Heterocyclic sulfonamides, uses and pharmaceutical compositions thereof

The method of claim 31, wherein the compound is:

• N-{1-[4-trans-({4-[(isopropylsulfonyl)amino]tetrahydrofuran-3-yl}oxy)phenyl]pyrrolidin-3-yl}acetamide;
• N-[(3S,4S)-4-(biphenyl-4-yloxy)tetrahydrofuran-3-yl]propane-2-sulfonamide;
• N-{(3S,4S)-4-[(2′-cyanobiphenyl-4-yl)oxy]tetrahydrofuran-3-yl}propane-2-sulfonamide;
• N-{(3S,4S)-4-[4-(5-cyano-2-thienyl)phenoxy]tetrahydrofuran-3-yl}propane-2-sulfonamide;
• N-{(1S,2R)-2-[(2′-cyanobiphenyl-4-yl)oxy]cyclopentyl}propane-2-sulfonamide;
• N-{(1S,2R)-2-[4-(5-cyano-2-thienyl)phenoxy]cyclopentyl}propane-2-sulfonamide;
• N-{(1S,2R)-2-[(2′-cyanobiphenyl-4-yl)oxy]cyclohexyl}propane-2-sulfonamide;
• cis-N-[4-(4-pyridin-3-ylphenoxy) tetrahydrofuran-3-yl]propane-2-sulfonamide;
• cis-N-{4-[4-(2-thienyl) phenoxy] tetrahydrofuran-3-yl}propane-2-sulfonamide;
• N-{(3S,4S)-4-[(2′-cyano-4′-fluoro biphenyl-4-yl)oxy]tetra hydrofuran-3-yl}propane-2-sulfonamide;
• N-{(3S,4S)-4-[(4′-fluoro biphenyl-4-yl)oxy]tetra hydrofuran-3-yl}propane-2-sulfonamide;
• N-{(3S,4S)-4-[(2′-ethoxy-4′-fluoro biphenyl-4-yl)oxy]tetra hydrofuran-3-yl}propane-2-sulfonamide;
• cis-N-[4-{[6-(5-cyano-2-thienyl) pyridin-3-yl]oxy}tetra hydrofuran-3-yl]propane-2-sulfonamide;
• cis-N-{4-[4-(3-thienyl) phenoxy] tetrahydrofuran-3-yl}propane-2-sulfonamide;
• 2-cyano-4′-({(1R,2S)-2-[(isopropyl sulfonyl) amino] cyclopentyl}oxy) biphenyl-4-carboxylic acid;
• N-{(1S,2R)-2-[(2′-cyano-2,4′-difluoro biphenyl-4-yl)oxy]cyclopentyl}propane-2-sulfonamide;
• N-{(1S,2R)-2-[(2′-ethoxy-2-fluoro biphenyl-4-yl)oxy] cyclopentyl}propane-2-sulfonamide;
• N-{(1S,2R)-2-[4-(5-cyano-2-thienyl)-3-fluoro phenoxy] cyclopentyl}propane-2-sulfonamide;
• N-{(1S,2R)-2-[(2′-cyano-2-fluoro biphenyl-4-yl)oxy]cyclohexyl} propane-2-sulfonamide;
• N-{(1S,2R)-2-[(2′-cyano-2,4′-difluoro biphenyl-4-yl)oxy] cyclohexyl} propane-2-sulfonamide;
• N-{(1S,2R)-2-[4-(5-cyano-2-thienyl)-3-fluoro phenoxy] cyclohexyl} propane-2-sulfonamide;
• N-[(1S,2R)-2-(4-pyrrolidin-1-ylphenoxy) cyclohexyl] propane-2-sulfonamide;
• N-[(1S,2R)-2-({6-[2-(2,2,2-trifluoro ethoxy) phenyl] pyridin-3-yl}oxy) cyclohexyl] propane-2-sulfonamide;
• N-[(1S,2R)-2-({6-[2-(trifluoro methoxy) phenyl] pyridin-3-yl}oxy) cyclohexyl] propane-2-sulfonamide;
• or
• N-[(1S,2R)-2-{[6-(5-cyano-2-thienyl) pyridin-3-yl]oxy} cyclohexyl] propane-2-sulfonamide,
• or a pharmaceutically acceptable salt thereof.

