Phenoxymethyl derivatives

Patent metadata

Field	Value
Publication number	US-11352330-B2
Application number	US-202016811656-A
Country	US
Kind code	B2
Filing date	Mar 6, 2020
Priority date	Sep 4, 2015
Publication date	Jun 7, 2022
Grant date	Jun 7, 2022

Abstract

The invention provides novel compounds having the general formula (I)wherein RA, RB, RC, RC1 and W are as defined herein, compositions including the compounds and methods of using the compounds.

First claim

The invention claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
(1) R A is selected from the group consisting of
i) C 1 -C 6 -alkyl,
ii) cyano-C 1 -C 6 -alkyl,
iii) C 3 -C 8 -cycloalkyl,
iv) halo-C 1 -C 6 -alkoxy,
v) halo-C 1 -C 6 -alkyl,
vi) aryl substituted with R G , R G1 and R G2 ,
vii) heterocycloalkyl substituted with R G , R G1 and R G2 , and
viii) heteroaryl substituted with R G , R G1 and R G2 ; and

R B is selected from the group consisting of
i) C 1 -C 6 -alkyl,
ii) C 3 -C 8 -cycloalkyl,
iii) C 1 -C 6 -alkylsulfonyl,
iv) C 3 -C 8 -cycloalkylsulfonyl,
v) C 1 -C 6 -alkylsulfonylamino,
vi) C 3 -C 8 -cycloalkylsulfonylamino,
vii) aminocarbonyl,
ix) halogen,
x) halo-C 1 -C 6 -alkoxy,
xi) halo-C 1 -C 6 -alkyl,
xii) heterocycloalkyl, and
xiii) heteroaryl substituted with one H, C 1 -C 6 -alkyl, or trialkylsilyl-C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl;

or
(2) R A is selected from the group consisting of
i) cyano-C 1 -C 6 -alkyl,
ii) C 3 -C 8 -cycloalkyl,
iii) halo-C 1 -C 6 -alkoxy,
iv) halo-C 1 -C 6 -alkyl,
v) aryl substituted with R G , R G1 and R G2 ,
vi) heterocycloalkyl substituted with R G , R G1 and R G2 , and
vii) heteroaryl substituted with R G , R G1 and R G2 ; and

R B is cyano;

and:
R C and R C1 are independently selected from the group consisting of
i) H,
ii) C 1 -C 6 -alkyl,
iii) C 3 -C 8 -cycloalkyl,
iv) halo-C 1 -C 6 -alkoxy,
v) halo-C 1 -C 6 -alkyl, and
vi) halogen;

or R B and R C together with the carbon atoms to which they are attached form a ring system selected from the group consisting of
i) C 3 -C 8 -cycloalkyl substituted with one to two substituent independently selected from H, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkyl and C 3 -C 8 -cycloalkyl,
ii) heterocycloalkyl substituted with one to two substituent independently selected from H, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkyl and C 3 -C 8 -cycloalkyl,
iii) aryl substituted with one to two substituent independently selected from H, halogen, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkyl and C 3 -C 8 -cycloalkyl, and
iv) heteroaryl substituted with one to two substituent independently selected from H, halogen, C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkoxy, halo-C 1 -C 6 -alkyl, and C 3 -C 8 -cycloalkyl;

W is ring system A:

R D1 is selected from the group consisting of
i) H,
ii) C 1 -C 6 -alkyl,
iii) halo-C 1 -C 6 -alkoxy,
iv) halo-C 1 -C 6 -alkyl, and
v) C 3 -C 8 -cycloalkyl,

R G is selected from the group consisting of
i) H,
ii) C 1 -C 6 -alkoxy,
iii) C 1 -C 6 -alkoxy-C 1 -C 6 -alkylcarbonylamino-C 1 -C 6 -alkyl,
iv) C 1 -C 6 -alkoxy-C 1 -C 6 -alkylcarbonyl(C 1 -C 6 -alkyl)amino-C 1 -C 6 -alkyl,
v) C 1 -C 6 -alkoxycarbonyl,
vi) C 1 -C 6 -alkyl,
vii) C 1 -C 6 -alkylsulfonyl,
viii) C 3 -C 8 -cyloalkylsulfonyl,
ix) carboxy,
x) cyano,
xi) C 3 -C 8 -cycloalkyl,
xii) C 3 -C 8 -cycloalkoxy,
xiii) C 3 -C 8 -cycloalkylcarbonylamino-C 1 -C 6 -alkyl,
xiv) C 3 -C 8 -cycloalkylcarbonyl(C 1 -C 6 -alkyl)amino-C 1 -C 6 -alkyl,
xv) C 1 -C 6 -alkylcarbonylamino-C 1 -C 6 -alkyl,
xvi) C 1 -C 6 -alkylcarbonyl(C 1 -C 6 -alkyl)amino-C 1 -C 6 -alkyl,
xvii) halo-C 1 -C 6 -alkyl,
xviii) halo-C 1 -C 6 -alkoxy,
xix) halogen,
xx) hydroxy,
xxi) aminocarbonyl substituted on the nitrogen atom with RN and Ro,
xxii) aminocarbonyl-C 1 -C 6 -alkoxy substituted on the nitrogen atom with RN and Ro,
xxiii) heteroaryl substituted with one H, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, alkyl, halo-C 1 -C 6 -alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, halo-C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkoxy,
xxiv) heterocycloalkyl-C 1 -C 6 -alkoxy substituted with one H, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, halo-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, halo-C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkoxy, and
xxv) heterocycloalkyl-C 1 -C 6 -alkyl substituted with one H, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, halo-C 1 -C 6 -alkyl, halo-C 1 -C 6 -alkoxy, benzyl or aryl, wherein benzyl and aryl are substituted with one to three substituents independently selected from H, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, halo-C 1 -C 6 -alkyl and halo-C 1 -C 6 -alkoxy;

