IP Library › Granted Patent US 8,546,374

Granted Patent B2

US 8,546,374 · App. 13/544,387 · Granted Oct 1, 2013

Amino-tetrazoles analogues and methods of use

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Patent No.: US 8,546,374
App. No.: 13/544,387
Granted: Oct 1, 2013
Kind: B2

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Abstract

A compound having Formula (I) or Formula (II) is disclosed as an P2X 7 antagonist, wherein A, B, C, Y, Y, Z, m, v, R 1 , R 2 , R 3 , R 4 , and R 5 , are as defined in the description. Methods and compositions for treating disease or condition modulated by P2X 7 are also disclosed.

Claims (473)

1. A compound having Formula (I) or Formula (II),

or a therapeutically acceptable salt thereof, in which

R 2 is 2,3-dichlorophenyl; SO 2 R 2a ;

m is 1, 2, or 3;

X and Y are each —H

Z is —H;

R 1 is

phenyl which is unfused or fused with a ring selected from the group consisting of cyclopentane, cyclohexane, cyclopentene, cyclohexene, dioxane, dioxolane, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, oxazolidinone, morpholinone, and piperazine, wherein each ring contained in R 1 , independently of each other, is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —NH 2 , —NO 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1d , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

isoxazolyl, oxazolyl, pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, pyrimidinyl, pyrazinyl, or imidazopyridinyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, or piperazine ring, in which each of the pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrazinyl, or imidazopyridinyl ring and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substitutents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —NH 2 , —NO 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e )—NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

bicyclo[2.2.1]heptyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, imidazoline, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazoline, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, or piperazine ring, in which the cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl ring and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —OH, —NH 2 , —NO 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

admantyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR ld , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ; or

2,3-dihydrospiroindene-1,4′-piperidinyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR 1d , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ;

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1b ;

R 1b is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NH 2 , —OH, —OR 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —R 1c , —N(R 1d ) 2 , and —NHR 1d ;

R 1c is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1c is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —NH 2 , —OR 1aa , —SR 1aa , —NHR 1aa , —N(R 1aa ) 2 , —C(O)R 1aa , —S(O) 2 R 1aa , —S(O) 2 NH 2 , —S(O) 2 N(R 1aa ) 2 , —C(O)NH 2 , —C(O)N(H)(R 1aa ), —C(O)N(R 1aa ) 2 , —C(O)OH, —C(O)OR 1aa , —OR 1h , —N(H)R 1h ), —N(R 1d )(R 1h ) and —R 1h ;

R 1aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1bb ;

R 1bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), —S(O) 2 N(R 1d ) 2 and —R 1h ;

R 1d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 1e is a monocyclic or bicyclic ring selected from the group consisting of cycloalkyl, heterocycle, aryl and heteroaryl, wherein each ring is unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —OR 1aa , —SR 1aa , —NH 2 , —NHR 1aa , and —N(R 1aa ) 2 ;

R 1f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, —R 1h , or R 1g ;

R 1g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of —R 1h ;R 1h is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1h is unsubstituted or substituted with one or two or three or four or five substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), and —S(O) 2 N(R 1d ) 2 ;

provided that when R 1 is phenyl fused with a pyrrole, thiophene, furan, pyrazole, isoxazole, or isothiazole ring, the pyrrole, thiophene, furan, pyrazole, isoxazole, or isothiazole ring is not substituted with —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, pyrrolidinyl, piperidyl, tetrahydropyridyl, pyrrolinyl, —C 1 -alkyl substituted with pyrrolidinyl or piperidyl, —C 2 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 3 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 4 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 5 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , or —C 6 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d ;

A is CR 6 ;

B is CR 7 ;

E is CR 8 ;

R 3 is —NH 2 , —R 3a , —OR 3a , —NHR 3a , —N(R 3a ) 2 , —NHC(O)R 3f , —N(R 3d )C(O)R 3f , —R 3c , —OR 3e , —SR 3e , —NH(R 3e ), or —N(R 3d )(R 3e );

R 3a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or R 3b ;

R 3b is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —NH 2 , —CN, —OH, —OR 3d , —R 3c , —N(R 3d ) 2 , and —NHR 3d ;

R 3c is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 3c is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —R 3aa , —NH 2 , —OR 3aa , —SR 3aa , —NHR 3aa , and —N(R 3aa ) 2 ;

R 3d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 3aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 3bb ;

R 3bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NH 2 , —OH, —OR 3d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 3d ) 2 , and —NHR 3d ;

R 3e is a monocyclic or bicyclic ring selected from the group consisting of cycloalkyl, heterocycle, aryl and heteroaryl, in which each ring is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —OH, —R 3aa , —NH 2 , —OR 3aa , —SR 3aa , —NHR 3aa , and —N(R 3aa ) 2 ;

R 3f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, or R 3g ;

R 3g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of aryl and heteroaryl;

v is one, two, or three, and when v is two or three, R 3 may be the same or different;

R 4 is —Cl;

R 5 is;

R 6 is —H;

R 7 is —H;

and

R 8 is —H.

