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Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks

Year 2022, , 1117 - 1130, 31.12.2022
https://doi.org/10.16984/saufenbilder.1085086

Abstract

Quinazoline and quinazolinone derivatives display an extensive application in organic and pharmaceutical chemistry, and they have been used as natural and synthetic materials for medicinal chemistry purposes. Here I reported an investigation of a new series of quinazolinone ring derivatives. In this context, starting from the methyl anthranilate, six quinazolinone derivatives (4a-f) with various aminomethyl moieties at position 2 were synthesized (89-80%). The structures of compounds 4a-f were identified using FTIR and NMR Spectroscopy (1H NMR - 13C NMR). The data obtained from the all spectra clearly identify the structures of the compounds.

References

  • [1] R. J. Abdel-Jalil, H. M. Aldoqum, M. T. Ayoub, W. Voelter, “Synthesis and Antitumor Activity of 2-aryl-7-fluoro-6-(4-methyl-1-piperazinyl)-4(3H)-quinazolinones,” Heterocycles-Sendai Institute Heterocyclic Chemistry, vol.65, pp.2061-2070, 2005.
  • [2] A. S. El-Azab, K. E. El-Tahir, “Design and Synthesis of Novel 7-Aminoquinazoline Derivatives: Antitumor and Anticonvulsant Activities,” Bioorganic and Medicinal Chemistry Letters, vol.22, pp.1879-1885, 2012.
  • [3] V. M. Sharma, P. Prasanna, K. A. Seshu, B. Renuka, C. L. Rao, G. S. Kumar, C. P. Narasimhulu, P. A. Babu, R. Puranik, D. Subramanyam, “Novel Indolo [2, 1-b] quinazoline Analogues as Cytostatic Agents: Synthesis, Biological Evaluation and Structure–activity Relationship,” Bioorganic and Medicinal Chemistry Letters, vol.12 pp.2303-2307, 2002.
  • [4] H. J. Park, Y-S. Kim, J. S. Kim, E-J. Lee, Y-J. Yi, H. J. Hwang, M-E. Suh, C-K. Ryu, S. K. Lee, “6-Arylamino-7-chloro-quinazoline-5,8-diones as Novel Cytotoxic and DNA Topoisomerase Inhibitory Agents,” Bioorganic and Medicinal Chemistry Letters, vol.14, pp.3385-3388, 2004.
  • [5] Z. Ma, Y. Hano, T. Nomura, Y. Chen, “Novel Quinazoline–quinoline Qlkaloids with Cytotoxic and DNA Topoisomerase II Inhibitory Activities,” Bioorganic and Medicinal Chemistry Letters, vol.14, pp.1193-1196, 2004.
  • [6] N. Malecki, P. Carato, B. T. Rigo, J-F. Goossens, R. Houssin, C. Bailly, J-P, Hénichart, “Synthesis of Condensed Quinolines and Quinazolines as DNA Ligands,” Bioorganic and Medicinal Chemistry, vol.12 pp.641-647, 2004.
  • [7] E. Manivannan, S. Chaturvedi, “Analogue-based Design, Synthesis and Molecular Docking Analysis of 2,3-Diaryl Quinazolinones as Non-ulcerogenic Anti-inflammatory Agents,” Bioorganic and Medicinal Chemistry, vol.19, pp.4520-4528, 2011.
  • [8] A. Gangjee, O. O. Adair, M. Pagley, S. F. Queener, “N9-substituted 2,4-diaminoquinazolines: Synthesis and Biological Evaluation of Lipophilic Inhibitors of Pneumocystis Carinii and Toxoplasma Gondii Dihydrofolate Reductase,” Journal of Medicinal Chemistry, vol.51, pp.6195-6200, 2008.
