Browse > Article
http://dx.doi.org/10.5012/bkcs.2012.33.9.2930

Pharmacophore Hypothesis for Atypical Antipsychotics  

Sekhar, Kondapalli Venkata Gowri Chandra (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District)
Vyas, Devambhatla Ravi Kumar (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District)
Nagesh, Hunsur Nagendra (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District)
Rao, Vajja Sambasiva (Department of Chemistry, BITS Pilani Hyderabad Campus, Jawahar Nagar, Shamirpet Mandal, Ranga Reddy District)
Publication Information
Bulletin of the Korean Chemical Society / v.33, no.9, 2012 , pp. 2930-2936 More about this Journal
Abstract
A three-dimensional pharmacophore hypothesis was developed for atypical antipsychotics in order to map common structural features of highly active compounds by using HipHop in CATALYST program. The pharmacophore hypotheses were generated using 12 compounds as training set and validated using 11 compounds as test set. The most predictive hypothesis (Hypo1) comprises five features viz. two hydrophobic regions, two hydrogen bond acceptor lipid and one aromatic ring. In the absence of information like crystallized structure of 5-$HT_{2A}$ receptor and binding mode of antipsychotics with 5-$HT_{2A}$ receptor, this hypothesis will serve as a potentially valuable tool in the design of novel atypical antipsychotics acting primarily at 5-$HT_{2A}$ and $D_2$ receptors.
Keywords
Pharmacophore; Hypothesis; HipHop; Atypical antipsychotics; CATALYST;
Citations & Related Records

