3D-QSAR analysis of TRPV1 inhibitors reveals a pharmacophore applicable to diverse scaffolds and clinical candidates

Journal of Molecular Graphics and Modelling

Volumn 45, Issue , 2013, Pages 157-172

  Kristam, Rajendra ^a,b   Parmar, Vinod ^a   Viswanadhan, Vellarkad N ^a  

^a JUBILANT BIOSYS LTD   (India)

^b SASTRA UNIVERSITY   (India)

Author keywords

3D QSAR analysis of; Phase; Piperazinyl aryl series; QSAR modeling; TRPV1 inhibitors; TRPV1 pharmacophore

Indexed keywords

3D-QSAR; PHARMACOPHORES; PHASE; PIPERAZINYL-ARYL SERIES; QSAR MODEL;

AROMATIC COMPOUNDS; COMPUTATIONAL CHEMISTRY; MOLECULAR GRAPHICS; PHARMACODYNAMICS; SCAFFOLDS;

THREE DIMENSIONAL;

(5 TERT BUTYL 2,3 DIHYDRO 1H INDEN 1 YL) 3 (1H INDAZOL 4 YL)UREA; 1 (2 BROMOPHENYL) 3 [1 (5 TRIFLUOROMETHYL 2 PYRIDINYL) 3 PYRROLIDINYL]UREA; 4 [3 (TRIFLUOROMETHYL) 2 PYRIDINYL] N [5 (TRIFLUOROMETHYL) 2 PYRIDINYL] 1 PIPERAZINECARBOXAMIDE; 4 CHLORO N (3 METHOXYPHENYL)CINNAMAMIDE; AMG 628; AZD 1386; BENZIMIDAZOLE DERIVATIVE; GRC 6211; IMIDAZOLE DERIVATIVE; JTS 653; M 68006; MK 2295; N (1,4 BENZODIOXAN 6 YL) 3 (4 TERT BUTYLPHENYL)ACRYLAMIDE; N (4 TERT BUTYLPHENYL) 4 (3 CHLORO 2 PYRIDINYL) 1 PIPERAZINECARBOXAMIDE; SAR 115740; SB 782443; UNCLASSIFIED DRUG; VANILLOID RECEPTOR 1 ANTAGONIST;

ARTICLE; HUMAN; HYDROGEN BOND; HYDROPHOBICITY; PAIN; PHARMACOPHORE; PREDICTION; PRIORITY JOURNAL; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STRUCTURE ACTIVITY RELATION; VALIDATION PROCESS;

3D-QSAR ANALYSIS OF TRPV1 INHIBITORS; PHASE QSAR MODELING; PIPERAZINYL-ARYL SERIES; TRPV1 INHIBITORS; TRPV1 PHARMACOPHORE;

HUMANS; HYDROGEN BONDING; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; IONS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PIPERAZINES; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; REPRODUCIBILITY OF RESULTS; STATIC ELECTRICITY; TRPV CATION CHANNELS;

EID: 84883612741     PISSN: 10933263     EISSN: 18734243     Source Type: Journal    
DOI: 10.1016/j.jmgm.2013.08.014     Document Type: Article

References (103)

