Structure-guided design of substituted aza-benzimidazoles as potent hypoxia inducible factor-1alpha prolyl hydroxylase-2 inhibitors

We report the structure-based design and synthesis of a novel series of aza-benzimidazoles as PHD2 inhibitors. These efforts resulted in compound 22, which displayed highly potent inhibition of PHD2 function in vitro.

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Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2008-09, Vol.18 (18), p.5023-5026
Hauptverfasser:	Frohn, Mike, Viswanadhan, Vellarkad, Pickrell, Alexander J, Golden, Jennifer E, Muller, Kristine M, Bürli, Roland W, Biddlecome, Gloria, Yoder, Sean C, Rogers, Norma, Dao, Jennifer H, Hungate, Randall, Allen, Jennifer R
Format:	Artikel
Sprache:	eng
Schlagworte:	Aza Compounds - chemical synthesis Aza Compounds - chemistry Aza Compounds - pharmacology Basic Helix-Loop-Helix Transcription Factors Benzimidazoles - chemical synthesis Benzimidazoles - chemistry Benzimidazoles - pharmacology Combinatorial Chemistry Techniques Crystallography, X-Ray Humans Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors Hypoxia-Inducible Factor-Proline Dioxygenases Models, Molecular Molecular Structure Procollagen-Proline Dioxygenase - antagonists & inhibitors Structure-Activity Relationship
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Beschreibung
Zusammenfassung:	We report the structure-based design and synthesis of a novel series of aza-benzimidazoles as PHD2 inhibitors. These efforts resulted in compound 22, which displayed highly potent inhibition of PHD2 function in vitro.
ISSN:	1464-3405
DOI:	10.1016/j.bmcl.2008.08.012