Login Register Cart 0
Generic placeholder image

Central Nervous System Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Glacial Acetic Acid Catalyzed Synthesis, Physicochemical and Biological Evaluation of Benzodiazepines as Potent CNS Agents

Author(s): Vipin Kumar, Shweta Verma* and Sushil Kumar

Volume 19, Issue 2, 2019

Page: [146 - 151] Pages: 6

DOI: 10.2174/1871524919666190227234238

Price: $65

Abstract

Background: Approach for green chemistry for chemical synthesis is found to be very efficient as it makes the reaction more easily, less tedious, maximize desired products and minimize by-products.

Materials & Methods: Utilizing this approach 1, 5-benzodiazepines and its derivatives have been synthesized and evaluated for skeletal muscle and antianxiety activity. 1, 5-benzodiazepine derivatives have attracted great attention due to its diversity of pharmacological activities and its application in heterocyclic synthesis and medicines. The target compounds were synthesized by first reacting o-phenylenediamine with acetophenone to yield 1, 5-benzodiazepines. In the next step the NH of 1, 5-benzodiazepines were chloroacetylated and then the chloro group was substituted with different anilines. The structures were confirmed on the basis of their TLC, IR, 1H NMR and CHN elemental studies. The physicochemical parameters were determined for BBB penetration through online software.

Results: The Log P values of the compounds tested showed that compounds have the potential to be CNS active. The compounds were evaluated for the skeletal muscle relaxant activity and antianxiety activity. It was investigated that 1, 5-benzodiazepines derivatives possess significant differences between control group and treated group.

Conclusion: Among these derivatives, the compound bearing chloro group possesses the highest skeletal muscle relaxant and antianxiety activity.

Keywords: 1, 5-benzodiazepines, anilines, antianxiety activity, cardiovascular disorders, green chemistry, skeletal muscle relaxant activity.

