SpringerLink
Log in

Characterization of β3-adrenergic receptor: determination of pharmacophore and 3D QSAR model for β3 adrenergic receptor agonism

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Summary

The β3-adrenoreceptor (β3-AR) has been shown to mediate various pharmacological and physiological effects such as lipolysis, thermogenesis, and intestinal smooth muscle relaxation. It also plays an important role in glucose homeostasis and energy balance. Molecular modeling studies were undertaken to develop predictive pharmacophoric hypothesis and 3D-QSAR model, which may explain variations in β3-AR agonistic activity in terms of chemical features and physicochemical properties. The two softwares, CATALYST for pharmacophoric alignment and APEX-3D for 3D-QSAR modeling were used to establish the structure activity relationships for β3-AR agonistic activity. Among the several statistically significant models, the selection of the best pharmacophore and 3D-QSAR model was based on its ability to estimate the activity of external test sets of similar and different structural types along with the reasonable consistency of the model with the limited information of the active site of β3-AR. The final 3D-QSAR model was derived using the pharmacophoric alignments from the hypothesis which consisted of four chemical features: basic or positive ionizable feature on the nitrogen of the aryloxypropylamino group, two ring aromatic features corresponding to the phenyl ring of the phenoxide and the benzenesulphonamido groups and a hydrogen-bond donor (HBD) in the vicinity of the nitrogen atom of the benzenesulphonamido group with the most active molecule map** in an energetically favorable extended conformation. This hypothesis was in agreement with the site directed mutagenesis studies on human β3-AR and correlated well the observed and estimated activity both in, training and both the external test sets. It also mapped reasonably well to six β3-AR agonists of different structural classes under clinical development and thus this hypothesis may have a universal applicability in providing a powerful template for virtual screening and also for designing new chemical entities (NCEs) as β3-AR agonists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. R.J. Mathvink J.S. Tolman D. Chitty M.R. Candelore M.A. Cascieri L.F. Colwell SuffixJr. L. Deng W.P. Feeney M.J. Forrest G.J. Hom D.E. MacIntyre R.R. Miller R.A. Stearns L. Tota M.J. Wyvratt M.H. Fisher Weber (2000) J. Med. Chem. 43 3832 Occurrence Handle10.1021/jm000286i Occurrence Handle11052788

    Article  PubMed  Google Scholar 

  2. Y. He V.I. Nikulin S.S. Vansal D.R. Feller D.D. Miller (2000) J. Med. Chem. 43 591 Occurrence Handle10.1021/jm990463j Occurrence Handle1:CAS:528:DC%2BD3cXotlOgtw%3D%3D Occurrence Handle10691685

    Article  CAS  PubMed  Google Scholar 

  3. W. Zheng V.I. Nikulin A.A. Konkar S.S. Vansal G. Shams D.R. Feller D.D. Miller (1999) J. Med. Chem., 42 2287

    Google Scholar 

  4. B. Hu J. Ellingboe S. Han E. Largis R. Mulvey A. Oliphant F.W.J. Sum Tillett (2001) J. Med. Chem., 44 1456

    Google Scholar 

  5. D.E. Uehling K.H. Donaldson D.N. Deaton C.E. Hyman E.E. Sugg D.G. Barrett R.G. Hughes B. Reitter K.K. Adkison M.E. Lancaster F. Lee R. Hart M.A. Paulik B.W. Sherman T. True C. Cowan (2002) J. Med. Chem. 45 567 Occurrence Handle10.1021/jm0101500 Occurrence Handle1:CAS:528:DC%2BD3MXptlKisbw%3D Occurrence Handle11806709

    Article  CAS  PubMed  Google Scholar 

  6. L.L. Brockunier M.R. Candelore M.A. Cascieri Y. Liu L. Tota M.J. Wyvratt M.H. Fisher A.E. Weber E.R. Parmee (2001) Bioorg. Med. Chem. Lett. 11 379 Occurrence Handle10.1016/S0960-894X(00)00669-7 Occurrence Handle1:CAS:528:DC%2BD3MXhtFylsLs%3D Occurrence Handle11212115

