N-Substituted Benzene Sulfonamides

A compound of the formula

• or a pharmaceutically acceptable salt thereof wherein
• n is 1, 2, or 3;
• R1 is aryl C1-C8 alkyl, aryl C2-C6 alkenyl, or arylalkynyl, wherein the aryl group is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently C1-C6 alkyl, C1-C6 alkoxy, halogen, haloalkyl, haloalkoxy, heteroaryl, heteroaryl(C1-C6)alkoxy, arylalkoxy, aryloxy, C1-C6 alkoxycarbonyl, —O—CH2CH2—O—, —O—CH2—O—, —C(O)NR30R31, —NHR′, —NR′R″, —N(R16)C(O)—R17, heterocycloalkyl, phenyl, aryl C1-C6 alkanoyl, phenylalkoxy, phenyloxy, CN, —SO2-aryl, —S(O)x—R25, —(C1-C4 alkyl)-S(O)x—R25, —(C1-C4 alkyl)-SO2-aryl, OH, C1-C6 thioalkoxy, C2-C6 alkenyl, —O—SO2-aryl, CO2H,
• wherein the heteroaryl portions of the above group are optionally substituted with 1, 2, or 3 groups that are independently C1-C6 alkyl, heteroaryl optionally substituted with 1 or 2 groups that are independently halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxyalkyl or CN(in one aspect, pyridyl, thienyl, furanyl, imidazolyl, or pyrazolyl), C1-C6 alkoxy, C1-C4 alkoxy C1-C4 alkyl, C3-C6 cycloalkyl, halogen, or phenyl optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, OH, C1-C6 alkyl, C1-C4 alkoxy, CF3, OCF3, CN, or C1-C6 thioalkoxy,
• wherein the heterocycloalkyl and aryl portions of the above substituents are optionally substituted with 1 or 2 groups that are independently heteroaryl optionally substituted with 1 or 2 groups that are independently halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, alkoxyalkyl or CN, (in one aspect, pyridyl, thienyl, furanyl, imidazolyl, or pyrazolyl), C1-C6 alkyl, C1-C6 alkoxy, C1-C4 alkoxy C1-C4 alkyl, C3-C6 cycloalkyl, halogen, or phenyl optionally substituted with 1, 2, 3, 4 or 5 groups that are independently halogen, OH, C1-C6 alkyl, C1-C4 alkoxy, CF3, OCF3, CN, or C1-C6 thioalkoxy,
• R16 is H or C1-C6 alkyl;
• R17 is C1-C6 alkyl, aryl, heteroaryl, C1-C6 alkoxy, OH, aryloxy, heteroaryloxy, aryl(C1-C6)alkoxy, —NR18R19, cycloalkyl, or arylalkyl, wherein the cyclic portions of each of the above are optionally substituted with 1, 2, 3, 4, or 5 groups that are independently alkyl, alkoxy, halo, haloalkyl, haloalkoxy, CN, NH2, NH(alkyl), N(alkyl)(alkyl), CO2H, or C1-C6 alkoxycarbonyl;
• R18 and R19 are independently H, C1-C6 alkyl, aryl, heteroaryl, heterocycloalkyl or aryl(C1-C6)alkyl, wherein the cyclic portions of each are optionally substituted with 1, 2, or 3 groups that are independently alkyl, alkoxy, halogen, hydroxyl, CF3, or OCF3;
• wherein R′ at each occurrence is independently H, C1-C6 alkyl, aryl, aryl(C1-C4)alkyl, C1-C6 alkanoyl, C3-C8 cycloalkyl, aryl(C1-C6)alkanoyl, heterocycloalkyl, heteroaryl(C1-C4)alkyl, —SO2-alkyl, —SO2-aryl, —SO2-heteroaryl, heterocycloalkyl(C1-C6)alkanoyl, or heteroaryl(C1-C6)alkanoyl, wherein the alkyl portion of the alkyl and alkanoyl groups are optionally substituted with halogen or C1-C6 alkoxy,
• wherein the aryl, and heteroaryl groups are optionally substituted with alkyl, alkoxy, halogen, haloalkyl, haloalkoxy,
• wherein R″ at each occurrence is independently H, or C1-C6 alkyl, wherein the alkyl group is optionally substituted with halogen, or
• R1 is C3-C7 cycloalkyl(C1-C6 alkyl) wherein the cyclic portion is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently halogen, C1-C6 alkyl, OH, alkoxycarbonyl, or C1-C6 alkoxy;
• or
• R1 is C1-C14 alkyl, C2-C16 alkenyl, or C2-C8 alkynyl, each of which is optionally substituted with 1 or 2 groups that are independently OH, halogen, C1-C6 alkoxy, aryl, arylalkoxy, aryloxy, heteroaryl, heterocycloalkyl, aryl(C1-C6)alkyl, —CO2—(C1-C6 alkyl), —NR′R″, C1-C6 thioalkoxy, —NH—S(O)x—R25, —N(C1-C6 alkyl)-S(O)x—R25, —S(O)x—R25, —C(O)NR30R31, —N(R16)C(O)NR16R17, or —N(R16)C(O)—R17;
• wherein the above aryl groups are optionally substituted with 1, 2, or 3 groups that are independently OH, C1-C6 alkoxy, C1-C6 alkyl, or halogen;
• R30 and R31 are independently H, C1-C6 alkyl, aryl (preferably phenyl), arylalkyl(preferably benzyl), heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, arylalkanoyl, alkenyl, cycloalkyl, alkynyl, cycloalkenyl, pyridyl, imidazolyl, thiazolyl, oxazolyl, or indolyl,
• wherein the alkyl portions of the above are optionally substituted with 1, 2, or 3 groups that are independently NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)(C1-C6 alkyl), OH, C1-C6 thioalkoxy, heterocycloalkyl, aryl, heteroaryl, CN, halogen, or alkoxy optionally substituted with OH or phenyl, wherein the aryl, heteroaryl and heterocycloalkyl groups are optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, CF3, OCF3, OH, halogen, thioalkoxy, phenyl or heteroaryl;
• or
• R30, R31, and the nitrogen to which they are attached form a heterocycloalkyl ring containing from 3 to 7 ring members, wherein
• the cyclic portions of R30 and R31 or the heterocyclic ring formed from R30, R31, and the nitrogen to which they are attached are optionally substituted with 1, 2, or 3 groups that are independently alkyl, alkoxy, halo, OH, thioalkoxy, NH2, NH(C1-C6 alkyl), N(C1-C6 alkyl)(C1-C6 alkyl), CF3, OCF3, phenyl optionally substituted with a halogen, —(C1-C4 alkyl)-N(H or C1-C4 alkyl)-phenyl, C1-C4 hydroxyalkyl, arylalkoxy, arylalkyl, arylalkanoyl, C(O)NH2, C(O)NH(C1-C6 alkyl), C(O)N(C1-C6 alkyl)(C1-C6 alkyl), heterocycloalkylalkyl, C1-C6 alkoxycarbonyl, C2-C6 alkanoyl, heteroaryl, or —SO2—(C1-C6 alkyl)
• x is 0, 1, or 2;
• R25 is C1-C6 alkyl, OH, NR26R27;
• R26 and R27 are independently H, C1-C6 alkyl, phenyl(C1-C4 alkyl), aryl, or heteroaryl;
• or
• R26, R27 and the nitrogen to which they are attached form a heterocycloalkyl ring;
• R1 is heteroaryl(C1-C6)alkyl wherein the cyclic portion is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, aryl, arylalkyl, aryloxy, heteroaryl, —SO2-aryl, —S(O)x—R25, —(C1-C4 alkyl)-S(O)x—R25, CN, C1-C6 thioalkoxy, C1-C6 alkoxycarbonyl, —NR′R″, —C(O)—NR′R″, heterocycloalkyl,
• wherein the above aryl groups are optionally substituted with 1, 2, 3, or 4 groups that are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, or CN;
• wherein the above heteroaryl and heterocycloalkyl groups are optionally substituted with 1, 2, or 3 groups that are independently halogen, CF3, (C1-C4)alkyl, C1-C6 thioalkoxy, OH, C1-C4 hydroxyalkyl, or C1-C4 alkoxy;
• or
• R1 is heterocycloalkyl(C1-C6 alkyl) wherein the cyclic portion is optionally substituted with 1, 2, 3, 4, or 5 groups that are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, aryl, arylalkyl, aryloxy, heteroaryl, —SO2-aryl, —S(O)x—R25, —(C1-C4 alkyl)-S(O)x—R25, CN, C1-C6 thioalkoxy, C1-C6 alkoxycarbonyl, —NR′R″, —C(O)—NR′R″, heterocycloalkyl;
• and
• R2 is H, C1-C6 alkyl, or phenyl(C1-C4)alkyl.

