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New pyrazolyl-dibenzo[b,e][1,4]diazepinones: room temperature one-pot synthesis and biological evaluation

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Abstract

Several new (5-aryloxy-pyrazolyl)- and (5-aryl/olefin-sulfanyl-pyrazolyl)-dibenzo[b,e] [1,4] diazepinone scaffolds have been synthesized, by assembling 5-substituted 3-methyl-1-phenyl-pyrazole-4-carbaldehydes of varied nature with different cyclic diketones and aromatic diamines successfully in the presence of indium chloride in acetonitrile, at room temperature. Desired products are excellent in the purity and isolated without chromatography. All new structures are confirmed, on the basis of single-crystal X-ray diffraction data of representative 29e. Compounds reported in the present work revealed good antioxidant, antimicrobial and antiproliferative activities with promising FRAP (ferric reducing antioxidant power), bacterial resistance and human solid tumor cell growth inhibitory values, respectively. Compounds 25c and 29e, overall, registered good to moderate activity against A549 (lung), HeLa (cervix), SW1573 (lung) T-47D (breast) and WiDr (colon) cell lines, with GI50 values in the 2.6–5.1 μM and 1.8–7.5 μM ranges, respectively. Molecular docking was carried out to elucidate the binding modes of the compounds (25c, 29e) to topoisomerase I and II.

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References

  1. Bock MG, DiPardo RM, Evans BE, Rittle KE, Whitter WL, Veber DF, Anderson PS, Freidinger RM (1989) Benzodiazepine gastrin and brain cholecystokinin receptor ligands, L–365, 260. J Med Chem 32:13–16. https://doi.org/10.1021/jm00121a004

    Article  CAS  PubMed  Google Scholar 

  2. Thurston DE, Bose DS (1994) Synthesis of DNA–interactive pyrrolo[2,1–c][1,4]benzodiazepines. Chem Rev 94:433–465. https://doi.org/10.1021/cr00026a006

    Article  CAS  Google Scholar 

  3. Kimata A, Nakagawa H, Ohyama R, Fukuuchi T, Ohta S, Suzuki T, Miyata N (2007) New series of antiprion compounds: pyrazolone derivatives have the potent activity of inhibiting protease–resistant prion protein accumulation. J Med Chem 50:5053–5056. https://doi.org/10.1021/jm070688r

    Article  CAS  PubMed  Google Scholar 

  4. Park HJ, Lee K, Park SJ, Ahn B, Lee JC, Cho HY, Lee KI (2005) Identification of antitumor activity of pyrazole oxime ethers. Bioorgan Med Chem Lett 15:3307–3312. https://doi.org/10.1016/j.bmcl.2005.03.082

    Article  CAS  Google Scholar 

  5. Ouyang G, Cai XJ, Chen Z, Song BA, Bhadury PS, Yang S, Jin LH, Xue W, Hu DY, Zeng S (2008) Synthesis and antiviral activities of pyrazole derivatives containing an oxime moiety. J Agric Food Chem 56:10160–10167. https://doi.org/10.1021/jf802489e

    Article  CAS  PubMed  Google Scholar 

  6. Reddy TS, Kulhari H, Reddy VG, Rao AVS, Bansal V, Kamal A, Shukla R (2015) Synthesis and biological evaluation of pyrazolo–triazole hybrids as cytotoxic and apoptosis inducing agents. Org Biomol Chem 13:1–6. https://doi.org/10.1039/C5OB00842E

    Article  CAS  Google Scholar 

  7. Devnath HP, Islam MR (2010) Synthesis of some pyrazolone derivatives from ciprofloxacin and study of their cytotoxicity. Bangladesh J Pharmacol 5:30–33. https://doi.org/10.3329/bjp.v5i1.4693

    Article  Google Scholar 

  8. Trippier PC, Zhao KT, Fox SG, Schiefer IT, Benmohamed R, Moran J, Kirsch DR, Morimoto RI, Silverman RB (2014) Proteasome activation is a mechanism for pyrazolone small molecules displaying therapeutic potential in amyotrophic lateral sclerosis. ACS Chem Neurosci 5:823–829. https://doi.org/10.1021/cn500147v

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pelcman B, Sanin A, Nilsson P, Schaal W, Olofsson K, Christian KJ, Forsell P, Hallberg A, Larhed M, Boesen T, Kromann H, Claesson HE (2015) N-Substituted pyrazole-3-carboxamides as inhibitors of human15-lipoxygenase. Bioorgan Med Chem Lett 25:3017–3023. https://doi.org/10.1016/j.bmcl.2015.05.007

    Article  CAS  Google Scholar 

  10. Akbarzadeh R, Amanpour T, Bazgir A (2014) Synthesis of 3-oxo-1,4-diazepine-5-carboxamides and 6-(4-oxo-chromen-3-yl)-pyrazinones via sequential Ugi 4CC/Staudinger/intramolecular nucleophilic cyclization and Ugi 4CC/Staudinger/aza-Wittig reactions. Tetrahedron 70:8142–8147. https://doi.org/10.1016/j.tet.2014.07.102

    Article  CAS  Google Scholar 

  11. Maleki A (2013) One-pot multicomponent synthesis of diazepine derivatives using terminal alkynes in the presence of silica-supported super paramagnetic iron oxide nano particles. Tetrahedron Lett 54:2055–2059. https://doi.org/10.1016/j.tetlet.2013.01.123