    Article  CAS  PubMed  Google Scholar 

  7. H.O. Ok L.B. Reigle M.R. Candelore M.A. Cascieri L.F. Colwell L. Deng W.P. Feeney M.J. Forrest G.J. Hom D.E. MacIntyre C.D. Strader L. Tota P. Wang M.J. Wyvratt M.H. Fisher A.E. Weber (2000) Bioorg. Med. Chem. Lett. 10 1531 Occurrence Handle10.1016/S0960-894X(00)00277-8 Occurrence Handle1:CAS:528:DC%2BD3cXkvFKisr8%3D Occurrence Handle10915043

    Article  CAS  PubMed  Google Scholar 

  8. D.D. Feng T. Biftu M.R. Candelore M.A. Cascieri L.F. Colwell SuffixJr. L. Deng W.P. Feeney M.J. Forrest G.J. Hom D.E. MacIntyre R.R. Miller R.A. Stearns C.D. Strader L. Tota M.J. Wyvratt M.H. Fisher A.E. Weber (2000) Bioorg. Med. Chem. Lett. 10 1427 Occurrence Handle10.1016/S0960-894X(00)00267-5 Occurrence Handle1:CAS:528:DC%2BD3cXksFynurg%3D Occurrence Handle10888324

    Article  CAS  PubMed  Google Scholar 

  9. E.R. Parmee L.L. Brockunier J. He S.B. Singh M.R. Candelore M.A. Cascieri L. Deng Y. Liu L. Tota M.J Wyvratt M.H. Fisher A.E. Weber (2000) Bioorg. Med. Chem. Lett. 10 2283 Occurrence Handle10.1016/S0960-894X(00)00459-5 Occurrence Handle1:CAS:528:DC%2BD3cXntF2lu7k%3D Occurrence Handle11055339

    Article  CAS  PubMed  Google Scholar 

  10. R.J. Steffan M.A. Ashwell W.R. Solvibile E. Matelan E. Largis S. Han J. Tillet R. Mulvey (2002) Bioorg. Med. Chem. Lett. 12 2957 Occurrence Handle10.1016/S0960-894X(02)00607-8 Occurrence Handle1:CAS:528:DC%2BD38Xntlagurc%3D Occurrence Handle12270183

    Article  CAS  PubMed  Google Scholar 

  11. A.E. Weber R.J. Mathvink L. Perkins J.E. Hutchins M.R. Candelore L. Tota C.D. Strader M.J. Wyvratt M.H. Fisher (1998) Bioorg. Med. Chem. Lett. 8 1110

    Google Scholar 

  12. E.R. Parmee H.O. Ok M.R. Candelore L. Tota L. Deng C.D. Stander M.J. Wyvaratt M.H. Fisher A.E. Weber (1998) Bioorg. Med. Chem. Lett. 8 1107 Occurrence Handle10.1016/S0960-894X(98)00170-X Occurrence Handle1:CAS:528:DyaK1cXjtlSnur4%3D Occurrence Handle9871717

    Article  CAS  PubMed  Google Scholar 

  13. R.J. Mathvink A.M. Barritta M.R. Candelore M.A. Cascieri L. Deng L. Tota C.D. Strader M.J. Wyvratt M.H. Fisher A.E. Weber (1999) Bioorg. Med Chem Lett. 9 1869 Occurrence Handle10.1016/S0960-894X(99)00277-2 Occurrence Handle1:CAS:528:DyaK1MXkt12hurY%3D Occurrence Handle10406657

    Article  CAS  PubMed  Google Scholar 

  14. (a) Steffan, R.J., Ashwell, M.A., Solvibile, W.R., Matelan, E., Largis, E., Han, S., Tillet, J. and Mulvey, R., Bioorg. Med. Chem. Lett., 12 (2002) 2957. (b) Berkowitz, D.E., Nardone, N.A., Smiley, R.M., Price, D.T., Kreutter, D.K. and Fremeau, R.T., Eur. J. Pharmacol., 289 (1995) 223

  15. K. Clement C. Vaisse B.S.J. Mannings A. Basdevant B. Guy-Grand J. Ruis (1995) N. Engl. J. Med. 333 352 Occurrence Handle10.1056/NEJM199508103330605 Occurrence Handle1:CAS:528:DyaK2MXnvValsL0%3D Occurrence Handle7609752