A compound of the formula

• or a pharmaceutically acceptable salt thereof wherein
• n is 1, 2, or 3;
• R2 is H, C1-C6 alkyl, or phenyl(C1-C4)alkyl;
• R3 is H, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, or CN;
• R4 is H, halogen, C1-C6 alkyl optionally substituted with —CO2—(C1-C6 alkyl), C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, CN, aryloxy, isocyanato, —SO2—(C1-C6 alkyl), —NHR′, —NR′R″, C1-C6 alkanoyl, heteroaryl, aryl, or
• R3 and R4 and the carbons to which they are attached form a heterocycloalkyl ring which is optionally substituted with 1, 2, or 3 groups that are independently C1-C4 alkyl, C1-C4 alkoxy, halogen, or C1-C4 alkanoyl wherein the alkanoyl group is optionally substituted with up to 3 halogen atoms;
• R3′ is H, —SO2—NR′R″, halogen, or
• R4 and R3′ and the carbons to which they are attached form a benzo ring;
• or
• R4 and R3′ and the carbons to which they are attached form a 1-oxa-2,3-diazacyclopentyl ring;
• R10 and R11 are independently H or F;
• or
• R10, R3, and the carbons to which they are attached for a 1,2,5-oxadiazolyl ring;
• or
• R10, R3, and the carbons to which they are attached form a naphthyl ring;
• and
• wherein R′ at each occurrence is independently H, C1-C6 alkyl, aryl, aryl(C1-C4)alkyl, C1-C6 alkanoyl, C3-C8 cycloalkyl, aryl(C1-C6)alkanoyl, heterocycloalkyl, heteroaryl(C1-C4)alkyl, —SO2-alkyl, —SO2-aryl, —SO2-heteroaryl, heterocycloalkyl(C1-C6)alkanoyl, or heteroaryl(C1-C6)alkanoyl, wherein the alkyl portion of the alkyl and alkanoyl groups are optionally substituted with halogen or C1-C6 alkoxy,
• wherein the aryl, and heteroaryl groups are optionally substituted with alkyl, alkoxy, halogen, haloalkyl, or haloalkoxy, and
• wherein R″ at each occurrence is independently H, or C1-C6 alkyl, wherein the alkyl group is optionally substituted with halogen.