Nitrogen-containing tricyclic derivatives having HIV replication inhibitory activity

Patent metadata

Field	Value
Publication number	US-10494380-B2
Application number	US-201615577795-A
Country	US
Kind code	B2
Filing date	May 27, 2016
Priority date	May 29, 2015
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

The present invention provides a novel compound having antiviral activity, especially HIV replication inhibitory activity and a medicament containing the same. The compound represented by the formula:

wherein A 3 is CR 3A , CR 3A R 3B , N or NR 3C ; R 3A , R 3B , R 4A and R 4B are each independently a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted non-aromatic carbocyclyl; R 3C is a hydrogen atom, substituted or unsubstituted alkyl, or substituted or unsubstituted non-aromatic carbocyclyl; ring T 1 is substituted or unsubstituted nitrogen-containing non-aromatic heterocycle; R 1 is a hydrogen atom, halogen, cyano, or substituted or unsubstituted alkyl; R 2 is each independently substituted or unsubstituted alkyl or the like: n is 1 or 2; R 3 is substituted or unsubstituted aromatic carbocyclyl or the like; R 4 is a hydrogen atom or a carboxy protecting group.

First claim

The invention claimed is:

1. A compound of formula (I′)

or a pharmaceutically acceptable salt thereof,
wherein
A 3 is CR 3A , or N;
R 3A is hydrogen or halogen;
R 4A is halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted non-aromatic carbocyclyl, where a substituent or substituents of R 4A are same or different 1 to 4 substituents selected from alkyloxy, hydroxy, halogen, haloalkyl, haloalkyloxy, amino, alkylamino, and aromatic carbocyclylalkyloxy;
a ring T 1 is substituted or unsubstituted nitrogen-containing non-aromatic heterocycle, where a substituent or substituents of T 1 ring are each independently oxo, hydroxy, halogen, amino, alkylamino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —COR a1 , —SOR a2 , —SO 2 R a3 , or —NR a4 R a5 or same or different 1 to 4 substituents selected from R a , R b , and R c , where a substituent or substituents of the substituent or substituents on the T 1 ring are same or different 1 to 4 substituents selected from alkyl, alkenyl, alkynyl, alkyloxy, hydroxy, alkyloxy alkyl, hydroxyalkyl, halogen, haloalkyl, haloalkyloxy, amino, alkylamino, dialkylamino, trialkylsilyl, non-aromatic carbocycle amino, substituted or unsubstituted phenyl where a substituent or substituents are selected from alkyl, alkyloxy, hydroxy, and halogen, substituted or unsubstituted phenyloxy where a substituent or substituents are selected from alkyl, alkyloxy, hydroxy, and halogen, substituted or unsubstituted benzyloxy where a substituent or substituents are selected from alkyl, alkyloxy, hydroxy, and halogen, substituted or unsubstituted aromatic heterocyclyl where a substituent or substituents are selected from alkyl, alkyloxy, hydroxy, and halogen, substituted or unsubstituted non-aromatic heterocyclyl where a substituent or substituents are selected from alkyl, alkyloxy, hydroxy, and halogen, and non-aromatic heterocycle amino;
R a is each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclylalkyl, substituted or unsubstituted non-aromatic carbocyclylalkyl, substituted or unsubstituted aromatic heterocyclylalkyl, substituted or unsubstituted non-aromatic heterocyclylalkyl, —COR a1 , —SOR a2 , —SO 2 R a3 , —CONR a4 R a5 , —CSNR a4 R a5 , —COCONR a4 R a5 , or —C(NR a6 )NR a4 R a5 , where a substituent or substituents of R a are same or different 1 to 4 substituents selected from alkyl, alkenyl, alkynyl, alkyloxy, hydroxy, alkyloxyalkyl, hydroxyalkyl, halogen, haloalkyl, haloalkyloxy, amino, alkylamino, dialkylamino, aminoalkyl, alkyloxyalkyl, alkylsulfonyl aminoalkyl, alkylcarbonylamino, alkylcarbonyl aminoalkyl, alkyloxyalkyloxycarbonylamino, alkylaminoalkyl, dialkyl aminoalkyl, amino alkyloxy, alkylamino alkyloxy, dialkylaminoalkyloxy, dialkylaminoalkyloxyalkyl, alkylcarbonylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, benzyl, halogenated benzyl, aromatic carbocyclyl which is optionally substituted with halogen, alkyl, alkyloxy, cycloalkyl and/or haloalkyl, non-aromatic carbocyclyl which is optionally substituted with halogen, alkyl, alkyloxy, oxo and/or haloalkyl, aromatic heterocyclyl which is optionally substituted with halogen, alkyl, alkenyl, hydroxyalkyl, alkyloxy, cycloalkyl, non-aromatic