    Article  CAS  PubMed  Google Scholar 

  16. Himms-Hagen, J., In Obesity, V., Johrporp, P. and Bordoll, B.N., Eds., Lippin Cott, Philadelphia, 1992, 15,␣2

  17. J.R.S. Arch A.T. Aimsworth M.A. Cawthorme V. Piercy M.V. Sennitt V.A. Thody C. Wilson S. Wilson (1984) Nature 309 163 Occurrence Handle10.1038/309163a0 Occurrence Handle1:CAS:528:DyaL2cXktFOitrw%3D Occurrence Handle6325935

    Article  CAS  PubMed  Google Scholar 

  18. R.L. Dow (1997) Exp. Opin. Invest. Drugs. 6 1811 Occurrence Handle10.1517/13543784.6.12.1811 Occurrence Handle1:CAS:528:DyaK2sXnvFGntr4%3D

    Article  CAS  Google Scholar 

  19. A.D. Strosberg (1997) Trends Pharmacol. Sci. 18 449 Occurrence Handle1:CAS:528:DyaK1cXlt1Oksg%3D%3D Occurrence Handle9458691

    CAS  PubMed  Google Scholar 

  20. J.R.S. Arch S. Wilson (1996) Int. J. Obes. 20 191 Occurrence Handle1:CAS:528:DyaK28**sVCisb8%3D

    CAS  Google Scholar 

  21. N. Sakane T. Yoshida K. Yoshioka Y. Nakamura T. Umekawa A. Kogure Y. Takakura M. Kondo (1998) Diabetologia. 41 1533 Occurrence Handle10.1007/s001250051103 Occurrence Handle1:STN:280:DyaK1M%2FotlWisQ%3D%3D Occurrence Handle9867224

    Article  CAS  PubMed  Google Scholar 

  22. M. Ghorbani T.H. Claus J. Himms-Hagen (1997) Biochem. Pharmacol. 54 21 Occurrence Handle10.1016/S0006-2952(97)00162-7

    Article  Google Scholar 

  23. A. Anthony S. Schepelmann J.L. Guillaume A.D. Strosberg A.P. Dhillon R.E. Pounder A.J. Wakefield (1998) Aliment Pharmacol. Ther. 12 519 Occurrence Handle10.1046/j.1365-2036.1998.00345.x Occurrence Handle1:CAS:528:DyaK1cXksVSntr8%3D Occurrence Handle9678810

    Article  CAS  PubMed  Google Scholar 

  24. C. Gauthier G. Tavernier F. Charpentier D. Langin H. Le Marec (1996) J. Clin. Invest. 98 556 Occurrence Handle1:CAS:528:DyaK28XksFClt7g%3D Occurrence Handle8755668

    CAS  PubMed  Google Scholar 

  25. S.T. Russell K. Hirai M.J. Tisdale (2002) Br. J. Cancer. 86 424 Occurrence Handle10.1038/sj.bjc.6600086 Occurrence Handle1:CAS:528:DC%2BD38**sFOls7o%3D Occurrence Handle11875710

    Article  CAS  PubMed  Google Scholar 

  26. Y. Igawa Y. Yamazaki H. Takeda K. Hayakawa M. Akahane Y. Ajisawa T. Yoneyama O. Nishizawa K.E Andersson (1999) Br. J. Pharmacol. 126 819 Occurrence Handle10.1038/sj.bjp.0702358 Occurrence Handle1:CAS:528:DyaK1MXhslWitb4%3D Occurrence Handle10188996

    Article  CAS  PubMed  Google Scholar 

  27. Y. Igawa Y. Yamazaki H. Takeda K. Hayakawa M. Akahane Y. Ajisawa T. Yoneyama O. Nishizawa K.E. Andersson (2001) J. Urol. 165 240 Occurrence Handle10.1097/00005392-200101000-00071 Occurrence Handle1:STN:280:DC%2BD3M%2FovFWqsQ%3D%3D Occurrence Handle11125417

    Article  CAS  PubMed  Google Scholar 

  28. N. Tanaka T. Tamai H. Mukaiyama A. Hirabayashi H. Muranaka S. Akahane H. Miyata M. Akahane (2001) J. Med. Chem. 44 1436 Occurrence Handle10.1021/jm000455z Occurrence Handle1:CAS:528:DC%2BD3M**tlCmsLg%3D Occurrence Handle11311067

