Novel Synthesis and Antimicrobial Activity of 7-Substituted Derivatives of 7-(methylthio)-5-oxo-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-b]pyrimidine-6-carbonitrile

Jaman A. Angulwar; Gopinath S. Khansole; Vijay N. Bhosale

doi:10.14233/ajomc.2019.AJOMC-P171

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Abstract

2-Amino-5-phenyl-1,3,4-thiadiazole on reaction with ethyl-2-cyano-3,3-bis(methylthio)acrylate in the presence of N,N′-dimethyl formamide and catalytic amount of anhydrous potassium carbonate afforded 7-(methylthio)-5-oxo-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-b]pyrimidine-6-carbonitrile under similar experimental condition, compounds 7-(methylthio)-5-oxo-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-b]pyrimidine-6-carbonitrile on treatment independently with aryl amines/ heteryl amines/phenols containing active methylene group yielded corresponding 7-substituted derivatives. All these newly synthesized compounds were screened for antimicrobial activity.

Keywords

Pyrimido-thiadiazoles Antimicrobial activity

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A. Angulwar, J., S. Khansole, G., & N. Bhosale, V. (2019). Novel Synthesis and Antimicrobial Activity of 7-Substituted Derivatives of 7-(methylthio)-5-oxo-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-b]pyrimidine-6-carbonitrile. Asian Journal of Organic & Medicinal Chemistry, 4(1), 40–45. https://doi.org/10.14233/ajomc.2019.AJOMC-P171

