2. Academic Validation
  3. Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists

Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists

  • J Med Chem. 2001 Nov 8;44(23):3978-84. doi: 10.1021/jm010237l.
H S Jae 1,  M Winn,  T W von Geldern,  B K Sorensen,  W J Chiou,  B Nguyen,  K C Marsh,  T J Opgenorth
Affiliations

Affiliation

  • 1 Metabolic Diseases Research and Drug Analysis Department, Pharmaceutical Products Research Division, Abbott Laboratories, Abbott Park, Illinois 60064-6098, USA. [email protected]
PMID: 11689084 DOI: 10.1021/jm010237l
Abstract

The synthesis and structure-activity relationships (SAR) of a series of pyrrolidine-3-carboxylic acids as endothelin antagonists are described. The data shows an increase in selectivity when the methoxy of Atrasentan (ABT-627) is replaced with methyl, and the benzodioxole is replaced with dihydrobenzofuran. Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ET(A)-selective antagonist.

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