1. R. Padinjat, and S. Andrews TRP channels at a glance J. Cell Sci. 117 2004 5707 5709 (Pubitemid 40123936)
2. M.M. Moran, M.A. McAlexander, T. Bíró, and A. Szallasi Transient receptor potential channels as therapeutic targets Nat. Rev. Drug Disc. 10 2011 601 620
3. M.A. Schumacher TRP channels in pain and inflammation: therapeutic opportunities Pain Pract. 10 2010 185 200
4. A. Messeguer, R. Planells-Cases, and A. Ferrer-Montiel Physiology and pharmacology of the vanilloid receptor Curr. Neuropharmacol. 4 2006 1 15
5. A. Jara-Oseguera, S.A. Simon, and T. Rosenbaum TRPV1: ON THE ROAD TO PAIN RELIEF Curr. Mol. Pharmacol. 1 2008 255 269
6. M. Trevisani, and A. Szallasi Targeting TRPV1-challenges and issues in pain management Open Drug Discov. J. 2 2010 37 49
7. B. Nilius, G. Owsianik, T. Voets, and J.A. Peters Transient receptor potential cation channels in disease Physiol. Rev. 87 2007 165 217 (Pubitemid 46207713)
8. P.M. Zygmunt, J. Petersson, D.A. Andersson, J. Chuang, M. Sorgard, V. DiMarzo, D. Julius, and E.D. Hogestatt Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide Nature 400 1999 452 457 (Pubitemid 29361798)
9. M. Tognetto, S. Amadesi, S. Harrison, C. Creminon, M. Trevisani, M. Carreras, M. Matera, P. Gepetti, and A. Bianchi Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation Neuroscience 21 2001 1104 1109 (Pubitemid 32128755)
10. S.W. Hwang, H. Cho, J. Kwak, S.Y. Lee, C.J. Kang, J. Jung, S. Cho, K.H. Min, Y.G. Suh, D. Kim, and U. Oh Direct activation of capsaicin receptors by products of lipoxygenases: endogenous capsaicin-like substances Proc. Natl. Acad. Sci. USA 97 2000 6155 6160 (Pubitemid 30367539)
11. C.M. Flores, and M.R. Vasko The deorphanization of TRPV1 and the emergence of octadecadienoids as a new class of lipid transmitters Mol. Interv. 10 2010 137 140
12. A.M. Patwardhan, P.E. Scotland, A.N. Akopian, and K.M. Hargreaves Activation of TRPV1 in the spinal cord by oxidized linoleic acid metabolites contributes to inflammatory hyperalgesia Proc. Natl. Acad. Sci. USA 106 2009 18820 18824
13. A.M. Patwardhan, A.N. Akopian, N.B. Ruparel, A. Diogenes, S.T. Weintraub, C. Uhlson, R.C. Murphy, and K.M. Hargreaves Heat generates oxidized linoleic acid metabolites that activate TRPV1 and produce pain in rodents J. Clin. Invest. 120 2010 1617 1626
14. M.J. Caterina, M.A. Schumacher, M. Tominaga, T.A. Rosen, J.D. Levine, and D. Julius The capsaicin receptor: a heat-activated ion channel in the pain pathway Nature 389 1997 816 824 (Pubitemid 27462969)
15. M.J. Caterina, T.A. Rosen, M. Tominaga, A.J. Brake, and D. Julius Capsaicin-receptor homologue with a high threshold for noxious heat Nature 398 1999 436 441 (Pubitemid 29180377)
16. M. Tominaga, M.J. Caterina, A.B. Malmberg, T.A. Rosen, H. Gilbert, K. Skinner, B.E. Raumann, A.I. Basbaum, and D. Julius The cloned capsaicin receptor integrates multiple pain-producing stimuli Neuron 21 1998 531 543 (Pubitemid 28475505)
17. A. Szallasi, and P.M. Blumberg Vanilloid (Capsaicin) receptors and mechanisms Pharmacol. Rev. 51 1999 159 212
18. L.A. Roberts, and M. Connor TRPV1 antagonists as a potential treatment for hyperalgesia Recent Pat CNS Drug Discov. 1 2006 65 76
19. S.E. Jordt, and D. Julius Molecular basis for species-specific sensitivity to "hot" chili peppers Cell 108 2002 421 430 (Pubitemid 34178405)
20. M.Z. Chou, T. Mtui, Y.D. Gao, M. Kohler, and R.E. Middleton Resiniferatoxin binds to the capsaicin receptor (TRPV1) near the extracellular side of the S4 transmembrane domain Biochemistry 43 2004 2501 2511 (Pubitemid 38327845)