2. A compound having Formula (I) or Formula (II),

or a therapeutically acceptable salt thereof, in which

R 2 is 2,3-dichlorophenyl;

m is 1, 2, or 3;

X and Y are each —H;

Z is —H;

R 1 is

phenyl which is unfused or fused with a ring selected from the group consisting of cyclopentane, cyclohexane, cyclopentene, cyclohexene, dioxane, dioxolane, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, oxazolidinone, morpholinone, and piperazine, wherein each ring contained in R 1 , independently of each other, is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 ,C(O)R 1d , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f and —R 1c ;

isoxazolyl, oxazolyl, pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, pyrimidinyl, pyrazinyl, or imidazopyridinyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, or piperazine ring, in which the pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrazinyl, or imidazopyridinyl ring and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substitutents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

bicyclo[2.2.1]heptyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, imidazoline, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazoline, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, or piperazine ring, in which the cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl ring and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

admantyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR 1d , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ; or

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1b ;

R 1c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]undecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, each of which is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, ═O, —NO 2 , —CN, —OH, —R 1aa , —NH 2 , —OR 1aa , —SR 1aa , —NHR 1aa , —N(R 1aa ) 2 , —C(O)R 1aa , S(O) 2 R 1aa , S(O) 2 NH 2 , S(O) 2 N(R 1aa ) 2 , —C(O)NH 2 , —C(O)N(H)(R 1aa ), —C(O)N(R 1aa ) 2 , —C(O)OH, —C(O)OR 1aa , —OR 1h , —N(H)R 1h ), —N(R 1d )(R 1h ) and —R 1h ;

R 1aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1bb ;

R 1bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d ; —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), —S(O) 2 N(R 1d ) 2 and —R 1h ;

R 1d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 1e is phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, imidazolyl, thiazolyl, pyrrolidinyl, piperidyl, azepinyl, tetrahydrofuryl, tetrahydropyranyl or oxazolyl; wherein each R 1e is unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —OR 1aa , —SR 1aa , —NH 2 , —NHR 1aa , and —N(R 1aa ) 2 ;

R 1f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, —R 1h , or R 1g ;

R 1g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of aryl and heteroaryl;

R 1h is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1h is unsubstituted or substituted with one or two or three or four or five substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)N H 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), and —S(O) 2 N(R 1d ) 2 ;

provided that when R 1 is phenyl fused with a pyrrole, thiophene, furan, pyrazole, isoxazole, or isothiazole ring, the pyrrole, thiophene, furan, pyrazole, isoxazole, or isothiazole ring is not substituted with —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, pyrrolidinyl, piperidyl, —C 1 -alkyl substituted with pyrrolidinyl or piperidyl, —C 2 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 3 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 4 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 5 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , or —C 6 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d ;

A is CR 6 ;

B is CR 7 ;

E is CR 8 ;

R 3 is —NH 2 , —R 3a , —OR 3a , —NHR 3a , —N(R 3a ) 2 , —NHC(O)R 3f , —N(R 3d )C(O)R 3f , —R 3c , —OR 3e , —SR 3e , —NH(R 3e ), or —N(R 3d )(R 3e );

R 3a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or R 3b ;

R 3c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]undecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, in which each ring is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —R 3aa , —NH 2 , —OR 3aa , —SR 3aa , —NHR 3aa , and —N(R 3aa ) 2 ;

R 3d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 3aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 3bb ;

R 3e is phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, imidazolyl, thiazolyl, pyrrolidinyl, piperidyl, azepinyl, tetrahydrofuryl, tetrahydropyranyl or oxazolyl; wherein each R 3e is unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —OH, —R 3aa , —OR 3aa , —SR 3aa , —NH 2 , —NHR 3aa , and —N(R 3aa ) 2 ;

R 3f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, or R 3g ;

v is one, two, or three, and when v is two or three, R 3 may be the same or different;

R 4 is —Cl;

R 5 is —Cl;

R 6 is —H;

R 7 is —H;

R 8 is —H.