Times Cited By Web Of Science : 0  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Lowe, J. A., III; Senger, T. F.; Nagel, A. A.; Howard, H. R.; Seymour, P. A.; Hetm, J. H.; Newman, E. M.; Scmidt, A. W.; Furman, J. S.; Vincent, L. A.; Robinson, G. L.; Reynolds, S. L.; Vinick, F. J. J. Med. Chem. 1991, 34, 1860.   DOI
2 Srinivas, P.; Subramanian, A. R.; Brust, P.; Raghavan, S. A. V.; Rangisetty, J. B.; Gupta, C. N. V. H. B.; Sridhar, N.; Veeranjaneyulu, A.; Parimoo, P. Il Farmaco 1999, 54, 567.   DOI
3 Masaguer, C. F.; Ravina, E.; Fontenl, J. A.; Brea, J.; Tristan, H.; Loza, M. I. Eur. J. Med. Chem. 2000, 35, 83.   DOI
4 Talaga, P.; Matagne, A.; Klitgaard, H. Bioorg. Med. Chem. Lett. 2001, 11, 1313.   DOI
5 Bolos, J.; Anglada, L.; Gubert, S.; Planas, J. M.; Agut, J.; Pr ncep, M.; Fuente, A. D.; Sacristan, A.; Ortiz, J. A. J. Med. Chem. 1998, 41, 5402.   DOI
6 Funakoshi, T.; Chaki, S.; Kawashima, N.; Suzuki, Y.; Yoshikawa, R.; Kumagai, T.; Nakazato, A.; Kameo, K.; Goto, M.; Okuyama, S. Life Sci. 2002, 71, 1371.   DOI
7 Alvarado, M.; Coelho, A.; Masaguer, C. F.; Raviña, E.; Brea, J.; Padín, J. F.; Loza, I. M. Bioorg. Med. Chem. Lett. 2005, 12, 3063.
8 Brooks, B. R.; Brucolleri, E.; Olafson, B. D.; States, J.; Swaminathan, S.; Karplus, M. J. Comp. Chem. 1983, 4, 187.   DOI
9 Smellie, A.; Kahn, S. D.; Teig, S. L. J. Chem. Inf. Comp. Sci. 1995, 35, 285.   DOI   ScienceOn
10 Kurogi, Y.; Güner, O. F. Curr. Med. Chem. 2001, 8, 1035.   DOI
11 Smellie, A.; Kahn, S. D.; Teig, S. L. J. Chem. Inf. Comp. Sci. 1995, 35, 295.   DOI   ScienceOn
12 Purushottamachary, P.; Khandelwal, A.; Chopra, P.; Maheshwari, N.; Gediya, L. K.; Vasaitis, T. S.; Bruno, R. D.; Clement, O. O.; Njar, V. C. O. Bioorg. Med. Chem. 2007, 15, 3413.   DOI
13 Hirashima, A.; Morimoto, M.; Ohta, H. Int. J. Mol. Sci. 2002, 3, 56.   DOI
14 Richelson, E. J. Clin. Psychiatry 1999, 60, 5.   DOI
15 Allison, D. B.; Mentore, J. L.; Heo, M.; Chandler, L. P.; Cappelleri, J. C.; Infante, M. C.; Weiden, P. J. Am. J. Psychiatry 1999, 156, 1686.
16 Newcomer, J. W. CNS Drugs 2005, 19, 1.   DOI
17 Koller, E. A.; Doraiswamy, P. M. Pharmacotherapy 2002, 22, 841.   DOI   ScienceOn
18 Chandra Sekhar, K. V. G.; Rao, V. S.; Conrad, W. D.; Reddy, A. S.; Brust, P.; Kumar, M. M. K. J. Enzyme Inhib. Med. Chem. 2011, 26, 561.   DOI
19 Chandra Sekhar, K. V. G.; Rao, V. S.; Krishna Kumar, M. M. J. Enzyme Inhib. Med. Chem. 2009, 24, 871.   DOI
20 Chandra Sekhar, K. V. G.; Rao, V. S.; Kumar Vyas, D. R.; Krishna Kumar, M. M. Bioorg. Med. Chem. Lett. 2008, 18, 6054.   DOI
21 Chandra Sekhar, K. V. G.; Rao, V. S.; Conrad, W. D.; Sridhar, D.; Nagesh, H. N.; Kumar, V. S.; Brust, P.; Kumar, M. M. K. Med. Chem. Res. 2012, DOI: 10.1007/s00044-012-0164-1.
22 Bender, A.; Glen, R. C. Org. Biomol. Chem. 2004, 2, 3204.   DOI
23 Kubinyi, H. J. Braz. Chem. Soc. 2002, 13, 717.
24 Mason, J. S.; Good, A. C.; Martin, E. J. Curr. Pharm. Des. 2001, 7, 567.   DOI
25 Willett, P.; Barnard, J.; Downs, G. J. Chem. Inf. Comput. Sci. 1998, 38, 983.   DOI
26 Prakash, A.; Lamb, H. M. CNS Drugs 1998, 9, 153.   DOI
27 Catalyst, version 4.11; Accelrys, 9685 Scranton Road, San Diego, CA 92121, 2006.
28 Horacek, J.; Bubenikova-Valesova, V.; Kopecek, M.; Palenicek, T.; Dockery, C.; Mohr, P.; Hoschl, C. CNS Drugs 2006, 20, 389.   DOI   ScienceOn
29 Meltzer, H. Y.; Matsubara, S.; Lee, J. C. J. Pharmacol. Exp. Ther. 1989, 251, 238.
30 Jablensky, A. Schizophr. Res. 1997, 28, 111.   DOI
31 Mueser, K. T.; McGurk, S. R. Lancet 2004, 363, 2063.   DOI
32 Toomey, R.; Kremen, W. S.; Simpson, J. C.; Samson, J. A.; Seidman, L. J.; Lyons, M. J.; Faraone, S. V.; Tsuang, M. V. Am. J. Psychiatry 1997, 154, 371.   DOI
33 Roth, B. L.; Sheffler, D.; Potkin, S. G. Clinical Neuroscience Research 2003, 3, 108.   DOI
34 Tamminga, C. A. Can. J. Psychiatry 1997, 42, 265.
35 Lange, J. H. M.; Reinders, J. H.; Tolboom, J. T. B. M.; Glennon, J. C.; Coolen, H. K. A. C.; Kruse, C. G. J. Med. Chem. 2007, 50, 5103.   DOI
36 Melkersson, K.; Dahl, M. L. Drugs 2004, 64, 701.   DOI   ScienceOn
37 Remington, G. J. Psychiatry Neurosci. 2003, 28, 275.