    Article  CAS  PubMed  Google Scholar 

  29. J. Gros B.S. Manning F. Pietri-Rouxel J.L. Guillaume M.F. Drumare A.D. Strosberg (1998) Eur. J. Biochem. 251 590 Occurrence Handle10.1046/j.1432-1327.1998.2510590.x Occurrence Handle1:CAS:528:DyaK1cXhtVKktb0%3D Occurrence Handle9490030

    Article  CAS  PubMed  Google Scholar 

  30. M.D. Amici C.D. Micheli L. Kassi G. Carrea G. Ottolina G. Colombo (2001) Tetrahedron 9 1849 Occurrence Handle10.1016/S0040-4020(00)01165-0

    Article  Google Scholar 

  31. X.M. Guan A. Amend C.D. Strader (1995) Mol. Pharmacol. 48 492 Occurrence Handle1:CAS:528:DyaK2MXosVKgsr0%3D Occurrence Handle7565630

    CAS  PubMed  Google Scholar 

  32. K.E. Furse T.P. Lybrand (2003) J. Med. Chem. 46 4450 Occurrence Handle10.1021/jm0301437 Occurrence Handle1:CAS:528:DC%2BD3sXnvVCjtbw%3D Occurrence Handle14521408

    Article  CAS  PubMed  Google Scholar 

  33. T. Nagatomo K. Koike (2000) Life Sci. 66 2419 Occurrence Handle1:CAS:528:DC%2BD3cXjtlOgs70%3D Occurrence Handle10894084

    CAS  PubMed  Google Scholar 

  34. Y. Patel V.J. Gillet G. Bravi A.R. Leach (2002) J.␣Comput. Aided Mol. Des. 16 653 Occurrence Handle10.1023/A:1021954728347 Occurrence Handle1:CAS:528:DC%2BD3s**slKgtQ%3D%3D Occurrence Handle12602956

    Article  CAS  PubMed  Google Scholar 

  35. CATALYST Version 4.6, Accerlys, San Diego, CA

  36. A.K. Debnath (2003) J. Med. Chem. 46 4501 Occurrence Handle10.1021/jm030265z Occurrence Handle1:CAS:528:DC%2BD3sXnt1Omsbo%3D Occurrence Handle14521412

    Article  CAS  PubMed  Google Scholar 

  37. O.O. Clement C.M. Freeman R.W. Hartmann V.D. Handratta T.S. Vasaitis A.M. Brodie V.C. Njar (2003) J.␣Med. Chem. 46 2345 Occurrence Handle10.1021/jm020576u Occurrence Handle1:CAS:528:DC%2BD3sXjs12ksL8%3D Occurrence Handle12773039

    Article  CAS  PubMed  Google Scholar 

  38. M.L. Barreca R. Gitto S. Quartarone L. Luca ParticleDe G. Sarro ParticleDe A. Chimirri (2003) J. Chem. Inf. Comput. Sci. 43 651 Occurrence Handle10.1021/ci025625q Occurrence Handle1:CAS:528:DC%2BD3sXnt1ShsQ%3D%3D Occurrence Handle12653534

    Article  CAS  PubMed  Google Scholar 

  39. A. Palomer F. Cabre J. Pascual J. Campos M.A. Trujillo A. Entrena M.A. Gallo L. Garcia D. Mauleon Espinosa (2002) J. Med. Chem. 45 1402 Occurrence Handle10.1021/jm010458r Occurrence Handle1:CAS:528:DC%2BD38XhsVGjsbY%3D Occurrence Handle11906281

    Article  CAS  PubMed  Google Scholar 

  40. A.K. Debnath (2002) J. Med. Chem. 45 41 Occurrence Handle10.1021/jm010360c Occurrence Handle1:CAS:528:DC%2BD3MXptlSrs7g%3D Occurrence Handle11754578

    Article  CAS  PubMed  Google Scholar 

  41. P. Kraft J.A. Bajgrowicz C. Denis G. Frater (2000) Angew. Chem. Int. Ed. 39 2980 Occurrence Handle10.1002/1521-3773(20000901)39:17<2980::AID-ANIE2980>3.0.CO;2-# Occurrence Handle1:CAS:528:DC%2BD3cXmsFWgtLs%3D