3. The compound of claim 2 having Formula (I),

or a therapeutically acceptable salt thereof, in which

R 2 is 2,3-dichlorophenyl;

X and Y are each —H,

Z is —H;

R 1 is

phenyl which is unfused or fused with a ring selected from the group consisting of cyclopentane, cyclohexane, cyclopentene, cyclohexene, dioxane, dioxolane, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, oxazolidinone, morpholidinone, and piperazine, wherein each ring contained in R 1 , independently of each other, is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1d , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

isoxazolyl, oxazolyl, pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, pyrimidinyl, pyrazinyl, or imidazopyridinyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, or piperazine ring, in which the pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrazinyl, or imidazopyridinyl ring and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substitutents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —NO 2 , —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

bicyclo[2.2.1]heptyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, imidazoline, tetrahydrofuran, tetrahydrothiophene, thiazole, thiophene, pyrrolidine, dioxolane, pyrazoline, pyrazolidine, pyran, piperidine, morpholine, thiomorpholine, or piperazine ring, in which the cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl ring and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —OH, —NO 2 , —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH (R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

admantyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR 1d , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ; or

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1b ;

R 1c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]undecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, each of which is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —NH 2 , —OR 1aa , —SR 1aa , —NHR 1aa , —N(R 1aa ) 2 , —C(O)R 1aa , —S(O) 2 R 1aa , —S(O) 2 NH 2 , —S(O) 2 N(R 1aa ) 2 , —C(O)NH 2 , —C(O)N(H)(R 1aa ), —C(O)N(R 1aa ) 2 , —C(O)OH, —C(O)OR 1aa , —OR 1h , —N(H)R 1h ), —N(R 1d )(R 1h ) and —R 1h ;

R 1aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1bb ;

R 1bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), —S(O) 2 N(R 1d ) 2 and —R 1h ;

R 1d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 1f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, —R 1h , or R 1g ;

R 1g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of R 1h ;

R 1h is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1h is unsubstituted or substituted with one or two or three or four or five substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), and —S(O) 2 N(R 1d ) 2 ;

provided that when R 1 is phenyl fused with a pyrrole, thiophene, furan, pyrazole, isoxazole, or isothiazole ring, the pyrrole, thiophene, furan, pyrazole, isoxazole, or isothiazole ring is not substituted with —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, pyrrolidinyl, piperidyl, —C 1 -alkyl substituted with pyrrolidinyl or piperidyl, —C 2 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 3 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 4 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , —C 5 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d , or —C 6 -alkyl substituted with —N(R 1d ) 2 , —NH 2 , or —NHR 1d .

4. The compound of claim 3 , or a therapeutically acceptable salt thereof, in which

R 1 is

unfused phenyl, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1d , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

isoxazolyl, oxazolyl, pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, pyrimidinyl, pyrazinyl, or imidazopyridinyl, each of which is unfused or fused with a cyclopentane, cyclohexane, cyclopentene, cyclohexene or benzene ring, in which the pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, pyrimidinyl, pyrazinyl, or imidazopyridinyl rings and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substitutents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR le , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ; or

bicyclo[2.2.1]heptyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl, each of which is fused with a benzene, furan, imidazole, isothiazole, oxazole, isoxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, or pyrrole ring, in which the cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl ring and the benzene ring are, independently of each other, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

admantyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR 1d , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ; or

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1b ;

R 1c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]undecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, each of which is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —SR 1aa , —NH 2 , —OR 1aa , —NHR 1aa , —N(R 1aa ) 2 —C(O)R 1aa , —S(O) 2 R 1aa , —S(O) 2 NH 2 , —S(O) 2 N(R 1aa ) 2 , —C(O)NH 2 , —C(O)N(H)(R 1aa ), —C(O)N(R 1aa ) 2 , —C(O)OH, —C(O)OR 1aa , —OR 1h , —N(H)R 1h ), —N(R 1d )(R 1h ) and —R 1h ;

R 1aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1bb ;

R 1bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), —S(O) 2 N(R 1d ) 2 and —R 1h ;

R 1d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 1f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, —R 1h , or R 1g ; and

R 1g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of —R 1h , R 1h is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1h is unsubstituted or substituted with one or two or three or four or five substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, ——C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), and —S(O) 2 N(R 1d ) 2 .

