Substituted nucleosides, nucleotides and analogs thereof

Patent metadata

Field	Value
Publication number	US-9862743-B2
Application number	US-201414510451-A
Country	US
Kind code	B2
Filing date	Oct 9, 2014
Priority date	Oct 11, 2013
Publication date	Jan 9, 2018
Grant date	Jan 9, 2018

Abstract

Disclosed herein are nucleosides, nucleotides and nucleotide analogs, methods of synthesizing the same and methods of treating diseases and/or conditions such as a Picornavirus and/or Flaviviridae infection with one or more nucleosides, nucleotides and nucleotide analogs.

First claim

What is claimed is:

1. A method for ameliorating or treating a Picornaviridae viral infection comprising contacting a cell infected with the Picornaviridae virus with an effective amount of a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) has the structure:

wherein:
B 1A is an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group.

2. The method of claim 1 , wherein B 1A is selected from the group consisting of:

wherein:
R A2 is selected from the group consisting of hydrogen, halogen and NHR J2 , wherein R J2 is selected from the group consisting of hydrogen, —C(═O)R K2 and —C(═O)OR L2 ;
R B2 is halogen or NHR W2 , wherein R W2 is selected from the group consisting of hydrogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl, an optionally substituted C 3-8 cycloalkyl, —C(═O)R M2 and —C(═O)OR N2 ;
R C2 is hydrogen or NHR O2 , wherein R O2 is selected from the group consisting of hydrogen, —C(═O)R P2 and —C(═O)OR Q2 ;
R D2 is selected from the group consisting of hydrogen, deuterium, halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl and an optionally substituted C 2-6 alkynyl;
R E2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted C 1-6 alkyl, an optionally substituted C 3-8 cycloalkyl, —C(═O)R R2 and —C(═O)OR S2 ;
R F2 is selected from the group consisting of hydrogen, halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl and an optionally substituted C 2-6 alkynyl;
Y 2 and Y 3 are independently N or CR 2 , wherein R 2 is selected from the group consisting of hydrogen, halogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 2-6 alkenyl and an optionally substituted C 2-6 alkynyl;
W 1 is NH, —NCH 2 —OC(═O)CH(NH 2 )—CH(CH 3 ) 2 or —(CH 2 ) 1-2 —O—P(═O)(OW 1A ) 2 , wherein W 1A is selected from the group consisting of absent, hydrogen and an optionally substituted C 1-6 alkyl;
R G2 is an optionally substituted C 1-6 alkyl;
R H2 is hydrogen or NHR T2 , wherein R T2 is independently selected from the group consisting of hydrogen, —C(═O)R U2 and —C(═O)OR V2 ; and
R K2 , R L2 , R M2 , R N2 , R P2 , R Q2 R R2 , R S2 , R U2 and R V2 are independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 3-6 cycloalkenyl, C 6-10 aryl, heteroaryl, heterocyclyl, aryl(C 1-6 alkyl), heteroaryl(C 1-6 alkyl) and heterocyclyl(C 1-6 alkyl).

3. The method of claim 2 , wherein B 1A is

4. The method of claim 2 , wherein B 1A is

5. The method of claim 2 , wherein B 1A is

6. The method of claim 2 , wherein B 1A is

Assignees

• Alios Biopharma Inc

Inventors

• Beigelman Leonid
• Wang Guangyi
• Smith David Bernard
• Prhavc Marija
• Jekle Christian Andreas
• Deval Jerome

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C07H19/10

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title

• A61K31/7072

  having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine · CPC title

• C07H19/11

  containing cyclic phosphate · CPC title