An Ultrasound-Promoted Efficient Synthesis of New 4-Hydroxy-2(1H)-quinolone-Derived Amino Nitrile Pyridines

  • Krishna Alla
  • S. SarveswariEmail author
Research Paper


Ultrasound-promoted efficient synthesis of new compounds 2-amino-6-(1, 2-dihydro-4-hydroxy-2-oxoquinolin-3-yl)-4-arylpyridine-3-carbonitriles (4ap) from 4-hydroxy-3-((E)-3-arylacryloyl) quinolin-2(1H)-ones (3ap) has been described. The effect of solvent and ultrasound irradiation has been described.


Ultrasound irradiation Quinolones Antimicrobial agents Quinolone chalcones Amino nitrile pyridines Malanonitrile Ammonium acetate 



We thank Mr. BRS Rao (Managing Director of LGC Promochem Private Limited, Bangalore) for his financial support. We thank VIT-SIF Vellore for providing NMR facility and SAIF-IIT Madras, Chennai for providing HR-MS analytical service.

Supplementary material

40995_2018_567_MOESM1_ESM.doc (15.4 mb)
Supplementary material 1 (DOC 15721 kb)


  1. Abass M, Mostafa BB (2005) Synthesis and evaluation of molluscicidal and larvicidal activities of some novel enaminones derived from 4-hydroxyquinolinones: Part IX. Bioorg Med Chem 13:6133–6144CrossRefGoogle Scholar
  2. Abdelhafez OM, Amin KM, Batran RZ, Maher TJ, Nada SA, Sethumadhavan S (2010) Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives. Bioorg Med Chem 18:3371–3378CrossRefGoogle Scholar
  3. Afonso A, Weinstein J, Gentles M (1992a) Antiviral compounds. WO 9204326, 1992. Chem Abstr 117:26358Google Scholar
  4. Afonso A, Weinstein J, Gentles MJ, Margaret J, Rosenblum SB (1992b) Antiviral compounds and antihypertensive compounds. WO 9204328, 1992. Chem Abstr 117:90161Google Scholar
  5. Andersson MI, MacGowan AP (2003) Development of the quinolones. J Antimicrob Chemother 51(Suppl. S1):1–11CrossRefGoogle Scholar
  6. Andriole VT (1989) The Quinolones. Academic PressGoogle Scholar
  7. Andriole VT (1994) Quinolones: the present and the future. Infect Dis Clin Pract 3:S211–S217CrossRefGoogle Scholar
  8. Bhupathi RS, Ramadevi B, Dbey PK (2012) L-Proline as an efficient catalyst for synthesis of N-heterocyclic chalcones as potential antibacterial agents. Indian J Chem 51B:855–859Google Scholar
  9. Cai SX, Zhou ZL, Huang J-C, Whittemore ER, Egbuwoku ZO, Lü Y, Hawkinson JE, Woodward RM, Weber E, Keana JFW (1996) Synthesis and structure−activity relationships of 1, 2, 3, 4-tetrahydroquinoline-2, 3, 4-trione 3-oximes: novel and highly potent antagonists for NMDA receptor glycine site. J Med Chem 39:3248–3255CrossRefGoogle Scholar
  10. Ghahremanzadeh R, Fereshtehnejad F, Mirzaei P, Bazgir A (2011) Ultrasound-assisted synthesis of 2, 2 ’-(2-oxoindoline-3, 3-diyl) bis (1H-indene-1, 3(2H)-dione) derivatives. Ultrason Sonochem 18:415–418CrossRefGoogle Scholar
  11. Hasegawa S, Matsunaga K, Muto M, Hanada S (1991) Platinum compound and agent for treating malignant tumor. Chem Abstr 114:34897Google Scholar
  12. Hayashi H, Miwa I, Ichikawa S, Yoda N, Miki I, Ishii A, Kono M, Yasuzawa T, Suzuki F (1993) 5-HT3 receptor antagonists. 2, 4-hydroxy-4-quinolinecarboxylic acid derivatives. J Med Chem 36:617–626CrossRefGoogle Scholar
  13. He JY, Xin HX, Yan H, Song XQ, Zhong RG (2011) Ultrason Sonochem 18:466–469Google Scholar
  14. Hennequin LF, Thomas AP, Johnstone C, Stokes ES, Plé PA, Lohmann JJM, Ogilvie DJ, Dukes M, Wedge SR, Curwen JO, Kendrew J, Brempt CLV (1999) Design and structure−activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J Med Chem 42:5369–5389CrossRefGoogle Scholar
  15. Indumathi T, Jamal Ahamed VS, Surk-Sik M, Fronczek FR, Rajendra Prasad KJ (2011) L-Proline anchored multicomponent synthesis of novel pyrido [2, 3-a] carbazoles; investigation of in vitro antimicrobial, antioxidant, cytotoxicity and structure activity relationship studies. Eur J Med Chem 46:5580–5590CrossRefGoogle Scholar