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References

M. Goke, B. Cakir, K. Earl and M. Sahin, Synthesis and Antinociceptive activity of [(2-Oxobenzothiazolin-3-yl)methyl]-4-alkyl/aryl-1,2,4-triazoline-5-thiones, Arch. Pharm., 334, 279 (2001); https://doi.org/10.1002/1521-4184(200109)334:8/9<279::AID-ARDP279>3.0.CO;2-W.
X.-J. Zou, L.-H. Lai, G.-Y. Jin and Z.-X. Zhang, Synthesis, Fungicidal Activity and 3D-QSAR of Pyridazinone-Substituted 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles, J. Agric. Food Chem., 50, 3757 (2002); https://doi.org/10.1021/jf0201677.
L. Labanauskas, V. Kalcas, E. Udernaite and P. Gaidelis, Synthesis of 3-(3,4-Dimethoxyphenyl)-1H-1,2,4-triazole-5-thiol and 2-Amino-5-(3,4-dimethoxyphenyl)-1,3,4-thiadiazole Derivatives Exhibiting Anti-inflammatory Activity, Pharmazie, 56, 617 (2001).
F. Clerici, D. Pocar, M. Guido, A. Loche, V. Perlini and M. Brufani, Synthesis of 2-Amino-5-sulfanyl-1,3,4-thiadiazole Derivatives and Evaluation of Their Antidepressant and Anxiolytic Activity, J. Med. Chem., 44, 931 (2001); https://doi.org/10.1021/jm001027w.
S.B. Ferreira, M.S. Costa, N. Boechat, R.J.S. Bezerra and V.F. Ferreira, Synthesis and Evaluation of New Difluoromethyl Azoles as Antileish-manial Agents, Eur. J. Med. Chem., 42, 1388 (2007); https://doi.org/10.1016/j.ejmech.2007.02.020.
C. Kus, G.A. Kilcigil, S. Ozbey, F.B. Kaynak, M. Kaya, T. Coban and B. Can-Eke, Synthesis and Antioxidant Properties of Novel N-Methyl-1,3,4-thiadiazol-2-amine and 4-Methyl-2H-1,2,4-triazole-3(4H)-thione Derivatives of Benzimidazole Class, Bioorg. Med. Chem., 16, 4294 (2008); https://doi.org/10.1016/j.bmc.2008.02.077.
A. Foroumadi, S.A. Tabatabai, G. Gitinezhad, M.R. Zarrindast and A. Shafiee, Synthesis and Anticonvulsant Activity of 5-Aryl-l,3,4-thiadiazole Derivatives, Pharm. Pharmacol. Commun., 6, 31 (2000); https://doi.org/10.1211/146080800128735430.
V. Sunel, C. Lionte, C. Basu and C. Cheptea, New Antitumour Alkyl-ating Compounds with N-[m-(Arylthiocarbamoyl)aminobenzoyl]-asparagic Acids Support, Chem. Indian J., 2, 1 (2005).
A. Faroumadi, M. Mirzaei and A. Shafiee, Antitubercular Agents, I: Synthesis and Antituberculosis Activity of 2-Aryl-1,3,4-thiadiazole Derivatives, Pharmazie, 56, 610 (2001).
V. Dudutiene, L. Baranauskiene and D. Matulis, Benzimidazo[1,2-c]-[1,2,3]thiadiazole-7-sulfonamides as Inhibitors of Carbonic Anhydrase, Bioorg. Med. Chem. Lett., 17, 3335 (2007); https://doi.org/10.1016/j.bmcl.2007.03.100.
U.K.M. Decking, M. Hartmann, H. Rose, R. Brückner, J. Meil and J. Schrader, Cardioprotective actions of KC 12291 I. Inhibition of Voltage-gated Na+ Channels in Ischemia Delays Myocardial Na+ Overload, Arch. Pharmacol., 358, 547 (1998); https://doi.org/10.1007/PL00005291.
M. Hartman, U.K.M. Decking and J. Schrader, Cardioprotective Actions of KC 12291 II. Delaying Na+ Overload in Ischemia Improves Cardiac Function and Energy Status in Reperfusion, Arch. Pharmacol., 358, 554 (1998); https://doi.org/10.1007/PL00005292.
A. Martinez, M. Alonso, A. Castro, C. Pérez and F.J. Moreno, First Non-ATP Competitive Glycogen Synthase Kinase 3b (GSK-3b) Inhibitors: Thiadiazolidinones (TDZD) as Potential Drugs for the Treatment of Alzheimer's Disease, J. Med. Chem., 45, 1292 (2002); https://doi.org/10.1021/jm011020u.
K.A. Jacobson, M.F. Jarvis and M. Williams, Purine and Pyrimidine (P2) Receptors as Drug Targets, J. Med. Chem., 45, 4057 (2002); https://doi.org/10.1021/jm020046y.
G.S. Khansole, J.A. Angulwar and V.N. Bhosale, A Facile Synthesis of Some New Pyrimido[2,3-d]-1,3,4-Thiadiazoles with their Biological Potential, Indian J. Heterocycl. Chem., 28, 267 (2018).
V.N. Bhosale, S.S. Choudhare, G.S. Khansole and N.B. Wadwale, Mole-cular Iodine Catalyzed Synthesis of 9-Substituted Derivatives of 9-Phenyl-2,9-diphenyl-5,9-dihydro-6H-pyrimido[4,5-d][1,3,4]thiadiazolo[3,2-a]- pyrimidine-6,8(7H)-dione, Der Pharma Chem., 9, 66 (2017).
J.A. Angulwar, G.S. Khansole and V.N. Bhosale, Synthesis, Antimicrobial Activities of Pyrano[2,3-d]pyrimidine Derivatives, Int. J. Chem. Phys. Sci., 7, 1 (2018).
J. Soloducho, J. Doskocz, J. Cabaj and S. Roszak, Practical Synthesis of Bis-Substituted Tetrazines with Two Pendant 2-Pyrrolyl or 2-Thienyl Groups, Precursors of New Conjugated Polymers, Tetrahedron, 59, 4761 (2003); https://doi.org/10.1016/S0040-4020(03)00709-9.
J.M. Lehn, Supramolecular Chemistry-Concepts and Perspectives, VCH: Weinheim, Chap. 9 (1995).
A. Harriman and R. Ziessel, Building Photoactive Molecular-Scale Wires, Coord. Chem. Rev., 171, 331 (1998); https://doi.org/10.1016/S0010-8545(98)90049-2.
R. Zrenner, M. Stitt, U. Sonnewald and R. Boldt, Pyrimidine and Purine Biosynthesis and Degradation in Plants, Annu. Rev. Plant Biol., 57, 805 (2006); https://doi.org/10.1146/annurev.arplant.57.032905.105421.
R.E. Looper, M.T.C. Runnegar and R.M. Williams, Syntheses of the Cylindrospermopsin Alkaloids, Tetrahedron, 62, 4549 (2006); https://doi.org/10.1016/j.tet.2006.02.044.
V.N. Bhosale, S.P. Vartale, V.K. Deshmukh and S.V. Kuberkar, Novel Synthesis and Antibacterial Activity of 3-Amino-8-chloro-4-oxo-(2H)/aryl/heteryl-pyrazolo[3',4':4,5]pyrimido[2, 1-b][1,3]benzothiazoles, J. Chem. Pharm. Res., 2, 51 (2010).
L.A. Agrofoglio, An Overview of Diazine Nucleoside Analogues, Curr. Org. Chem., 10, 333 (2006); https://doi.org/10.2174/138527206775473850.
R.B. George, M.H. David, S.E.S. Elaine, W. David, S.C. David, J.F. Allan, C.G. Steven, F. Mc Taggart, J.M. Donald, J.S. Graham and W. Robon, J. Med. Chem., 358, 1623 (2000).
F. Carlomagno, D. Vitagliano, T. Guida, F. Basolo, M.D. Castellone, R.M. Melillo, A. Fusco and M. Santoro, Efficient Inhibition of RET/Papillary Thyroid Carcinoma Oncogenic Kinases by 4-Amino-5-(4-chloro-phenyl)-7-(t-Butyl)pyrazolo[3,4-d]pyrimidine (PP2), J. Clin. Endocrinol. Metab., 88, 1897 (2003); https://doi.org/10.1210/jc.2002-021278.
C.F. George, Pyrazolopyrimidines, Lancet, 358, 1623 (2001); https://doi.org/10.1016/S0140-6736(01)06656-9.
P.M. Chauhan and S. Srivastava Present Trends and Future Strategy in Chemotherapy of Malaria, Curr. Med. Chem., 8, 1535 (2001); https://doi.org/10.2174/0929867013371851.