  • [9] J. Chevalier, A. Mahamoud, M. Baitiche, E. Adam, M. Viveiros, A. Smarandache, A. Militaru, M. L. Pascu, L. Amaral, J-M, Pagès, “Quinazoline Derivatives are Efficient Chemosensitizers of Antibiotic Activity in Enterobacter Aerogenes, Klebsiella Pneumoniae and Pseudomonas Aeruginosa Resistant Strains,” International Journal of Antimicrobial Agents, vol.36, pp.164-168, 2010.
  • [10] A. Mahamoud, J. Chevalier, M. Baitiche, E. Adam, J-M, Pages, “An Alkylaminoquinazoline Restores Antibiotic Activity in Gram-negative Resistant Isolates,” Microbiology, vol.157, pp.566-571, 2011.
  • [11] K. Bajaj, V. K. Srivastava, A. Kumar, “Newer Substituted Benzoxazepinyl quinazolinones as Potent Antipsychotic and Anticonvulsant Agents,” ArzneimittelForschung, vol.53, pp.480-485, 2003.
  • [12] M. Amir, I. Ali, M. Z. Hassan, “Design and Synthesis of Some New Quinazolin-4-(3H)-ones as Anticonvulsant and Antidepressant Agents,” Archives of Pharmacal Research, vol.36, pp.61-68, 2013.
  • [13] M. Shivananda, B. S. Holla, “Antifungal Activity Studies of Some Quinazolinone Derivatives,” Journal of Chemical and Pharmaceutical Research, vol.3, pp.83-86, 2011.
  • [14] M. Decker, “Novel Inhibitors of Acetyl and Butyrylcholinesterase Derived from the Alkaloids Dehydroevodiamine and Rutaecarpine,” European Journal of Medicinal Chemistry, vol.40, pp.305-313, 2005.
  • [15] F. S. Tokalı, P. Taslimi, İ. H. Demircioğlu, M. Karaman, M. S. Gültekin, K. Şendil, İ. Gülçin, “Design, Synthesis, Molecular Docking, and Some Metabolic Enzyme Inhibition Properties of Novel Quinazolinone Derivatives,” Archiv der Pharmazie (Weinheim, Germany), vol.354, no.5, pp.2000455, 2021.
  • [16] A. Gürsoy, N. Karalı, “Synthesis and Primary Cytotoxicity Evaluation of 3-[[(3-Phenyl-4(3H)-quinazolinone-2-yl) mercaptoacetyl] hydrazono]-1H-2-indolinones,” European Journal of Medicinal Chemistry, vol.38, pp.633-643, 2003.
  • [17] M. S. Malamas, J. Millen, “Quinazolineacetic Acids and Related Analogs as Aldose Reductase Inhibitors,” Journal of Medicinal Chemistry, vol.34 pp.1492-1503, 1991.
  • [18] F. S. Tokalı, Y. Demir, İ. H. Demircioğlu, C. Türkeş, E. Kalay, K. Şendil, Ş. Beydemir, “Synthesis, in silico docking study and biological evaluation of novel library sulfonates containing quinazolin-4(3H)-one derivatives as potential aldose reductase inhibitors,” Drug Development Research, vol.83, no.3, pp.586-604 2022.
  • [19] A. Gangjee, M. Kothare, R. L. Kisliuk, “The Synthesis of Novel Nonclassical Reversed Bridge Quinazoline Antifolates as Inhibitors of Thymidylate Synthase,” Journal of Heterocyclic Chemistry, vol.37, pp.1097-1102, 2000.
  • [20] R-D. Li, X. Zhang, Q-Y. Li, Z-M. Ge, R-T. Li, “Novel EGFR Inhibitors Prepared by Combination of Dithiocarbamic Acid Esters and 4-Anilinoquinazolines,” Bioorganic and Medicinal Chemistry Letters, vol.21, pp.3637-3640, 2011.