5. The compound of claim 3 , or a therapeutically acceptable salt thereof, in which

R 1 is

unfused phenyl, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —NO 2 , —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1d , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR le , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ) —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

isoxazolyl, oxazolyl, pyrrolidinyl, pyridyl, thienyl, pyrrolyl, pyridazinyl, pyrazolyl, imidazolyl, thiazolyl, furyl, tetrahydrofuryl, tetrahydropyranyl, pyrimidinyl, pyrazinyl, or imidazopyridinyl ring, each of which is unfused and each of which is, independently of each other, unsubstituted or substituted with one, two, three, or four substitutents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —NO 2 , —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ; or

bicyclo[2.2.1]heptyl, cyclopentyl, cyclohexyl, cyclopentenyl, or cyclohexenyl ring, each of which is unfused and each of which is, independently of each other, unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

admantyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR 1d , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ; or

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1b ;

R 1c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]nundecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, each of which is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —SR 1aa , —NH 2 , —OR 1aa , —NHR 1aa , —N(R 1aa ) 2 —C(O)R 1aa , —S(O) 2 R 1aa , —S(O) 2 NH 2 , —S(O) 2 N(R 1aa ) 2 , —C(O)NH 2 , —C(O)N(H)(R 1aa ), —C(O)N(R 1aa ) 2 , —C(O)OH, —C(O)OR 1aa , —OR 1h , —N(H)R 1h ), —N(R 1d )(R 1h ) and —R 1h ;

R 1aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1bb ;

R 1bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), —S(O) 2 N(R 1d ) 2 and —R 1h ;

R 1d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 1f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, —R 1h , or R 1g ; and

R 1g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of R 1h ;

R 1h is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1h is unsubstituted or substituted with one or two or three or four or five substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), and —S(O) 2 N(R 1d ) 2 .

6. The compound of claim 3 , or a therapeutically acceptable salt thereof, in which

R 1 is

unfused phenyl, unsubstituted or substituted with one, two, three, or four substituents selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1 a, —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1d , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

isoxazolyl, oxazolyl, pyridyl, thienyl, pyrrolyl, tetrahydropyranyl, or pyrazolyl, each of which is unfused or fused with a cyclopentane, cyclohexane, or benzene ring, in which the pyridyl, thienyl, pyrrolyl, or pyrazolyl rings and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one, two, three or four substitutents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1a , —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a , —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , —SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ; or

cyclopentyl or cyclohexyl, each of which is fused with a benzene or pyridine ring, in which the cyclopentyl or cyclohexyl ring and the benzene ring are, independently of each other, unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1a , —OR 1 a, —NHR 1a , —N(R 1a ) 2 , —CN, —SR 1a , —SO 2 R 1a —SO 2 NH 2 , —SO 2 N(H)(R 1a ), —SO 2 N(R 1a ) 2 , —C(O)R 1a , —C(O)OH, —C(O)OR 1a , —C(O)NH 2 , —C(O)N(H)(R 1a ), —C(O)N(R 1a ) 2 , —OR 1e , 13 SR 1e , —SO 2 R 1e , —SO 2 N(H)(R 1e ), —SO 2 N(R 1d )(R 1e ), —NH(R 1e ), —N(R 1d )(R 1e ), —NHC(O)R 1f , —N(R 1d )C(O)R 1f , and —R 1c ;

adamantyl unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —NO 2 , —OH, —NH 2 , —R 1d , —OR 1d , —NHR 1d , —N(R 1d ) 2 , —CN, —SR 1d , —SO 2 R 1d , —SO 2 NH 2 , —SO 2 N(H)(R 1d ), —SO 2 N(R 1d ) 2 , —C(O)R 1d , —COOH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), and —C(O)N(R 1d ) 2 ; or

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1b ;

R 1c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]undecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, each of which is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of ═O, —Cl, —F, —Br, —I, —NO 2 , —CN, —OH, —R 1aa , —NH 2 , —OR 1aa , —SR 1aa , —NHR 1aa , —N(R 1aa ) 2 , —C(O)R 1aa , —S(O) 2 R 1aa , —S(O) 2 NH 2 , —S(O) 2 N(R 1aa ) 2 , —C(O)N H 2 , —C(O)N(H)(R 1aa ), —C(O)N(R 1aa ) 2 , —C(O)OH, —C(O)OR 1aa , —OR 1h , —N(H)R 1h ), —N(R 1d )(R 1h ) and —R 1b ;

R 1aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 1bb ;

R 1bb is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d —C(O)OH, —C(O)OR 1d , —C(O)NH 2 , —C(O)N(H)(R 1d ), —C(O)N(R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), —S(O) 2 N(R 1d ) 2 and —R 1b ;

