Synthesis and Structure Activity Relationship of 3-(Arylsulfonyl)-8-(piperidin-4-yl amino)quinoline Derivatives as 5-HT6 Receptor Antagonists

Ramakrishna V.S. Nirogi; Rajeshkumar Badange; Parandhama Gudla; Mukkanti Khagga

doi:10.14233/ajchem.2014.15904

Issue

Vol. 26 No. 13 (2014): Vol 26 Issue 13

Issue Published : June 23, 2014

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

Synthesis and Structure Activity Relationship of 3-(Arylsulfonyl)-8-(piperidin-4-yl amino)quinoline Derivatives as 5-HT6 Receptor Antagonists

https://doi.org/10.14233/ajchem.2014.15904

Ramakrishna V.S. Nirogi

Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad-500 034, India

Rajeshkumar Badange

Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad-500 034, India; Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, India

Parandhama Gudla

Discovery Research, Suven Life Sciences Ltd, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad-500 034, India

Mukkanti Khagga

Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, India

Corresponding Author(s) : Ramakrishna V.S. Nirogi

nvsrk@suven.com

Asian Journal of Chemistry, Vol. 26 No. 13 (2014): Vol 26 Issue 13
Article Published : June 26, 2014

Abstract

As part of our efforts to develop better therapies for the treatment of cognitive impairment associated with Alzheimer's disease and Schizophrenia, we have focused our research towards 5-HT₆ receptor (5-HT₆R) in order to identify potent and selective ligands for this purpose. Herein, we report the synthesis, structure activity relationship and biological evaluation of a novel series of 3-(arylsulfonyl)-8-(piperidin-4-yl amino)quinoline derivatives, as 5-HT₆ receptor (5-HT₆R) antagonists. In this work, we have shown that moving from aryl sulfonamide platform to biaryl sulfone platform retains the 5-HT₆R affinity when tested in vitro in cell based reporter gene functional assay.

Keywords

5-HT6R Cognitive impairment Structure Activity Relationship Pharmacokinetic profile Alzheimer’s disease

V.S. Nirogi, R., Badange, R., Gudla, P., & Khagga, M. (2014). Synthesis and Structure Activity Relationship of 3-(Arylsulfonyl)-8-(piperidin-4-yl amino)quinoline Derivatives as 5-HT6 Receptor Antagonists. Asian Journal of Chemistry, 26(13), 3779–3784. https://doi.org/10.14233/ajchem.2014.15904

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References

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R. Bernotas, S. Lenicek, S. Antane, G.M. Zhang, D. Smith, J. Coupet, B. Harrison and L.E. Schechter, Bioorg. Med. Chem. Lett., 14, 5499 (2004); doi:10.1016/j.bmcl.2004.09.003.

References

C.A. Gold and A.E. Budson, Expert Rev. Neurother., 8, 1879 (2008); doi:10.1586/14737175.8.12.1879.

(a) R.S. Doody, S.H. Ferris, S. Salloway, Y. Sun, R. Goldman, W.E. Watkins, Y. Xu and A.K. Murthy, Neurology, 72, 1555 (2009); doi:10.1212/01.wnl.0000344650.95823.03; (b) R. Marum, Neuropsychiatr. Dis. Treat., 5, 237 (2009); doi:10.2147/NDT.S4048.

M. Hamon, E. Doucet, K. Lefèvre, M.C. Miquel, L. Lanfumey, R. Insausti, D. Frechilla, J.D. Rio and D. Vergé, Neuropsychopharmacology, 21, 68S (1999); doi:10.1016/S0893-133X(99)00044-5.

(a) L.A. Dawson, H.Q. Nguyen and P. Li, Neuropsychopharmacol., 25, 662 (2001); doi:10.1016/S0893-133X(01)00265-2; (b) L.A. Dawson, H.Q. Nguyen and P. Li, Br. J. Pharmacol., 130, 23 (2000); doi:10.1038/sj.bjp.0703288.

K.G. Liu and A.J. Robichaud, Drug Dev. Res., 70, 145 (2009); doi:10.1002/ddr.20293.

G. Maher-Edwards, R. Dixon, J. Hunter, M. Gold, G. Hopton, G. Jacobs, J. Hunter and P. Williams, Int. J. Geriatr. Psychiatry, 26, 536 (2011); doi:10.1002/gps.2562.

J. Arnt, B. Bang-Andersen, B. Grayson, F.P. Bymaster, M.P. Cohen, N.W. DeLapp, B. Giethlen, M. Kreilgaard, D.L. McKinzie, J.C. Neill, D.L. Nelson, S.M. Nielsen, M.N. Poulsen, J.M. Schaus and L.M. Witten, Int. J. Neuropsychopharmacol., 13, 1021 (2010); doi:10.1017/S1461145710000659.

R. Nirogi, V. Kandikere, K. Mudigonda, G. Bhyrapuneni and V. Jasti, Alzheimers Dement., 5, 252 (2009); doi:10.1016/j.jalz.2009.04.260.

J. Holenz, R. Merce, J.L. Diáz, X. Guitart, X. Codony, A. Dordal, G. Romero, A. Torrens, J. Mas, B. Andaluz, S. Hernández, X. Monroy, E. Sánchez, E. Hernández, R. Pérez, R. Cubi, O. Sanfeliu and H. Buschmann, J. Med. Chem., 48, 1781 (2005); doi:10.1021/jm049615n.

R. Nirogi, A. Shinde, A. Daulatabad, R. Kambhampati, P. Gudla, M. Shaik, M. Gampa, S. Balasubramaniam, P. Gangadasari, V. Reballi, R. Badange, K. Bojja, R. Subramanian, G. Bhyrapuneni, N. Muddana and P. Jayarajan, J. Med. Chem., 55, 9255 (2012); doi:10.1021/jm300955x.

D.F.V. Lewis, Cytochromes P450: Structure, Function and Mechanism; Taylor and Francis Publishing: London (1996).

R. Bernotas, S. Lenicek, S. Antane, G.M. Zhang, D. Smith, J. Coupet, B. Harrison and L.E. Schechter, Bioorg. Med. Chem. Lett., 14, 5499 (2004); doi:10.1016/j.bmcl.2004.09.003.

Issue

Vol. 26 No. 13 (2014): Vol 26 Issue 13

Synthesis and Structure Activity Relationship of 3-(Arylsulfonyl)-8-(piperidin-4-yl amino)quinoline Derivatives as 5-HT6 Receptor Antagonists

Corresponding Author(s) : Ramakrishna V.S. Nirogi

Abstract

Keywords

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