  • [21] J. P. Patil, S. V. Amrutkar, M. S. Ranawat, “Microwave Assisted Synthesis of Quinazolinone Using Different Bases,” Journal of Pharmaceutical Sciences and Research, vol.1, no.3, pp.52-54, 2009.
  • [22] S. G. Davies, K. B. Ling, R. M. Roberts, A. J. Russell, J. E. Thomson, P. A. Woods, “The Stereodivergent Aziridination of Allylic Carbamates, Amides and Sulfonamides,” Tetrahedron, vol.66, no.34, pp.6806-6813, 2010.
  • [23] A. M. F. Eissa, A. M. El-Metwally, M. A. El-Hashash, A. M. F. El-Gohary, “Synthesis and Biological Evaluation of Some New 2-Propyl-4(3H)-quinazolinone Derivatives as Anti-bacteria,” Journal of the Korean Chemical Society, vol.52, no.3, pp.328-337, 2008.
  • [24] A. F. M. Fahmy, M. A. El-Hashash, M. M. Habashy, S. A. El-Wannise, “Some Reactions of 2-Isopropyl-[4H]-3,1-benzoxazin-4-one,” Revue Roumaine de Chimie, vol.23, no.11-12, pp.1567-1573, 1978.
  • [25] V. Alagarsamy, V. Rajasolomon, R. Meena, K. V. Ramseshu, “Synthesis and Analgesic, Anti-inflammatory and Antibacterial Activities of Some Novel 3-substituted 2-butylquinazolin-4(3H)-ones,” Biological & Pharmaceutical Bulletin, vol.28, no.6, pp.1091-1094, 2005.
  • [26] M. A. El-Sherbeny, “Synthesis, Antitumor Activity, and Anti-HIV-1 Testing of Certain Heterocyclic Systems Containing an Adamantane Nucleus,” Archiv der Pharmazie (Weinheim, Germany), vol.333, no.10, pp.323-328, 2000.
  • [27] P. Kumar, B. Shrivastava, S. N. Pandeya, J. P. Stables, “Design, Synthesis and Potential 6 Hz Psychomotor Seizure Test Activity of Some Novel 2-(Substituted)-3-{[substituted]amino}quinazolin-4(3H)-one,” European Journal of Medicinal Chemistry, vol.46, no.4, pp.1006-1018, 2011.
  • [28] C. K. Reddy, P. S. N. Reddy, C. V. Ratnam, “A New Synthesis of 2-Aryl-3,4-dihydro-5H-1,3,4-benzotriazepin-5-ones,” Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, vol.24B, no.9, pp.902-904, 1985.
  • [29] H. Patel, R. Pawara, S. Surana, “Resolving the Mystery of Ring Opening in the Synthesis of Benzo[d][1, 3]oxazin-4-one and Quinazolin-4(3H)-one,” Letters in Organic Chemistry, vol.16, no.11, pp.898-905, 2019.
  • [30] L. M. Deck, S. D. Turner, J. A. Deck, E. P. Papadopoulos, “ Synthesis of Derivatives of Thiophene Using Methyl 2-isothiocyanatobenzoate,” Journal of Heterocyclic Chemistry, vol.38, no.2, pp.343-347, 2001.
  • [31] F. Sauter, P. Stanetty, U. Jordis, “New 3-Aminoquinazolinones,” Archiv der Pharmazie (Weinheim, Germany), vol.310, no.8, pp.680-682, 1977.
  • [32] F. S. Tokalı, P. Taslimi, İ. H. Demircioğlu, K. Şendil, B. Tüzün, İ. Gülçin, “Novel Phenolic Mannich Base Derivatives: Synthesis, Bioactivity, Molecular Docking, and ADME-Tox Studies,” Journal of the Iranian Chemical Society, vol.19, pp.563–577, 2022.
  • [33] G. Roman, “Mannich bases in medicinal chemistry and drug design,” European Journal of Medicinal Chemistry, vol. 89, pp. 743 – 816, 2015.
Year 2022, , 1117 - 1130, 31.12.2022
https://doi.org/10.16984/saufenbilder.1085086

