279261-54-0

Upstream product

• 39969-56-7 1-bromo-4-propoxybenzene 
• 279261-19-7 methyl 7-bromo-2,3-dihydro-1-benzothiepine-4-carboxylate 1,1-dioxide 
• 229008-66-6 7-bromo-5-hydroxy-2,3,4,5-tetrahydro-benzo[b]thiepine-4-carboxylic acid methyl ester 
• 229008-65-5 methyl 7-bromo-5-oxo-2,3,4,5-tetrahydro-1-benzothiepine-4-carboxylate 
• 229008-67-7 methyl 7-bromo-2,3-dihydro-1-benzothiepine-4-carboxylate 
• 15084-55-6 7-bromo-3,4-dihydro-1-benzothiepin-5(2H)-one 
• 93777-26-5 5-bromo-2-fluorobenzaldehyde 
• 307556-97-4 ethyl 7-(4-propoxyphenyl)-2,3-dihydro-1-benzothiepine-4-carboxylate 
• 307556-96-3 2-fluoro-5-(4-propoxyphenyl)benzaldehyde 
• 279261-53-9 methyl 7-(4-propoxyphenyl)-2,3-dihydro-1-benzothiepine-4-carboxylate 1,1-dioxide 
• 307556-98-5 ethyl 7-(4-propoxyphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxylate 

Downstream Products

• 279261-14-2 N-[4-[hydroxy(2-pyridyl)methyl]phenyl]-7-(4-propoxyphenyl)-1,1-dioxo-2,3-dihydro-1-benzothiepine-4-carboxamide 

Relevant academic research and scientific papers

Efficient synthesis of CCR5 antagonist, 2,3-dihydro-1-benzothiepine derivatives by improved intramolecular Claisen type reaction using dialkylcarbonate

The efficient synthesis of 2,3-dihydro-1-benzothiepine derivatives 4 has been developed. The intramolecular Claisen type reaction of the new products, 4-(o-formylphenylthio)butyrate 9, with alcoholate in dialkylcarbonate as a solvent afforded 4 in good yields. According to this new procedure, we have accomplished the practical preparation of CCR5 antagonist 1 as a candidate for oral HIV-1 therapy.

Orally active CCR5 antagonists as anti-HIV-1 agents: Synthesis and biological activity of 1-benzothiepine 1,1-dioxide and 1-benzazepine derivatives containing a tertiary amine moiety

The search for orally active CCR5 antagonists was performed by chemical modification of the 1-benzothiepine 1,1-dioxide 3 and 1-benzazepine 4 lead compounds containing a tertiary amine moiety. Replacement of methyl group with a 2-(C2-4 alkoxy)ethoxy group at the 4-position on the 7-phenyl group of the 1-benzothiepine ring resulted in both enhanced activity and significant improvement in the pharmacokinetic properties upon oral administration in rats. Introduction of C2-4 alkyl, phenyl or (hetero)arylmethyl groups as the 1-substituent on the 1-benzazepine ring together with the 2-(butoxy)ethoxy group led to further increase of activity. Among the 1- benzazepine derivatives, the isobutyl (6i), benzyl (6o) or 1-methylpyrazol-4-ylmethyl (6s) compounds were found to exhibit highly potent inhibitory effects, equivalent to the injectable CCR5 antagonist 1, in the HIV-1 envelopemediated membrane fusion assay. In particular, compound 6s showed the most potent CCR5 antagonistic activity (IC50=2.7 nM) and inhibitory effect (IC50=1.2 nM) on membrane fusion, together with good pharmacokinetic properties in rats. The synthesis of 1-benzothiepine 1,1-dioxide and 1-benzazepine derivatives and their biological activity are described.

Processes for the preparation of 2,3-dihydrothiepine derivatives

A process for preparing a compound represented by the following formula: wherein each symbol is as defined below, or a salt thereof, characterized by subjecting a compound represented by the following formula: wherein R1 is an electron-attracting group; R2, R3, R4, R5, R6 and R7 are each a hydrogen atom, a halogen atom, an optionally substituted amino group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group, provided that R6 and R7 may be united to form a ring; and R8 is a hydrogen atom or an optionally substituted hydrocarbon group, or a salt thereof, to a ring-closing reaction.

PROCESSES FOR THE PREPARATION OF 2,3-DIHYDROTHIEPINE DERIVATIVES

A process for preparing a compound represented by the following formula: wherein each symbol is as defined below, or a salt thereof, characterized by subjecting a compound represented by the following formula: wherein R1 is an electron-attracting group; R2, R3, R4, R5, R6 and R7 are each a hydrogen atom, a halogen atom, an optionally substituted amino group, an optionally substituted hydroxyl group, an optionally substituted thiol group, an optionally substituted hydrocarbon group, or an optionally substituted heterocyclic group, provided that R6 and R7 may be united to form a ring; and R8 is a hydrogen atom or an optionally substituted hydrocarbon group, or a salt thereof, to a ring-closing reaction.

Anilide derivative, production and use thereof

This invention is to provide a compound of the formula: wherein R1is an optionally substituted 5- to 6-membered ring; the ring A is an optionally substituted 6- to 7-membered ring; the ring B is an optionally substituted benzene ring; n is an integer of 1 or 2; Z is a chemical bond or a divalent group; R2is (1) an optionally substituted amino group in which a nitrogen atom may form a quaternary ammonium, (2) an optionally substituted nitrogen-containing heterocyclic ring group which may contain a sulfur atom or an oxygen atom as ring constituting atoms and wherein a nitrogen atom may form a quaternary ammonium, (3) a group binding through a sulfur atom or (4) a group of the formula: ?wherein k is 0 or 1, and when k is 0, a phosphorus atom may form a phosphonium; and R5and R6are independently an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted amino group, and R5and R6may bind to each other to form a cyclic group together with the adjacent phosphorus atom, or a salt thereof , which is useful for antagonizing CCR5 and also for the prevention and treatment of infectious disease of HIV.