Substituted triazolo quinoxaline derivatives

Patent metadata

Field	Value
Publication number	US-12110293-B2
Application number	US-202117152930-A
Country	US
Kind code	B2
Filing date	Jan 20, 2021
Priority date	Jul 20, 2018
Publication date	Oct 8, 2024
Grant date	Oct 8, 2024

Abstract

The present invention relates to compounds according to general formula (I)which act as modulators of the glucocorticoid receptor and can be used in the treatment and/or prophylaxis of disorders which are at least partially mediated by the glucocorticoid receptor.

First claim

The invention claimed is:

1. A compound according to general formula (I),

wherein
R 1 represents H; C 1-10 -alkyl; C 3-10 -cycloalkyl; 3 to 7 membered heterocycloalkyl; aryl; or 5 or 6-membered heteroaryl;
wherein C 3-10 -cycloalkyl, 3 to 7 membered heterocycloalkyl, aryl and 5 or 6-membered heteroaryl can optionally be bridged via C 1-6 -alkylene;

R 2 represents H; F; Cl; Br; I; CN; C 1-10 -alkyl; C 3-10 -cycloalkyl; O—C 1-10 -alkyl; N(H)(C 1-10 -alkyl), N(C 1-10 -alkyl) 2 ; C(O)—C 1-10 -alkyl; C(O)—O—C 1-10 -alkyl; C(O)—NH 2 ; C(O)—N(H)(C 1-10 -alkyl); C(O)—N(C 1-10 -alkyl) 2 ; O—C 3-10 -cycloalkyl; N(H)(C 3-10 -cycloalkyl), N(C 1-10 -alkyl)(C 3-10 -cycloalkyl); C(O)—C 3-10 -cycloalkyl; C(O)—O—C 3-10 -cycloalkyl; C(O)—N(H)(C 3-10 -cycloalkyl) or C(O)—N(C 1-10 -alkyl)(C 3-10 -cycloalkyl);
wherein C 3-10 -cycloalkyl can optionally be bridged via C 1-6 -alkylene;

R 3 represents H; F; Cl; Br; I; CN; C 1-10 -alkyl; C 3-10 -cycloalkyl; O—C 1-10 -alkyl; N(H)(C 1-10 -alkyl); N(C 1-10 -alkyl) 2 ; C(O)—C 1-10 -alkyl; C(O)—O—C 1-10 -alkyl; C(O)—NH 2 ; C(O)—N(H)(C 1-10 -alkyl); C(O)—N(C 1-10 -alkyl) 2 ; O—C 3-10 -cycloalkyl; N(H)(C 3-10 -cycloalkyl), N(C 1-10 -alkyl)(C 3-10 -cycloalkyl); C(O)—C 3-10 -cycloalkyl; C(O)—O—C 3-10 -cycloalkyl; C(O)—N(H)(C 3-10 -cycloalkyl) or C(O)—N(C 1-10 -alkyl)(C 3-10 -cycloalkyl);
wherein C 3-10 -cycloalkyl can optionally be bridged via C 1-6 -alkylene;

R 5 and R 6 represent independently from one another H or unsubstituted C 1-4 -alkyl;
X represents N or NR 7 ;
Z represents N, NR 7 or CR 9 ;
with the proviso that
when X represents NR 7 , Z represents N or CR 9 ;
when X represents N, Z represents NR 7 ;

R 7 represents H or L-R 8 ; wherein
L represents bond; S(O); S(O) 2 ; C 1-6 -alkylene; C(O); C 1-6 -alkylene-C(O); C(O)—O; C 1-6 -alkylene-C(O)—O; C 1-6 -alkylene-N(H)—C(O); C 1-6 -alkylene-N(C 1-10 -alkyl)-C(O); C 1-6 -alkylene-N(H)—C(O)—O; C 1-6 -alkylene-N(C 1-10 -alkyl)-C(O)—O; O; NH or N(C 1-10 -alkyl);
R 8 represents C 1-10 -alkyl; C 3-10 -cycloalkyl or 3 to 7 membered heterocycloalkyl;
wherein C 3-10 -cycloalkyl and 3 to 7 membered heterocycloalkyl can optionally be bridged via C 1-6 -alkylene;