Abstract

References

  • [1] R. J. Abdel-Jalil, H. M. Aldoqum, M. T. Ayoub, W. Voelter, “Synthesis and Antitumor Activity of 2-aryl-7-fluoro-6-(4-methyl-1-piperazinyl)-4(3H)-quinazolinones,” Heterocycles-Sendai Institute Heterocyclic Chemistry, vol.65, pp.2061-2070, 2005.
  • [2] A. S. El-Azab, K. E. El-Tahir, “Design and Synthesis of Novel 7-Aminoquinazoline Derivatives: Antitumor and Anticonvulsant Activities,” Bioorganic and Medicinal Chemistry Letters, vol.22, pp.1879-1885, 2012.
  • [3] V. M. Sharma, P. Prasanna, K. A. Seshu, B. Renuka, C. L. Rao, G. S. Kumar, C. P. Narasimhulu, P. A. Babu, R. Puranik, D. Subramanyam, “Novel Indolo [2, 1-b] quinazoline Analogues as Cytostatic Agents: Synthesis, Biological Evaluation and Structure–activity Relationship,” Bioorganic and Medicinal Chemistry Letters, vol.12 pp.2303-2307, 2002.
  • [4] H. J. Park, Y-S. Kim, J. S. Kim, E-J. Lee, Y-J. Yi, H. J. Hwang, M-E. Suh, C-K. Ryu, S. K. Lee, “6-Arylamino-7-chloro-quinazoline-5,8-diones as Novel Cytotoxic and DNA Topoisomerase Inhibitory Agents,” Bioorganic and Medicinal Chemistry Letters, vol.14, pp.3385-3388, 2004.
  • [5] Z. Ma, Y. Hano, T. Nomura, Y. Chen, “Novel Quinazoline–quinoline Qlkaloids with Cytotoxic and DNA Topoisomerase II Inhibitory Activities,” Bioorganic and Medicinal Chemistry Letters, vol.14, pp.1193-1196, 2004.
  • [6] N. Malecki, P. Carato, B. T. Rigo, J-F. Goossens, R. Houssin, C. Bailly, J-P, Hénichart, “Synthesis of Condensed Quinolines and Quinazolines as DNA Ligands,” Bioorganic and Medicinal Chemistry, vol.12 pp.641-647, 2004.
  • [7] E. Manivannan, S. Chaturvedi, “Analogue-based Design, Synthesis and Molecular Docking Analysis of 2,3-Diaryl Quinazolinones as Non-ulcerogenic Anti-inflammatory Agents,” Bioorganic and Medicinal Chemistry, vol.19, pp.4520-4528, 2011.
  • [8] A. Gangjee, O. O. Adair, M. Pagley, S. F. Queener, “N9-substituted 2,4-diaminoquinazolines: Synthesis and Biological Evaluation of Lipophilic Inhibitors of Pneumocystis Carinii and Toxoplasma Gondii Dihydrofolate Reductase,” Journal of Medicinal Chemistry, vol.51, pp.6195-6200, 2008.
  • [9] J. Chevalier, A. Mahamoud, M. Baitiche, E. Adam, M. Viveiros, A. Smarandache, A. Militaru, M. L. Pascu, L. Amaral, J-M, Pagès, “Quinazoline Derivatives are Efficient Chemosensitizers of Antibiotic Activity in Enterobacter Aerogenes, Klebsiella Pneumoniae and Pseudomonas Aeruginosa Resistant Strains,” International Journal of Antimicrobial Agents, vol.36, pp.164-168, 2010.
  • [10] A. Mahamoud, J. Chevalier, M. Baitiche, E. Adam, J-M, Pages, “An Alkylaminoquinazoline Restores Antibiotic Activity in Gram-negative Resistant Isolates,” Microbiology, vol.157, pp.566-571, 2011.
  • [11] K. Bajaj, V. K. Srivastava, A. Kumar, “Newer Substituted Benzoxazepinyl quinazolinones as Potent Antipsychotic and Anticonvulsant Agents,” ArzneimittelForschung, vol.53, pp.480-485, 2003.
  • [12] M. Amir, I. Ali, M. Z. Hassan, “Design and Synthesis of Some New Quinazolin-4-(3H)-ones as Anticonvulsant and Antidepressant Agents,” Archives of Pharmacal Research, vol.36, pp.61-68, 2013.
  • [13] M. Shivananda, B. S. Holla, “Antifungal Activity Studies of Some Quinazolinone Derivatives,” Journal of Chemical and Pharmaceutical Research, vol.3, pp.83-86, 2011.
  • [14] M. Decker, “Novel Inhibitors of Acetyl and Butyrylcholinesterase Derived from the Alkaloids Dehydroevodiamine and Rutaecarpine,” European Journal of Medicinal Chemistry, vol.40, pp.305-313, 2005.
  • [15] F. S. Tokalı, P. Taslimi, İ. H. Demircioğlu, M. Karaman, M. S. Gültekin, K. Şendil, İ. Gülçin, “Design, Synthesis, Molecular Docking, and Some Metabolic Enzyme Inhibition Properties of Novel Quinazolinone Derivatives,” Archiv der Pharmazie (Weinheim, Germany), vol.354, no.5, pp.2000455, 2021.
  • [16] A. Gürsoy, N. Karalı, “Synthesis and Primary Cytotoxicity Evaluation of 3-[[(3-Phenyl-4(3H)-quinazolinone-2-yl) mercaptoacetyl] hydrazono]-1H-2-indolinones,” European Journal of Medicinal Chemistry, vol.38, pp.633-643, 2003.
