030.05021025 Journal Website: www.ijac.latticescipub.com 7-(2-Bromophenyl)-5-(2-(trifluoromethyl)-5methylthiazol-4-yl)-2-methyl-[1,2,4]-triazolo[1,5a]pyridine-8-carbonitrile (6a): Colour: Yellow, Yield: 74%, Mp: 120-122 0C, IR (KBr, ν, cm-1): 3056 (C-H, Ar), 2968 (C-H, CH3), 2242 (C≡N), 1574 (C=C, Ar), 1456 (C=N); PMR (DMSO-d6, δ, ppm): 7.74-7.48 (m, 5H, Ar-H), 2.89 (s, 3H, CH3), 2.52 (s, 3H, CH3); Mass (EI, m/z): 477; Elemental analysis: Calculated for C19H11BrF3N5S: C-47.71, H2.32, Br-16.71, F-11.92, N-14.64, S-6.70. Found: C47.65, H-2.32, Br-16.70, F-11.90, N-14.62, S-6.70. 7-(2-Nitrophenyl)-5-(2-(trifluoromethyl)-5methylthiazol-4-yl)-2-methyl-[1,2,4]-triazolo[1,5a]pyridine-8-carbonitrile (6b): Colour: Pale yellow, Yield: 79%, Mp: 108-110 0C, IR (KBr, ν, cm-1): 3062 (C-H, Ar), 2971 (C-H, CH3), 2252 (C≡N), 1579 (C=C, Ar), 1462 (C=N); PMR (CDCl3, δ, ppm): 7.70-7.45 (m, 5H, Ar-H), 2.86 (s, 3H, CH3), 2.50 (s, 3H, CH3); Mass (EI, m/z): 444; Elemental analysis: Calculated for C19H11F3N6O2S: C-51.35, H-2.49, F-12.83, N-18.91, S-7.22. Found: C-51.28, H-2.49, F-12.81, N-18.89, S-7.22 7-(2-Methoxyphenyl)-5-(2-(trifluoromethyl)-5methylthiazol-4-yl)-2-methyl-[1,2,4]-triazolo[1,5a]pyridine-8-carbonitrile (6c): Colour: Yellow, Yield: 78%, Mp: 118-120 0C, IR (KBr, ν, cm-1): 3055 (C-H, Ar), 2977 (C-H, CH3), 2259 (C≡N), 1565 (C=C, Ar), 1468 (C=N); PMR (DMSO-d6, δ, ppm): 7.68-7.41 (m, 5H, Ar-H), 2.80 (s, 3H, OCH3), 2.55 (s, 3H, CH3), 2.59 (s, 3H, CH3); Mass (EI, m/z): 429; Elemental analysis: Calculated for C20H14F3N5OS: C-55.94, H-3.29, F-13.27, N-16.31, O-3.73, S-7.47. Found: C-55.88, H-3.29, F-13.26, N-16.29, O-3.73, S-7.47. VI. CONCLUSION In conclusion, we have successfully synthesised a modern series of heterocyclic derivatives, such as thiazolo- [1,2,4]triazolo[1,5-a]pyridine and its derivatives (6a-c), as target moieties in good overall yields using readily available chemicals with a conventional and simple methodology. Eventually, the synthesised compounds were used to evaluate their pharmacological ability against some familiar bacterial strains, and we noticed that the prepared compounds exhibited moderate to good antibacterial activity. DECLARATION STATEMENT After aggregating input from all authors, I must verify the accuracy of the following information as the article's author. ▪ Conflicts of Interest/ Competing Interests: Based on my understanding, this article has no conflicts of interest. ▪ Funding Support: This article has not been funded by any organizations or agencies. This independence ensures that the research is conducted with objectivity and without any external influence. ▪ Ethical Approval and Consent to Participate: The content of this article does not necessitate ethical approval or consent to participate with supporting documentation. ▪ Data Access Statement and Material Availability: The adequate resources of this article are publicly accessible. ▪ Authors Contributions: The authorship of this article is contributed equally to all participating individuals. REFERENCES 1. Musarurwa, H. & Tavengwa, N. T. (2021) Sustainable extraction of pesticides in food and environmental samples using emerging green adsorbents. Sustainable Chemistry and Pharmacy (CSP) (Vol. 24, Issue 12, Article number 100545). DOI: https://doi.org/10.1016/j.jfca.2019.103314 2. Rodrigues, L. D. Sunil, D. Chaithra, D. Bhagavath, P. (2020), 1,2,3/1,2,4-Triazole containing liquid crystalline materials: An up-todate review of their synthetic design and mesomorphic behaviour, Journal of Molecular Liquids (JML) (Vol. 297, Issue 1, Article number 111909. DOI: https://doi.org/10.1016/j.molliq.2019.111909. 