Substituted polycyclic carbamolypyridone derivative

Patent metadata

Field	Value
Publication number	US-9815835-B2
Application number	US-201615252791-A
Country	US
Kind code	B2
Filing date	Aug 31, 2016
Priority date	Jun 15, 2009
Publication date	Nov 14, 2017
Grant date	Nov 14, 2017

Abstract

This invention provides compounds having antiviral activities especially inhibiting activity for influenza virus, more preferably provides substituted 3-hydroxy-4-pyridone derivatives having cap-dependent endonuclease inhibitory activity.

First claim

The invention claimed is:

1. A compound represented by formula (II), or a pharmaceutically acceptable salt thereof or a solvate thereof:

(wherein
R 1a is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkenyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocycleoxy optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C,
—Z—N(R A1 )(R A2 ),
—Z—N(R A3 )—SO 2 —(R A4 ),
—Z—C(═O)—N(R A5 )—SO 2 —(R A6 ),
—Z—N(R A7 )—C(═O)—R A8 ,
—Z—S—R A9 ,
—Z—SO 2 —R A10 ,
—Z—S(═O)—R A11 ,
—Z—N(R A12 )—C(═O)—O—R A13 ,
—Z—N(R A14 )—C(═O)—N(R A15 )(R A16 ),
—Z—C(═O)—N(R A17 )—C(═O)—N(R A18 )(R A19 ), or
—Z—N(R A20 )—C(═O)—C(═O)—R A21
(wherein R A1 , R A2 , R A3 , R A5 , R A7 , R A8 , R A9 , R A12 , R A13 , R A14 , R A15 , R A16 , R A17 , R A18 , R A19 , R A20 , and R A21 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C,
R A4 , R A6 , R A10 , and R A11 are each independently selected from a substituent group consisting of, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C,
R A1 and R A2 , R A15 and R A16 , and R A18 and R A19 each ma y be taken together with an adjacent atom to form heterocycle, and
Z is a bond or straight or branched lower alkylene);
R 2a is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyloxy optionally substituted by substituent group C, lower alkenyloxy optionally substituted by substituent group C, lower alkylcarbonyl optionally substituted by substituent group C, lower alkyloxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocyclecarbonyl optionally substituted by substituent group C, carbocycleoxy optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocyclecarbonyl optionally substituted by substituent group C, heterocycleoxy optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C,
—Z—N(R B1 )—SO 2 —R B2 ,
—Z—N(R B3 )—C(═O)—R B4 ,
—Z—N(R B5 )—C(═O)—O—R B6 ,
—Z—C(═O)—N(R B7 )(R B8 ),
—Z—N(R B9 )(R B10 ), or
—Z—SO 2 —R B11
(wherein R B1 , R B3 , R B4 , R B5 , R B6 , R B7 , R B8 , R B9 , and R B10 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C,
R B2 and R B11 are each independently selected from a substituent group consisting of lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, and heterocycle lower alkyl optionally substituted by substituent group C,
R B7 and R B8 , and R B9 and R B10 each may be taken together with an adjacent atom to form heterocycle, and
Z is a bond or straight or branched lower alkylene);
B 1 is NR 7a and B 2 is CR 5a R 6a ,
R 3a and R 6a are taken together with an adjacent atom to form heterocycle optionally substituted by substituent group D,
R 5a and R 7a are each independently selected from a substituent group consisting of hydrogen, carboxy, cyano, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, lower alkyl carbonyl optionally substituted by substituent group C, lower alkyl oxycarbonyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, carbocycle lower alkyl optionally substituted by substituent group C, carbocycleoxy lower alkyl optionally substituted by substituent group C, carbocyclecarbonyl optionally substituted by substituent group C, carbocycleoxycarbonyl optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, heterocycle lower alkyl optionally substituted by substituent group C, heterocycleoxy lower alkyl optionally substituted by substituent group C, heterocyclecarbonyl optionally substituted by substituent group C, heterocycleoxycarbonyl optionally substituted by substituent group C,
—Y—S—R D1 ,
—Z—S(═O)—R D2 ,
—Z—SO 2 —R D3 ,
—C(═O)—C(═O)—R D4 ,
—C(═O)—N(R D5 )(R D6 ),
—Z—C(R D7 )(R D8 )(R D9 ),
—Z—CH 2 —R D10 ,
—Z—N(R D11 )—C(═O)—O—R D12 , or
—Z—N(R D13 )—C(═O)—R D14
(wherein R D1 , R D4 , R D5 , R D6 , R D9 , R D11 , R D12 , R D13 , and R D14 are each independently selected from a substituent group consisting of hydrogen, lower alkyl optionally substituted by substituent group C, lower alkenyl optionally substituted by substituent group C, lower alkynyl optionally substituted by substituent group C, carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted

Assignees

• Shionogi & Co

Inventors

• Akiyama Toshiyuki
• Takaya Kenji
• Kawai Makoto
• Taoda Yoshiyuki
• Mikamiyama Minako
• Morimoto Kenji
• Tomita Kenji
• Mikamiyama Hidenori
• Suzuki Naoyuki

Classifications

• C07D471/14

  Ortho-condensed systems · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D487/20

  Spiro-condensed systems · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title