21. A. Szallasi, D.N. Cortright, C.A. Blum, and S.R. Eid The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist proof-of-concept Nat. Rev. Drug Discov. 6 2007 357 372 (Pubitemid 46705200)
22. S.G. Lehto, R. Tamir, H. Deng, L. Klionsky, R. Kuang, A. Le, D. Lee, J.C. Louis, E. Magal, B.H. Manning, J. Rubino, S. Surapaneni, N. Tamayo, T. Wang, J. Wang, J. Wang, W. Wang, B. Youngblood, M. Zhang, D. Zhu, M.H. Norman, and N.R. Gavva Antihyperalgesic effects of (R,E)-N-(2-hydroxy-23-dihydro-1H-inden-4-yl)- 3-(2-(piperidin-1-yl)-4-(trifluoromethyl)phenyl)-acrylamide (AMG8562), a novel transient receptor potential vanilloid type 1 modulator that does not cause hyperthermia in rats J. Pharmacol. Exp. Ther. 326 2008 218 229 (Pubitemid 351872146)
23. G.Y. Wong, and N.R. Gavva Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: recent advances and setbacks Brain Res. Rev. 60 2009 267 277
24. N.R. Gavva, R. Tamir, Y. Qu, L. Klionsky, T.J. Zhang, D. Immke, J. Wang, D. Zhu, T.W. Vanderah, F. Porreca, E.M. Doherty, M.H. Norman, K.D. Wild, A.W. Bannon, J.C. Louis, and J.J. Treanor AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(23- dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties J. Pharmacol. Exp. Ther. 313 2005 474 484 (Pubitemid 40411374)
25. Q. Sun, L. Tafesse, K. Islam, X. Zhou, S.F. Victory, C. Zhang, M. Hachicha, L.A. Schmid, A. Patel, Y. Rotshteyn, K.J. Valenzano, and D.J. Kyle 4-(2-Pyridyl)piperazine-1-carboxamides: potent vanilloid receptor 1 antagonists Bioorg. Med. Chem. Lett. 13 2003 3611 3616 (Pubitemid 37150471)
26. K.J. Valenzano, E.R. Grant, G. Wu, M. Hachicha, L. Schmid, L. Tafesse, Q. Sun, Y. Rotshteyn, J. Francis, J. Limberis, S. Malik, E.R. Whittemore, and D. Hodges N-(4-Tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine- 1(2H)-carbox-amide (BCTC), a novel, orally effective vanilloid receptor 1 antagonist with analgesic properties: I. In vitro characterization and pharmacokinetic properties J. Pharmacol. Exp. Ther. 306 2003 377 386 (Pubitemid 36734395)
27. V.N. Viswanadhan, Y. Sun, and M.H. Norman Three-dimensional quantitative structure-activity relationships and activity predictions of human TRPV1 channel antagonists: comparative molecular field analysis and comparative molecular similarity index analysis of cinnamides J. Med. Chem. 50 2007 5608 5619 (Pubitemid 350110297)
28. R.D. Cramer, D.E. Patterson, and J.D. Bunce Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins J. Am. Chem. Soc. 110 1988 5959 5967
29. G. Klebe, U. Abraham, and T. Mietzner Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity J. Med. Chem. 37 1994 4130 4146 (Pubitemid 24379702)
30. T. Taskin, and F. Sevin QSAR approach to correlate TRPV1 antagonist activity for a series of heteroaromatic urea QSAR Comb. Sci. 28 2009 1098 1111
31. W.S. Cheung, R.R. Calvo, B.A. Tounge, S.P. Zhang, D.R. Stone, M.R. Brandt, T. Hutchinson, C.M. Flores, and M.R. Player Discovery of piperidine carboxamide TRPV1 antagonists Bioorg. Med. Chem. Lett. 18 2008 4569 4572
32. K.H. Kim 3-D-QSAR analysis of N-(3-acyloxy-2-benzylpropyl)-N′- dihydroxytetrahydrobenzazepine and tetrahydroisoquinoline and N-(3-acyloxy-2-benzylpropyl)-N-(4-hydroxy-3-methoxybenzyl) thioureas analogues as potent vanilloid receptor ligands Bioorg. Med. Chem. 10 2002 1367 1372 (Pubitemid 34214701)
33. Phase, version 2.0.212, 2005, Schrodinger LLC, New York, NY 10036-4041.