R G1 and R G2 are independently selected from the group consisting of
i) H,
ii) halogen,
iii) C 1 -C 6 -alkyl,
iv) C 3 -C 8 -cycloalkyl,
v) halo-C 1 -C 6 -alkoxy, and
vi) halo-C 1 -C 6 -alkyl;

R N is selected from the group consisting of
i) H,
ii) C 1 -C 6 -alkoxy,
iii) C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl,
iv) C 1 -C 6 -alkoxycarbonyl-C 1 -C 6 -alkyl,
v) C 1 -C 6 -alkyl,
vi) carboxy-C 1 -C 6 -alkyl,
vii) C 3 -C 8 -cycloalkyl,
viii) C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl,
ix) hydroxy-C 1 -C 6 -alkyl,
x) phenyl, and
xi) heteroaryl-C 1 -C 6 -alkyl; and

R O is selected from the group consisting of
i) H, and
ii) C 1 -C 6 -alkyl;

or R N and R O together with the nitrogen atom to which they are attached form a heterocycloalkyl.

2. The compound of claim 1 , wherein the compound is:
3-[(2-tert-butyl-4-chloro-5-methylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(2-tert-butyl-4-chloro-5-fluorophenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(3,3-dimethyl-6-propan-2-yl-1,2-dihydroinden-5-yl)oxymethyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[[2-tert-butyl-4-(3-methyl-1,2,4-oxadiazol-5-yl)phenoxy]methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(2-tert-butyl-4-[1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]phenoxy]methyl-4-methyl-1H-1,2,4-triazol-5-one;
3-[[2-tert-butyl-4-(1-methylimidazol-2-yl)phenoxy]methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[[2-tert-butyl-4-(1,3-oxazol-2-yl)phenoxy]methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(2-tert-butyl-4-morpholin-4-ylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[[2-tert-butyl-4-(3-methylimidazol-4-yl)phenoxy]methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[[2-tert-butyl-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenoxy]methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(4-chloro-2-cyclopropyl-5-methylsulfonylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(2-tert-butyl-4-methylsulfonylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[[2-tert-butyl-4-[3-(2-trimethyl silyl-ethoxymethyl)imidazol-4-yl]phenoxy]-methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(4-chloro-2-cyclopropyl-5-methylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(4-chloro-2-cyclohexyl-5-methylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[[4-chloro-5-methyl-2-(oxan-4-yl)phenoxy]methyl]-4-methyl-1H-1,2,4-triazol-5-one;
2-chloro-4-cyclopropyl-5-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzonitrile;
N-[2-chloro-4-cyclopropyl-5-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]phenyl]methanesulfonamide;
4-tert-butyl-3-[(4-methyl-5-oxo-1H-1,2,4-triazol-3-yl)methoxy]benzamide;
4-methyl-3-[(5-methyl-2-propan-2-ylphenoxy)methyl]-1H-1,2,4-triazol-5-one;
3-[(4-chloro-5-methyl-2-propan-2-ylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(4-chloro-2-propan-2-ylphenoxy)methyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(6-cyclopropyl-2-methyl-1,3-benzothiazol-5-yl)oxymethyl]-4-methyl-1H-1,2,4-triazol-5-one;
3-[(4-chloro-2-cyclobutyl-5-methylphenoxy

Assignees

• Hoffmann La Roche

Inventors

• Hert Jerome
• Hunziker Daniel
• Kuehne Holger
• Luebbers Thomas
• Martin Rainer E
• Mattei Patrizio
• Neidhart Werner
• Richter Hans
• Rudolph Markus
• Pinard Emmanuel

Classifications

• C07D407/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D403/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D231/20

  One oxygen atom attached in position 3 or 5 · CPC title

• A61K31/4196

  1,2,4-Triazoles · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title