3. Sharma, A. Agrahari, A. K. Rajkhowa, S. Tiwari, V. K. (2022). Emerging impact of triazoles as anti-tubercular agent. European Journal of Medicinal Chemistry (EJMC) (Vol. 238, Issue-5, Article number 114454). DOI: https://doi.org/10.1016/j.ejmech.2022.114454 4. Zhang, S. Xu, Z. Gao, C. Ren, Q.C. Chang, L. Lv, Z.S. (2017). Triazole derivatives and their anti-tubercular activity. European Journal of Medicinal Chemistry (EJMC) (Vol. 138, Issue 29, pp. 501513). DOI: https://doi.org/10.1016/j.ejmech.2017.06.051 5. Feng, Gao. Tengfei, W. Jiaqi, X. Gang, H. (2019). Antibacterial activity study of 1,2,4-triazole derivatives. European Journal of Medicinal Chemistry (EJMC) (Vol. 173, Issue 1, pp. 274-281) DOI: https://doi.org/10.1016/j.ejmech.2019.04.043 6. Li, Z. Cao, Y. Zhan, P. Pannecouque, C. Balzarini, J. De Clercq, E. Liu, X. (2013). Synthesis and anti-HIV evaluation of novel 1,2,4triazole derivatives as potential non-nucleoside HIV-1 reverse transcriptase inhibitors. Letters in Drug Design & Discovery (LDDD) (Vol. 10, Issue 1, pp. 27-34). DOI: https://doi.org/10.2174/ 15701801380 4142429 7. Pinto, A. Chan, R. C. (2009). Lack of allergic cross-reactivity between fluconazole and voriconazole. Antimicrobial Agents and Chemotherapy (AAC) (Vol. 53, Issue-4, pp. 1715-1716. DOI: https://doi.org/:10.1128/ AAC.01500-08 8. Smith, J., Safdar, N., Knasinski, V., Simmons, W., Bhavnani, S. M., Ambrose, P. G. (2006). Voriconazole herapeutic drug monitoring. Antimicrobial Synthesis, Characterization, and Evaluation of the Antibacterial Activity of Some Novel Thiazolo- [1,2,4] Triazolo [1,5-a] Pyridine Derivatives 6 Published By: Lattice Science Publication (LSP) © Copyright: All rights reserved. Retrieval Number: 100.1/ijac.B203005021025 DOI: 10.54105/ijac.B2030.05021025 Journal Website: www.ijac.latticescipub.com Agents and Chemotherapy (AAC) (Vol. 50, Issue-4, pp. 1570-1572). DOI: https://doi.org/10.1128/AAC.50.4.1570-1572.2006 9. Graci, J. D. Cameron, C. E. (2006). Mechanisms of action of ribavirin against distinct viruses. Reviews in Medical Virology (RMV) (Vol. 16, Issue 1, pp 37-48). DOI: https://doi.org/10.1002/rmv.483 10. Wellington, K., Plosker, G. L. (2002). Rizatriptan: an update of its use in the management of migraine. Drugs (Vol. 62, Issue-10, pp. 15391574) DOI: https://doi.org/10.2165/00003495-200262100-00007 11. Slomovitz, B. M. Filiaci, V. L. Walker, J. L. Taub, M.C. Finkelstein, K. A. Moroney, J. W. (2022). A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study. Gynecologic Oncology (GO). (Vol. 164, Issue-3, pp. 481-491). DOI: https://doi.org/10.1016/j.ygyno.2021.12.031. 12. Kucukguzel, S.G and Cikla-Suzgun, P. (2015). Recent advances in bioactive 1,2,4-triazole-3-thiones. European Journal of Medicinal Chemistry (EJMC) (Vol. 97, pp. 830-870). DOI: https://doi.org/10.1016/j.ejmech.2014.11.033 13. Takahashi, K. Yamagishi, G. Hiramatsu, T. Hosoya, A. Onoe, K. Doi, H. (2011). Practical synthesis of precursor of [N-methyl-11C] vorozole, an efficient PET tracer targeting aromatase in the brain. Bioorganic Medicinal Chemistry (BMC). (Vol. 19, Issue4, pp. 1464-1470). DOI: https://doi.org/10.1016/j.bmc.2010.12.057 14. Striano, P., McMurray, R., Santamarina, E., Falip, M. (2018). Rufinamide for the treatment of Lennox-Gastaut syndrome: evidence from clinical trials and clinical practice. Epileptic Disorders (ED) (Vol. 20, Issue-1, pp. 13-29) DOI: https://doi.org/10.1684/epd. 2017.0950 15. Yang, Y. Rasmussen, B. A. Shlaes, D. M. (1999). Class A betalactamases--enzyme-inhibitor interactions and resistance. Pharmacology & Therapeutics (PT) (Vol. 83, Issue-2, pp. 141-151) DOI: https://doi.org/10.1016/S0163-7258(99)00027-3 16. Gomez, I. Alonso, E. Ramon, D. J. Yus, M. (2000). Naphthalenecatalysed Lithiation of Chlorinated Nitrogenated Aromatic Heterocycles and Reaction with Electrophiles. Tetrahedron (Vol. 56, Issue24, pp. 4043-4052). DOI: https://doi.org/10.1016/S0040-4020(00)00318-5 17. Altaf, A. A. Shahzad, A. Gul, Z. Rasool, N. Badshah, A. Lal, B. Khan, E. J. (2015). Synthesis, Crystal Structure, and DFT Calculations of 1,3-Diisobutyl Thiourea. Drug Design and Medicinal Chemistry (DDMC) (Vol. 1, 1, pp. 1-11) DOI: https://doi.org/10.1155/2015/913435 18. Man, X. Yongzhi, P. Li, Z. Shulin, W. Jiayou, J. Rakesh, K. P. (2019). Triazole derivatives as inhibitors of Alzheimer's disease: Current developments and structure-activity relationships. European Journal of Medicinal Chemistry (EJMC) (Vol. 180, Issue 15 pp. 656-672) DOI: https://doi.org/10.1016/j.ejmech.2019.07.059. 