34. P.R. Kym, M.E. Kort, and C.W. Hutchins Analgesic potential of TRPV1 antagonists Biochem. Pharmacol. 78 2009 211 216
35. L. Tafesse, Q. Sun, L. Schmid, K.J. Valenzano, Y. Rotshteyn, X. Su, and D.J. Kyle Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists Bioorg. Med. Chem. Lett. 14 2004 5513 5519 (Pubitemid 39346336)
36. R. Bakthavatchalam, Capsaicin receptor ligands, WO 02008221-A2, 2002.
37. S. Dax, A. Dublin, M. Jetter, N. Nasser, C. Shah, D. Swanson, and N.I. Carruthers Vanilloid receptor antagonists: structure-activity relationships via parallel and targeted synthesis Drugs Fut. 27 Suppl. A 2002 93
38. T. Yura, M. Mogi, Y. Ikegami, T. Masuda, T. Kokubo, K. Urbahns, N. Yoshida, M. Marumo, M. Shiroo, M. Tajimi, K. Takeshita, T. Moriwaki, Y. Tsukumi, Piperazinecarboxamide derivative, JP 2003192673-A2, 2003.
39. H.K. Rami, M. Thompson, G.J. Macdonald, S.M. Westaway, D.J. Mitchell, Vanilloid receptor modulators, WO 03068749-A1, 2003.
40. C.H. Lee, E.K. Bayburt, S. Didomenico. Jr, I. Drizin, A.R. Gomtsyan, J.R. Koenig, R.J. Perner, R.G. Schmidt, S.C. Turner, T.K. White, G.Z. Zheng, Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor, WO 03070247, 2003.
41. V.I. Ognyanov, C. Balan, A.W. Bannon, Y. Bo, C. Dominguez, C. Fotsch, V.K. Gore, L. Klionsky, V.V. Ma, Y.X. Qian, R. Tamir, X. Wang, N. Xi, S. Xu, D. Zhu, N.R. Gavva, J.J. Treanor, and M.H. Norman Design of potent, orally available antagonists of the transient receptor potential vanilloid 1Structure-activity relationships of 2-Piperazin-1-yl-1H-benzimidazoles J. Med. Chem. 49 2006 3719 3742 (Pubitemid 43902478)
42. V.K. Gore, V.V. Ma, R. Tamir, N.R. Gavva, J.J. Treanor, and M.H. Norman Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonists Bioorg. Med. Chem. Lett. 17 2007 5825 5830 (Pubitemid 47446224)
43. J. Ghosh, and A. Liu K-Means X. Wu, V. Kumar, The Top Ten Algorithms in Data Mining (Chapman & Hall/CRC Data Mining and Knowledge Discovery Series) Chapman & Hall/CRC, Taylor & Francis Group, Boca Raton, FL 2009
44. CIMPL, 2008, Cimplsoft Inc, Newbury Park, CA, www.cimplsoft.com.
45. S.L. Dixon, A.M. Smondyrev, E.H. Knoll, S.N. Rao, D.E. Shaw, and R.A. Friesner PHASE: a new engine for pharmacophore perception 3D QSAR model development, and 3d database screening. 1. Methodology and preliminary results J. Comput. Aided Mol. Des. 20 2006 647 671 (Pubitemid 46023928)
46. S.L. Dixon, A.M. Smondyrev, and S.N. Rao PHASE: a novel approach to pharmacophore modeling and 3D database searching Chem. Biol. Drug Des. 67 2006 370 372
47. A.K. Ghose, G.M. Crippen, G.R. Revankar, P.A. McKernan, D.F. Smee, and R.K. Robins Analysis of the in vitro antiviral activity of certain ribonucleosides against parainfluenza virus using a novel computer aided receptor modeling procedure J. Med. Chem. 32 1989 746 756 (Pubitemid 19100186)
48. G.M. Crippen Validation of EGSITE2, a mixed integer program for deducing objective site models from experimental binding data J Med. Chem. 40 1997 3161 3172 (Pubitemid 27413740)
49. G.M. Crippen, and S.A. Wildman Quantitative structure-activity relationships (QSAR) A.K. Ghose, V.N. Viswanadhan, A Review of 3D-QSAR. Combinatorial Library Design and Evaluation 2001 Marcel Dekker, Inc. New York, NY 131 156
50. C. Rücker, G. Rücker, and M. Meringer y-Randomization and its variants in QSPR/QSAR J. Chem. Inf. Model. 47 2007 2345 2357 (Pubitemid 350284525)