carbocyclyl, non-aromatic heterocyclyl, and/or haloalkyl, non-aromatic heterocyclyl which is optionally substituted with halogen, alkyl, alkyloxy, oxo and/or haloalkyl, aromatic carbocyclylalkyl which is optionally substituted with halogen, alkyl, and/or haloalkyl, non-aromatic carbocycle which is optionally substituted with halogen, alkyl, and/or haloalkyl, aromatic heterocyclylalkyl which is optionally substituted with halogen, alkyl, and/or haloalkyl, non-aromatic heterocyclylalkyl which is optionally substituted with halogen, alkyl, and/or haloalkyl, non-aromatic heterocyclyl which is optionally substituted with alkylhalogen, non-aromatic carbocycle amino, non-aromatic heterocyclylalkyl which is optionally substituted with oxo, halogen, and/or alkyl, and trialkylsilyl;
R a1 , R a2 and R a3 are each independently alkyl optionally substituted with one or more groups selected from Substituent Group A, alkenyl, alkyloxy, amino, aromatic carbocyclyl, non-aromatic carbocyclyl optionally substituted with one or more groups selected from Substituent Group B, aromatic heterocyclyl optionally substituted with one or more groups selected from the Substituent Group B, or non-aromatic heterocyclyl;
the Substituent Group A is each independently halogen, amino, hydroxy, carboxy, oxo, monoalkyl amino, dialkyl amino, carbamoyl, monoalkyl carbamoyl, dialkyl carbamoyl, alkyloxy, haloalkyloxy, sulfamoyl, monoalkyl sulfamoyl, dialkyl sulfamoyl, alkyloxyalkyloxy, haloalkyloxyalkyloxy, alkylcarbonyl, alkylsulfonyl, alkylcarbonylamino, alkylcarbonyl(alkyl)amino, alkylsulfonylamino, alkylsulfonyl(alkyl)amino, trialkylsilyl, alkyl and/or halogeno aromatic carbocyclyl, non-aromatic carbocyclyl optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic heterocyclyl, non-aromatic heterocyclyl optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic carbocyclyloxy, non-aromatic carbocyclyloxy optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic heterocyclyloxy, or non-aromatic heterocyclyloxy optionally substituted with oxo, alkyl and/or halogen;
the Substituent Group B is each independently halogen, amino, hydroxy, carboxy, oxo, monoalkyl amino, dialkyl amino, carbamoyl, monoalkyl carbamoyl, dialkyl carbamoyl, alkyl, haloalkyl, alkyloxy, haloalkyloxy, hydroxyalkyl, amino alkyl, monoalkyl amino alkyl, dialkyl amino alkyl, sulfamoyl, monoalkyl sulfamoyl, dialkyl sulfamoyl, alkyl oxy alkyl, alkyl oxy alkyl oxy, haloalkyloxyalkyl, haloalkyloxyalkyloxy, alkylcarbonylamino, alkylcarbonyl(alkyl)amino, alkylsulfonylamino, alkylsulfonyl(alkyl)amino, alkyl and/or halogeno aromatic carbocyclyl, non-aromatic carbocyclyl optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic heterocyclyl, non-aromatic heterocyclyl optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic carbocyclyloxy, non-aromatic carbocyclyloxy optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic heterocyclyloxy, non-aromatic heterocyclyloxy optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic carbocyclylalkyl, non-aromatic carbocyclylalkyl optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic heterocyclylalkyl, non-aromatic heterocyclylalkyl optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic carbocyclylalkyloxy, non-aromatic carbocyclylalkyloxy optionally substituted with oxo, alkyl and/or halogen, alkyl and/or halogeno aromatic heterocyclylalkyloxy, or non-aromatic heterocyclylalkyloxy optionally substituted with oxo, alkyl and/or halogen;
R a4 and R a5 are each independently hydrogen, hydroxy, alkyl optionally substituted with one or more groups selected from the Substituent Group A, alkenyl, alkynyl, alkyloxy, aromatic carbocyclyl optionally substituted with amino or halogen, non-aromatic carbocyclyl optionally substituted with one or more groups selected from the Substituent Group B, aromatic heterocyclyl optionally substituted with one or more groups selected from the Substituent Group B, or non-aromatic heterocyclyl;
R a6 is

Assignees

• Shionogi & Co

Inventors

• Tamura Yoshinori
• Sugiyama Shuichi
• Matsumura Akira
• Akiyama Toshiyuki
• Tomida Yutaka

Classifications

• C07D513/06 Primary

  Peri-condensed systems · CPC title

• C07D487/06 Primary

  Peri-condensed systems · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K31/554

  having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem · CPC title