US 10,239,869 B2 · Sulfonamide compounds as voltage-gated sodium channel modulators

Abstract

The present invention relates to sulfonamide compounds Formula (I) wherein the substituents are as described herein, and their use in a medicine for the treatment of diseases, disorders associated with the inhibition of Voltage-gated sodium channels (VGSC) particularly NaV1.7. It further relates to the compounds herein and their pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof useful in treating diseases, disorders, syndromes and/or conditions associated with the inhibition of Voltage-gated sodium channels (VGSC) particularly NaV1.7. The invention also relates to process for the preparation of the compounds of the invention.

A compound having the Formula (I):

wherein,
A1 and A2 are independently hydrogen or substituted or unsubstituted (C1-C6)alkyl;
or
A1 and A2, together with the carbon atom to which they are attached, form a substituted or unsubstituted 3- to 6-membered cycloalkyl ring or 4- to 6-membered heterocyclic ring;
R1 is selected from the group consisting of hydrogen, halogen, cyano, substituted or unsubstituted (C1-C6)alkyl and substituted or unsubstituted (C1-C6)alkoxy;
R2, which may be same or different at each occurrence, is independently selected from the group consisting of halogen, cyano, substituted or unsubstituted (C1-C6)alkyl, (C1-C6)haloalkyl, —(CH2)0-2—S(O)2-alkyl, —O—R6, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted (C3-C8)cycloalkyl, substituted or unsubstituted (C6-C10)aryl, substituted or unsubstituted 5- to 6-membered monocyclic heteroaryl, substituted or unsubstituted 4- to 6-membered monocyclic heterocyclyl, —C(O)OH, —C(O)O-alkyl and —C(O)NR4R5;
ring A is monocyclic six membered heteroaryl containing 1- to 3-nitrogen atoms in the ring;
R3, which may be same or different at each occurrence, is independently selected from the group consisting of halogen, cyano, substituted or unsubstituted (C1-C6)alkyl and substituted or unsubstituted (C1-C6)alkoxy;
R4 and R5 are independently selected from hydrogen or substituted or unsubstituted (C1-C6)alkyl;
or R4 and R5 together with the nitrogen atom to which they are attached, form substituted or unsubstituted 5- to 6-membered heterocylic ring;
R6 is selected from the group consisting of hydrogen, substituted or unsubstituted (C1-C6)alkyl, (C1-C6)haloalkyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted (C3-C8)cycloalkyl, substituted or unsubstituted (C6-C10)aryl, substituted or unsubstituted 5- to 6-membered monocyclic heteroaryl and substituted or unsubstituted 4- to 6-membered monocyclic heterocyclyl;
‘m’ is an integer ranging from 0 to 3, both inclusive;
‘n’ is an integer ranging from 0 to 3, both inclusive;
wherein the substituents for substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted alkoxyalkyl are one or more same or different and independently selected from the group consisting of hydroxy, halogen, carboxy, cyano, nitro, oxo (═O), (C1-C6)alkyl, (C1-C6)haloalkyl, hydroxy (C1-C6)alkyl, alkoxyalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl, arylalkyl, (C3-C8)cycloalkyl, cycloalkylalkyl, 5 to 10 membered heteroaryl, 4 to 10 membered heterocyclic ring, 3 to 10 membered heterocyclylalkyl, heteroarylalkyl, —C(O)ORx, —C(O)Ry, —C(S)Ry, —C(O)NRxRz, —NRxC(O)NRxRz, —N(Rx)S(O)2Ry, —NRxRz, —NRxC(O)Ry, —NRxC(S)Ry, —NRxC(S)NRxRz, —S(O)2NRxRz, —ORx, —OC(O)Ry, —C(RaRb)1-3C(O)ORx, —C(RaRb)1-3C(O)NRxRz, —OC(RaRb)2-3—ORx, —OC(RaRb)2-3—NRxRz, —OC(RaRb)2-3—S(O)0-2Ry, —C(RaRb)1-3—NRxRz, —C(RaRb)1-3—S(O)0-2Ry, —OC(RaRb)1-3—C(O)NRxRz, —OC(RaRb)1-3—C(O)ORx and —S(O)0-2Ry;
each of Rx is selected from the group consisting hydrogen, (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl, arylalkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, 5 to 10 membered heteroaryl, heterocyclic ring, heterocyclylalkyl and heteroarylalkyl;
each of Ry is selected from the group consisting (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl, arylalkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, 5 to 10 membered heteroaryl, heterocyclic ring, heterocyclylalkyl and heteroarylalkyl;
each of Rz is selected from the group consisting hydrogen, (C1-C6)alkyl, (C1-C6)haloalkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C6-C10)aryl, arylalkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkenyl, 5 to 10 membered heteroaryl, heterocyclic ring, heterocyclylalkyl and heteroarylalkyl;
or Rx and Rz together with the nitrogen atom to which they are attached form a substituted or unsubstituted, saturated or unsaturated 4- to 8-membered cyclic ring, wherein the unsaturated cyclic ring may have one or two double bonds;
and
each of Ra and Rb are independently selected from the group consisting of hydrogen, halogen and substituted or unsubstituted (C1-C6)alkyl;
or N-oxides thereof or a pharmaceutically acceptable salt thereof or stereoisomer thereof.

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Sulfonamide compounds as voltage-gated sodium channel modulators

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Sulfonamide compounds as voltage-gated sodium channel modulators

Life of this patent

Abstract

Claims21