A method for the treatment or prevention in a mammal of a condition selected from the group consisting of acute neurological and psychiatric disorders, stroke, cerebral ischemia, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest, hypoglycemic neuronal damage, Huntington's Chorea, amyotrophic lateral sclerosis, ocular damage, retinopathy, muscular spasms and disorders associated with muscular spasticity including tremors, epilepsy, convulsions, migraine, urinary incontinence, substance tolerance, substance withdrawal, anxiety, trigeminal neuralgia, hearing loss, tinnitus, macular degeneration of the eye, emesis, brain edema, pain, tardive dyskinesia, sleep disorders, and conduct disorder, comprising administering a compound of formula I, or a pharmaceutically acceptable salt thereof,

• wherein each R1 and each R2 and each R7 is independently selected from the group consisting of hydrogen, halogen, hydroxyl, —CF3, —CN, —(C═O)R8, —O—(C═O)—R8, —(NR8)—(C═O)—R8, —(C═O)—OR8, —(C═O)—N(R8)2, —OR8, —O—(C═O)—OR8, —O—(C═O)—N(R8)2, —NO2, —N(R8)2, —(NR8)—SO2—R8, —S(O)wR8, —SO2—N(R8)2, (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, and (C3-C10)cycloalkyl;
• wherein said (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, or (C3-C10)cycloalkyl are each independently optionally substituted with one, two, three or four R9;
• w is 0, 1 or 2;
• m is zero, one, two or three;
• n is zero, one, two or three;
• p is zero, one, two or three;
• q is zero, one, two or three;
• s is one and t is one;
• or one of s or t is one and the other of s or t is two;
• R3 is hydrogen or (C1-C6)alkyl;
• each R4 is independently selected from hydrogen, or (C1-C6)alkyl;
• wherein said (C1-C6)alkyl may be optionally substituted with one, two, three or four halogen, —CN, or —OR9;
• or two R4 groups on the same carbon atom may be taken together to form an oxo (═O) radical or a (C3-C6)spirocycloalkyl;
• R5 is hydrogen, or (C1-C6)alkyl;
• R6 is (C1-C6)alkyl-(C═O)—, [(C1-C6)alkyl]2N—(C═O)—, (C1-C6)alkyl-SO2—, (C3-C10)cycloalkyl-SO2—, or [(C1-C6)alkyl]2N—SO2—;
• wherein said (C1-C6)alkyl moieties of said [(C1-C6)alkyl]2N—(C═O)— and [(C1-C6)alkyl]2N—SO2— may optionally be taken together with the nitrogen atom to which they are attached to form a four to six membered heterocyclic ring;
• R8 is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, and (C3-C10)cycloalkyl;
• wherein said (C1-C6)alkyl may be optionally substituted with one, two or three substituents independently selected from hydrogen, halo, —CN, perfluoro(C1-C6)alkyl, hydroxy, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, (C1-C6)alkoxy, perfluoro(C1-C6)alkoxy, HO—(C═O)—, (C1-C6)alkyl-O—(C═O)—, formyl, (C1-C6)alkyl-(C═O)—, H2N—(C═O)—, (C1-C6)alkyl]-(NH)—(C═O)—, [(C1-C6)alkyl]2N—(C═O)—, (C1-C6)alkyl-(C═O)—O—, H(C═O)—NH—, (C1-C6)alkyl(C═O)—NH—, (C1-C6)alkyl(C═O)—[N((C1-C6)alkyl)]-, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-SO2—NH—, (C1-C6)alkyl-SO2—[N((C1-C6)alkyl)]-, H2N—SO2—, [(C1-C6)alkyl]-NH—SO2—, and [(C1-C6)alkyl]2N—SO2—;