R 1d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl or —C 6 -alkyl;

R 1e is phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, furyl, thienyl, imidazolyl, thiazolyl, pyrrolidinyl, piperidyl, azepinyl, tetrahydrofuryl, tetrahydropyranyl or oxazolyl; wherein each R 1e is unsubstituted or substituted with one, two, three or four substituents independently selected from the group consisting of ═O, —NO 2 , —CN, —Cl, —F, —Br, —I, —OH, —OR 1aa , —SR 1aa , —NH 2 , —NHR 1aa , and —N(R 1aa ) 2 ;

R 1f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, —R 1h , or R 1g ;

R 1g is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one substituent selected from the group consisting of —R 1h ;

and R 1h is cycloalkyl, cycloalkenyl, aryl, heteroaryl or heterocycle, in which each R 1h is unsubstituted or substituted with one or two or three or four or five substituents independently selected from the group consisting of —F, —Cl, —Br, —I, —NO 2 , —CN, haloalkyl, haloalkoxy, —NH 2 , —OH, —OR 1d , —SR 1d , —S(O) 2 R 1d , —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, ——C 6 -alkyl, —N(R 1d ) 2 , —NHR 1d , —C(O)OH, —C(O)OR 1d , —C(O)N H 2 , —C(O)N(H)(R 1d ), —C(O) N (R 1d ) 2 , —S(O) 2 NH 2 , —S(O) 2 N(H)(R 1d ), and —S(O) 2 N(R 1d ) 2 .

7. The compound of claim 3 , or a therapeutically acceptable salt thereof, in which

m is 0, 1 or 2;

R 1 is

unfused phenyl, unsubstituted or substituted with one, two, three, or four substituents selected from the group consisting of —R 1a , —N(R 1a ) 2 , —SR 1a , —O(pyridyl), —O(phenyl), —O(pyrazinyl), pyrrolyl or morpholinyl; in which the phenyl moiety of —O(phenyl) is unsubstituted or substituted with one substituent independently selected from the group consisting of —Cl, —F, —Br, and —I;

unfused pyridyl, unsubstituted or substituted with one —R 1a substituent;

pyridyl fused with a cyclopentane, cyclohexane, or benzene ring, in which the pyridyl and the cyclopentane ring are, independently of each other, unsubstituted or substituted with one —R 1a substituent;

thienyl, pyrrolyl, or pyrazolyl, each of which is unfused and each of which is independently unsubstituted or substituted with one or two substitutents independently selected from the group consisting of —R la , unsubstituted phenyl and phenyl substituted with one —R 1a substituent; or

R 1a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl or —C 6 -alkyl.

8. The compound of claim 3 , or a therapeutically acceptable salt thereof, in which

m is 0, 1 or 2;

R 1 is

unfused phenyl, unsubstituted or substituted with one, two, three, or four substituents selected from the group consisting of —C 1 -alkyl, —N(C 1 -alkyl) 2 , —S(C 1 -alkyl), —O(pyridyl), —O(phenyl), —O(pyrazinyl), pyrrolyl or morphlinyl; in which the phenyl moiety of —O(phenyl) is unsubstituted or substituted with one —F substituent;

unfused pyridyl, unsubstituted or substituted with one —C 1 -alkyl substituent;

pyridyl fused with a cyclopentane, cyclohexane, or benzene ring, in which the pyridyl ring and the cyclopentane ring are, independently of each other, unsubstituted or susbstituted with one —C 1 -alkyl substituent;

thienyl, pyrrolyl, or pyrazolyl, each of which is unfused and each of which is independently unsubstituted or substituted with one or two substitutents independently selected from the group consisting of —C 1 -alkyl, unsubsubstituted phenyl and phenyl substituted with one —C 1 -alkyl; or

9. The compound of claim 3 , or a therapeutically acceptable salt thereof, in which

m is 1 or 2;

and

R 1 is 2-methylphenyl, 2-(morpholin-4-yl)phenyl, 2-(dimethylamino)phenyl, 2-(pyridine-2-yloxy)phenyl, phenyl, 3-(dimethylamino)phenyl, 2-(methylthio)phenyl, 2-(4-fluorophenoxy)phenyl, 3-(pyrazin-2-yloxy)phenyl, 2-(1H-pyrrol-1-yl)phenyl, 4-(pyridine-2-yloxy)phenyl, 3-(pyridine-2-yloxy)phenyl, 4-(morpholin-4-yl)phenyl, pyridine-4-yl, pyridine-3-yl, pyridine-2-yl, quinolin-4-yl, 3-methylpyridin-4-yl, 6,7-dihydro-5H-cyclopenta[b]pyridine-3-yl, 5,6,7,8-tetrahydroquinolin-3-yl, 1-methyl-1H-pyrrol-2-yl, 2-methylthien-3-yl, 3-methyl-1-phenyl-1H-pyrazol-5-yl, 1,5-dimethyl-1H-pyrazol-4-yl, 2,3-dihydro-1H-inden-1-yl, or 5,6,7,8-tetrahydroquinolin-5-yl.