References

M. Goke, B. Cakir, K. Earl and M. Sahin, Synthesis and Antinociceptive activity of [(2-Oxobenzothiazolin-3-yl)methyl]-4-alkyl/aryl-1,2,4-triazoline-5-thiones, Arch. Pharm., 334, 279 (2001); https://doi.org/10.1002/1521-4184(200109)334:8/9<279::AID-ARDP279>3.0.CO;2-W.

X.-J. Zou, L.-H. Lai, G.-Y. Jin and Z.-X. Zhang, Synthesis, Fungicidal Activity and 3D-QSAR of Pyridazinone-Substituted 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles, J. Agric. Food Chem., 50, 3757 (2002); https://doi.org/10.1021/jf0201677.

L. Labanauskas, V. Kalcas, E. Udernaite and P. Gaidelis, Synthesis of 3-(3,4-Dimethoxyphenyl)-1H-1,2,4-triazole-5-thiol and 2-Amino-5-(3,4-dimethoxyphenyl)-1,3,4-thiadiazole Derivatives Exhibiting Anti-inflammatory Activity, Pharmazie, 56, 617 (2001).

F. Clerici, D. Pocar, M. Guido, A. Loche, V. Perlini and M. Brufani, Synthesis of 2-Amino-5-sulfanyl-1,3,4-thiadiazole Derivatives and Evaluation of Their Antidepressant and Anxiolytic Activity, J. Med. Chem., 44, 931 (2001); https://doi.org/10.1021/jm001027w.

S.B. Ferreira, M.S. Costa, N. Boechat, R.J.S. Bezerra and V.F. Ferreira, Synthesis and Evaluation of New Difluoromethyl Azoles as Antileish-manial Agents, Eur. J. Med. Chem., 42, 1388 (2007); https://doi.org/10.1016/j.ejmech.2007.02.020.

C. Kus, G.A. Kilcigil, S. Ozbey, F.B. Kaynak, M. Kaya, T. Coban and B. Can-Eke, Synthesis and Antioxidant Properties of Novel N-Methyl-1,3,4-thiadiazol-2-amine and 4-Methyl-2H-1,2,4-triazole-3(4H)-thione Derivatives of Benzimidazole Class, Bioorg. Med. Chem., 16, 4294 (2008); https://doi.org/10.1016/j.bmc.2008.02.077.

A. Foroumadi, S.A. Tabatabai, G. Gitinezhad, M.R. Zarrindast and A. Shafiee, Synthesis and Anticonvulsant Activity of 5-Aryl-l,3,4-thiadiazole Derivatives, Pharm. Pharmacol. Commun., 6, 31 (2000); https://doi.org/10.1211/146080800128735430.

V. Sunel, C. Lionte, C. Basu and C. Cheptea, New Antitumour Alkyl-ating Compounds with N-[m-(Arylthiocarbamoyl)aminobenzoyl]-asparagic Acids Support, Chem. Indian J., 2, 1 (2005).

A. Faroumadi, M. Mirzaei and A. Shafiee, Antitubercular Agents, I: Synthesis and Antituberculosis Activity of 2-Aryl-1,3,4-thiadiazole Derivatives, Pharmazie, 56, 610 (2001).

V. Dudutiene, L. Baranauskiene and D. Matulis, Benzimidazo[1,2-c]-[1,2,3]thiadiazole-7-sulfonamides as Inhibitors of Carbonic Anhydrase, Bioorg. Med. Chem. Lett., 17, 3335 (2007); https://doi.org/10.1016/j.bmcl.2007.03.100.

U.K.M. Decking, M. Hartmann, H. Rose, R. Brückner, J. Meil and J. Schrader, Cardioprotective actions of KC 12291 I. Inhibition of Voltage-gated Na+ Channels in Ischemia Delays Myocardial Na+ Overload, Arch. Pharmacol., 358, 547 (1998); https://doi.org/10.1007/PL00005291.

M. Hartman, U.K.M. Decking and J. Schrader, Cardioprotective Actions of KC 12291 II. Delaying Na+ Overload in Ischemia Improves Cardiac Function and Energy Status in Reperfusion, Arch. Pharmacol., 358, 554 (1998); https://doi.org/10.1007/PL00005292.