R 9 and R 10 represent independently from one another H; F; Cl; Br; I; CN; C 1-10 -alkyl; C 3-10 -cycloalkyl; 3 to 7 membered heterocycloalkyl; S(O)-(C 1-10 -alkyl); S(O)-(C 3-10 -cycloalkyl); S(O)-(3 to 7-membered heterocycloalkyl); S(O) 2 —(C 1-10 -alkyl); S(O) 2 —(C 3-10 -cycloalkyl); S(O) 2 -(3 to 7-membered heterocycloalkyl); P(O)-(C 1-10 -alkyl) 2 ; P(O)(C 1-10 -alkyl)(C 3-10 -cycloalkyl); P(O)(C 1-10 -alkyl)(3 to 7-membered heterocycloalkyl); P(O)—(O—C 1-10 -alkyl) 2 ; P(O)(O—C 1-10 -alkyl)(O—C 3-10 -cycloalkyl); P(O)(O—C 1-10 -alkyl)(O-(3 to 7-membered heterocycloalkyl)); O—C 1-10 -alkyl; S—C 1-10 -alkyl; N(H)(C 1-10 -alkyl), N(C 1-10 -alkyl) 2 ; C(O)—C 1-10 -alkyl; C(O)—O—C 1-10 -alkyl; C(O)—NH 2 ; C(O)—N(H)(C 1-10 -alkyl); C(O)—N(C 1-10 -alkyl) 2 ; O—C 3-10 -cycloalkyl; N(H)(C 3-10 -cycloalkyl), N(C 1-10 -alkyl)(C 3-10 -cycloalkyl); C(O)—C 3-10 -cycloalkyl;
C(O)—O—C 3-10 -cycloalkyl; C(O)—N(H)(C 3-10 -cycloalkyl); C(O)—N(C 1-10 -alkyl)(C 3-10 -cycloalkyl); O-3 to 7-membered heterocycloalkyl; N(H)(3 to 7-membered heterocycloalkyl), N(C 1-10 -alkyl)(3 to 7-membered heterocycloalkyl); C(O)-3 to 7-membered heterocycloalkyl; C(O)—O-(3 to 7-membered heterocycloalkyl); C(O)—N(H)(3 to 7-membered heterocycloalkyl) or C(O)—N(C 1-10 -alkyl)(3 to 7-membered heterocycloalkyl);
wherein C 3-10 -cycloalkyl and 3 to 7 membered heterocycloalkyl can optionally be bridged via C 1-6 -alkylene;

R 11 represents F; Cl; Br; I; CN; C 1-10 -alkyl; O—C 1-10 -alkyl; NO 2 ; OH, NH 2 ; C 3-10 -cycloalkyl; 3 to 7-membered heterocycloalkyl; S(O)-(C 1-10 -alkyl); S(O)-(C 3-10 -cycloalkyl); S(O)-(3 to 7-membered heterocycloalkyl); S(O) 2 —(C 1-10 -alkyl); S(O) 2 —(C 3-10 -cycloalkyl); S(O) 2 -(3 to 7-membered heterocycloalkyl); P(O)-(C 1-10 -alkyl) 2 ; P(O)(C 1-10 -alkyl)(C 3-10 -cycloalkyl); P(O)(C 1-10 -alkyl)(3 to 7-membered heterocycloalkyl); P(O)—(O—C 1-10 -alkyl) 2 ; P(O)(O—C 1-10 -alkyl)(O—C 3-10 -cycloalkyl); P(O)(O—C 1-10 -alkyl)(O-(3 to 7-membered heterocycloalkyl)); O—C 1-10 -alkyl; N(H)(C 1-10 -alkyl), N(C 1-10 -alkyl) 2 ; C(O)—C 1-10 -alkyl; C(O)—O—C 1-10 -alkyl; C(O)—NH 2 ; C(O)—N(H)(C 1-10 -alkyl); C(O)—N(C 1-10 -alkyl) 2 ; O—C 3-10 -cycloalkyl; N(H)(C 3-10 -cycloalkyl), N(C 1-10 -alkyl)(C 3-10 -cycloalkyl); C(O)—C 3-10 -cycloalkyl; C(O)—O—C 3-10 -cycloalkyl; C(O)—N(H)(C 3-10 -cycloalkyl); C(O)—N(C 1-10 -alkyl)(C 3-10 -cycloalkyl); O-3 to 7-membered heterocycloalkyl; N(H)(3 to 7-membered heterocycloalkyl), N(C 1-10 -alkyl)(3 to 7-membered heterocycloalkyl); C(O)-3 to 7-membered heterocycloalkyl; C(O)—O-(3 to 7-membered heterocycloalkyl); C(O)—N(H)(3 to 7-membered heterocycloalkyl) or C(O)—N(C 1-10 -alkyl)(3 to 7-membered heterocycloalkyl);
wherein C 3-10 -cycloalkyl and 3 to 7 membered heterocycloalkyl can optionally be bridged via C 1-6 -alkylene;