10. A compound, or a therapeutically acceptable salt thereof, is selected from the group consisting of:

1-(2,3-dichlorophenyl)-N-[(2-methylphenyl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(1R)-2,3-dihydro-1H-inden-1-yl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-morpholin-4-ylphenyl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(pyridin-4-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(dimethylamino)phenyl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(pyridin-3-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(pyridin-2-yloxy)phenyl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-pyridin-2-ylethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(quinolin-4-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-pyridin-3-ylethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(2-methylphenypethyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(3-methylpyridin-4-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(1-methyl-1H-pyrrol-2-yl)methyl]-1H-tetraazol-5-amine;

N-[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]-5,6,7,8-tetrahydroquinolin-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-methylthien-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[3-(dimethylamino)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(4-fluorophenoxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(methylthio)benzyl]-1H-tetraazol-5-amine;

N-benzyl-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[3-(pyrazin-2-yloxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(1H-pyrrol-1-yl)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[4-(pyridin-2-yloxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[3-(pyridin-2-yloxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(3-methyl-1-phenyl-1H-pyrazol-5-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(1S)-2,3-dihydro-1-H-inden-1-yl]tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(6,7-dihydro-5H-cyclopenta[b]pyridin-3-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(5,6,7,8-tetrahydroquinolin-3-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(4-morpholin-4-ylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-methylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-2,3-dihydro-1-benzofuran-3-yl-1H-tetraazol-5-amine;

N-(1,1′-biphenyl-2-ylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-ethoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-isopropoxybenzyl)-1H-tetraazol-5-amine;

N-(2-adamantylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-phenoxypyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(2-methoxyphenoxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-3,4-dihydro-2H-chromen-4-yl-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(5-methyl-3-phenylisoxazol-4-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(2-methylphenoxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N[2-(pyrazin-2-yloxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(3-nitrobenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-methoxypyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,2,2-trifluoroethoxy)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(4-methylpiperazin-1-yl)benzyl]-1H-tetraazol-5-amine;

N-(5-chloro-2-methoxybenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(6-fluoro-4H-1,3-benzodioxin-8-yl)methyl]-1H-tetraazol-5-amine;

4-({[1-(2,3-dichlorophenyl)-1H-tetraazol1-5-yl]amino}methyl)-3-methoxybenzonitrile;

1-(2,3-dichlorophenyl)-N-(quinolin-3-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-piperidin-1-ylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[(6-methylpyridin-3-yl)oxy]pyridin-3-yl}methyl)-1H-tetraazol-5-amine;

N-[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]-2,3-dihydrofuro[2,3-b]pyridin-3-amine;

1-(2,3-dichlorophenyl)-N-(2,4-difluorobenzyl)-1H-tetraazol-5-amine;

N-(2-chloro-4fluorobenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-[3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)phenyl]-N-methylacetamide;

1-(2,3-dichlorophenyl)-N-[4-fluoro-2-(trifluoromethyl)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(5-fluoro-2-methylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,4,5-trifluorobenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(5-fluoro-2,3-dihydro-1H-inden-1-yl)-1H-tetraazol-5-amine;

N-({6-chloro-5-fluoro-2-[(1-methylpyrrolidin-3-yl)oxy]pyridin-3-yl}methyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[4-(4-fluorophenyl)-1,3-thiazol-5-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(4-thien-3-yl-1,3-thiazol-5-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(pyridin-2-ylmethyl)-1H-tetraazol-5-amine;

3-{[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-ylamino]-methyl}-phenol;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[3-(pyrimidin-2-yloxy)-benzyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[3-(5-methyl-pyridin-2-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[3-(1-methyl-piperidin-4-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[3-(5-nitro-pyridin-2-yloxy)-benzyl]amine;