A. Martinez, M. Alonso, A. Castro, C. Pérez and F.J. Moreno, First Non-ATP Competitive Glycogen Synthase Kinase 3b (GSK-3b) Inhibitors: Thiadiazolidinones (TDZD) as Potential Drugs for the Treatment of Alzheimer's Disease, J. Med. Chem., 45, 1292 (2002); https://doi.org/10.1021/jm011020u.

K.A. Jacobson, M.F. Jarvis and M. Williams, Purine and Pyrimidine (P2) Receptors as Drug Targets, J. Med. Chem., 45, 4057 (2002); https://doi.org/10.1021/jm020046y.

G.S. Khansole, J.A. Angulwar and V.N. Bhosale, A Facile Synthesis of Some New Pyrimido[2,3-d]-1,3,4-Thiadiazoles with their Biological Potential, Indian J. Heterocycl. Chem., 28, 267 (2018).

V.N. Bhosale, S.S. Choudhare, G.S. Khansole and N.B. Wadwale, Mole-cular Iodine Catalyzed Synthesis of 9-Substituted Derivatives of 9-Phenyl-2,9-diphenyl-5,9-dihydro-6H-pyrimido[4,5-d][1,3,4]thiadiazolo[3,2-a]- pyrimidine-6,8(7H)-dione, Der Pharma Chem., 9, 66 (2017).

J.A. Angulwar, G.S. Khansole and V.N. Bhosale, Synthesis, Antimicrobial Activities of Pyrano[2,3-d]pyrimidine Derivatives, Int. J. Chem. Phys. Sci., 7, 1 (2018).

J. Soloducho, J. Doskocz, J. Cabaj and S. Roszak, Practical Synthesis of Bis-Substituted Tetrazines with Two Pendant 2-Pyrrolyl or 2-Thienyl Groups, Precursors of New Conjugated Polymers, Tetrahedron, 59, 4761 (2003); https://doi.org/10.1016/S0040-4020(03)00709-9.

J.M. Lehn, Supramolecular Chemistry-Concepts and Perspectives, VCH: Weinheim, Chap. 9 (1995).

A. Harriman and R. Ziessel, Building Photoactive Molecular-Scale Wires, Coord. Chem. Rev., 171, 331 (1998); https://doi.org/10.1016/S0010-8545(98)90049-2.

R. Zrenner, M. Stitt, U. Sonnewald and R. Boldt, Pyrimidine and Purine Biosynthesis and Degradation in Plants, Annu. Rev. Plant Biol., 57, 805 (2006); https://doi.org/10.1146/annurev.arplant.57.032905.105421.

R.E. Looper, M.T.C. Runnegar and R.M. Williams, Syntheses of the Cylindrospermopsin Alkaloids, Tetrahedron, 62, 4549 (2006); https://doi.org/10.1016/j.tet.2006.02.044.

V.N. Bhosale, S.P. Vartale, V.K. Deshmukh and S.V. Kuberkar, Novel Synthesis and Antibacterial Activity of 3-Amino-8-chloro-4-oxo-(2H)/aryl/heteryl-pyrazolo[3',4':4,5]pyrimido[2, 1-b][1,3]benzothiazoles, J. Chem. Pharm. Res., 2, 51 (2010).

L.A. Agrofoglio, An Overview of Diazine Nucleoside Analogues, Curr. Org. Chem., 10, 333 (2006); https://doi.org/10.2174/138527206775473850.

R.B. George, M.H. David, S.E.S. Elaine, W. David, S.C. David, J.F. Allan, C.G. Steven, F. Mc Taggart, J.M. Donald, J.S. Graham and W. Robon, J. Med. Chem., 358, 1623 (2000).

F. Carlomagno, D. Vitagliano, T. Guida, F. Basolo, M.D. Castellone, R.M. Melillo, A. Fusco and M. Santoro, Efficient Inhibition of RET/Papillary Thyroid Carcinoma Oncogenic Kinases by 4-Amino-5-(4-chloro-phenyl)-7-(t-Butyl)pyrazolo[3,4-d]pyrimidine (PP2), J. Clin. Endocrinol. Metab., 88, 1897 (2003); https://doi.org/10.1210/jc.2002-021278.

C.F. George, Pyrazolopyrimidines, Lancet, 358, 1623 (2001); https://doi.org/10.1016/S0140-6736(01)06656-9.

P.M. Chauhan and S. Srivastava Present Trends and Future Strategy in Chemotherapy of Malaria, Curr. Med. Chem., 8, 1535 (2001); https://doi.org/10.2174/0929867013371851.

Novel Synthesis and Antimicrobial Activity of 7-Substituted Derivatives of 7-(methylthio)-5-oxo-2-phenyl-5H-[1,3,4]thiadiazolo[3,2-b]pyrimidine-6-carbonitrile

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