  • [17] M. S. Malamas, J. Millen, “Quinazolineacetic Acids and Related Analogs as Aldose Reductase Inhibitors,” Journal of Medicinal Chemistry, vol.34 pp.1492-1503, 1991.
  • [18] F. S. Tokalı, Y. Demir, İ. H. Demircioğlu, C. Türkeş, E. Kalay, K. Şendil, Ş. Beydemir, “Synthesis, in silico docking study and biological evaluation of novel library sulfonates containing quinazolin-4(3H)-one derivatives as potential aldose reductase inhibitors,” Drug Development Research, vol.83, no.3, pp.586-604 2022.
  • [19] A. Gangjee, M. Kothare, R. L. Kisliuk, “The Synthesis of Novel Nonclassical Reversed Bridge Quinazoline Antifolates as Inhibitors of Thymidylate Synthase,” Journal of Heterocyclic Chemistry, vol.37, pp.1097-1102, 2000.
  • [20] R-D. Li, X. Zhang, Q-Y. Li, Z-M. Ge, R-T. Li, “Novel EGFR Inhibitors Prepared by Combination of Dithiocarbamic Acid Esters and 4-Anilinoquinazolines,” Bioorganic and Medicinal Chemistry Letters, vol.21, pp.3637-3640, 2011.
  • [21] J. P. Patil, S. V. Amrutkar, M. S. Ranawat, “Microwave Assisted Synthesis of Quinazolinone Using Different Bases,” Journal of Pharmaceutical Sciences and Research, vol.1, no.3, pp.52-54, 2009.
  • [22] S. G. Davies, K. B. Ling, R. M. Roberts, A. J. Russell, J. E. Thomson, P. A. Woods, “The Stereodivergent Aziridination of Allylic Carbamates, Amides and Sulfonamides,” Tetrahedron, vol.66, no.34, pp.6806-6813, 2010.
  • [23] A. M. F. Eissa, A. M. El-Metwally, M. A. El-Hashash, A. M. F. El-Gohary, “Synthesis and Biological Evaluation of Some New 2-Propyl-4(3H)-quinazolinone Derivatives as Anti-bacteria,” Journal of the Korean Chemical Society, vol.52, no.3, pp.328-337, 2008.
  • [24] A. F. M. Fahmy, M. A. El-Hashash, M. M. Habashy, S. A. El-Wannise, “Some Reactions of 2-Isopropyl-[4H]-3,1-benzoxazin-4-one,” Revue Roumaine de Chimie, vol.23, no.11-12, pp.1567-1573, 1978.
  • [25] V. Alagarsamy, V. Rajasolomon, R. Meena, K. V. Ramseshu, “Synthesis and Analgesic, Anti-inflammatory and Antibacterial Activities of Some Novel 3-substituted 2-butylquinazolin-4(3H)-ones,” Biological & Pharmaceutical Bulletin, vol.28, no.6, pp.1091-1094, 2005.
  • [26] M. A. El-Sherbeny, “Synthesis, Antitumor Activity, and Anti-HIV-1 Testing of Certain Heterocyclic Systems Containing an Adamantane Nucleus,” Archiv der Pharmazie (Weinheim, Germany), vol.333, no.10, pp.323-328, 2000.
  • [27] P. Kumar, B. Shrivastava, S. N. Pandeya, J. P. Stables, “Design, Synthesis and Potential 6 Hz Psychomotor Seizure Test Activity of Some Novel 2-(Substituted)-3-{[substituted]amino}quinazolin-4(3H)-one,” European Journal of Medicinal Chemistry, vol.46, no.4, pp.1006-1018, 2011.
  • [28] C. K. Reddy, P. S. N. Reddy, C. V. Ratnam, “A New Synthesis of 2-Aryl-3,4-dihydro-5H-1,3,4-benzotriazepin-5-ones,” Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, vol.24B, no.9, pp.902-904, 1985.
  • [29] H. Patel, R. Pawara, S. Surana, “Resolving the Mystery of Ring Opening in the Synthesis of Benzo[d][1, 3]oxazin-4-one and Quinazolin-4(3H)-one,” Letters in Organic Chemistry, vol.16, no.11, pp.898-905, 2019.
  • [30] L. M. Deck, S. D. Turner, J. A. Deck, E. P. Papadopoulos, “ Synthesis of Derivatives of Thiophene Using Methyl 2-isothiocyanatobenzoate,” Journal of Heterocyclic Chemistry, vol.38, no.2, pp.343-347, 2001.
  • [31] F. Sauter, P. Stanetty, U. Jordis, “New 3-Aminoquinazolinones,” Archiv der Pharmazie (Weinheim, Germany), vol.310, no.8, pp.680-682, 1977.
  • [32] F. S. Tokalı, P. Taslimi, İ. H. Demircioğlu, K. Şendil, B. Tüzün, İ. Gülçin, “Novel Phenolic Mannich Base Derivatives: Synthesis, Bioactivity, Molecular Docking, and ADME-Tox Studies,” Journal of the Iranian Chemical Society, vol.19, pp.563–577, 2022.
  • [33] G. Roman, “Mannich bases in medicinal chemistry and drug design,” European Journal of Medicinal Chemistry, vol. 89, pp. 743 – 816, 2015.
There are 33 citations in total.