    Article  CAS  Google Scholar 

  12. Huang SG, Mao HF, Zhou SF, Zou JP, Zhang W (2013) Recyclable gallium(III) triflate-catalyzed [4 + 3] cycloaddition for synthesis of 2,4-disubstituted-3H-benzo[b][1,4]diazepines. Tetrahedron Lett 5:6178–6180. https://doi.org/10.1016/j.tetlet.2013.08.092

    Article  CAS  Google Scholar 

  13. Nadin A, Lo´pez JMS, Owens AP, Howells DM, Talbot AC, Harrison T (2003) New synthesis of 1, 3-dihydro-1, 4-benzodiazepin-2(2H)-ones and 3-amino-1,3-dihydro-1,4-benzodiazepin-2(2H)-ones: pd-catalyzed cross-coupling of imidoyl chlorides with organoboronic acids. J Org Chem 68:2844–2852. https://doi.org/10.1021/jo026860a

    Article  CAS  PubMed  Google Scholar 

  14. Hu X, Dong Y, Liu G (2015) Copper-catalyzed ligand-free amidation of aryl iodides and amino acid amides to synthesize C3-(Z)-1H-benzo[e][1,4]diazepin-2(3H)-ones. Mol Divers 19:695–701. https://doi.org/10.1007/s11030-015-9603-5

    Article  CAS  PubMed  Google Scholar 

  15. Wang XL, Zheng XF, Liu RH, Reiner J, Chang JB (2007) Synthesis of novel substituted naphthoquino[b]-benzo[e][1,4]diazepines via Pictet-Spengler cyclization. Tetrahedron 63:3389–3394. https://doi.org/10.1016/j.tet.2007.02.002

    Article  CAS  Google Scholar 

  16. Bouakher AE, Prié G, Aadil M, Lazar S, Hakmaoui AE, Akssira M, Massuar MCV (2012) An efficient and convenient method for synthesizing new derivatives of pyrido[2,3-e]pyrrolo[1,2-a][1,4]diazepine-5,10-dione via Sonogashira, Suzuki-Miyaura, and stille cross-coupling reactions. Tetrahedron Lett 53:6401–6405. https://doi.org/10.1016/j.tetlet.2012.09.041

    Article  CAS  Google Scholar 

  17. Tucker H, Le Count DJ (1996) 1,4-Diazepines. Compr Heterocycl Chem II 9:151–182. https://doi.org/10.1016/B978-008096518-5.00214-8

    Article  CAS  Google Scholar 

  18. Fader LD, Bethell R, Bonneau P, Bös M, Bousquet Y, Cordingley MG, Coulombe R, Deroy P, Faucher AM, Gagnon A, Goudreau N, Grand-Maître C, Guse I, Hucke O, Kawai SH, Lacoste JE, Landry S, Lemke CT, Malenfant E, Mason S, Morin S, O’Meara J, Simoneau B, Titolo SS, Yoaki C (2011) Discovery of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly. Bioorgan Med Chem Lett 21:398–404. https://doi.org/10.1016/j.bmcl.2010.10.131

    Article  CAS  Google Scholar 

  19. Pitt G, Batt A, Haigh R, Penson A, Robson P, Rooker D, Tartar A, Trim J, Yea C, Roe M (2004) Non-peptide oxytocin agonists. Bioorgan Med Chem Lett 14:4585. https://doi.org/10.1016/j.bmcl.2004.04.107

    Article  CAS  Google Scholar 

  20. Jorgensen WT, Gulliver DW, Werry EL, Reekie T, Connor M, Kassiou M (2016) Flexible analogues of WAY-267,464: synthesis and pharmacology at the human oxytocin and vasopressin 1a receptors. Eur J Med Chem 108:730–740. https://doi.org/10.1016/j.ejmech.2015.11.050

    Article  CAS  PubMed  Google Scholar 

  21. Chaouloff F, Durand M, Mormède P (1997) Anxiety- and activity-related effects of diazepam and chlordiazepoxide in the rat light/dark and dark/light tests. Behave Brain Res 85:27–35. https://doi.org/10.1016/S0166-4328(96)00160-X

    Article  CAS  Google Scholar 

  22. Hung YY, Yang PS, Huang TL (2006) Clozapine in schizophrenia patients with recurrent catatonia: report of two cases. Psychiatry Clin Neurosci 60:256–258

    Article  Google Scholar 

  23. Huang TL (2005) Lorazepam and diazepam rapidly relieve catatonic signs in patients with schizophrenia. Psychiatry Clin Neurosci 59:52–55. https://doi.org/10.1111/j.1440-1819.2006.01495.x

    Article  CAS  PubMed  Google Scholar 

  24. Hammer R, Giachetti A (1982) Muscarinic receptor subtypes: M1 and M2 biochemical and functional characterization. Life Sci 31:2991–2998. https://doi.org/10.1016/0024-3205(82)90066-2

    Article  CAS  PubMed  Google Scholar 

  25. Kato M, Imoto K, Miyake H, Oda T, Miyaji S, Nakamura M (2004) Apafant, a potent platelet-activating factor antagonist, blocks eosinophil activation and is effective in the chronic phase of experimental allergic conjunctivitis in guinea pigs. J Pharmacol Sci 95:435–442. https://doi.org/10.1254/jphs.FP0040265

    Article  CAS  PubMed  Google Scholar 

  26. Kato M, Kurose T, Oda T, Miyaji S (2004) The role of platelet activating factor and the efficacy of apafant ophthalmic solution in experimental allergic conjunctivitis. J Ocular Pharmacol Ther 19(4):315–324. https://doi.org/10.1089/108076803322279372

