Synthesis of certain pyrrole derivatives as antimicro-bial agents

Mohamed, Mosaad; El-Domany, Ramdan; Abd El-Hameed, Rania

doi:10.2478/v10007-009-0016-9

Abstract

In an effort to establish new pyrroles and pyrrolo[2,3-d] pyrimidines with improved antimicrobial activity we report here the synthesis and in vitro microbiological evaluation of a series of pyrrole derivatives. A series of new 2-aminopyrrole-3-carbonitriles (1a-d) were synthesized from the reaction of benzoin, primary aromatic amines and malononitrile, from which a number of pyrrole derivatives (2a-d to 5a-d) and pyrrolo[2,3-d]pyrimidines (6a-d to 10a, d) were synthesized. The in vitro antimicrobial testing of the synthesized compounds was carried out against Gram-positive, Gram-negative bacteria and fungi. Some of the prepared compounds, [2-amino-1-(2-methylphenyl)-4,5-diphenyl-1H-pyrrole-3-carbonitriles (1b), 2-amino-3-carbamoyl-1-(3-methylphenyl)-4,5-diphenyl-1H-pyrroles (2b), N-(3-cyano-1-(2-methylphenyl)-4,5-diphenyl-1H-pyrrol-2-yl)-acetamides (3b), N-(3-cyano-1-(3-methylphenyl)-4,5-diphenyl-1H-pyrrol-2-yl)-acetamides (3c), 2-amino-1-(4-methoxyphenyl)-4,5-diphenyl-3-tetrazolo-1H-pyrroles (5d), 7-(4-methoxyphenyl)-5,6-diphenyl-7H-pyrrolo [2,3-d]pyrimidin-4(3H)-ones (7d), 7-(3-methylphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4(3H)-thione (9b) and N-(7-(2-methylphenyl)-5,6-diphenyl-7H-pyrrolo[2,3-d] pyrimidine)-N-aryl amines (10a)] showed potent antimicrobial activity.

