US 10,538,532 B2Granted

Hepatitis B antiviral agents

AssigneeEnanta Pharmaceuticals, Inc.

InventorsYao-Ling Qiu, Xuri Gao, Wei Li, Hui Cao, Meizhong Jin, Jorden Kass, Xiaowen Peng, Yat Sun Or

Life of this patent

Estimating the term…

Loading patent…

Abstract

The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: X-A-Y-L-R (I) which inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV life cycle of the hepatitis B virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HBV infection. The invention also relates to methods of treating an HBV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Claims15

Dependent claims

A method of treating an HBV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound represented by Formula (IIIa):

or a pharmaceutically acceptable salt thereof, wherein:
each m is independently 0, 1, 2, 3 or 4;
R14 at each occurrence is independently selected from the group consisting of hydroxy, protected hydroxy, halogen, —CN, —NO2, optionally substituted amino, N3, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted —C1-C6 alkoxy, —C(O)2—C1-C6 alkyl, —C(O)NH—C1-C6 alkyl, and —C(O)—C1-C6 alkyl;
and
R is
wherein n at each occurrence is independently selected from 0, 1, 2, or 3;
v at each occurrence is independently selected from 1 and 2;
T at each occurrence is independently selected from C(R10) and N;
E at each occurrence is independently selected from —C(R10)2—, —N(R10)—, O, S, S(O), and S(O)2;
R10 at each occurrence is independently selected from the group consisting of hydrogen, halo, —CN, —NO2, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, optionally substituted heteroaryl, and -L1-R1;
wherein L1 is —O—, —S—, —NR1—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R1)—, —N(R1)C(O)—, —OC(O)N(R1)—, —N(R1)C(O)O—, —N(R1)C(O)N(R1)—, —S(O)—, —S(O)2—, —S(O)2N(R1)—, —N(R1)S(O)2—;
R1 at each occurrence is independently selected from the group consisting of hydrogen, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl;
alternatively, two adjacent R10 groups are taken together with the carbon or nitrogen atoms to which they are attached to form an olefinic or iminic double-bond or a fused ring;
two geminal R10 groups together form an oxo, an optionally substituted olefin, an optionally substituted oxime, or a spiro ring;
and/or two remote R10 groups are taken together with the atoms to which they are attached to form a bridging moiety.

12 more elements

A method of treating an HBV infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound represented by Formula (VIIIa), (VIIIb), (VIIIc), or (VIIId), or a pharmaceutically acceptable salt thereof:

wherein R11 at each occurrence is independently selected from a group consisting of hydrogen, halogen, hydroxy, protected hydroxy, —CN, amino, protected amino, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted —C1-C6 alkoxy, optionally substituted —NH—C1-C6 alkyl, optionally substituted —N(C1-C6 alkyl)2, —CO2H, optionally substituted —C(O)2—C1-C6 alkyl, optionally substituted —C(O)NH—C1-C6 alkyl, and optionally substituted —C(O)—C1-C6 alkyl;
each m is independently 0, 1, 2, 3 or 4;
R14 at each occurrence is independently selected from the group consisting of hydroxy, protected hydroxy, halogen, —CN, —NO2, optionally substituted amino, N3, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted —C1-C6 alkoxy, —C(O)2—C1-C6 alkyl, —C(O)NH—C1-C6 alkyl, and —C(O)—C1-C6 alkyland;
n at each occurrence is independently selected from 0, 1, 2, and 3;
v at each occurrence is independently selected from 1 and 2;
T at each occurrence is independently selected from C(R10) and N;
E at each occurrence is independently selected from —C(R10)2—, —N(R10)—, O, S, S(O), and S(O)2;
and R10 at each occurrence is independently selected from the group consisting of hydrogen, halo, —CN, —NO2, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, optionally substituted heteroaryl, and -L1-R1;
wherein L1 is —O—, —S—, —NR1—, —C(O)—, —C(O)O—, —OC(O)—, —C(O)N(R1)—, —N(R1)C(O)—, —OC(O)N(R1)—, —N(R1)C(O)O—, —N(R1)C(O)N(R1)—, —S(O)—, —S(O)2—,—S(O)2N(R1)—, —N(R1)S(O)2—;
R1 at each occurrence is independently selected from the group consisting of hydrogen, optionally substituted —C1-C6 alkyl, optionally substituted —C2-C8 alkenyl, optionally substituted —C2-C8 alkynyl, optionally substituted —C3-C8 cycloalkyl, optionally substituted 3- to 8-membered heterocyclic, optionally substituted aryl, and optionally substituted heteroaryl;
alternatively, two adjacent R10 groups are taken together with the carbon or nitrogen atoms to which they are attached to form an olefinic or iminic double-bond or a fused ring;
two geminal R10 groups together form an oxo, an optionally substituted olefin, an optionally substituted oxime, or a spiro ring;
and/or two remote R10 groups are taken together with the atoms to which they are attached to form a bridging moiety.

10 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/194,608Filed 19 Nov 2018 · division
Priority: 7 Mar 2016
Published: US 2019/0084994 A121 Mar 2019
Granted: 21 Jan 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification80 codes

C07D 493/08
In which the condensed system contains two hetero rings: bridged systems
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…
A61K 31/18
Amides, e.g. hydroxamic acids: sulfonamides
A61K 31/196
Having an amino group: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil

Family

Application62/304,671Us provisional application · filed 7 Mar 2016
Application62/337,675Us provisional application · filed 17 May 2016
Application15/450,125Parent of this division · filed 6 Mar 2017
US 2019/0084994 A1Pre-grant publication · published 21 Mar 2019
US 10,179,792 B2Parent of this division
US 2017/0253609 A1Published application
US 10,538,532 B2This patent

From the US filing history. Foreign family members aren’t listed.