• wherein said (C1-C6)alkyl may be additionally optionally substituted with an optionally substituted (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl, or (C3-C10)cycloalkyl;
• wherein said optional substituents may be independently selected from one, two, three or four radicals independently selected from halogen, hydroxyl, —CF3, —CN, (C1-C3)alkyl, (C1-C3)alkoxy, and amino;
• wherein each of said R8 (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl or (C3-C10)cycloalkyl substituents may be optionally additionally substituted with one, two, three or four radicals independently selected from halogen, hydroxyl, —CF3, —CN, (C1-C3)alkyl, (C1-C3)alkoxy and amino;
• each R9 is independently selected from the group consisting of halogen, hydroxyl, —CF3, —CN, —(C═O)R10, —O—(C═O)—R10, —(NR10)—(C═O)—R10, —(C═O)—OR10, —(C═O)—N(R10)2, —OR10, —O—(C═O)—OR10, —O—(C═O)—N(R10)2, —NO2, —N(R10)2, —(NR10)—SO2—R10, —S(O)uR10, —SO2—N(R10)2,
• R10 is independently selected from the group consisting of hydrogen, (C1-C6)alkyl, (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl and (C3-C10)cycloalkyl;
• wherein said (C1-C6)alkyl may be optionally substituted with one, two or three substituents independently selected from hydrogen, halo, —CN, perfluoro(C1-C6)alkyl, hydroxy, amino, (C1-C6)alkylamino, [(C1-C6)alkyl]2amino, (C1-C6)alkoxy, perfluoro(C1-C6)alkoxy, HO—(C═O)—, (C1-C6)alkyl-O—(C═O)—, formyl, (C1-C6)alkyl-(C═O)—, H2N—(C═O)—, (C1-C6)alkyl]-(NH)—(C═O)—, [(C1-C6)alkyl]2N—(C═O)—, (C1-C6)alkyl-(C═O)—O—, H(C═O)—NH—, (C1-C6)alkyl(C═O)—NH—, (C1-C6)alkyl(C═O)—[N((C1-C6)alkyl)]-, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-SO2—NH—, (C1-C6)alkyl-SO2—[N((C1-C6)alkyl)]-, H2N—SO2—, [(C1-C6)alkyl]-NH—SO2—, and [(C1-C6 alkyl]2N—SO2—;
• wherein said (C1-C6)alkyl may also be additionally optionally substituted with an optionally substituted (C6-C10)aryl, (C1-C9)heteroaryl, (C1-C9)heterocycloalkyl or (C3-C10)cycloalkyl;
• wherein said optional substituents may be independently selected from one, two, three or four radicals independently selected from halogen, hydroxyl, —CF3, —CN, (C1-C3)alkyl, (C1-C3)alkoxy, and amino;
• wherein each of said R10 (C6—C)aryl, (C1-C2)heteroaryl, (C1-C2)heterocycloalkyl, or (C3-C10)cycloalkyl substituents may be optionally additionally substituted with one, two, three or four radicals independently selected from halogen, hydroxyl, —CF3, —CN, (C1-C3)alkyl, (C1-C3)alkoxy, and amino;
• R11 is hydrogen or (C1-C6)alkyl;
• ring “A” is (C6-C10)aryl, (C1-C9)heteroaryl, (C4-C10)cycloalkyl, or (C1-C9)heterocycloalkyl;
• wherein two of said R1 substituents on said (C4-C10)cycloalkyl and (C1-C9)heterocycloalkyl may optionally be attached to the same carbon atom and may optionally be taken together to be oxo;
• ring “B” is (C6-C10)aryl, (C1-C9)heteroaryl, (C4-C10)cycloalkyl, or (C1-C9)heterocycloalkyl;
• “X” is —O— or >C(R4)2;
• “Y” is absent, >NR11, —(NR11)—(C═O)—, >C═O, —O— or >C(R7)2;
• and
• “Z” is —O—, —S—, —(S═O)—, or —(SO2)— to the mammal.