Some New NSAIDs Prodrugs: An Efficient Synthesis, Spectral Characterization and X-ray Crystal Structure Studies

Tarek Aboul-Fadl1; Tilal Elsaman; Omar A. Al-Deeb; Hazem A. Ghabbour; C.S. Chidan Kumar; Hoong-Kun Fun

doi:10.14233/ajchem.2014.16949

Issue

Vol. 26 No. 16 (2014): Vol 26 Issue 16

Issue Published : July 28, 2014

This work is licensed under a Creative Commons Attribution 4.0 International License.

Some New NSAIDs Prodrugs: An Efficient Synthesis, Spectral Characterization and X-ray Crystal Structure Studies

https://doi.org/10.14233/ajchem.2014.16949

Tarek Aboul-Fadl1

1Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt 2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia 3X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia 4Department of Chemistry, Alva's Institute of Engineering & Technology, Mijar, Moodbidri-574 225, India *Corresponding author: E-mail: hkfun@usm.my

Tilal Elsaman

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Omar A. Al-Deeb

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

Hazem A. Ghabbour

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia

C.S. Chidan Kumar

X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia ; Department of Chemistry, Alva's Institute of Engineering & Technology, Mijar, Moodbidri-574 225, India

Hoong-Kun Fun

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia ;X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia

Corresponding Author(s) : Hoong-Kun Fun

hkfun@usm.my

Asian Journal of Chemistry, Vol. 26 No. 16 (2014): Vol 26 Issue 16
Article Published : August 4, 2014

Abstract

An efficient synthesis of some new NSAIDs prodrugs viz., (S)-ethyl 2-[(S)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (1), (S)-ethyl 2-[(R)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (2), (S)-dimethyl 2-[2-(2,3-dimethylphenylamino)benzamido]-succinate (3) and (RS)-methyl-2-(2-(2,6-dichloro-3- methylphenylamino)benzamido)butanoate (4) with high purity were carried out by the amidation of RS-ibuprofen, mefenamic acid and meclofenamic acid with methyl ester and ethyl ester of amino acids L-leucine, L-aspartic acid and DL-2-aminobutyric acid. The products formed were confirmed by IR, ¹H NMR, ¹³C NMR, HR MS (1-4) and single crystal X-ray crystallography analysis (2-4). Compound (2) crystallizes in orthorhombic space group P212121 with unit cell dimensions a = 5.1931 (2) Å, b = 10.0031 Å, c = 41.0764 (11) Å, a = b = g = 90°, V = 2133.80 (12) Å³, Z = 4. Compound (3) crystallizes in hexagonal space group P6₅ with unit cell dimensions a = 11.4965 (3) Å, b = 11.4965 (3) Å, c = 26.5323 (12) Å, a = b = 90°, g = 120°, V = 3036.94 (18) Å³, Z = 6. Compound (4) crystallizes in triclinic space group Pi with unit cell dimensions a = 8.7969 (3) Å, b = 10.6307 (3) Å, c = 11.8469 (4) Å, a = 76.724 (3)°, b = 89.066 (3)°, g = 66.169 (2)°, V = 982.70 (5) Å³, Z = 2.

Keywords

NSAIDs Prodrug Conjugation Crystal structure Packing

Aboul-Fadl1, T., Elsaman, T., A. Al-Deeb, O., A. Ghabbour, H., Chidan Kumar, C., & Fun, H.-K. (2014). Some New NSAIDs Prodrugs: An Efficient Synthesis, Spectral Characterization and X-ray Crystal Structure Studies. Asian Journal of Chemistry, 26(16), 5249–5254. https://doi.org/10.14233/ajchem.2014.16949

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References

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References

F. Bessone, World J. Gastroenterol., 16, 5651 (2010); doi:10.3748/wjg.v16.i45.5651.

H.E. Vonkeman and M.A. van de Laar, Semin. Arthritis Rheum., 39, 294 (2010); doi:10.1016/j.semarthrit.2008.08.001.

J. Steinmeyer, Arthritis Res., 2, 379 (2000); doi:10.1186/ar116.

T. Aboul-Fadl, S.S. Al-Hamad, M.K. Abdel-Hamid, H.A. Abdel-Aziz, A.M. Al-Obaid, J.D. Whitt, B.D. Gary, A.B. Keeton and G.A. Piazza, 243rd American Chemical Society Meeting, ACS, San Diego, California, USA, March (2012).

R.T. Schoen and R.J. Vender, Am. J. Med., 86, 449 (1989); doi:10.1016/0002-9343(89)90344-6.

H. Hao, G. Wang and J. Sun, Drug Metab. Rev., 37, 215 (2005); doi:10.1081/DMR-47999.

A. Rasheed and C.K. Ashok-Kumar, Int. J. Curr. Pharm. Res., 1, 47 (2009).

T. Aboul-Fadl and E.A. Fouad, Pharmazie, 51, 30 (1996).

H. Bundgaard, Adv. Drug Deliv. Rev., 3, 39 (1989); doi:10.1016/0169-409X(89)90004-5.

H. Bundgaard, In Design of Prodrugs, Elsevier, New York, Plenum Press (1986).

E. Banoglu, B. Okcelik, E. Kupeli, S. Unlu, E. Yesilada, M. Amat, J.F. Caturla and M.F. Sahin, Arch. Pharm., 336, 251 (2003); doi:10.1002/ardp.200300723.

G.M. Sheldrick, Acta Crystallogr. A, 64, 112 (2008); doi:10.1107/S0108767307043930.

J. Bernstein, R.E. Davis, L. Shimoni and N.L. Chang, Angew. Chem. Int. Ed. Engl., 34, 1555 (1995); doi:10.1002/anie.199515551.

Issue

Vol. 26 No. 16 (2014): Vol 26 Issue 16

Some New NSAIDs Prodrugs: An Efficient Synthesis, Spectral Characterization and X-ray Crystal Structure Studies

Corresponding Author(s) : Hoong-Kun Fun

Abstract

Keywords

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