    Article  CAS  Google Scholar 

  27. Insuasty B, Ramírez J, Becerra D, Echeverry C, Quiroga J, Abonia R, Robledo SM, Velez ID, Upegui Y, Munoz JA, Ospina V, Nogueras M, Cobo J (2015) An efficient synthesis of new caffeine-based chalcones, pyrazolines and pyrazolo[3,4-b][1,4]diazepines as potential antimalarial, antitrypanosomal and antileishmanial agents. Eur J Med Chem 93:401–413. https://doi.org/10.1016/j.ejmech.2015.02.040

    Article  CAS  PubMed  Google Scholar 

  28. Carabateas PM, Harris LS (1966) Analgesic Antagonists 1 4-Substituted 1-Acyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepines. J Med Chem 9(1):6–10

    Article  CAS  Google Scholar 

  29. Hurley LH (1980) Elucidation and formulation of novel biosynthetic pathways leading to the pyrrolo[l,4]Benzodiazepine antibiotics anthramycin, tomaymycin, and sibiromycin. Acc Chem Res 13:263–269. https://doi.org/10.1021/ar50152a003

    Article  CAS  Google Scholar 

  30. Insuasty B, Orozco F, Quiroga J, Abonia R, Nogueras M, Cobo J (2008) Microwave induced synthesis of novel 8, 9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor agents. Eur J Med Chem 43:1955–1962. https://doi.org/10.1016/j.ejmech.2007.12.005

    Article  CAS  PubMed  Google Scholar 

  31. Chobanian HR, Guo Y, Liu P, Chioda M, Lanza TJ, Chang L, Kelly TM, Kan Y, Palyha O, Guan XM, Marsh DJ, Metzger JM, Gorski JN, Raustad K, Wang SP, Strack AM, Miller R, Pang J, Madeira M, Lyons K, Dragovic J, Reitman ML, Nargund RP, Lin LS (2012) Discovery of MK–7725, A potent, selective bombesin receptor subtype-3 agonist for the treatment of obesity. ACS Med Chem Lett 3:252–256. https://doi.org/10.1021/ml200304j

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. El–Subbagh HI, Hassan GS, El–Azab AS, Abdel-Aziz AAM, Kadi AA, Al–Obaid AM, Al–Shabanah OA, Sayed-Ahmed MM (2011) Synthesis and anticonvulsant activity of some new thiazolo[3, 2-a][1, 3]diazepine, benzo[d]thiazolo[5, 2-a][6, 12]diazepine and benzo[d]oxazolo[5,2-a][6, 12]diazepine analogues. Eur J Med Chem 46:5567–5572. https://doi.org/10.1016/j.ejmech.2011.09.021

    Article  CAS  PubMed  Google Scholar 

  33. Zhang N, Zhang P, Baier A, Cova L, Hosmane RS (2014) Dual inhibition of HCV and HIV by ring–expanded nucleosides containing the 5:7-fused imidazo[4,5-e][1, 3]diazepine ring system In vitro results and implications. Bioorgan Med Chem Lett 24:1154–1157. https://doi.org/10.1016/j.bmcl.2013.12.121

    Article  CAS  Google Scholar 

  34. Jadhav VB, Kulkarnia MV, Rasalb VP, Biradarb SS, Vinay MD (2008) Synthesis and anti-inflammatory evaluation of methylene bridged benzofuranyl imidazo[2,1-b][1, 3, 4]thiadiazoles. Eur J Med Chem 43(8):1721–1729. https://doi.org/10.1016/j.ejmech.2007.06.023

    Article  CAS  PubMed  Google Scholar 

  35. Jolivet-Fouchet S, Fabis F, Rault S (1998) First direct synthesis of pyrrolo[2,1-c]thieno[3,2-e]- or [2,3-e][1,4]diazepines, thiophene analogues of pyrrolo[2,1-c][1,4]benzodiazepines. Tetrahedron Lett 39:5369–5372. https://doi.org/10.1016/s0040-4039(98)01108-3

    Article  CAS  Google Scholar 

  36. Tristan AR, McGregor IS, Kassiou M (2014) Pyrazolo[1,4]diazepines as non-peptidic probes of the oxytocin and vasopressin receptors. Tetrahedron Lett 55(33):4568–4571. https://doi.org/10.1016/j.tetlet.2014.06.022

    Article  CAS  Google Scholar 

  37. Fuller RW, Mason NR (1986) Flumezapine, an antagonist of central dopamine and serotonin receptors. Res Commun Chem Pathol Pharmacol 54(1):23–34 (PMID:2879325)

    CAS  PubMed  Google Scholar 

  38. Eberlein WE, Engel WW, Trummlitz G, Schmidt G, Hammer R (1988) Tricyclic compounds as selective antimuscarinics 2 structure-activity relationships of m1-selective antimuscarinics related to pirenzepine. J Med Chem 31:1169

    Article  CAS  Google Scholar 

  39. Colgate SM, Dorling PR, Huxtable CR, Shaw TJ, Skelton BW, Vogel P, White AH (1989) (+)–Iforresthe: a novel heterocyclic nephrotoxin from isotropis forrestii. Aust J Chem 42:1249–1255. https://doi.org/10.1071/CH9891249

    Article  Google Scholar 

  40. Kariyone K, Yazawa H, Kohsaka M (1971) The structures of tomaymycin and oxotomaymycin. Chem Pharm Bull 19:2289–2293. https://doi.org/10.1248/cpb.19.2289

