Synthesis, Toxicity Profile and Pharmacological Evaluation of Some New N,N-Diphenyl Amine Derivatives with Special Reference to Analgesic and Anti-inflammatory Activity

Author(s): Arvind Kumar*, Arun K. Mishra

Journal Name: Letters in Organic Chemistry

Volume 17 , Issue 7 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

The present work was aimed to synthesize eight new diphenylamine derivatives by the reactions of 2-chloro-N-(4-(diphenyl amino) thiazol-2-yl)acetamide with substituted phenols in the chloroform along with anhydrous potassium carbonate and potassium iodide. The structures of newly synthesized compounds were characterized by IR, NMR, Mass and elemental analysis techniques. Toxicity profile (acute and subacute oral toxicity) and biological activity (analgesic and anti-inflammatory activity) of the synthesized derivatives was performed. Findings of the present work suggested that the synthesized compounds may be one of the excellent potent compounds to treat pain and inflammation. Therefore compounds of this group especially AK-4 (N-(4-(diphenylamino)thiazol-2-yl)-2-(2- nitrophenoxy)acetamide) could be an excellent starting point to build up new lead compounds in the management of pain and inflammation.

Keywords: Diphenylamine, chloroacetylation, acute and subacute oral toxicity, analgesic activity, anti-inflammatory activity, anhydrous potassium carbonate.

[1]
Abbas, H.S.; Abdel-Karim, S.S.; Ahmed, E.M.; Eweas, A.F.; El-Awdan, S.A. Pharma. Drug Res., 2016, 73, 1163-1180.
[2]
Gouda, A.A.; El-Sayed, M.I.K.; Amin, A.S.; Sheikh, R.E. Arab. J. Chem., 2013, 6, 145-163.
[http://dx.doi.org/10.1016/j.arabjc.2010.12.006]
[3]
Hawkey, C.J. Gut, 2005, 54(11), 1509-1514.
[http://dx.doi.org/10.1136/gut.2005.065003] [PMID: 16227351]
[4]
Abdellatif, K.R.; Lamie, P.F.; Omar, H.A. J. Enzyme Inhib. Med. Chem., 2016, 31(2), 318-324.
[http://dx.doi.org/10.3109/14756366.2015.1022174] [PMID: 25798690]
[5]
Ottanà, R.; Maccari, R.; Barreca, M.L.; Bruno, G.; Rotondo, A.; Rossi, A.; Chiricosta, G.; Di Paola, R.; Sautebin, L.; Cuzzocrea, S.; Vigorita, M.G. Bioorg. Med. Chem., 2005, 13(13), 4243-4252.
[http://dx.doi.org/10.1016/j.bmc.2005.04.058] [PMID: 15905093]
[6]
Maria, V.; Gomez, G. J. Biochem., 2002, 277, 38212-38221.
[7]
Li, H.; Guan, A.; Huang, G.; Liu, C.L.; Li, Z.; Xie, Y.; Lan, J. Bioorg. Med. Chem., 2016, 24(3), 453-461.
[http://dx.doi.org/10.1016/j.bmc.2015.09.032] [PMID: 26432603]
[8]
Kumar, A.; Mishra, A.K. J. Pharm. Bioallied Sci., 2015, 7(1), 81-85.
[http://dx.doi.org/10.4103/0975-7406.148774] [PMID: 25709343]
[11]
Kumar, S.; Wahi, A.K.; Singh, R. Eur. J. Med. Chem., 2011, 46(9), 4753-4759.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.028] [PMID: 21824691]
[12]
Singh, S.; Kumar, V.; Sharma, S.K.; Kumar, A.; Sharma, S. Orient. J. Chem., 2010, 26, 93-101.
[13]
Organization for Economic Co-operation and Development (OECD). Guidance Document on Acute Oral Toxicity Testing 420; Organization for Economic Co-operation and Development: Paris, France, 2008.
[14]
Nakache, R.; Touil, T.; El Hessni, A.; Ouichou, A.; Bahbiti, Y.; Berkiks, I.; Chakit, M.; Mesfioui, A. Cogent Chem., 2017, 3, 1-11.
[http://dx.doi.org/10.1080/23312009.2017.1301242]
[15]
Organization for Economic Co-operation and Development (OECD). Guidance Document on Subacute Oral Toxicity Testing 407; Organization for Economic Co-operation and Development: Paris, France, 2008.
[16]
World Health Organization (WHO). General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine; WHO: Geneva, Switzerland, 2000, p. 35.
[17]
Subha, D.; Geetha, N. J. Scient. Innov. Res., 2017, 6, 113-115.
[18]
Nyunza, F.; Makule, E.; Chacha, M. Complem. Med. Alt. Healthcare., 2017, 4, 001-0011.
[19]
Yuet, P.K.; Darah, I.; Chen, Y.; Sreeramanan, S.; Sasidharan, S. BioMed Res. Int., 2013, 182064-182071.
[20]
Prasanth, K.M.; Suba, V.; Ramireddy, B.; Srinivasa, B.P. Trop. J. Pharm. Res., 2015, 14, 1849-1855.
[http://dx.doi.org/10.4314/tjpr.v14i10.16]
[21]
Mariappan, G.; Saha, B.P.; Sutharson, L.; Singh, A.; Garg, S.; Pandey, L.; Kumar, D. Saudi Pharm. J., 2011, 19(2), 115-122.
[http://dx.doi.org/10.1016/j.jsps.2011.01.003] [PMID: 23960749]
[22]
Eddy, N.B.; Leimbach, D.J. J. Pharmacol. Exp. Ther., 1953, 107, 38593.
[23]
Dhall, H.; Kumar, A.; Mishra, A.K. Curr. Bioact. Compd., 2018, 14, 26-32.
[http://dx.doi.org/10.2174/1573407213666161205161135]
[24]
Winter, C.A.; Risley, E.A.; Nuss, G.W. Proc. Soc. Exp. Biol. Med., 1962, 111, 544-547.
[http://dx.doi.org/10.3181/00379727-111-27849] [PMID: 14001233]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 7
Year: 2020
Page: [560 - 570]
Pages: 11
DOI: 10.2174/1570178617666191220150024
Price: $65

Article Metrics

PDF: 15
HTML: 1