Synthesis of 1-Benzothiepine and 1-Benzazepine Derivatives as Orally Active CCR5 Antagonists

Quaternary ammonium benzocycloheptene compound 1 has previously been reported as a clinical candidate for an injectable CCR5 antagonist. In order to develop an orally active CCR5 antagonist, derivatives of tertiary amine benzocycloheptene 2, the chemical precursor to 1, were investigated. The benzoc...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Chemical & Pharmaceutical Bulletin 2004, Vol.52(2), pp.254-258
Hauptverfasser: Aramaki, Yoshio, Seto, Masaki, Okawa, Tomohiro, Oda, Tsuneo, Kanzaki, Naoyuki, Shiraishi, Mitsuru
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Quaternary ammonium benzocycloheptene compound 1 has previously been reported as a clinical candidate for an injectable CCR5 antagonist. In order to develop an orally active CCR5 antagonist, derivatives of tertiary amine benzocycloheptene 2, the chemical precursor to 1, were investigated. The benzocycloheptene ring was converted to benzothiepine and benzazepine rings and it was found that these changes could enhance the potency of tertiary amine derivatives. In particular, the 1-benzothiepine-1,1-dioxide 11b and the N-methyl-1-benzazepine 18 showed increased activity and good preliminary pharmacokinetic properties. The synthesis of 1-benzothiepine and 1-benzazepine derivatives and their activity are described.
ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.52.254