    Article  CAS  Google Scholar 

  42. http://www.accelrys.com/references/rdd_pub.html(CATALYST

  43. Golender, V.E. and Rozenblit, A.B. (1983) Logical and Combinatorial Algorithms in Drug Design, Research Studies Press: Letchworth, UK, Golender, V.E., Vorpagel E.R. In: 3D QSAR in Drug Design: Theory, Methods and Applications, Kubinyi H. (Ed), ESCOM, Leiden, 1993, 137–149

  44. Y.C. Martin M.G. Bures E.A. Danaher J. DeLazzer I.P.A. Lico Pavlik (1993) J. Comput. Aided Mol. Des. 7 83 Occurrence Handle10.1007/BF00141577 Occurrence Handle1:CAS:528:DyaK3sXksVSht7s%3D Occurrence Handle8097240

    Article  CAS  PubMed  Google Scholar 

  45. Norinder U. (1995) The Alignment problem in 3D-QSAR: A combined approach using CATALYST and a 3D-QSAR technique, QSAR and Molecular Modelling: Concepts, Computational Tools and Biological Applications In Sanz, F. Giraldo, J., Manaut F. (Eds.), Prous Science Publishers, Barcelona, pp. 433–438

  46. R.D. Hoffmann T. Langer (1995) NoChapterTitle Sanz F. Giraldo J.F. Manaut (Eds) Use of the CATALYST program as a new alignment tool for 3D-QSAR”, QSAR and Molecular Modelling: Concepts, Computational Tools and Biological Applications Prous Science Publishers Barcelona 466–469

    Google Scholar 

  47. T. Langer R.D. Hoffmann (1998) J. Chem. Inf. Comput. Sci. 38 325 Occurrence Handle10.1021/ci970448s Occurrence Handle1:CAS:528:DyaK1cXhvVWhsr4%3D

    Article  CAS  Google Scholar 

  48. A. Palomer J. Pascual F. Cabré M.L. García D. Mauleón (2000) J. Med. Chem. 43 392 Occurrence Handle10.1021/jm990387k Occurrence Handle1:CAS:528:DC%2BD3cXksVSksg%3D%3D Occurrence Handle10669566

    Article  CAS  PubMed  Google Scholar 

  49. R. Bureau C. Daveu I. Baglin J. Sopkova-De Olivera Santos J.-C. Lancelot S. Rault (2001) J. Chem. Inf. Comput. Sci. 41 815 Occurrence Handle10.1021/ci000058x Occurrence Handle1:CAS:528:DC%2BD3M**vFCjsLY%3D Occurrence Handle11410063

    Article  CAS  PubMed  Google Scholar 

  50. A. Golbraikh A. Tropsha (2002) J. Mol. Graphics Model. 20 269 Occurrence Handle10.1016/S1093-3263(01)00123-1 Occurrence Handle1:CAS:528:DC%2BD3MXpt1art7o%3D

    Article  CAS  Google Scholar 

  51. Wold S., Martens, H., Wold, H. (1983) In Ruhe, A., Agstrom B.K (Eds.), Springer Verlag, Heidelberg

  52. S. Wold (1978) Technometrics 20 397

    Google Scholar 

  53. A.K.P. Saxena Prathipati (2003) SAR and QSAR Environ. Res. 14 433 Occurrence Handle10.1080/10629360310001624015

    Article  Google Scholar 

  54. P.W. Sprague (1995) Automated chemical hypothesis generation and database searching with CATALYST K. Muller (Eds) perspectives in Drug Discovery and Design ESCOM: Leiden 1–20

    Google Scholar 

  55. Apex-3D version 1.4 user guide, Biosym MSI, San Diego, Sept. 1993

  56. T. Pandya S.K. Pandey M. Tiwari S.C. Chaturvedi A.K. Saxena (2001) Bioorg. Med. Chem. 9 291 Occurrence Handle10.1016/S0968-0896(00)00243-1 Occurrence Handle1:CAS:528:DC%2BD3MXhs1artb0%3D Occurrence Handle11249122

