PYRIMIDINE CARBOXAMIDES AS SODIUM CHANNEL BLOCKERS

摘要

The present disclosure provides substituted pyrimidine carboxamides of Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein A1, X, A2, W1, W2, W3, E, Z, and R4 are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of sodium channels. Compounds of the present disclosure are especially useful for treating pain.;

主权项

1. A compound having Formula II: or a pharmaceutically acceptable salt or solvate thereof, wherein:
W2 is N and W3 is CH; orW2 is CH and W3 is N;A1 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, and aralkyl;X is selected from the group consisting of —O—, —N(H)—, and —(C═O)—; or X is absent;A2 is selected from the group consisting of optionally substituted aryl and optionally substituted heterocyclo; or A2 is absent;
with the provisos:a) when X is absent, A2 is selected from the group consisting of optionally substituted aryl and optionally substituted heterocyclo; orb) when A2 is absent, X is selected from the group consisting of —O—, —N(H)—, and —(C═O)—;E is selected from the group consisting of —N(H)R1 and —OH;R1 is selected from the group consisting of hydrogen and (heterocyclo)alkyl;Z is selected from the group consisting of —NR5— and —O—;R4 is selected from the group consisting of: R1a is selected from the group consisting of hydrogen and (heterocyclo)alkyl;R10a is selected from the group consisting of alkyl and hydroxyalkyl;R12 is selected from the group consisting of hydrogen, alkyl, alkenyl, and hydroxyalkyl;R5 is hydrogen; orR4 and R5 taken together with the nitrogen atom to which they are attached form an optionally substituted heterocyclo selected from the group consisting of:and
R14 is selected from the group consisting of hydrogen and C1-C4 alkyl.