    Article  CAS  Google Scholar 

  41. Kshirsagar UA, Puranik VG, Argade NP (2010) Total synthesis of proposed auranthine. J Org Chem 75:2702–2705. https://doi.org/10.1021/jo100400z

    Article  CAS  PubMed  Google Scholar 

  42. Dourlat J, Liu WQ, Gresh N, Garbay C (2007) Novel 1, 4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines. Bioorgan Med Chem Lett 17:2527–2530. https://doi.org/10.1016/j.bmcl.2007.02.016

    Article  CAS  Google Scholar 

  43. Churcher I, Williams S, Kerrad S (2003) Design and synthesis of highly potent benzodiazepine g-secretase inhibitors: preparation of (2S, 3R)-3-(3,4- difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-1-methyl-2-oxo-5-phenyl-2, 3-dihydro-1H-benzo[e] [1,4]-diazepin-3-yl)butyramide by use of an asymmetric Ireland–Claisen rearrangement. J Med Chem 46:2275–2278. https://doi.org/10.1021/jm034058a

    Article  CAS  PubMed  Google Scholar 

  44. Wolkowitz OM, Turetsky N, Reus VI, Hargreaves WA (1992) Benzodiazepine augmentation of neuroleptics in treatment–resistant schizophrenia. Psychopharmacol Bull 28:291–295

    CAS  PubMed  Google Scholar 

  45. Spencer J, Rathnam RP, Chowdhry BZ (2010) 1, 4-Benzodiazepin-2-ones in medicinal chemistry. Future Med Chem 2:1441–1449. https://doi.org/10.4155/fmc.10.226

    Article  CAS  PubMed  Google Scholar 

  46. Sangshetti JN, Chouthe RS, Jadhav MR, Sakle NS, Chabukswar A, Gonjari I, Darandale S, Shinde DB (2017) Green synthesis and anxiolytic activity of some new dibenz-[1,4]diazepine-1-one analogues. Arab J Chem 10:1356–1363. https://doi.org/10.1016/j.arabjc.2013.04.004

    Article  CAS  Google Scholar 

  47. Liegeois JF, Bruhwyler J, Damas J, Nguyen TP, Chleide EM, Mercier MG, Rogister FA, Delarge JE (1993) New pyridobenzodiazepine derivatives as potential antipsychotics: synthesis and neurochemical study. J Med Chem 36:2107–2114

    Article  CAS  Google Scholar 

  48. El–Sabbagh OI, El–Nabtity SM (2009) Synthesis and pharmacological studies for new benzotriazole and dibenzodiazepine derivatives as antipsychotic agents. Bull Korean Chem Soc 30:1445–1451. https://doi.org/10.5012/bkcs.2009.30.7.1445

    Article  Google Scholar 

  49. Savari A, Heidarizadeh F, Pourreza N (2019) Synthesis and characterization of CoFe2O4@SiO2@NH-NH-PCuW as an acid nano catalyst for the synthesis of 1,4-benzodiazepines and a powerful dye remover. Polyhedron. https://doi.org/10.1016/j.poly.2019.03.046

    Article  Google Scholar 

  50. Kausar N, Mukherjee P, Das AR (2016) Practical carbocatalysis by grapheme oxide nanosheets in aqueous medium towards the synthesis of diversified dibenzo[1,4]diazepine scaffolds. RSC Adv 6:88904–88910. https://doi.org/10.1039/c6ra17520a

    Article  CAS  Google Scholar 

  51. Jiasheng F, Stephen JS, Richard VC, Anne C, Peter C (2009) Discovery and optimization of a novel neuromedin B receptor antagonist. Bioorgan Med Chem Lett 19:4264–4267. https://doi.org/10.1016/j.bmcl.2009.05.124

    Article  CAS  Google Scholar 

  52. Tonkikh NN, Strakovs A, Rizhanova KV, Petrova MV (2004) 11-aryl-3,3-dimethyl-7- and 7,8-substituted 1, 2, 3, 4, 10, 11-hexahydro-5H-dibenzo[b, e][1,4]diazepin-1-ones. Chem Heterocycl Compd 40:949–955

    Article  CAS  Google Scholar 

  53. Zhu XT, Liu JY, Jiang B, Tua SJ (2014) Microwave–assisted aqueous reactions: an efficient route to benzodiazepines. J Heterocycl Chem 52:92–96. https://doi.org/10.1002/jhet.1988

    Article  CAS  Google Scholar 

  54. Cortés EC, Sanabria AMH, Mellado OG (2002) Synthesis and spectral properties of 11-[(o-, and p-substituted)-phenyl]-8-[(o-, m-, p-methoxy)phenylthio]-3,3-dimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b, e][1,4]diazepin-1-ones. J Heterocycl Chem 39(1):55–59. https://doi.org/10.1002/jhet.5570390107

    Article  Google Scholar 

  55. Parmar NJ, Barad HA, Pansuriya BR, Teraiya SB, Gupta VK, Kant R (2012) An efficient one-pot synthesis, structure, antimicrobial and antioxidant investigations of some novel quinolyldibenzo[b, e][1,4]diazepinones. Bioorgan Med Chem Lett 22:3816–3821. https://doi.org/10.1016/j.bmcl.2012.03.100

