Indanylidenes. 1. Design and synthesis of (E)-2-(4,6-difluoro-1-indanylidene)acetamide, a potent, centrally acting muscle relaxant with antiinflammatory and analgesic activity

  • J Med Chem. 2003 Jan 30;46(3):399-408. doi: 10.1021/jm020067s.
David L Musso  1 ,  Felicia R Cochran ,  James L Kelley ,  Ed W McLean ,  Jeffrey L Selph ,  Greg C Rigdon ,  G Faye Orr ,  Ronda G Davis ,  Barrett R Cooper ,  Virgil L Styles ,  James B Thompson ,  William R Hall
Affiliations
  • 1. GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. [email protected]
PMID: 12540239 DOI: 10.1021/jm020067s
Abstract

The design of rigid cyclic analogues derived from cinnamamide 1, (E)-N-cyclopropyl-3-(3-fluorophenyl)prop-2-enamide, and beta-methylcinnamamide 2, (E)-N-cyclopropyl-3-(3-fluorophenyl)but-2-enamide, has led to the discovery of the potent, centrally acting muscle relaxant (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 17. Compound 17 also possesses potent antiinflammatory and analgesic activity. This paper describes the synthesis and the muscle relaxant, antiinflammatory, and analgesic structure-activity relationships of 17 and 67 of its analogues. Compound 17 has been taken into phase I clinical trials.

Products