title: 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.
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.
authors.affiliation: GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. dm12907@gsk.com
authors.forename: David L
authors.initials: DL
authors.lastname: Musso
authors.forename: Felicia R
authors.initials: FR
authors.lastname: Cochran
authors.forename: James L
authors.initials: JL
authors.lastname: Kelley
authors.forename: Ed W
authors.initials: EW
authors.lastname: McLean
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Selph
authors.forename: Greg C
authors.initials: GC
authors.lastname: Rigdon
authors.forename: G Faye
authors.initials: GF
authors.lastname: Orr
authors.forename: Ronda G
authors.initials: RG
authors.lastname: Davis
authors.forename: Barrett R
authors.initials: BR
authors.lastname: Cooper
authors.forename: Virgil L
authors.initials: VL
authors.lastname: Styles
authors.forename: James B
authors.initials: JB
authors.lastname: Thompson
authors.forename: William R
authors.initials: WR
authors.lastname: Hall
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009125:Muscle Relaxants, Central / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C471168:2-(4,6-difluoro-1-indanylidene)acetamide; D000081:Acetamides; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006993:Hypnotics and Sedatives; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D009125:Muscle Relaxants, Central; D008995:Monoamine Oxidase