    Article  CAS  Google Scholar 

  56. Barad HA, Sutariya TR, Brahmbhatt GC, Parmar NJ, Lagunes I, Padro´n JM, Murumkar P, Sharma M, Yadav MR (2016) A catalyst- and solvent-free multicomponent synthesis and docking study of some new antiproliferative N5-allyl-quinolylpyrido[2,3-b]-[1,4]benzodiazepinone precursors. New J Chem 40:4931–4939. https://doi.org/10.1039/C5NJ03280F

    Article  CAS  Google Scholar 

  57. Hamilton RW (1976) Esters and amides of 4,5-dihydrobenz[g]indazole-3-carboxylic acids and related compounds. US 3940418 A:418

  58. Abdel–Wahab BA, Abdel-Aziz HA, Ahmed EM (2008) Convenient synthesis and antimicrobial activity of new 3-substituted 5-(benzofuran-2-yl)-pyrazole derivatives. Arch Pharm Chem Life Sci 341:734–739. https://doi.org/10.1002/ardp.200800119

    Article  CAS  Google Scholar 

  59. Prakash O, Kumar R, Parkash V (2008) Synthesis and antifungal activity of some new 3-hydroxy-2-(1-phenyl-3-aryl-4-pyrazolyl) chromenes. Eur J Med Chem 43:435–440. https://doi.org/10.1016/j.ejmech.2007.04.004

    Article  CAS  PubMed  Google Scholar 

  60. Menozzi G, Mosti L, Schenone P, Donnoli D, Schiariti F, Marmo E (1990) 1-Phenyl-1H-pyrazole derivatives with anti-inflammatory, analgesic, and antipyretic activities. J Cheminform 21:173 (PMID:2133993)

    Google Scholar 

  61. Kocyigit–Kaymakcioglu B, Toklu HZ, İkiz S, Bagcigil AF, Rollas S, Ozgur NY, Ak S (2008) Synthesis and antinociceptive–antimicrobial activities of some new amide derivatives of 3, 5-di/-and 1, 3, 5-trimethylpyrazoles. J Enzyme Inhib Med Chem 23:454–461. https://doi.org/10.1080/14756360701631686

    Article  CAS  PubMed  Google Scholar 

  62. Demirayak S, Kayagil I, Yurttas L, Aslan R (2010) Synthesis of some imidazolyl-thioacetyl-pyrazolinone derivatives and their antinociceptive and anticancer activities. J Enzyme Inhib Med Chem 25(1):74–79. https://doi.org/10.3109/14756360903016751

    Article  CAS  PubMed  Google Scholar 

  63. Godoy MCM, Fighera MR, Souza FR, Flores AE, Rubin MA, Oliveira MR, Zanatta N, Martins MAP, Bonacorso HG, Mello CF (2004) α2-Adrenoceptors and 5-HT receptors mediate the antinociceptive effect of new pyrazolines, but not of dipyrone. Eur J Pharmacol 496:93–97. https://doi.org/10.1016/j.ejphar.2004.05.045

    Article  CAS  PubMed  Google Scholar 

  64. Khan R, Uddin I, Alam M, Sultan D (2008) Synthesis and cytotoxic activity of pyrazolone derivatives. Bangladesh J Pharmacol 3:27–35

    Google Scholar 

  65. Kumari S, Paliwal S, Chauhan R (2014) Synthesis of pyrazole derivatives possessing anticancer activity current status. Commun 44:1521–1578. https://doi.org/10.1080/00397911.2013.828757

    Article  CAS  Google Scholar 

  66. Kumari S, Paliwal S, Chauhan R (2014) Anticancer activity of pyrazole via different biological mechanisms. Synth Commun 44:1333–1374. https://doi.org/10.1080/00397911.2013.837186

    Article  CAS  Google Scholar 

  67. Saleh AM, Taha MO, Aziz MA, Al–Qudah MA, AbuTayeh RF, Rizvi SA (2016) Novel anticancer compound [trifluoromethyl-substituted pyrazole N-nucleoside] inhibits FLT3 activity to induce differentiation in acute myeloid leukemia cells. Cancer Lett 375:199–208. https://doi.org/10.1016/j.canlet.2016.02.028

    Article  CAS  PubMed  Google Scholar 

  68. Koca I, Ozgür A, Coskun KA, Tutar Y (2013) Synthesis and anticancer activity of acyl thioureas bearing pyrazole moiety. Bioorgan Med Chem 21:3859–3865. https://doi.org/10.1016/j.bmc.2013.04.021

    Article  CAS  Google Scholar 

  69. Parmar NJ, Shashikant T, Rikin P, Barad H, Jajda H, Thakkar V (2015) Synthesis, antimicrobial and antioxidant activities of some 5–pyrazolone based schiff bases. J Saudi Chem Soc 19:36–41. https://doi.org/10.1016/j.jscs.2011.12.014

    Article  Google Scholar 

  70. Kumar SK, Rajasekharan A (2012) Synthesis and characterization, in vitro antioxidants activity of mannich base of pyrazolone derivatives. Int J Res Pharm Chem 2:327–337

    Google Scholar 

  71. Bule SS, Kumbhare MR, Dighe PR (2013) Synthesis and in-vitro biological evaluation of a novel series of 4-(substituted)-5-methyl-2-phenyl-1, 2-dihydro-3H-pyrazol-3-one as antioxidant. J Chem Biol Phys Sci Sec B 3:1996–2005