51. A. Tropsha, P. Gramatica, and V.K. Gombar The importance of being earnest: validation is the absolute essential for successful application and interpretation of QSPR models QSAR Comb. Sci. 22 2003 69 77 (Pubitemid 36717473)
52. K. Urbahns, T. Yura, M. Mogi, M. Tajimi, H. Fujishima, T. Masuda, N. Yoshida, T. Moriwaki, T.B. Lowinger, H. Meier, F. Chan, D. Madge, and J.B. Gupta Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence Bioorg. Med. Chem. Lett. 21 2011 3354 3357
53. H.G. Park, M.K. Park, J.Y. Choi, S.H. Choi, J. Lee, B.S. Park, M.G. Kim, Y.G. Suh, H. Cho, U. Oh, J. Lee, H.D. Kim, Y.H. Park, H.J. Koh, K.M. Lim, J.H. Moh, and S.S. Jew Synthesis of N,N′,N″-trisubstituted thiourea derivatives and their antagonist effect on the vanilloid receptor Bioorg. Med. Chem. Lett. 13 2003 601 604 (Pubitemid 36298450)
54. H. Ryu, M.K. Jin, S.Y. Kim, H.K. Choi, S.U. Kang, D.W. Kang, J. Lee, L.V. Pearce, V.A. Pavlyukovets, M.A. Morgan, R. Tran, A. Toth, D.J. Lundberg, and P.M. Blumberg Stereospecific high-affinity TRPV1 antagonists: chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues J. Med. Chem. 51 2008 57 67
55. E.A. Voight, and M.E. Kort Transient receptor potential vanilloid-1 antagonists: a survey of recent patent literature Exp. Opin. Ther. Patents 20 2010 1107 1122
56. N. Khairatkar-Joshi, and A. Szallasi TRPV1 antagonists: the challenges for therapeutic targeting Trends Mol. Med. 15 2009 14 22
57. M.J. Gunthorpe, and B.A. Chizh Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway Drug Discov. Today 14 2009 56 67
58. A. Patapoutian, S. Tate, and C.J. Woolf Transient receptor potential channels: targeting pain at the source Nat. Rev. Drug Discov. 8 2009 55 68
59. M. Trevisani, and A. Szallasi Targeting TRPV1: challenges and issues in pain management Open Drug Discov. J. 2 2010 37 49
60. J.J. Adcock TRPV1 receptors in sensitisation of cough and pain reflexes Pulm. Pharmacol. Ther. 22 2009 65 70
61. M.J. Gunthorpe, H.K. Rami, J.C. Jerman, D. Smart, C.H. Gill, E.M. Soffin, S. Luis Hannan, S.C. Lappin, J. Egerton, G.D. Smith, A. Worby, L. Howett, D. Owen, S. Nasir, C.H. Davies, M. Thompson, P.A. Wyman, A.D. Randall, and J.B. Davis Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist Neuropharmacology 46 2004 133 149 (Erratum in: Neuropharmacology 46(2004) 905) (Pubitemid 37494747)
62. D.M. Swanson, A.E. Dubin, C. Shah, N. Nasser, L. Chang, S.L. Dax, M. Jetter, J.G. Breitenbucher, C. Liu, C. Mazur, B. Lord, L. Gonzales, K. Hoey, M. Rizzolio, M. Bogenstaetter, E.E. Codd, D.H. Lee, S.P. Zhang, S.R. Chaplan, and N.I. Carruthers Identification and biological evaluation of 4-(3- trifluoromethylpyridin-2-yl)piperazine-1-carboxylic acid (5- trifluoromethylpyridin-2-yl)amide, a high affinity TRPV1 (VR1) vanilloid receptor antagonist J. Med. Chem. 48 2005 1857 1872 (Pubitemid 40396317)
63. H.K. Rami, M. Thompson, G. Stemp, S. Fell, J.C. Jerman, A.J. Stevens, D. Smart, B. Sargent, D. Sanderson, A.D. Randall, M.J. Gunthorpe, and J.B. Davis Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development Bioorg. Med. Chem. Lett. 16 2006 3287 3291 (Pubitemid 43732339)
64. B.A. Chizh, M.B. O'Donnell, A. Napolitano, J. Wang, A.C. Brooke, M.C. Aylott, J.N. Bullman, E.J. Gray, R.Y. Lai, P.M. Williams, and J.M. Appleby The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans Pain 132 2007 132 141 (Pubitemid 47494566)
65. M.J. Gunthorpe, S.L. Hannan, D. Smart, J.C. Jerman, S. Arpino, G.D. Smith, S. Brough, J. Wright, J. Egerton, S.C. Lappin, V.A. Holland, K. Winborn, M. Thompson, H.K. Rami, A. Randall, and J.B. Davis Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor, J Pharmacol. Exp. Ther. 321 2007 1183 1192 (Pubitemid 46762715)