Details

Primary Language English
Subjects Chemical Engineering
Journal Section Research Articles
Authors

Feyzi Sinan Tokalı 0000-0001-5532-8802

Publication Date December 31, 2022
Submission Date March 9, 2022
Acceptance Date September 29, 2022
Published in Issue Year 2022

Cite

APA Tokalı, F. S. (2022). Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks. Sakarya University Journal of Science, 26(6), 1117-1130. https://doi.org/10.16984/saufenbilder.1085086
AMA Tokalı FS. Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks. SAUJS. December 2022;26(6):1117-1130. doi:10.16984/saufenbilder.1085086
Chicago Tokalı, Feyzi Sinan. “Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-Ones As Organic Building Blocks”. Sakarya University Journal of Science 26, no. 6 (December 2022): 1117-30. https://doi.org/10.16984/saufenbilder.1085086.
EndNote Tokalı FS (December 1, 2022) Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks. Sakarya University Journal of Science 26 6 1117–1130.
IEEE F. S. Tokalı, “Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks”, SAUJS, vol. 26, no. 6, pp. 1117–1130, 2022, doi: 10.16984/saufenbilder.1085086.
ISNAD Tokalı, Feyzi Sinan. “Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-Ones As Organic Building Blocks”. Sakarya University Journal of Science 26/6 (December 2022), 1117-1130. https://doi.org/10.16984/saufenbilder.1085086.
JAMA Tokalı FS. Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks. SAUJS. 2022;26:1117–1130.
MLA Tokalı, Feyzi Sinan. “Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-Ones As Organic Building Blocks”. Sakarya University Journal of Science, vol. 26, no. 6, 2022, pp. 1117-30, doi:10.16984/saufenbilder.1085086.
Vancouver Tokalı FS. Synthesis and Structural Characterization of Novel 2-Aminomethyl Quinazolin-4(3H)-ones as Organic Building Blocks. SAUJS. 2022;26(6):1117-30.

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