AMIDE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF, PREPARATION METHOD THEREOF AND MEDICINAL APPLICATION THEREOF

摘要

Amide derivatives and pharmaceutically acceptable salts thereof, preparation method thereof and medicinal application thereof are provided. Specifically, amide derivatives represented by general formula (I) are provided. The amide derivatives represented by general formula (I) can be used as a therapeutic agent, particularly as an inhibitor for microsomal prostaglandin E synthase-1 (mPGES-1), and also to treat and/or prevent diseases or illnesses such as inflammation and/or pain etc. The definition of each substituent group in general formula (I) is the same as the definition in the description.;

主权项

1. A compound of formula (I), or a tautomer, mesomer, racemate, enantiomer, diastereomer, or mixture thereof, or pharmaceutically acceptable salt thereof: wherein:
ring P is selected from the group consisting of five-membered heteroaryl and five-membered heterocyclyl;ring Q is selected from the group consisting of aryl and heteroaryl;A, B and Y are selected from the group consisting of —CH— and N;R1 is selected from the group consisting of alkyl and cycloalkyl, wherein the alkyl or cycloalkyl is optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen and haloalkyl;R2 is selected from the group consisting of halogen and haloalkyl;each R3 is the same or different and each is independently selected from the group consisting of hydrogen, halogen, alkoxy, cyano, nitro, alkyl, cycloalkyl, heterocyclyl, oxo, —C(O)OR5, —OC(O)R5, —NHS(O)mR5, —C(O)R5, —NHC(O)R5, —NHC(O)OR5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7, wherein the alkyl, cycloalkyl and heterocyclyl are each optionally further substituted by one or more groups selected from the group consisting of halogen, hydroxyl, alkoxy, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —NHS(O)mR5, —C(O)R5, —NHC(O)R5, —NHC(O)OR5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7;R4 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each optionally further substituted by one or more groups selected from the group consisting of halogen, alkoxy, hydroxyl, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)OR5, —OC(O)R5, —NHS(O)mR5, —C(O)R5, —NHC(O)R5, —NHC(O)OR5, —NR6R7, —OC(O)NR6R7 and —C(O)NR6R7,R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl and heteroaryl are each optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid and carboxylate group;R6 and R7 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently and optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, hydroxyalkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid and carboxylate group; orR6 and R7 are taken together with the nitrogen atom to which they are attached to form a heterocyclyl, wherein the heterocyclyl optionally contains one or more heteroatoms selected from the group consisting of N, O and S(O)m, and wherein the heterocyclyl is optionally further substituted by one or more groups selected from the group consisting of alkyl, halogen, hydroxyl, alkoxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxylic acid and carboxylate group;m is 0, 1 or 2;s is 0, 1, 2, or 3; andt is 0 or 1.