    Article  CAS  PubMed  Google Scholar 

  57. A.K. Saxena S.K. Pandey P. Seth M.P. Singh M. A. Dikshit Carpy (2001) Bioorg. Med. Chem. 9 2025 Occurrence Handle10.1016/S0968-0896(01)00082-7 Occurrence Handle1:CAS:528:DC%2BD3MXlvFWiurs%3D Occurrence Handle11504639

    Article  CAS  PubMed  Google Scholar 

  58. S.K. Pandey N.B. Naware P. Trivedi A.K. Saxena (2001) SAR and QSAR Envir. Res. 12 547 Occurrence Handle1:CAS:528:DC%2BD38XkvFSmsw%3D%3D

    CAS  Google Scholar 

  59. M.A. Babu N. Shakya P. Prathipati S.G. Kaskhedikar A.K. Saxena (2002) Bioorg. Med. Chem. 10 4035 Occurrence Handle10.1016/S0968-0896(02)00313-9 Occurrence Handle12413856

    Article  PubMed  Google Scholar 

  60. A.K. Saxena S.K. Pandey R.C. Tripathi R Raghubir. (2001) Bioorg. Med. Chem. 9 1559 Occurrence Handle10.1016/S0968-0896(01)00042-6 Occurrence Handle1:CAS:528:DC%2BD3MXkt1Kjsb8%3D Occurrence Handle11408175

    Article  CAS  PubMed  Google Scholar 

  61. S.K. Kashaw L. Rathi P. Mishra A.K. Saxena (2003) Bioorg. Med. Chem. Lett. 13 2481 Occurrence Handle10.1016/S0960-894X(03)00491-8 Occurrence Handle1:CAS:528:DC%2BD3sXlt1WgsLw%3D Occurrence Handle12852947

    Article  CAS  PubMed  Google Scholar 

  62. L. Rathi S.K. Kashaw A Dixit G Pandey P. Mishra A.K. Saxena (2004) Bioorg. Med. Chem. 1 1

    Google Scholar 

  63. B.R. Brooks R.E. Bruccoleri B.D. Olafson D.J. States S. Swaminathan A.M. Karplus (1983) J. Comp. Chem. 4 187 Occurrence Handle10.1002/jcc.540040211 Occurrence Handle1:CAS:528:DyaL3s**t1aiu7w%3D

    Article  CAS  Google Scholar 

  64. K. Gundertofte T. Liljefors P-O Norrby I. Pattesson (1996) J Comp. Chem. 17 429 Occurrence Handle10.1002/(SICI)1096-987X(199603)17:4<429::AID-JCC5>3.0.CO;2-W Occurrence Handle1:CAS:528:DyaK28XhtVylt7o%3D

    Article  CAS  Google Scholar 

  65. J. Bostrom (2001) J. Comput. Aided Mol. Des. 12 1137 Occurrence Handle10.1023/A:1015930826903

    Article  Google Scholar 

  66. A.S. Smellie S.D. Kahm S.L. Teig (1995) J. Chem. Inf. Comput. Sci. 35 285 Occurrence Handle10.1021/ci00024a018 Occurrence Handle1:CAS:528:DyaK2MXktleksr4%3D

    Article  CAS  Google Scholar 

  67. A.S. Smellie S.L. Teig S.D. Kahm (1995) J. Chem. Inf. Comput. Sci. 35 295 Occurrence Handle10.1021/ci00024a019 Occurrence Handle1:CAS:528:DyaK2MXktleksr8%3D

    Article  CAS  Google Scholar 

  68. J. Greene S. Kahn H. Savoj P. Sprague S. Teig (1994) J.␣Chem. Inf. Comput Sci. 34 1297 Occurrence Handle10.1021/ci00022a012 Occurrence Handle1:CAS:528:DyaK2cXmsFCrurg%3D

    Article  CAS  Google Scholar 

  69. Sutter, J., Guner, O., Hoffman, R., Li, H. and Waldman, M., Effect of Variable Weights and Tolerances on Predictive Model Generation, in Pharmacophore Perception, Development, and Use in Drug Design, O.F. Guner, Ed., International University Line, La Jolla, CA, 2000

  70. P. Dauber-Osguthorpe V.A. Roberts D.J. Osguthorpe J. Wolff M. Genest A.T. Hagler (1988) ArticleTitleProteins: Struct. Funct Genet 4 31 Occurrence Handle1:CAS:528:DyaL1M**tVegsw%3D%3D

