Structure-activity relationship of thiopyrimidines as mGluR5 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 9, 2006, Pages 2467-2469

  Hammerland, Lance G ^a   Johansson, Martin ^b   Malmström, Jonas ^b   Mattsson, Jan P ^c   Minidis, Alexander B E ^b   Nilsson, Karolina ^c   Peterson, Alecia ^a   Wensbo, David ^b   Wållberg, Andreas ^c   Österlund, Krister ^c  

^a NPS Pharmaceutical Inc   (United States)

^b ASTRAZENECA R AND D   (Sweden)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

Metabotropic glutamate receptor; mGluR5; Thiopyrimidine

Indexed keywords

METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; PYRIMIDINE DERIVATIVE; THIOPYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; IN VITRO STUDY; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE; DRUG EVALUATION, PRECLINICAL; HUMANS; LIVER; MICROSOMES; MOLECULAR STRUCTURE; PYRIMIDINES; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIONUCLEOSIDES;

EID: 33644973239     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.01.100     Document Type: Article

References (20)

1. P.J. Conn, and J.-P. Pin Annu. Rev. Pharmacol. Toxicol. 37 1997 205
2. J.-P. Pin, and R. Duvoisin Neuropharmacology 34 1995 1
3. V. Mutel Expert Opin. Ther. Patents 12 2002 1845
4. F.M. Sabbatini, and F. Micheli Expert Opin. Ther. Patents 14 2004 1593
5. W. Spooren, and F. Gasparini Drug News Perspect. 17 2004 251
6. M.A. Varney, and R.W. Gereau CNS Neurol. Disord. 1 2002 283
7. C.Z. Zhu, S.G. Wilson, J.P. Mikusa, C.T. Wismer, D.M. Gauvin, J.M. Lynch, C.L. Wade, M.W. Decker, and P. Honore Eur. J. Pharmacol. 506 2004 107
8. J. Brodkin, C. Busse, S.J. Sukoff, and M.A. Varney Pharmacol. Biochem. Behav. 73 2002 359
9. W.P.J.M. Spooren, A. Vassout, H.C. Neijt, R. Kuhn, F. Gasparini, S. Roux, R.D. Porsolt, and C. Gentsch J. Pharmacol. Exp. Ther. 295 2000 1267
10. E. Tatarczynska, A. Klodzinska, E. Chojnacka-Wojcik, A. Palucha, F. Gasparini, R. Kuhn, and A. Pilc Br. J. Pharmacol. 132 2001 1423
11. C.S. Busse, J. Brodkin, D. Tattersall, J.J. Anderson, N. Warren, L. Tehrani, L.J. Bristow, M.A. Varney, and N.D.P. Cosford Neuropsychopharmacology 29 2004 1971
12. C. Chiamulera, M.P. Epping-Jordon, A. Zocchi, C. Marcon, C. Cottiny, S. Tacconi, M. Corsi, F. Orzi, and F. Conquet Nat. Neurosci. 4 2001 873
13. J. Jensen, A. Lehmann, A. Uvebrant, A. Carlsson, G. Jerndal, K. Nilsson, C. Frisby, L.-A. Blackshaw, and J.P. Mattsson Eur. J. Pharmacol. 519 2005 154
14. J.B. Medwid, R. Paul, J.S. Baker, J.A. Brockman, M.T. Du, W.A. Hallet, J.W. Hanifin, R.A. Hardy, M.E. Tarrant, L.W. Torley, and S. Wrenn J. Med. Chem. 33 1990 1230
15. J.S. Moffatt J. Chem. Soc. 9 1950 1603
16. 2 is commercially available, 3 was made according to Gabriel, S. Ber. Dtsch. Chem. Ges. 1904, 37, 3638.
17. Intermediate for regioisomer 24 was synthesized according to K. Araki, T. Mutai, Y. Shigemitsu, M. Yamada, T. Nakajima, S. Kuroda, and I.J. Shimao Chem. Soc. Perkin Trans. 2 1996 613
18. 2S (M+H) 333.9972. Found 333.9981.
19. 2SF (M+H) 351.9878. Found 351.9868.
20. A. Pagano, D. Ruegg, S. Litschig, N. Stoehr, C. Stierlin, M. Heinrich, P. Floersheim, L. Prezèau, F. Carroll, J.-P. Pin, A. Cambria, I. Vranesic, P.J. Flor, F. Gasparini, and R. Kuhn J. Biol. Chem. 275 2000 33750