19. Litvinov, P. V. Dotsenko, V. V. Krivokolysko, S. G. Thienopyridines: synthesis, properties, and biological activity (2005). Russian Chemical Bulletin, International Edition (RCBIE) (Vol. 54, Issue4, pp. 864904. DOI: https://doi.org/ 10665285/05/54040864/2005. 20. Schnute, M. E. Anderson, D. J. Brideau, R. J. (2007). 2-Aryl-2hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno- [2,3b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases. Bioorganic & Medicinal Chemistry Letters (BMCL) (Vol. 17, Issue 12, pp. 3349-3353). DOI: https://doi.org/10.1016/j.bmcl.2007.03.102 21. Bahekar, R. H. Jain, M. R. Jadav, P.A. Prajapati, V.M. Patel, D.N. Gupta, A.A. Sharma, A. Tom, Andyopadhya, D. Modi, H. Patel, P. R. (2007). Design, synthesis, and biological evaluation of substituted-N- (thieno[2,3-b]pyridin-3-yl)-guanidines, N-(1H-pyrrolo[2,3-b]pyridin3-yl)-guanidines, and N-(1H-indol-3-yl)-guanidines. Bioorganic & Medicinal Chemistry (BMC) (Vol. 15, Issue 9, pp. 3248-3265). DOI: https://doi.org/10.1016/j.bmc.2007.02.029 22. Abdel-Rahman, A. E. Bakhite, E. A. Al-Taifi, E. A. (2003). Synthesis and antimicrobial testing of some new S-substituted-thiopyridines, thienopyridines, pyridothienopyrimidines and pyridothienotriazines Pharmazie (Vol. 58, Issue 6, pp. 372-379). DOI: https://doi.org/10.1002/chin.200339135 23. Hayakawa, I. Shioya, R. Agatsuma, T. Furukawa, H. Sugano, Y. (2004). Thienopyridine and benzofuran derivatives as potent antitumour agents possessing different structure–activity relationships. Bioorganic & Medicinal Chemistry Letters (BMCL) (Vol. 14, Issue 13, pp. 3411-3415). DOI: https://doi.org/10.1016/j.bmcl.2004.04.079 24. Ichiro, H, Rieko, S., Toshinori, A., Hidehiko, F., Yuichi, S. (2004) Thienopyridine and benzofuran derivatives as potent anti-tumour agents possessing different structure-activity relationships, Bioorganic Medicinal Chemistry Letters (BMCL) (Vol. 14, Issue-13, pp. 34113414) DOI: https://doi.org/10.1016/j.bmcl.2004.04.079. 25. Krauze, A. Germame, S. Eberlins, O. Sturms, I. Klusa, V. Duburs, G. (1999). Derivatives of 3-cyano-6-phenyl-4-(3`-pyridyl)-pyridine2(1H)-thione and their Neurotropic activity. European Journal of Medicinal Chemistry (EJMC) (Vol. 34, Issue-4, pp. 301-310). DOI: https://doi.org/10.1016/S0223-5234(99)80081-6. 26. Barry, A. I. (1976). The antimicrobial Susceptibility Test, Principles and Practices. 4th Ed. (ELBS), 1976, 80. https://books.google.co.in/books/about/The_Antimicrobic_Susceptibil ity_Test.html?id=LPNqAAAAMAAJ&redir_esc=y AUTHOR’S PROFILE Dr. Pendam Prashanth Babu is working as Professor for Chemistry in the Department of Humanities and Sciences in Sree Chaitanya College of Engineering, Karimnagar. He completed his Ph.D from Kakatiya University, Warangal, Telangana. His research focuses on the synthesis, characterisation and biocidal properties of organometallic complexes, heterocyclic compounds and copolymer and terpolymer resins. Dr. Pingili Upendra is working as an Assistant Professor of Chemistry in the Department of Chemistry, Govt. Degree college for women (A), Nalgonda. He completed his Ph.D. at Kakatiya University, supported by a CSIR fellowship, at the Indian Institute of Chemical Technology (IICT), Hyderabad, Telangana. His research focuses on “Total synthesis of (-)- Varitriol, Obolactines, Myristict NEW Methodologies based on Th (II) complexes. Dr. Dharanipathi Venkateshwar Rao is working as Assistant Professor of Chemistry in the Govt Degree College, Ibrahimpatnam. He completed his Ph.D from Osmania University, Hyderabad, Telangana. His research interests are photo degradation of pollutants and Dyes. Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of the Lattice Science Publication (LSP)/ journal and/ or the editor(s). The Lattice Science Publication (LSP)/ journal and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.