SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure

Bioorg Med Chem. 2008 Mar 1;16(5):2499-512. doi: 10.1016/j.bmc.2007.11.055. Epub 2007 Nov 28.

Abstract

Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchodilator Agents / chemical synthesis*
  • Bronchodilator Agents / chemistry
  • Bronchodilator Agents / pharmacology*
  • Capsaicin / analogs & derivatives*
  • Capsaicin / chemical synthesis
  • Capsaicin / chemistry
  • Capsaicin / pharmacology
  • Catechols / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Respiration / drug effects
  • Structure-Activity Relationship

Substances

  • Bronchodilator Agents
  • Catechols
  • catechol
  • capsazepine
  • Capsaicin