References

S. Petruso, S. Bonanno, S. Caronna, M. Ciofalo, B. Maggio and D. Schillaci, A new synthesis of bioactive analogs of monodeoxypyoluteorin, J. Heterocyclic Chem. 31 (1994) 941--945.
Search in Google Scholar
M. V. Raimondi, S. Cascioferro, D. Schillaci and S. Petruso, Synthesis and antimicrobial activity of new bromine-rich pyrrole derivatives related to monodeoxypyoluteorin, Eur. J. Med. Chem. 41 (2006) 1439--1445; DOI 10.1016/j.ejmech.2006.0.009.
Search in Google Scholar
D. Schillaci, S. Petruso and V. Sciortino, 3,4,5,3,5-Pentabromo-2-(2-hydroxybenzoyl)pyrrole: a potential lead compound as anti-Gram-positive and anti-biofilm agent, Int. J. Antimicrob. Ag. 25 (2005) 338--340; DOI: 10.1016/j.ijantimicag.2004.11.014.10.1016/j.ijantimicag.2004.11.014
Search in Google Scholar
M. Biava, R. Fioravanti, G. C. Porretta, D. Deidda, C. Maullu and R. Pompei, New pyrrole derivatives as antimycobacterial agents analogs of BM 212, Bioorg. Med. Chem. Lett. 9 (1999) 2983--2988; DOI: 10.1016/s0960-894x(99)00510-7.10.1016/S0960-894X(99)00510-7
Search in Google Scholar
M. Biava, G. C. Porretta, D. Deidda, R. Pompei, A. Tafi and F. Manetti, Importance of the thiomorpholine introduction in new pyrrole derivatives as antimycobacterial agents analogues of BM 212, Bioorg. Med. Chem. 11 (2003) 515--520; DOI: 10.1016/s0968-0896(02)00455-8.10.1016/S0968-0896(02)00455-8
Search in Google Scholar
G. H. Jana, S. Jain, S. K. Arora and N. Sinha, Synthesis of some diguanidino 1-methyl-2,5-diaryl-1H-pyrroles as antifungal agents, Bioorg. Med. Chem. Lett. 15 (2005) 3592--3595; DOI: 10.1016/j.bmcl.2005.05.080.10.1016/j.bmcl.2005.05.080
Search in Google Scholar
Y. Misumo, M. J. Ikehara, K. A. Watanabe, S. Suzuki and T. Itoh, Synthetic studies of potential antimetabolites. IX. The anomeric configuration of tubercidin, J. Org. Chem. 28 (1969) 3329--3331.
Search in Google Scholar
Q. Dang and J. E. Gomez-Galeno, An efficient synthesis of pyrrolo[2,3-d]pyrimidines via inverse electron demand Diels-Alder reactions of 2-amino-4-cyanopyrroles with 1,3,5-triazines, J. Org. Chem. 67 (2002) 8703--8705; DOI: 10.1021/jo026309d.10.1021/jo026309d
Search in Google Scholar
K. V. Rao, Structure of sangivamycin, J. Med. Chem. 11 (1968) 939--941; DOI: 10.1021/jm00311a005.10.1021/jm00311a005
Search in Google Scholar
A. Gangjee, X. Lin and S. F. Queener, Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6-substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors, J. Med. Chem. 47 (2004) 3689--3692; DOI: 10.1021/jm0306327.10.1021/jm0306327
Search in Google Scholar
P. M. Traxler, P. Furet, H. Mett, E. Buchdunger, T. Meyer and N. Lydon, 4-(Phenylamino)pyrrolopyrimidines: Potent and selective, ATP site directed inhibitors of the EGF-receptor protein tyrosine kinase, J. Med. Chem. 39 (1996) 2285--2290; DOI: 10.1021/jm960118j.10.1021/jm960118j
Search in Google Scholar
M. S. Mohamed, A. E. Rashad, M. E. A. Zaki and S. S. Fatahala, Synthesis and antimicrobial screening of some fused heterocyclic pyrroles, Acta Pharm. 55 (2005) 237--249.
Search in Google Scholar
H. J. Roth und K. Eger, Synthese von 2-Amino-3-cyano-pyrrolen, Arch. Pharm. 18 (1974) 179--185.
Search in Google Scholar
H. J. Roth und K. Eger, Synthese von pyrrolo[2,3-d]pyrimidinen, Arch. Pharm. 18 (1974) 252--258.
Search in Google Scholar
A. C. Gales, H. S. Sader and R. N. Jones, Urinary tract infection trends in Latin American hospitals: report from the SENTRY antimicrobial surveillance program, Diagn. Mic. Infec. Dis. 44 (1997--2000) 289--294.10.1016/S0732-8893(02)00470-4
Search in Google Scholar
A. Jorgensen, K. A. M. El-Bayouki and E. B. Pedersen, Phosphorus pentoxide in organic synthesis. XX: Synthesis of N-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines, J. Heterocyclic Chem. 22 (1985) 859--863.
Search in Google Scholar
C. G. Dave and M. C. Shukla, Diethyl ethoxymethylenemalonate in triheterocycles: a new synthesis of pyrido[3,2-e]pyrimido[1,2-c]pyrimidines, J. Heterocyclic Chem. 34 (1997) 1805--1808.
Search in Google Scholar
C. G. Dave and R. D. Shah, Synthesis of 7H-tetrazolo[1,5-c]pyrrolo[3,2-e]pyrimidines and their reductive ring cleavage to 4-aminopyrrolo[2,3-d]pyrimidines, J. Heterocyclic Chem. 35 (1998) 1295--1300.
Search in Google Scholar
C. G. Dave, Synthesis and reactions of fluoroaryl substituted 2-amino-3-cyanopyrroles and pyrrolo[2,3-d]pyrimidines, J. Heterocyclic Chem. 36 (1999) 729--733.
Search in Google Scholar
G. F. Gad, R. A. El-Domany and H. M. Ashour, Antimicrobial susceptibility profile of Pseudomonas aeruginosa isolates in Egypt, J. Urol. 180 (2008) 176--181; DOI: 10.1016/j.juro.2008.03.081.10.1016/j.juro.2008.03.08118499192
Search in Google Scholar

Synthesis of certain pyrrole derivatives as antimicro-bial agents

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