Synthesis, SAR and pharmacology of CP-293,019: a potent, selective dopamine D4 receptor antagonist

M A Sanner; T A Chappie; A R Dunaiskis; A F Fliri; K A Desai; S H Zorn; E R Jackson; C G Johnson; J M Morrone; P A Seymour; M J Majchrzak; W S Faraci; J L Collins; D B Duignan; C C Prete Di; J S Lee; A Trozzi

doi:10.1016/s0960-894x(98)00108-5

Synthesis, SAR and pharmacology of CP-293,019: a potent, selective dopamine D4 receptor antagonist

Bioorg Med Chem Lett. 1998 Apr 7;8(7):725-30. doi: 10.1016/s0960-894x(98)00108-5.

Authors

M A Sanner¹, T A Chappie, A R Dunaiskis, A F Fliri, K A Desai, S H Zorn, E R Jackson, C G Johnson, J M Morrone, P A Seymour, M J Majchrzak, W S Faraci, J L Collins, D B Duignan, C C Prete Di, J S Lee, A Trozzi

Affiliation

¹ Pfizer Central Research, Groton, CT 06340, USA.

PMID: 9871530
DOI: 10.1016/s0960-894x(98)00108-5

Abstract

A series of novel, potent and selective pyrido[1,2-a]pyrazine dopamine D4 receptor antagonists are reported including CP-293,019 (D4 Ki = 3.4 nM, D2 Ki > 3,310 nM), which also inhibits apomorphine-induced hyperlocomotion in rats after oral dosing.

MeSH terms

Animals
Apomorphine / pharmacology
Dopamine Antagonists / chemical synthesis*
Dopamine Antagonists / chemistry
Dopamine Antagonists / pharmacology
Dopamine D2 Receptor Antagonists*
Drug Design
Haloperidol / pharmacology
Indicators and Reagents
Molecular Structure
Motor Activity / drug effects*
Pyrazines / chemical synthesis*
Pyrazines / chemistry
Pyrazines / pharmacology
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology
Rats
Receptors, Dopamine D4
Structure-Activity Relationship

Substances

CP 293019
Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Drd4 protein, rat
Indicators and Reagents
Pyrazines
Pyrimidines
Receptors, Dopamine D4
Haloperidol
Apomorphine