66. H.L. Wang, J. Katon, C. Balan, A.W. Bannon, C. Bernard, E.M. Doherty, C. Dominguez, N.R. Gavva, V. Gore, V. Ma, N. Nishimura, S. Surapaneni, P. Tang, R. Tamir, O. Thiel, J.J.S. Treanor, and M.H. Norman Novel vanilloid receptor-1 antagonists: 3. The identification of a second-generation clinical candidate with improved physicochemical and pharmacokinetic properties J. Med. Chem. 50 2007 3528 3539 (Pubitemid 47195461)
67. H.L. Wang, C. Balan, E.M. Doherty, J.R. Falsey, V.K. Gore, J. Katon, M.H. Norman, Vanilloid receptor ligands and their use in treatments, US 050176726-A1, 2005.
68. C. Balan, N. Chen, E.M. Doherty, V.K. Gore, M.H. Norman, H.L. Wang, Vanilloid receptor ligands and their use in treatments, US 050182067-A1, 2005.
69. http://clinicaltrials.gov/ct2/show/NCT00387140, accessed 17 May 2012.
70. R. Bakthavatchalam, C.A. Blum, H.L. Brielmann, T.M. Caldwell, S. De Lombaert, Substituted Quinazolin-4-ylamine analogues, WO 03062209-A2, 2003.
71. http://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId= JapicCTI-101177
72. Y. Koga, S. Yata, T. Watanabe, T. Matsuo, T. Yamasaki, M. Sakata, W. Kondo, H. Ozeki, Y. Hori, Fused benzamide compound and vanilloid receptor 1 (VR1) activity inhibitor, WO 06006741-A1, 2006.
73. S.M. Westaway, M. Thompson, H.K. Rami, G. Stemp, L.S. Trouw, D.J. Mitchell, J.T. Seal, S.J. Medhurst, S.C. Lappin, J. Biggs, J. Wright, S. Arpino, J.C. Jerman, J.E. Cryan, V. Holland, K.Y. Winborn, T. Coleman, A.J. Stevens, J.B. Davis, and M.J. Gunthorpe Design and synthesis of 6-phenylnicotinamide derivatives as antagonists of TRPV1 Bioorg. Med. Chem. Lett. 18 2008 5609 5613
74. G.J. Macdonald, D.J. Mitchell, H.K. Rami, L.S. Trouw, M. Thompson, S.M. Westaway, Carboxamide Derivatives, WO 04072069-A1, 2004.
75. H. Uchida, N. Kosuga, T. Satoh, D. Hotta, T. Kamino, Y. Maeda, K. Amano, Y. Akada, Novel heterocyclidene acetamide derivative, WO 07010383-A1, 2007.
76. H. Uchida, S. Ogawa, M. Makabe, Y. Maeda, Heterocyclidene-N-(aryl) acetamide derivative, WO 08091021-A1, 2008.
77. L. Dubois, Y. Evanno, A. Malanda, N-(arylalkyl)-1H-pyrrolopyridine-2- carboxamide derivatives, preparation and therapeutic use thereof, WO 07010138-A2 and WO 07010138-A3, 2007.
78. L. Horoszok, C. Leung, M. Tomaszewski, C. Walpole, New compounds I, WO 07091948-A2 and WO 07091948-A3, 2007.
79. A. Gomtsyan, E.K. Bayburt, R.G. Schmidt, C.S. Surowy, P. Honore, K.C. Marsh, S.M. Hannick, H.A. McDonald, J.M. Wetter, J.P. Sullivan, M.F. Jarvis, C.R. Faltynek, and C.H. Lee Identification of (R)-1-(5-tert-Butyl-23-dihydro-1H- inden-1-yl)-3-(1H-indazol-4-yl)urea (ABT-102) as a potent TRPV1 antagonist for pain management J. Med. Chem. 51 2008 392 395 (Pubitemid 351252266)
80. A. Gomtsyan, E.K. Bayburt, J.R. Koenig, C.H. Lee, Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor, US 040254188-A1, 2004.
81. C.S. Surowy, T.R. Neelands, B.R. Bianchi, S. McGaraughty, R. El Kouhen, P. Han, K.L. Chu, H.A. McDonald, M. Vos, W. Niforatos, E.K. Bayburt, A. Gomtsyan, C.H. Lee, P. Honore, J.P. Sullivan, M.F. Jarvis, and C.R. Faltynek (R)-(5-tert-butyl-23-dihydro-1H-inden-1-yl)-3-(1H-indazol-4-yl)-urea (ABT-102) blocks polymodal activation of transient receptor potential vanilloid 1 receptors in vitro and heat-evoked firing of spinal dorsal horn neurons in vivo J. Pharmacol. Exp. Ther. 326 2008 879 888
