1-Phenylpyrazolo[3,4-dlpyrimidines:Structure-Activity Relationships for C6 Substituents at A1 and A2a Adenosine Receptors
Author(s)
Chebib, M
McKeveney, D
Quinn, RJ
Griffith University Author(s)
Year published
2000
Metadata
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Substitution of 1-phenylpyrazolo[3,4-d]pyrimidines at C6 with N-alkyl-2-thiopropionamide groups has resulted in a series of 18 compounds which have been evaluated for binding at A1 and A2A adenosine receptors. Introduction of an N-ethyl group gave increased affinity at both A1 and A2A receptors for the amino compound 7b compared to the primary amide 7a. An additional hydrophobic pocket exists for substituents on the amide. This pocket allows an N-ethyl group for increased affinity at both A1 and A2A receptors, allows larger alkyl groups at A2A receptors but not at A1 receptors and there is an H-bond interaction requiring one ...
View more >Substitution of 1-phenylpyrazolo[3,4-d]pyrimidines at C6 with N-alkyl-2-thiopropionamide groups has resulted in a series of 18 compounds which have been evaluated for binding at A1 and A2A adenosine receptors. Introduction of an N-ethyl group gave increased affinity at both A1 and A2A receptors for the amino compound 7b compared to the primary amide 7a. An additional hydrophobic pocket exists for substituents on the amide. This pocket allows an N-ethyl group for increased affinity at both A1 and A2A receptors, allows larger alkyl groups at A2A receptors but not at A1 receptors and there is an H-bond interaction requiring one H-bond donor. Molecular modeling studies have also enabled a proposal of the amino acid residues involved in ligand binding at both the A1 and A2A receptors.
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View more >Substitution of 1-phenylpyrazolo[3,4-d]pyrimidines at C6 with N-alkyl-2-thiopropionamide groups has resulted in a series of 18 compounds which have been evaluated for binding at A1 and A2A adenosine receptors. Introduction of an N-ethyl group gave increased affinity at both A1 and A2A receptors for the amino compound 7b compared to the primary amide 7a. An additional hydrophobic pocket exists for substituents on the amide. This pocket allows an N-ethyl group for increased affinity at both A1 and A2A receptors, allows larger alkyl groups at A2A receptors but not at A1 receptors and there is an H-bond interaction requiring one H-bond donor. Molecular modeling studies have also enabled a proposal of the amino acid residues involved in ligand binding at both the A1 and A2A receptors.
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Journal Title
Bioorganic & Medicinal Chemistry
Volume
8
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Pharmacology and pharmaceutical sciences
History, heritage and archaeology