« Previous Next »
Graphical Abstract

[1]
de Baun, J.R.; Pallos, F.M.; Baker, D.R. “5-furoyl-2,2,4-trimethyl- 1,4-dihydro-1H-1,5-benzodiazepine as an anti-inflamma-tory agent,” 1976, US Patent 3,978,227. Available from: http://scholar.google.com/ scholar_lookup?title=5-furoyl-2%2c2%2c4-trimethyl-1%2c4-dihyd ro-1H-1%2c5-benzodiazepine+as+an+anti-inflammatory+agent& author=J.+R.+de+Baun&author=F.+M.+Pallos&author=D.+R.+ Baker&publication_year=1976.
[2]
de Baun, J.R.; Pallos, F.M.; Baker, D.R. 5-furoyl-2,2,4-trimethyl-1,4-dihydro-1H-1,5-benzodiazepine as an anti-inflamma-tory agent. Chem. Abstr., 1977, 86, 5498d.
[3]
Schultz, H. Benzodiazepines; Springer: Heidelberg, Germany, 1982.
[4]
Smiley, R.K. Comprehensive Organic Chemistry; Pergamon: Oxford, UK, 1979.
[5]
Landquist, J.K. Comprehensive Heterocyclic Chemistry; Pergamon: Oxford, UK, 1984.
[6]
Randall, L.O.; Kappel, B. Pharmacological activity of some benzodiazepines and their metabolites. In:Benzodiazepines; Garattini, S.; Mussini, E., Eds.; Raven: New York, NY, USA, 1973.
[7]
Haris, R.C.; Straley, J.M. Lifting apparatus. 1968, US Patent 1,537,757, Available from: https://scholar.google.com/scholar_ lookup?title=Lifting+apparatus&author=R.+C.+Haris&author=J.+ M.+Straley&publication_year=1968
[8]
El-Sayed, A.M.; Abdel-Ghany, H.; El-Saghier, A.M.M. A novel synthesis of pyrano(2,3-c)-, 1,3-oxazino(2,3 b)-,1,2,4- triazolo(3,4-b)-, oxazolo(2,3-b)-, furano(3,2-c)-, and 3-substituted- (1,5)benzo-diazepin-2-ones. Synth. Commun., 1999, 29(20), 3561-3572.
[9]
Xu, J.X.; Wu, H.T.; Jin, S. Cycloaddition of benzoheteroazepine II reactions and conformations of cycloadducts on 1, 5-benzothia-zepines and 1,5-benzodiazepines with nitrile imine and nitrile oxides. Chin. J. Chem., 1999, 17(1), 84-91.
[10]
Zhang, X.Y.; Xu, J.X.; Jin, S. Cycloaddition of benzoheteroazepine reaction of 2,3-dihydro-lh-l,5-benzodiazepines with dichlorocarbene and stereo-structures of products. Chin. J. Chem., 1999, 17(4), 404-410.
[11]
Kim, K.; Volkman, S.K.; Ellman, J.A. Synthesis of 3-substituted 1,4-benzodiazepin-2-ones. J. Braz. Chem. Soc., 1998, 9(4), 375-379.
[12]
Reid, W.; Torinus, E. Über heterocyclische Siebenringsysteme, X. Synthesen kondensierter 5-, 7-und 8-gliedriger Heterocyclen mit 2 Stickstoffatomen. Chem. Ber., 1959, 92(11), 2902-2916.
[13]
Herbert, J.A.L.; Suschitzky, H. Syntheses of heterocyclic compounds substituted 2,3-dihydro-1h-1,5-benzodiazepines. J. Chem. Soc., 1974, 1, 2657-2661.
[14]
Morales, H.R.; Bulbarela, A.; Contreras, R. New synthesis of dihydro-and tetrahydro-1,5-benzodiazepines by reductive condensation of o-phenylenediamine and ketones in the presence of sodium borohydride. Heterocycles, 1986, 24(1), 135-139.
[15]
Jung, D.I.; Choi, T.W.; Kim, Y.Y.; In-Shik, K.; You-Mi, P.; Yong-Gyun, L.; Doo-Hee, J. Synthesis Of 1,5-benzodiazepine derivatives. Synth. Commun., 1999, 29(11), 1941-1951.
[16]
Balakrishna, M.S.; Kaboudin, B. A simple and new method for the synthesis of 1,5-benzodiazepine derivatives on a solid surface. Tetrahedron Lett., 2001, 42(6), 1127-1129.
[17]
Curini, M.; Epifano, F.; Marcotullio, M.C.; Rosati, O. Ytterbium triflate promoted synthesis of 1,5-benzodiazepine derivatives. Tetrahedron Lett., 2001, 42(18), 3193-3195.
[18]
Pan, X.Q.; Zou, J.P.; Huang, Z.H.; Zhang, W. Ga(otf)3-promoted condensation reactions for 1,5-benzodiazepines and 1,5-benzothiazepines. Tetrahedron Lett., 2008, 49(36), 5302-5308.
[19]
Kumar, R.; Chaudhary, P.; Nimesh, S.; Verma, A.K.; Chandra, R. An efficient synthesis of 1,5-benzadiazepine derivatives catalyzed by silver nitrate. Green Chem., 2006, 8(6), 519-521.
[20]
Sivamurugan, V.; Deepa, K.; Palanichamy, M.; Murugesan, V. [(l)proline]2zn catalysed synthesis of 1,5-benzodiazepine derivatives under solvent-free condition. Synth. Commun., 2004, 34(21), 3833-3846.
[21]
Minothora, P.; Julia, S.S.; Constantinos, A.T. An efficient method for the synthesis of 1,5-benzodiazepine derivatives under microwave irradiation without solvent. Tetrahedron Letters, vol. 43, no.9, 1755-1758. 2002
[22]
Chen, W.Y.; Lu, J. Molecular iodine catalyzed one-pot synthesis of 1, 5-benzodiazepine derivatives under solvent-free conditions. Synlett, 2005, 8, 1337-1339.
[23]
Jarikote, D.V.; Siddiqui, S.A.; Rajagopal, R.; Thomas, D.; Lahoti, R.J.; Srinivasan, K.V. Room temperature ionic liquid promoted synthesis of 1,5-benzodiazepine derivatives under ambient conditions. Tetrahedron Lett., 2003, 44(9), 1835-1838.
[24]
Reddy, B.M.; Sreekamth, P.M.; Reddy, V.R. Modified zirconia solid acid catalysts for organic synthesis and transformations. J. Mol. Catal. A, 2005, 225, 71-78.
[25]
Kaboudin, B.; Navaee, K. Alumina/phosphorus pentoxide (app) as an efficient reagent for the synthesis of 1,5-benzodiazepines under microwave irradiation. Heterocycles, 2001, 55(8), 1443-1446.
[26]
Yadav, J.S.; Reddy, B.V.S.; Praveenkumar, S.; Nagaiah, K.; Lingaiah, N.; Saiprasad, P.S. Ag3pw12o40: A novel and recyclable heteropoly acid for the synthesis of 1,5-benzodiazepines under solvent-free conditions. Synthesis, 2004, 6, 901-904.

Rights & Permissions Print Cite
Article Metrics
66
6
© 2024 Bentham Science Publishers | Privacy Policy