    CAS  Google Scholar 

  71. P. Hobza M. Kabelac J. Sponer P. Mejzlik J. Vondrasek (2000) J. Comp. Chem. 18 1136 Occurrence Handle10.1002/(SICI)1096-987X(19970715)18:9<1136::AID-JCC3>3.0.CO;2-S

    Article  Google Scholar 

  72. C. Weyer C.J Souza Particlede (2000) Drug Dev. Res. 51 80 Occurrence Handle10.1002/1098-2299(200010)51:2<80::AID-DDR4>3.0.CO;2-E Occurrence Handle1:CAS:528:DC%2BD3M**t1CjsQ%3D%3D

    Article  CAS  Google Scholar 

  73. C.J. Souza Particlede M.F. Hirshman E.S. Horton (1997) Diabetes 46 1257 Occurrence Handle9231648

    PubMed  Google Scholar 

  74. T.L. Shih M.R. Candelore M.A. Cascieri S.H. Chiu L.F Colwell SuffixJr. L. Deng W.P. Feeney M.J. Forrest G.J. Hom D.E. MacIntyre R.R. Miller R.A. Stearns C.D. ␣Strader L. Tota M.J. Wyvratt M.H. Fisher A.E. Weber (1999) Bioorg Med. Chem. Lett. 9 1251 Occurrence Handle10.1016/S0960-894X(99)00182-1 Occurrence Handle10340609

    Article  PubMed  Google Scholar 

  75. E.R. Parmee E.M. Naylor L. Perkins V.J. Colandrea H.O. Ok M.R. Candelore M.A. Cascieri L. Deng W.P. Feeney M.J. Forrest G.J. Hom D.E. MacIntyre R.R. Miller R.A. Stearns C.D. Strader L. Tota M.J. Wyvratt M.H. Fisher A.E. Weber (1999) Bioorg. Med. Chem. Lett. 9 749 Occurrence Handle10.1016/S0960-894X(99)00073-6 Occurrence Handle1:CAS:528:DyaK1MXhvFehsro%3D Occurrence Handle10201841

    Article  CAS  PubMed  Google Scholar 

  76. Dianippon Pharma Co. 1998. AJ-9677: β3-adrenoceptor agonist. Pharmacological study report Ed. #1 (non-confidential information). Research and Development Headquarters.; Kawashima, H., Nomura, A., Ohue, M., Kato, H., Kuwajima, J., Furutani, Y., Hosoki, K., Diabetologia, 40 (1997) A374

  77. D.M. Hargrove R.L. Dow K.A. Martin N.A. Nardone S.J. Orena A.M. Brodeur A.J. Torchia D.K. Kreutter S. Yee R.W. Stevenson (1999) Obes Res. 7 72S

    Google Scholar 

  78. J.W. Miller N.A. Farid R.D. Johnson B.P. Smith J. Dananberg (1999) Obes. Res. 7 121S

    Google Scholar 

  79. T.-L. Lee C.-T. Hsu S.-T. Yen C.-W. Lai J.-T. Cheng (1998) J. Auton. Nerv. Sys. 11 86 Occurrence Handle10.1016/S0165-1838(98)00120-9 Occurrence Handle1:STN:280:DyaK1c7kvVCmug%3D%3D

    Article  CAS  Google Scholar 

  80. N. Blin L. Camoin B. Maigret A.D. Strosberg (1994) Mol. Phar. 44 1094–1104

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Medicinal and Process Chemistry, Central Drug Research Institute, 226001, Lucknow, India

    Philip Prathipati & Anil K. Saxena

Authors
  1. Philip Prathipati
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anil K. Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

★CDRI communication number 6202.

*To whom correspondence should be addressed. Fax: +91-0522-223405; E-mail: anilsak@hotmail.com

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prathipati, P., Saxena, A.K. Characterization of β3-adrenergic receptor: determination of pharmacophore and 3D QSAR model for β3 adrenergic receptor agonism. J Comput Aided Mol Des 19, 93–110 (2005). https://doi.org/10.1007/s10822-005-1558-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10822-005-1558-7

Keywords

Search

Navigation