Abstract
A novel class of pyrrolidinyl-acetyleneic thieno[3,2-d]pyrimidines has been identified which potently inhibit the EGFR and ErbB-2 receptor tyrosine kinases. Synthetic modifications of the pyrrolidine carbamate moiety result in a range of effects on enzyme and cellular potency. In addition, the impact of the absolute stereochemical configuration on cellular potency and oral mouse pharmacokinetics is described.
MeSH terms
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Administration, Oral
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Animals
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Antineoplastic Agents / chemistry*
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ErbB Receptors / antagonists & inhibitors*
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Mice
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Pharmacokinetics
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Pyrimidines / chemical synthesis
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Pyrimidines / pharmacology*
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Pyrrolidines / chemical synthesis
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Pyrrolidines / pharmacology*
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Receptor, ErbB-2 / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Pyrimidines
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Pyrrolidines
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ErbB Receptors
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Receptor, ErbB-2
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pyrrolidine