    CAS  Google Scholar 

  72. Neochoritis CG, Tsoleridis CA, Stephanatou JS, Kontogiorgis CA, Hadjipavlou-Litina DJ (2010) 1, 5-Benzoxazepines vs 1, 5-benzodiazepines, one-pot microwave-assisted synthesis and evaluation for antioxidant activity and lipid peroxidation inhibition. J Med Chem 53:8409–8420. https://doi.org/10.1021/jm100739n

    Article  CAS  PubMed  Google Scholar 

  73. Musavi S, Kakkar P (2003) Effect of diazepam treatment and its withdrawal on pro/antioxidative processes in rat brain. Mol Cell Biochem 245:51–56. https://doi.org/10.1023/A:1022857508987

    Article  CAS  PubMed  Google Scholar 

  74. Laxminarayan R, Duse A, Wattal C, Zaidi AKM, Wertheim HFL, Sumpradit N, Vlieghe E, Hara GL, Gould IM, Goossens H, Greko C, So AD, Bigdeli M, Tomson G, Woodhouse W, Ombaka E, Peralta AQ, Qamar FN, Mir F, Kariuki S, Bhutta Z, Coates A, Bergstrom R, Wright GD, Brown ED, Cars O (2013) Antibiotic resistance—the need for global solutions. Lancet Infect Dis 13:1057–1098. https://doi.org/10.1016/S1473-3099(13)70318-9

    Article  PubMed  Google Scholar 

  75. Ballell L, Field RA, Duncan K, Young RJ (2005) New small–molecule synthetic antimycobacterials Antimicrob Agents. Chemother 49:2153–2163. https://doi.org/10.1128/AAC.49.6.2153-2163.2005

    Article  CAS  Google Scholar 

  76. Rachel N, Pickett J, Back E (2008) Drug resistance as a global health policy priority. Center for Global Development, Washington, DC

    Google Scholar 

  77. Szakács G, Paterson JG, Ludwig JA, Booth-Genthe C, Gottesman MM (2006) Targeting multidrug resistance in cancer. Nat Rev Drug Discov 5:219–234

    Article  Google Scholar 

  78. Veronica E, Mercedes V, Mene´ndez JC (2010) Multicomponent reactions for the synthesis of pyrroles. Chem Soc Rev 39:4402–4421. https://doi.org/10.1039/b917644f

    Article  CAS  Google Scholar 

  79. Yu J, Shi F, Gong LZ (2011) Brønsted-acid-catalyzed asymmetric multicomponent reactions for the facile synthesis of highly enantioenriched structurally diverse nitrogenous heterocycles. Acc Chem Res 44:1156–1171. https://doi.org/10.1021/ar2000343

    Article  CAS  PubMed  Google Scholar 

  80. Ma C, Zhou JY, Zhang YZ, Jiao Y, Mei GJ, Shi F (2018) Synergistic catalysis-enabled reaction of 2-indolymethanols with oxonium ylides: construction of 3-indolyl-3-alkoxy oxindole framework. Chem Asian J 13:2549–2560. https://doi.org/10.1002/asia.201800620

    Article  CAS  PubMed  Google Scholar 

  81. Wang YM, Zhang HH, Li C, Fan T, Shi F (2016) Catalytic asymmetric chemoselective 1,3-dipolar cycloadditions of azomethine ylide with isatinderived imines: diastereo- and enantioselective construction of spiro[imidazolidine-2,3′-oxindole] framework. Chem Commun 52:1804–1808. https://doi.org/10.1039/x0xx00000x

    Article  CAS  Google Scholar 

  82. Ma C, Jiang F, Sheng FT, Jiao Y, Mei GJ, Shi F (2018) Design and catalytic asymmetric construction of axially chiral 3,3′- bisindole skeletons. Angew Chem Int Ed 58:3014–3021. https://doi.org/10.1002/anie.201811177

    Article  CAS  Google Scholar 

  83. Michael H (2010) The (4 + 3)-cycloaddition reaction: heteroatom-substituted allylic cations as dienophiles. Chem Commun 46:8904–8922. https://doi.org/10.1039/c0cc03621h

    Article  CAS  Google Scholar 

  84. Dai W, Jiang XL, Wu Q, Shi F, Tu SJ (2015) Diastereo- and enantioselective construction of 3,3′-pyrrolidinyldispirooxindole framework via catalytic asymmetric 1,3- dipolar cycloadditions. J Org Chem 80:5737–5744. https://doi.org/10.1021/acs.joc.5b00708

    Article  CAS  PubMed  Google Scholar 

  85. Michael H (2010) The (4 + 3)-cycloaddition reaction: simple allylic cations as dienophiles. Chem Commun 46:8886–8903. https://doi.org/10.1039/c0cc03620j

    Article  CAS  Google Scholar 

  86. Andrew GL, Richard PH (2011) (4 + 3) Cycloaddition reactions of nitrogen-stabilized oxyallyl cations. Chem Eur J 17:3812–3822. https://doi.org/10.1002/chem.201100260

    Article  CAS  Google Scholar 

  87. Zhu CZ, Feng JJ, Zhang J (2016) Rhodium(I)-catalyzed intermolecular aza-[4 + 3] cycloaddition of vinyl aziridines and dienes: atom-economical synthesis of enantiomerically enriched functionalized azepines. Angew Chem Int Ed 55:1–6. https://doi.org/10.1002/anie.201609608

    Article  CAS  Google Scholar 

  88. Jiang F, Yuan FR, Jin LW, Mei GJ, Shi F (2018) Metal-catalyzed (4 + 3) cyclization of vinyl aziridines with para-quinone methide derivatives. ACS Catal 8:10234. https://doi.org/10.1021/acscatal.8b03410