[3-(5-Chloro-pyridin-2-yloxy)-benzyl]-[1-(2,3-dichloro-phenyl)-1H-tetrazol-5-yl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[3-(3-methyl-pyridin-2-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[3-(4-methyl-pyridin-2-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(1-methyl-piperidin-4-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(1-methyl-piperidin-4-yloxy)-pyridin-3-ylmethyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(1-methyl-piperidin-3-yloxy)-pyridin-3-ylmethyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(1-methyl-pyrrolidin-3-yloxy)-pyridin-3-ylmethyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl)-pyridin-3-ylmethyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-methyl-3-(pyridin-2-yloxy)-benzyl]amine;

2-{[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-ylamino]-methyl}-benzonitrile;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(2-methyl-pyridin-3-yloxy)-pyridin-3-ylmethyl]-amine;

[2-(5-Chloro-pyridin-3-yloxy)-pyridin-3-ylmethyl]-[1-(2,3-dichloro-phenyl)-1H-tetrazol-5-y 1 ]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[6-methyl-2-(pyridin-3-yloxy)-pyridin-3-ylmethyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(pyridin-3-yloxy)-pyridin-3-ylmethyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(5-fluoro-pyridin-3-yloxy)-pyridin-3-ylmethyl]-amine;

[2-(2-Chloro-pyridin-3-yloxy)-pyridin-3-ylmethyl]-[1-(2,3-dichloro-phenyl)-1H-tetrazol-5-yl]amine;

[2-(6-Chloro-5-fluoro-pyridin-3-yloxy)-pyridin-3-ylmethyl]-[1-(2,3-dichloro-phenyl)-1H-tetrazol-5-yl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[5-fluoro-2-(pyridin-2-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[5-fluoro-2-(pyridin-3-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[5-fluoro-2-(2,2,2-trifluoro-ethoxy)-benzyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[4,5-difluoro-2-(pyridin-2-yloxy)-benzyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[4-fluoro-2-(pyridin-2-yloxy)-benzyl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-(4-fluoro-2-pyridin-2-yl-benzyl)amine;

[6-Chloro-5-fluoro-2-(2,2,2-trifluoro-ethoxy)-pyridin-3-ylmethyl]-[1-(2,3-dichloro-phenyl)-1H-tetrazol-5-yl]amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[4-fluoro-2-(3-fluoro-pyridin-2-yl)-benzyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[4-fluoro-2-(6-fluoro-pyridin-3-yl)-benzyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[2-(5,6-difluoro-pyridin-3-yl)-4-fluoro-benzyl]-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[4,5-difluoro-2-(2,2,2-trifluoro-ethoxy)-benzyl]-amine;

4-[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-ylamino]-4,5-dihydro-cyclopenta[b]thiophen-6-one;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-(4-methyl-oxazol-5-ylmethyl)-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-(6-fluoro-2-methyl-pyridin-3-ylmethyl)-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-[4-fluoro-2-(2,2,2-trifluoro-ethoxy)-benzyl]-amine;

[4-(4-Chloro-phenyl)-thiazol-5-ylmethyl]-[1-(2,3-dichloro-phenyl)-1H-tetrazol-5-yl]amine;

1-(2,3-dichlorophenyl)-N-(quinolin-5-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-morpholin-4-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(pyridin-3-yloxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-pyridin-3-ylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-pyridin-4-ylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(4-methyl-1,3-thiazol-5-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

{1-[2-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl) phenyl]piperidin-4-yl}methanol;

1-(2,3-dichlorophenyl)-N-[(2-ethylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-fluoropyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{2-[2-(diethylamino)ethoxy]benzyl}-1H-tetraazol-5-amine;

N-[(2chloro-5-fluoropyridin-3-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[4-fluoro-3-(pyrazin-2-yloxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(3-fluoropyridin-4-yl)methyl]-1H-tetraazol-5-amine;

N-[(3-chloropyridin-4-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2,2-difluoro-1,3-benzodioxol-4-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,6-dimethylmorpholin-4-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(6-fluoro-2,3-dihydro-1H-inden-1-yl)-1H-tetraazol-5-amine;

N-[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]-2,3-dihydrospiro[indene-1,4′-piperidin]-3-amine;

N-[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]-1′-methyl-2,3-dihydrospiro[indene-1,4′-piperidin]-3-amine;

N-[(2-chloropyridin-3-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-[(2-bromopyridin-3-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-fluoropyridin-4-yl)methyl]-1H-tetraazol-5-amine;

N-[(2-bromopyridin-4-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-pyrrolidin-1-ylpyridin-4-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-phenylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4-ethoxyphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4-fluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4-methylphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

