Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 9, 2008, Pages 2920-2923

  Gillespie, Roger J ^a   Cliffe, Ian A ^a   Dawson, Claire E ^a   Dourish, Colin T ^a   Gaur, Suneel ^a   Giles, Paul R ^a   Jordan, Allan M ^a   Knight, Antony R ^a   Lawrence, Anthony ^a   Lerpiniere, Joanne ^a   Misra, Anil ^a   Pratt, Robert M ^a   Todd, Richard S ^a   Upton, Rebecca ^a   Weiss, Scott M ^a   Williamson, Douglas S ^a  

^a Vernalis PLC   (United Kingdom)

Author keywords

Adenosine A2A receptor; In vivo activity; Parkinson's disease; Thienopyrimidine

Indexed keywords

ADENOSINE A1 RECEPTOR; ADENOSINE A2A RECEPTOR; ADENOSINE A2A RECEPTOR ANTAGONIST; ADENOSINE A2B RECEPTOR; ADENOSINE A3 RECEPTOR; HALOPERIDOL; RECEPTOR SUBTYPE; THIENO[3,2 D]PYRIMIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; IN VIVO STUDY; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANTIPARKINSON AGENTS; DRUG DESIGN; HUMANS; MODELS, CHEMICAL; PARKINSONIAN DISORDERS; PYRIMIDINES; RECEPTOR, ADENOSINE A1; RECEPTOR, ADENOSINE A2A; RECEPTOR, ADENOSINE A2B; RECEPTOR, ADENOSINE A3; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 42949141669     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.03.076     Document Type: Article

References (10)

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2. Gillespie R.J., Adams D.R., Bebbington D., Benwell K., Cliffe I.A., Dawson C.E., Dourish C.T., Fletcher A., Gaur S., Giles P.R., Jordan A.M., Knight A.R., Knutsen L.J.S., Lawrence A., Lerpiniere J., Misra A., Porter R.H.P., Pratt R.M., Shepherd R., Upton R., Ward S.E., Weiss S.M., and Williamson D.S. Bioorg. Med. Chem. Lett. 18 (2008) 2916
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4. i determination, see:. Weiss S.M., Benwell K., Cliffe I.A., Gillespie R.J., Knight A.R., Lerpiniere J., Misra A., Pratt R.M., Revell D., Upton R., and Dourish C.T. Neurology 61 (2003) S101 (all values are the mean of at least two separate values)
5. -1 test compound. See:. Bezard E., Imbert C., and Gross C.E. Rev. Neurosci. 9 (1998) 71
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8. Synthetic procedures are described in more detail in: Gillespie, R. J.; Lerpiniere, J.; Dawson, C. E.; Gaur, S.; Pratt, R. M. PCT Int. Appl. WO2002055524, 2002.
9. The alternative 4-chloro-2-(2-thienyl)thienopyrimidine regioisomer was prepared by an unambiguous route related to that shown in Scheme 3 for the synthesis of compound 47, and was shown not to correspond to 3, confirming the desired 4-aryl regiochemistry.
10. Gillespie R.J., Cliffe I.A., Dawson C.E., Dourish C.T., Gaur S., Jordan A.M., Knight A.R., Lerpiniere J., Misra A., Pratt R.M., Roffey J., Stratton G.C., Upton R., Weiss S.M., and Williamson D.S. Bioorg. Med. Chem. Lett. 18 (2008) 2924