title: Structure and activity relationship in the (S)-N-chroman-3-ylcarboxamide series of voltage-gated sodium channel blockers.
abstract: Recent findings showing a relation between mutations in the Na(V)1.7 channel in humans and altered pain sensation has contributed to increase the attractiveness of this ion channel as target for development of potential analgesics. Amido chromanes 1 and 2 were identified as blockers of the Na(V)1.7 channel and analogues with modifications of the 5-substituent and the carboxamide part of the molecule were prepared to establish the structure-activity relationship. Compounds 13 and 29 with good overall in vitro and in vivo rat PK profile were identified. Furthermore, 29 showed in vivo efficacy in a nociceptive pain model.
authors: Medicinal Chemistry, CNSP iMed Science, AstraZeneca R&D, Innovative Medicines, SE-15185 Södertälje, Sweden. inger.kers@telia.com
authors: Inger
authors: I
authors: Kers
authors: Gabor
authors: G
authors: Csjernyik
authors: Istvan
authors: I
authors: Macsari
authors: Martin
authors: M
authors: Nylöf
authors: Lars
authors: L
authors: Sandberg
authors: Karin
authors: K
authors: Skogholm
authors: Tjerk
authors: T
authors: Bueters
authors: Anders B
authors: AB
authors: Eriksson
authors: Sandra
authors: S
authors: Oerther
authors: Per-Eric
authors: PE
authors: Lund
authors: Elisabet
authors: E
authors: Venyike
authors: Jan-Erik
authors: JE
authors: Nyström
authors: Yevgeni
authors: Y
authors: Besidski
mesh_terms: D000700:Analgesics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002839:Chromans / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D005557:Formaldehyde; D006801:Humans; D062556:NAV1.7 Voltage-Gated Sodium Channel / Q000378:metabolism*; D059226:Nociceptive Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D013329:Structure-Activity Relationship; D061567:Voltage-Gated Sodium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D002839:Chromans; D062556:NAV1.7 Voltage-Gated Sodium Channel; D061567:Voltage-Gated Sodium Channel Blockers; D005557:Formaldehyde