n represents 0, 1, 2 or 3;
wherein C 1-10 -alkyl, C 1-4 -alkyl and C 1-6 -alkylene in each case independently from one another is linear or branched, saturated or unsaturated;
wherein C 1-10 -alkyl, C 1-4 -alkyl, C 1-6 -alkylene, C 3-10 -cycloalkyl and 3 to 7 membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; Br; I; CN; C 1-6 -alkyl; CF 3 ; CF 2 H; CFH 2 ; CF 2 Cl; CFCl 2 ; C(O)—C 1-6 -alkyl; C(O)—OH; C(O)—OC 1-6 -alkyl; C(O)—NH 2 ; C(O)—N(H)(C 1-6 -alkyl); C(O)—N(C 1-6 -alkyl) 2 ; OH; ═O; OCF 3 ; OCF 2 H; OCFH 2 ; OCF 2 Cl; OCFCl 2 ; O—C 1-6 -alkyl; O—C(O)—C 1-6 -alkyl; O—C(O)—O—C 1-6 -alkyl; O—(CO)—N(H)(C 1-6 -alkyl); O—C(O)—N(C 1-6 -alkyl) 2 ; O—S(O) 2 —NH 2 ; O—S(O) 2 —N(H)(C 1-6 -alkyl); O—S(O) 2 —N(C 1-6 -alkyl) 2 ; NH 2 ; N(H)(C 1-6 -alkyl); N(C 1-6 -alkyl) 2 ; N(H)—C(O)—C 1-6 -alkyl; N(H)—C(O)—O—C 1-6 -alkyl; N(H)—C(O)—NH 2 ; N(H)—C(O)—N(H)(C 1-6 -alkyl); N(H)—C(O)—N(C 1-6 -alkyl) 2 ; N(C 1-6 -alkyl)-C(O)—C 1-6 -alkyl; N(C 1-6 -alkyl)-C(O)—O—C 1-6 -alkyl; N(C 1-6 -alkyl)-C(O)—NH 2 ; N(C 1-6 -alkyl)-C(O)—N(H)(C 1-6 -alkyl); N(C 1-6 -alkyl)-C(O)—N(C 1-6 -alkyl) 2 ; N(H)—S(O) 2 OH; N(H)—S(O) 2 —C 1-6 -alkyl; N(H)—S(O) 2 —O—C 1-6 -alkyl; N(H)—S(O) 2 —NH 2 ; N(H)—S(O) 2 —N(H)(C 1-6 -alkyl); N(H)—S(O) 2 N(C 1-6 -alkyl) 2 ; N(C 1-6 -alkyl)-S(O) 2 —OH; N(C 1-6 -alkyl)-S(O) 2 —C 1-6 -alkyl; N(C 1-6 -alkyl)-S(O) 2 —O—C 1-6 -alkyl; N(C 1-6 -alkyl)-S(O) 2 —NH 2 ; N(C 1-6 -alkyl)-S(O) 2 —N(H)(C 1-6 -alkyl); N(C 1-6 -alkyl)-S(O) 2 —N(C 1-6 -alkyl) 2 ; SCF 3 ; SCF 2 H; SCFH 2 ; S—C 1-6 -alkyl; S(O)—C 1-6 -alkyl; S(O) 2 —C 1-6 -alkyl; S(O) 2 —OH; S(O) 2 —O—C 1-6 -alkyl; S(O) 2 —NH 2 ; S(O) 2 —N(H)(C 1-6 -alkyl); S(O) 2 —N(C 1-6 -alkyl) 2 ; C 3-6 -cycloalkyl; 3 to 6-membered heterocycloalkyl; phenyl; 5 or 6-membered heteroaryl; O—C 3-6 -cycloalkyl; O-(3 to 6-membered heterocycloalkyl); O-phenyl; O-(5 or 6-membered heteroaryl); C(O)—C 3-6 -cycloalkyl; C(O)-(3 to 6-membered heterocycloalkyl); C(O)-phenyl; C(O)-(5 or 6-membered heteroaryl); S(O) 2 —(C 3-6 -cycloalkyl); S(O) 2 -(3 to 6-membered heterocycloalkyl); S(O) 2 -phenyl or S(O) 2 -(5 or 6-membered heteroaryl);
wherein aryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; Br; I; CN; C 1-6 -alkyl; CF 3 ; CF 2 H; CFH 2 ; CF 2 Cl; CFCl 2 ; C 1-4 -alkylene-CF 3 ; C 1-4 -alkylene-CF 2 H; C 1-4 -alkylene-CFH 2 ; C(O)—C 1-6 -alkyl; C(O)—OH; C(O)—OC 1-6 -alkyl; C(O)—N(H)(OH); C(O)—NH 2 ; C(O)—N(H)(C 1-6 -alkyl); C(O)—N(C 1-6 -alkyl) 2 ; OH; OCF 3 ; OCF 2 H; OCFH 2 ; OCF 2 Cl; OCFCl 2 ; O—C 1-6 -alkyl; O—C 3-6 -cycloalkyl; O-(3 to

Assignees

• Gruenenthal Gmbh

Inventors

• Jakob Florian
• Alen Jo
• Lucas Simon
• Craan Tobias
• Konetzki Ingo
• Kless Achim
• Schunk Stefan
• Ratcliffe Paul
• Wachten Sebastian
• Cruwys Simon

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title