    Article  CAS  Google Scholar 

  89. Savaria A, Heidarizadeh F, Pourreza N (2019) Synthesis and characterization of CoFe2O4@SiO2@NH-NH2-PCuW as an acidic nano catalyst for the synthesis of 1,4-benzodiazepines and a powerful dye remover. Polyhedron. https://doi.org/10.1016/j.poly.2019.03.046

    Article  Google Scholar 

  90. McGowan D, Nyanguile O, Cummings MD, Vendeville S, Vandyck K, den Broeck WV, Boutton CW, Bondt HD, Quirynen L, Amssoms K, Bonfanti JF, Last S, Rombauts K, Tahri A, Hu L, Delouvroy F, Vermeiren K, Vandercruyssen G, derHelm LV, Cleiren E, Mostmans W, Lory P, Pille G, Emelen KV, Fanning G, Pauwels F, Lin TI, Simmen K, Raboisson P (2009) 1, 5-Benzodiazepine inhibitors of HCV NS5B polymerase. Bioorgan Med Chem Lett 19:2492–2496. https://doi.org/10.1016/j.bmcl.2009.03.035

    Article  CAS  Google Scholar 

  91. Kolos NN, Yurchenko EN, Orlov VD, Shishkina SV, Shishkin OV (2004) Investigation of the products of interaction of cyclic diketones with nitrogen-containing 1,4-binucleophiles. Chem Heterocycl Compd 40:1550–1559

    Article  CAS  Google Scholar 

  92. Chavan HV, Adsul LK, Kotmale AS, Dhakane VD, Thakare VN, Bandgar BP (2015) Design, synthesis, characterization and in vitro and in vivo anti–inflammatory evaluation of novel pyrazole–based chalcones. J Enzyme Inhib Med Chem 30:22–31. https://doi.org/10.3109/14756366.2013.873037

    Article  CAS  PubMed  Google Scholar 

  93. Nagarapu L, Materi J, Gaikwad HK (2011) Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4-phenylpiperazin-1yl) propyl]-1H-pyrazole-5-carboxamide derivatives. Bioorgan Med Chem Lett 21:4138–4140. https://doi.org/10.1016/j.bmcl.2011.05.105

    Article  CAS  Google Scholar 

  94. Bekhit AA, Ashour HMA, Ghany YSA (2008) Synthesis and biological evaluation of some thiazolyl and thiadiazolyl derivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. Eur J Med Chem 43:456–463. https://doi.org/10.1016/j.ejmech.2007.03.030

    Article  CAS  PubMed  Google Scholar 

  95. Wang Y, Tu MS, Shi F, Tua SJ (2014) Enantioselective construction of the biologically significant Dibenzo[1,4]diazepine scaffold via organocatalytic asymmetric three-component reactions. Adv Synth Catal 356:2009–2019. https://doi.org/10.1002/adsc.201400095

    Article  CAS  Google Scholar 

  96. Xu CJ, Yan-Qin Shi YQ (2011) Synthesis and crystal structure of 5-Chloro-3-Methyl-1-Phenyl-1H-Pyrazole-4-Carbaldehyde. J Chem Crystallogr 41:1816–1819. https://doi.org/10.1007/s10870-011-0178-4

    Article  CAS  Google Scholar 

  97. Srivastava A, Singh RM (2005) Vilsmeier-Haack reagent: A facile synthesis of 2-chloro-3-formylquinolines from N-arylacetamides and transformation into different functionalities. Indian J Chem B 44B:1868–1875

    CAS  Google Scholar 

  98. L’abbe G, Emmers S, Dehaen W, Dyall LK (1994) 5-Chloropyrazole-4-carbaldehyde as synthons for intramolecular 1, 3-dipolar cycloadditions. J Chem Soc Perkin Trans 1:2553–2558. https://doi.org/10.1039/P19940002553

    Article  Google Scholar 

  99. Farrugia LJ (1999) WinGX suite for small–molecule single–crystal crystallography. J Appl Cryst 32:837–838. https://doi.org/10.1107/S0021889899006020

    Article  CAS  Google Scholar 

  100. Nardelli M (1995) PARST95—an update to PARST: a system of fortran routines for calculating molecular structure parameters from the results of crystal structure analyses. J Appl Cryst 28:659. https://doi.org/10.1107/S0021889895007138

    Article  CAS  Google Scholar 

  101. Spek AL (2009) Structure validation in chemical crystallography. Acta Cryst D 65:148–155

    Article  CAS  Google Scholar 

  102. NCCLS (National Committee for Clinical Laboratory Standards) (2002) Performance standards for antimicrobial susceptibility testing: Twelfth Informational Supplement, ISBN 1-56238-454-6 M100-S12 (M7)

  103. NCCLS (2009) National Committee on Clinical Laboratory Standards. Susceptibility testing of mycobacteria, nocardiae and other aerobic actinomycetes; approved standard. Wayne, PA, USA. https://doi.org/10.1016/0732-8893(95)00276-6

    Article  CAS  Google Scholar 

  104. Rattan A (2001) Antimicrobials in Laboratory Medicine. In: Churchill BI (ed) Livingstone, New Delhi. Indian J Med Microbiol 19:109. ISBN-81-7042-160-8

