Arenavirus growth inhibitor comprising polycyclic carbamoylpyridone derivative

Patent metadata

Field	Value
Publication number	US-11492352-B2
Application number	US-201917255566-A
Country	US
Kind code	B2
Filing date	Jun 29, 2019
Priority date	Jun 27, 2018
Publication date	Nov 8, 2022
Grant date	Nov 8, 2022

Abstract

The present invention provides a compound having antiviral activity, especially having arenavirus proliferation inhibitory activity, and/or a medicament comprising the compound. More preferably, the present invention provides a compound having proliferation inhibitory activity on the Old World arenaviruses such as Luna virus, Lassa virus, and lymphocytic choriomeningitis virus and/or the New World arenaviruses such as Junin virus, and/or a medicament comprising the compound.An arenavirus proliferation inhibitor comprising a compound represented by Formula (I) or a prodrug thereof or a pharmaceutically acceptable salt thereof:(wherein R1 is carboxy, or the like; A3 is CR2 or N; R2 is a hydrogen atom, halogen, hydroxy, or the like; R3 is a hydrogen atom, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with Substituent group F, or the like; either A1 or A2 is CR6R6, and the other is NR7, or A1 is CR8R9, and A2 is CR10R11; and R5, R6, R7, R8, R9, R10, and R11 are each independently a hydrogen atom, carboxy, cyano, alkyl optionally substituted with Substituent group F, or the like).

First claim

The invention claimed is:

1. A method for inhibiting arenavirus proliferation in a human or an animal, comprising administering an effective amount of a compound represented by Formula (I) or a prodrug thereof or a pharmaceutically acceptable salt thereof to the human or animal:

wherein:
R 1 is —Z X —C(═O)—O—R X15 , —Z X —C(═O)—N(R X9 )(R X10 ), or —Z X —N(R X14 )—C(═O)—O—R X15 ,
wherein R X9 , R X14 , and R X15 are each independently a hydrogen atom, alkyl optionally substituted with Substituent group E, alkenyl optionally substituted with Substituent group E, or alkynyl optionally substituted with Substituent group E;
R X10 is a hydrogen atom, alkyl optionally substituted with Substituent group E, alkenyl optionally substituted with Substituent group E, alkynyl optionally substituted with Substituent group E, or alkyloxy optionally substituted with Substituent group E;
Z X is a single bond or a linear or branched alkylene;
R X9 and R X10 may be taken together with an adjacent atom to form a heterocycle;
A 3 is CR 2 or N;
R 2 is a hydrogen atom, halogen, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, or alkyloxy optionally substituted with Substituent group F;
R 3 is a hydrogen atom, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, alkyloxy optionally substituted with Substituent group F, alkenyloxy optionally substituted with Substituent group F, alkylcarbonyl optionally substituted with Substituent group F, alkyloxycarbonyl optionally substituted with Substituent group F, a carbocyclic group optionally substituted with Substituent group A, carbocyclealkyl optionally substituted with Substituent group A, carbocycleoxyalkyl optionally substituted with Substituent group A, carbocyclecarbonyl optionally substituted with Substituent group A, carbocycleoxy optionally substituted with Substituent group A, carbocycleoxycarbonyl optionally substituted with Substituent group A, a heterocyclic group optionally substituted with Substituent group A, heterocyclealkyl optionally substituted with Substituent group A, heterocycleoxyalkyl optionally substituted with Substituent group A, heterocyclecarbonyl optionally substituted with Substituent group A, heterocycleoxy optionally substituted with Substituent group A, heterocycleoxycarbonyl optionally substituted with Substituent group A,
—Z Z —N(R Z1 )—SO 2 —R Z2 ,
—Z Z —N(R Z3 )—C(═O)—R Z4 ,
—Z Z —N(R Z5 )—C(═O)—O—R Z6 ,
—Z Z —C(═O)—N(R Z7 )(R Z8 ),
—Z Z —N(R Z9 )(R Z10 ),
—Z Z —SO 2 —R Z11 , or
—Z Z —N(R Z12 )—O—C(═O)—R Z13 ,
wherein R Z1 , R Z3 , R Z4 , R Z5 , R Z6 , R Z7 , R Z8 , R Z9 , Z 10 , Z 12 , and Z 13 are each independently selected from the group consisting of a hydrogen atom, alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, a carbocyclic group optionally substituted with Substituent group A, a heterocyclic group optionally substituted with Substituent group A, carbocyclealkyl optionally substituted with Substituent group A, and heterocyclealkyl optionally substituted with Substituent group A;
R Z2 and R Z11 are each independently selected from the group consisting of alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, a carbocyclic group optionally substituted with Substituent group A, a heterocyclic group optionally substituted with Substituent group A, carbocyclealkyl optionally substituted with Substituent group A, and heterocyclealkyl optionally substituted with Substituent group A;
R Z7 and R Z8 may be taken together with an adjacent atom to form a heterocycle;
Z Z is a single bond or a linear or branched alkylene;
a) either A 1 or A 2 is CR 5 R 6 , and the other is NR 7 ,
or
b) A 1 is CR 8 R 9 , and A 2 is CR 10 R 11 ;
R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are each independently a hydrogen atom, carboxy, cyano, alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, alkylcarbonyl optionally substituted with Substituent group F, alkyloxycarbonyl optionally substituted with Substituent group F, a carbocyclic group optionally substituted with Substituent group B, carbocyclealkyl optionally substituted with Substituent group B, carbocycleoxyalkyl optionally substituted with Substituent group B, carbocyclecarbonyl optionally substituted with Substituent group B, carbocycleoxycarbonyl optionally substituted with Substituent group B, a heterocyclic group optionally substituted with B, heterocyclealkyl optionally substituted with Substituent group B, heterocycleoxyalkyl optionally substituted with Substituent group B, heterocyclecarbonyl optionally substituted with Substituent group B, heterocycleoxycarbonyl optionally substituted with Substituent group B,
—Z V —S—R V1 ,
—Z V —S(═O)—R V2 ,
—Z V —SO 2 —R V3 ,
—C(═O)—C(═O)—R V4 ,
—C(═O)—N(R V5 )(R V6 ),
—Z V —N(R V7 )—C(═O)—O—R V8 , or
—Z V —N(R V9 )—C(═O)—R V10 ,
wherein R V1 , R V4 , R V5 , R V6 , R V7 , R V8 , R V9 , and R V10 are each independently selected from the group consisting of a hydrogen atom, alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, a carbocyclic group optionally substituted with Substituent group A, a heterocyclic group optionally substituted with Substituent group A, carbocyclealkyl optionally substituted with Substituent group A, and heterocyclealkyl optionally substituted with Substituent group A;
R V2 and R V3 are each independently selected from the group consisting of alkyl optionally substituted with Substituent group F, alkenyl optionally substituted with Substituent group F, alkynyl optionally substituted with Substituent group F, a carbocyclic group optionally substituted with Substituent group A, a heterocyclic group optionally substituted with Substituent group A, carbocyclealkyl optionally substituted with Substituent group A, and heterocyclealkyl optionally substituted with Substituent group A;
R V5 and R V6 may be taken together with an adjacent atom to form a heterocycle;
Z V is a single bond or a linear or branched alkylene;
R 5 and R 6 may be taken together with an adjacent atom to form a carbocycle optionally substituted with Substituent group B or a heterocycle optionally substituted with Substituent group B, wherein the carbocycle or the heterocycle may form a condensed ring and/or a bridged structure;
R 8 and R 9 may be taken together with an adjacent atom to form a carbocycle optionally substituted with Substituent group B or a heterocycle optionally substituted with Substituent group B, wherein the carbocycle or the heterocycle may form a condensed ring and/or a bridged structure;
R 10 and R 11 may be taken together with an adjacent atom to form a carbocycle optionally substituted with Substituent group B or a heterocycle optionally substituted with Substituent group B, wherein the carbocycle or the heterocycle may form a c

Assignees

• Univ Hokkaido Nat Univ Corp
• Shionogi & Co

Inventors

• Ishii Akihiro
• Sato Akihiko
• Kawai Makoto
• Taoda Yoshiyuki

Classifications

• C07D498/14 Primary

  Ortho-condensed systems · CPC title

• C07D471/14

  Ortho-condensed systems · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61P31/14

  for RNA viruses · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title