KR20210094707A - Manufacturing method including secondary infection prevention molecule - Google Patents

Abstract

The present invention relates to a novel benzofuran derivative, analogs thereof, a composition containing the same, and a use thereof for the treatment or prevention of viral infections and related diseases, in particular for the treatment or prevention of viral infections and related diseases caused by hepatitis C virus.

Description

Manufacturing method including secondary infection prevention molecule

This application was filed on November 1, 2002 in U.S. Provisional Application No. 60/423,291, and in U.S. Provisional Application No. 60/461,077, filed on April 8, 2003

No., U.S. Provisional Application No. 60/489,060, filed July 23, 2003 (Case No. PCHC-0264P3-US); and filed on October 30, 2003

We claim priority in U.S. Provisional Application No. (Case No. PCHC-0264P4-US). These applications are incorporated herein by reference in their entirety.

is used

Interferon and interferon in combination with ribavirin are used in the United States for the treatment of hepatitis due to HCV. These treatments are in some patients

has been associated with an improved serum enzymatic response of The remaining patients do not respond to treatment. For responders, a small percentage of

Only patients showed sustained clinical improvement, and most patients relapsed upon discontinuation of treatment. Therefore, chronic hepatitis C

is variable, and its rate of treatment is low. In addition, treatment is often accompanied by significant side effects.

The alkyl radical substituent and the alkoxy group substituent are alkenyl, amino, monoalkylamino, dialkylamino, alkoxy, cycloal

Kill, hydroxy, carboxyl, halogen, cyano, polyfluoroalkyl, polyfluoroalkoxy, sulfonamide, carboxamide, alkylsulfo

nyl, alkylcarbonyl, alkoxycarbonyl, mercapto, 2,2-dimethyl-4-oxo-4H-benzo [1,3] dioxynyl, substituted or unsubstituted aryl groups and

at least one radical independently selected from the group consisting of cyclic or unsubstituted heterocyclic radicals;

Said heterocyclic radical substituent is alkyl, amino, amido, monoalkylamino, cycloalkyl-alkylamino, dialkylamino, alkoxy, al

Coxyalkyl, hydroxy, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, carboxyl, carboxamide, halogen, haloalkyl, cyano,

Polyfluoroalkyl, polyfluoroalkoxy, alkylsulfonyl, alkylcarbonyl, cycloalkylcarbonyl, alkoxycarbonyl, mercapto, oxo,

At least one radical independently selected from the group consisting of a substituted or unsubstituted aryl group, an arylalkyl group, and a substituted or unsubstituted heteroaryl group

a sword;

The antiviral activity of a representative compound of the present invention was demonstrated in a human liver-derived cell line (Huh-7-) containing an HCV replicating unit (BB7 sequence).

Clone A) was first measured [Lohmann et al. Science. 1999, 285:110-3; Blight KJ et al., Science. 2000,

290:1972-4; Pietschmann, T. et al., J. Virol. 2001, 73:1252-1264; and Lohmann, V. et al., J. Virol. 2001, 75:1437-

1449)]. The HCV replication unit is a subgenome virus RNA that expresses the HCV protein necessary for its own replication. these steps

White matter includes the non-structural proteins NS3, NS4A, NS4B, NS5A and NS5B. The replication unit is also a drug-selective marker (neomy

G418 (neomycin) selection of cells containing the replication unit by containing a foreign gene encoding a neophosphotransferase).

make it possible

Inhibition of viral RNA-dependent RNA polymerase (RdRp)

Standards using purified HCV NS5B protein derived from the consensus sequence of patients infected with HCV genotype 1b virus (BB7)

HCV NS5B-induced RdRp activity was formed and characterized by in vitro biochemical assays (Blight KJ et al., Science.

2000, 290:1972-4)]. The NS5B consensus sequence was cloned and the carboxyl terminal 21 amino acid was removed to increase the solubility of Hiss

E. tidine-tagged (GSHHHHHH) as a fusion protein. was expressed in coli.

Carboxylic acid methylamide and 5-hydroxy-2-phenyl-benzofuran-3-carboxylic acid

Claims (1)

R3 is hydrogen, a substituted or unsubstituted alkyl radical, a substituted or unsubstituted alkoxy group, alkenyl, halogen, hydroxy, polyfluoroalkyl, pol
Lifluoroalkoxy, formyl, carboxyl, alkylcarbonyl, alkoxycarbonyl, hydroxyalkylcarbonyl, amino, substituted or unsubstituted
monoalkylamino, dialkylamino, cyano, amido, alkoxyamido, substituted or unsubstituted heteroarylamino, acetylsulfonylamino;
Ureido, carboxamide, sulfonamide, substituted sulfonamide, substituted or unsubstituted heterocyclosulfonyl, alkylthio, alkylsulfonyl
nyl, alkylsulfonyl, alkylsulfonic acid, substituted or unsubstituted heterocyclic radicals and -O(CH2
A radical selected from the group consisting of )-C(=O)-R7 is
as;

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