  105. Benzie IFF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76. https://doi.org/10.1006/abio.1996.0292

    Article  CAS  PubMed  Google Scholar 

  106. Miranda PO, Padro´n JM, Padro´n JI, Villar J, Martı´n VS (2006) Prins-type synthesis and SAR study of cytotoxic alkyl chloro dihydropyrans. Chem Med Chem 1:323–329. https://doi.org/10.1002/cmdc.200500057

    Article  CAS  PubMed  Google Scholar 

  107. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, Warren JT, Bokesch H, Kenney S, Boyd MR (1990) New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 82:1107–1112. https://doi.org/10.1093/jnci/82.13.1107

    Article  CAS  PubMed  Google Scholar 

  108. Murumkar PR, Sharma MK, Giridhar R, Yadav MR (2015) Virtual screening-based identification of lead molecules as selective TACE inhibitors. Med Chem Res 24:226–244. https://doi.org/10.1007/s00044-014-1097-7

    Article  CAS  Google Scholar 

  109. Lee SH, Van HTM, Yang SH, Lee KT, Kwon Y, Cho WJ (2009) Molecular design, synthesis and docking study of benz [b] oxepines and 12-oxobenzo [c] phenanthridinones as topoisomerase 1 inhibitors. Bioorgan Med Chem Lett 19:2444–2447. https://doi.org/10.1016/j.bmcl.2009.03.058

    Article  CAS  Google Scholar 

  110. Khadka DB, Le QM, Yang SH, Van HTM, Le TN, Cho SH, Kwon Y, Lee KT, Lee ES, Cho WJ (2011) Design, synthesis and docking study of 5-amino substituted indeno[1,2-c]isoquinolines as novel topoisomerase I inhibitors. Bioorgan Med Chem 19:1924–1929. https://doi.org/10.1016/j.bmc.2011.01.064

    Article  CAS  Google Scholar 

  111. Van HTM, Khadka DB, Yang SH, Le TN, Cho SH, Zhao C, Lee IS, Kwon Y, Lee KT, Kim YC, Cho WJ (2011) Synthesis of benzo[3, 4]azepino[1,2-b]isoquinolin-9-ones from 3-arylisoquinolines via ring closing metathesis and evaluation of topoisomerase I inhibitory activity, cytotoxicity and docking study. Bioorgan Med Chem 19:5311–5318. https://doi.org/10.1016/j.bmc.2011.08.006

    Article  CAS  Google Scholar 

  112. Sengupta P, Puri CS, Chokshi HA, Sheth CK, Ajay S, Midha AS, Chitturi TR, Thennati R, Murumkar PR, Yadav MR (2011) Synthesis, preliminary biological evaluation and molecular modeling of some new heterocyclic inhibitors of TACE. Eur J Med Chem 46:5549–5555. https://doi.org/10.1016/j.ejmech.2011.09.018

    Article  CAS  PubMed  Google Scholar 

  113. DasGupta S, Murumkar PR, Giridhar R, Yadav MR (2009) Studies on novel 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones as potential TACE inhibitors: design, synthesis, molecular modeling, and preliminary biological evaluation. Bioorgan Med Chem 17:3604–3617. https://doi.org/10.1016/j.bmc.2009.04.003

    Article  CAS  Google Scholar 

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Acknowledgements

All authors sincerely express thanks to the Head, Department of Chemistry of Sardar Patel University, for providing necessary research facilities. Particularly, authors GCB and TRS are grateful to the UGC, New Delhi, for research fellowships under the UGC scheme of BSR and RFSMS. IL thanks CONACYT (Mexico) for a postdoctoral grant. IL and JMP thank the Spanish Government for financial support through project PGC2018-094503-B-C22 (MCIU/AEI/FEDER, UE). The authors also acknowledge financial support (Project No. 699 EMEQ-404/2014, dated March 11, 2016) of the SERB, DST, New Delhi, India. M.R.Y. is thankful to UGC, New Delhi, for awarding UGC-BSR Faculty Fellowship [No. F.18-1/2011(BSR)]. Thanks are also due to DST, New Delhi, in general, and PURSE central facility (vide sanction letter DO. no. SR/59/Z–23/2010/43 dated March 16, 2011) for mass analysis, in particular, as well as UGC-CPEPA, Phase II for the assistance in general and for NMR facility, in particular, sponsored under award letter no.F.No.1-14/2002-2016(NS/PE) dated April 28, 2016.

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Authors and Affiliations

  1. Department of Chemistry, Sardar Patel University, Dist. Anand, Vallabh Vidyanagar, Gujarat, 388120, India

    Gaurangkumar C. Brahmbhatt, Tushar R. Sutariya, Hiralben D. Atara & Narsidas J. Parmar

  2. Post–Graduate Department of Physics, University of Jammu, Jammu, Tawi, 180006, India

    Vivek K. Gupta

  3. BioLab, Instituto Universitario de Bio-Orgánica ‘‘Antonio González’’ (IUBO–AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, C/Astrofísico Francisco Sánchez 2, 38206, La Laguna, Spain

    Irene Lagunes & José M. Padrón

  4. Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, 390 001, India

    Prashant R. Murumkar & Mange Ram Yadav

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  1. Gaurangkumar C. Brahmbhatt
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Brahmbhatt, G.C., Sutariya, T.R., Atara, H.D. et al. New pyrazolyl-dibenzo[b,e][1,4]diazepinones: room temperature one-pot synthesis and biological evaluation. Mol Divers 24, 355–377 (2020). https://doi.org/10.1007/s11030-019-09958-z

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