  16. Ivanov DV, Budanov SV (2006) Ciprofloxacin and antibacterial therapy of respiratory tract infections. Antibiot Khimioter. 51(5):29–37 (in Russian) Google Scholar
  17. Katritzky AR (1984) Pergamon Press, Oxford, p 25Google Scholar
  18. Kobayashi T, Sasaki S, Tomita N, Fukui S, Kuroda N, Nakayama M, Kiba A, Takatsu Y, Ohtaki T, Itoh F, Baba A (2010) Synthesis and structure–activity relationships of 2-acylamino-4, 6-diphenylpyridine derivatives as novel antagonists of GPR54. Bioorg Med Chem 18:3841–3859CrossRefGoogle Scholar
  19. Kowsari E, Mallakmohammadi M (2011) Ultrasound promoted synthesis of quinolines using basic ionic liquids in aqueous media as a green procedure. Ultrason Sonochem 18:447–454CrossRefGoogle Scholar
  20. Kulagowski JJ, Baker R, Curtis NR, Leeson PD, Mawer IM, Moseley AM, Ridgill MP, Rowely M, Stansfield I, Foster AC, Grimwood S, Hill RG, Kemp JA, Marshall GR, Saywell KL, Tricklebank MD (1994) 3'-(arylmethyl) - and 3'-(aryloxy)-3-phenyl-4-hydroxyquinolin- 2(1H)-ones: orally active antagonists of the glycine site on the NMDA receptor. J Med Chem 37:1402–1405CrossRefGoogle Scholar
  21. Kumar N, Chauhan A, Drabu S (2011) Synthesis of cyanopyridine and pyrimidine analogues as new anti-inflammatory and antimicrobial agents. Biomed Pharmacother 65:375–380CrossRefGoogle Scholar
  22. Lange JHM, Verveer CP, Osanabrug JM, Visser GM (2001) Rapid microwave-enhanced synthesis of 4-hydroxyquinolinones under solvent-free conditions. Tetrahedron Lett 42:1367–1369CrossRefGoogle Scholar
  23. Lauria A, Abbate I, Gentile C, Angileri F, Martorana A, Almerico AM (2013) Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening. J Med Chem 56:3424–3428CrossRefGoogle Scholar
  24. Li JT, Han JF, Yang JH, Li TS (2003) An efficient synthesis of 3, 4-dihydropyrimidin-2-ones catalyzed by NH2SO3H under ultrasound irradiation. Ultrason Sonochem 10:119–122CrossRefGoogle Scholar
  25. Li JT, Wang SX, Chen GF, Li TS (2005) Some Applications of Ultrasound Irradiation in Organic Synthesis. Curr Org Synth 2:415–436CrossRefGoogle Scholar
  26. Li JT, Yin Y, Sun MX (2010) An efficient one-pot synthesis of 2, 3-epoxyl-1, 3-diaryl-1-propanone directly from acetophenones and aromatic aldehydes under ultrasound irradiation. Ultrason Sonochem 17:363–366CrossRefGoogle Scholar
  27. Li JT, Li YW, Song YL, Chen GF (2012) Improved synthesis of 2, 2'-arylmethylene bis (3-hydroxy-5, 5- dimethyl-2-cyclohexene-1-one) derivatives catalyzed by urea under ultrasound. Ultrason Sonochem 19:1–4CrossRefGoogle Scholar
  28. Luche JL (1998) Synthetic organic sonochemistry. Plenum Press, New YorkCrossRefGoogle Scholar
  29. Mcnulty J, Steere JA, Wolf S (1998) The ultrasound promoted Knoevenagel condensation of aromatic aldehydes. Tetrahedron Lett 39:8013–8016Google Scholar
  30. McQuaid LA, Smith ECR, Lodge D, Pralong E, Wikel JH, Calligaro DO, O’Malley PJ (1992) 3-Phenyl-4-hydroxyquinolin-2(1H)-ones: potent and selective antagonists at the strychnine-insensitive glycine site on the N-methyl-D-aspartate receptor complex. J Med Chem 35:3423–3425CrossRefGoogle Scholar
  31. Morinaka Y, Takahashi K, Hata S, Yamada S (1981) Antiallergic agents. I. Pyranoquinoline derivatives. Eur J Med Chem 16(3):251–256Google Scholar
  32. Moussaoui F, Belfaitah A, Debache A, Rhouati S (2002) Synthesis and characterization of some new aryl quinolyl α, β-unsaturated ketones. J Soc Alger Chim 12:71Google Scholar
  33. Munawar MA, Azad M, Siddiquia HL, Nasim FH (2008) Synthesis and antimicrobial studies of some quinolinylpyrimidine derivatives. J Chin Chem Soc 55:394–400CrossRefGoogle Scholar
  34. Ohashi T, Oguro Y, Tanaka T, Shiokawa Z, Shibata S, Sato Y, Yamakawa H, Hattori H, Yamamoto Y, Kondo S, Miyamoto M, Tojo I, Baba A, Sasaki S (2012) Discovery of pyrrolo [3, 2-c] quinoline-4-one derivatives as novel hedgehog signaling inhibitors. Bioorg Med Chem 20:5496–5506CrossRefGoogle Scholar