82. ClinicalTrials.gov identifier NCT00854659, accessed 17 May 2012.
83. L.A. Gharat, U.M. Joshi, N.K. Joshi, Substituted benzofused derivatives and their use as vanilloid receptor ligands, WO 07042906-A1, 2007.
84. A. Charrua, C.D. Cruz, S. Narayanan, L. Gharat, S. Gullapalli, F. Cruz, and A. Avelino GRC-6211, a new oral specific TRPV1 antagonist, decreases bladder overactivity and noxious bladder input in cystitis animal models J. Urol. 181 2009 379 386
85. A. Kahraman, R.J. Morris, R.A. Laskowski, and J.M. Thornton Shape variation in protein binding pockets and their ligands J. Mol. Biol. 368 2007 283 301 (Pubitemid 46454307)
86. LigPrep, version 2.5, 2011, Schrödinger LLC, New York, NY 10036-4041.
87. Epik, version 2.2, 2011, Schrödinger LLC, New York, NY 10036-4041.
88. J.C. Shelley, A. Cholleti, L.L. Frye, J.R. Greenwood, M.R. Timlin, and M. Uchiyama Epik: a software program for pKa prediction and protonation state generation for druglike molecules J. Comput. Aided Mol. Des. 21 2007 681 691
89. J.R. Greenwood, D. Calkins, A.P. Sullivan, and J.C. Shelley Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution J. Comput. Aided Mol. Des. 24 2010 591 604
90. W.L. Jorgensen, and J. Tirado-Rives The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin J. Am. Chem. Soc. 110 1988 1657 1666
91. W.L. Jorgensen, D.S. Maxwell, and J. Tirado-Rives Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids J. Am. Chem. Soc. 118 1996 11225 11235
92. G.A. Kaminski, R.A. Friesner, J. Tirado-Rives, and W.L. Jorgensen Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides J. Phys. Chem. B 105 2001 6474 6487 (Pubitemid 35339015)
93. MacroModel, version 9.9, 2011, Schrödinger LLC, New York, NY 10036-4041.
94. W.C. Still, A. Tempczyk, R.C. Hawley, and T. Hendrickson Semianalytic treatment of solvation for molecular mechanics and dynamics J. Am. Chem. Soc. 112 1990 6127 6129
95. G. Chang, W. Guida, and W.C. Still An internal coordinate Monte-Carlo method for searching conformational space J. Am. Chem. Soc. 111 1989 4379 4386
96. M. Saunders, K.N. Houk, Y.D. Wu, W.C. Still, M. Lipton, G. Chang, and W.C. Guida Conformations of cycloheptadecane: a comparison of methods for conformational searching J. Am. Chem. Soc. 112 1990 1419 1427
97. I. Kolossváry, and W.C. Guida Low Mode Search. An efficient automated computational method for conformational analysis: application to cyclic and acyclic alkanes and cyclic peptides J. Am. Chem. Soc. 118 1996 5011 5019 (Pubitemid 26200976)
98. I. Kolossváry, and W.C. Guida Low-mode conformational search elucidated. Application to C39H80 and flexible docking of 9-deazaguanine inhibitors to PNP J. Comput. Chem. 20 1999 1671 1684 (Pubitemid 129653223)
99. R.A. Jarvis, and E.A. Patrick Clustering using a similarity measure based on shared nearest neighbors IEEE Trans. Comput. C-22 1973 1025 1034
100. A. Golbraikh, and A. Tropsha Predicitve QSAR modeling based on diversity sampling of experimental datasets for the test and training set selection J. Comput. Aided Mol. Des. 160 2002 356 369
101. A.R. Leach, and V.J. Gillet An Introduction to Chemoinformatics, revised edition 2007 Springer Dordrecht, The Netherlands 121 123
102. Canvas, version 1.5, 2012, Schrödinger, LLC, New York, NY 10036-4041.
103. V.N. Viswanadhan, H. Rajesh, and V.N. Balaji Atom type preferences, structural diversity, and property profiles of known drugs, leads, and nondrugs: a comparative assessment ACS Comb. Sci. 13 2011 327 336