  35. Ratoarinoro N, Wilhelm AM, Berlan J, Delmas H (1992) Effects of ultrasound emitter type and power on a heterogeneous reaction. Chem Eng J 50:27–31CrossRefGoogle Scholar
  36. Reddy TR, Reddy GR, Reddy LS, Jammula S, Lingappa Y, Kapavarapu R, Meda CLT, Parsa KVL, Pal M (2012) Montmorillonite K-10 mediated green synthesis of cyano pyridines: their evaluation as potential inhibitors of PDE4. Eur J Med Chem 48:265–274CrossRefGoogle Scholar
  37. Roussaki M, Hall B, Lima SC, da Silva AC, Wilkinson S, Detsi A (2013) Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series. Bioorg Med Chem Lett 23(23):6436–6441CrossRefGoogle Scholar
  38. Rowely M, Leeson PD, Stevenson GI, Moseley AM, Stansfield I, Sanderson I, Robinson I, Baker R (1993) 3-Acyl-4-hydroxyquinolin-2(1H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of the N-methyl-D-aspartate receptor complex. J Med Chem 36:3386CrossRefGoogle Scholar
  39. Sarveswari S, Raja TK (2006) A rapid microwave assisted synthesis of 3-acetyl-4-hydroxyquinolin-2(1H)-one and its conversion to quinolin-3-yl isoxazolines and pyrazolines. Indian J Heterocycl Chem 16(2):171–174Google Scholar
  40. Sarveswari S, Vijayakumar V (2015) Synthesis and antibacterial screening of 3-(4, 5-dihydro-5-aryl-1H-pyrazol-3-yl)-4-hydroxyquinolin-2(1H)-ones. Int J Chem Tech Res 8(6):782–788Google Scholar
  41. Sarveswari S, Vijayakumar V, Siva R, Priya R (2015) Synthesis of 4-hydroxy-2(1H)-quinolone derived chalcones, pyrazolines and their antimicrobial, in silico antimalarial evaluations. Appl Biochem Biotechnol 175:43–64CrossRefGoogle Scholar
  42. Sayed AA, Elfayoumi A, Sami SM, Mohamed EA (1977) Some 3-substituted-4-hydroxycarbostyrils. Acta Chimica Academiae Scientiarum Hungaricae 94(2):131–139Google Scholar
  43. Siporin C, Heifetz CL, Domagala JM (1990) The new generation of quinolones. Marcel Dekker INC., New York, pp 2–42Google Scholar
  44. Stanczyk T, Kubiak W, Wawrzynowicz W, Wenerska B (1991) Chem Abstr 114:44453Google Scholar
  45. Toche RB, Kazi AM, Jachak NM, Desai AE (2010a) Synthesis and molluscicidal activities of quinolone substituted pyrazoline and isoxazoline derivatives. J Appl Sci Res 6(6):637–641Google Scholar
  46. Toche RB, Kazi AM, Patil SP, Kanawade SB, Jachak MN (2010b) Synthesis of quinolone substituted pyrazoles, isoxazoles and pyridines as a potential blue luminophores. J Fluoresc 20(5):1129–1137CrossRefGoogle Scholar
  47. Toche RB, Kazi AM, Nikam PS, Bhavsar DC (2011) Synthesis of nicotinonitrile derivatives and study of their photophysical properties. Monatshefte fuer Chemie 142(3):261–269CrossRefGoogle Scholar
  48. Ukrainets V, Taran SG, Sidorenko LV, Gorokhova OV, Ogirenko AA, Turov NI (1996) Chemistry of substituted quinolinones. III. Synthesis ans reactions of some novel 3-pyrazolyl-2-quinolinones. Filimonova Khim Geterotsikl Soedin 8:1113Google Scholar
  49. Ukrainets IV, Tkach AA, Yang LY (2009) 4-Hydroxy-2-quinolones. 152*. 3-acetyl-4-hydroxy-2-oxo-1, 2- dihydroquinoline and its biologically active derivatives. Chem Heterocycl Compd 45(2):169–175CrossRefGoogle Scholar
  50. Wentland MP (1993) In memoriam: George Y, Lesher, Ph.D. In: Hooper DC, Wolfson JS (eds) Quinolone antimicrobial agents. American Society for Microbiology, pp XIII–XIVGoogle Scholar
  51. Zhang F, Zhao Y, Sun L, Ding L, Gu Y, Gong Ping (2011) Synthesis and anti-tumor activity of 2-amino-3-cyano-6-(1H-indol-3-yl)-4-phenylpyridine derivatives in vitro. Eur J Med Chem 46:3149–3157CrossRefGoogle Scholar

Copyright information

© Shiraz University 2018

Authors and Affiliations

  1. 1.Centre for Organic and Medicinal ChemistryVIT UniversityVelloreIndia
  2. 2.LGC Promochem Private LimitedBangaloreIndia

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