N-{[2-(4-chlorophenyl)pyridin-3-yl]methyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-{[2-(3-chlorophenyl)pyridin-3-yl]methyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(3-methylphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-methoxyphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(3,4-difluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-fluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[3-(trifluoromethoxy)phenyl]pyridin-3-yl}-methyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-methylphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(3-fluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[4-(trifluoromethoxy)phenyl]pyridin-3-yl}-methyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[2-(trifluoromethoxy)phenyl]pyridin-3-yl}methyl)-1H-tetraazol-5-amine;

N-{[2-(2-chlorophenyl)pyridin-3-yl]methyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-phenoxyphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[2-(trifluoromethyl)phenyl]pyridin-3-yl}methyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-thien-2-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-thien-3-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

N-(2,3′-bipyridin-3-ylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-(2,4′-bipyridin-3-ylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(1,3-thiazol-2-pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[5-fluoro-2-(4-fluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-methoxyphenyl)-6-(trifluoromethyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(5-fluoro-2-methoxyphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4-fluoro-2-methoxyphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-fluoro-6-methoxyphenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,4-difluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,3-difluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,5-difluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,4,6-trifluorophenyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-pyrrolidin-1-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-piperidin-1-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

N-[(2-azetidin-1-ylpyridin-3-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(3-pyrrolidin-1-ylpyridin-4-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(5-fluoro-2-pyrrolidin-1-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

N-benzyl-3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)pyridin-2-amine;

1-(2,3-dichlorophenyl)-N-{[2-(3,3-difluoroazetidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

N-[(2-chloro-3-pyrrolidin-1-ylpyridin-4-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-[(2-azetidin-1-yl-5-fluoropyridin-3-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2,5-difluoro-6-pyrrolidin-1-ylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(2-phenyl-3-pyrrolidin-1-ylpyridin-4-yl)methyl]-1H-tetraazol-5-amine;

N-[(2-azepan-1-ylpyridin-3-yl)methyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-pyrrolidin-1-yl-6-(trifluoromethyl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

N-benzyl-3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)-N-methylpyridin-2-amine;

1-(2,3-dichlorophenyl)-N-{[2-(trifluoromethyppyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[1-(4-methoxyphenyl)-3-methyl-1H-pyrazol-5-yl]methyl}-1H-tetraazol-5-amine;

N-{[1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5-yl]nethyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-1H-tetraazol-5-amine;

N-(cyclohexylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,3,6-trifluorobenzyl)-1H-tetraazol-5-amine;

N-(2-chloro-3,6-difluorobenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(3-methoxy-2-methylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(5-fluoro-2-methoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,3-dimethylbenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,3-dihydro-1,4-benzodioxin-5-ylmethyl)-1H-tetraazol-5-amine;

N-(1,3-benzodioxol-4-ylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-1H-tetraazol-5-amine;

N-(1,3-benzodioxol-5-ylmethyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,3-dimethoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(3,5-dimethoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,4-dimethoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,5-dimethylbenzyl)-1H-tetraazol-5-amine;

N-(3-chloro-2-methylbenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-(5-chloro-2-methylbenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,5-difluorobenzyl)-1H-tetraazol-5-amine;

N-(5-chloro-2-fluorobenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N[2-chloro-5-(trifluoromethyl)benzyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,5-dimethoxybenzyl)-1H-tetraazol-5-amine;

N-(2-chloro-6-methylbenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2,3-difluorobenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(3-isobutylbenzyl)-1H-tetraazol-5-amine;

N-(2-chlorobenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-(3-chlorobenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

N-(4-chlorobenzyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-fluorobenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(3-fluorobenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(4-fluorobenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(2-methoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(3-methoxybenzyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(trifluoromethyl)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[3-(trifluoromethyl)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[4-(trifluoromethyl)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(difluoromethoxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(trifluoromethoxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[3-(trifluoromethoxy)benzyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[4-(trifluoromethoxy)benzyl]-1H-tetraazol-5-amine;

N-[2-(benzyloxy)benzyl]-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(methylsulfonyl)benzyl]-1H-tetraazol-5-amine;

N-{[2-(3-azabicyclo[3.2.2]non-3-yl)pyridin-3-yl]methyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(3,3-difluoropiperidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4,4-difluoropiperidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2[4-(trifluoromethyl)piperidin-1-yl]pyridin-3-yl}methyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(3-fluoropiperidin-1-yppyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4-fluoropiperidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[3-(trifluoromethyl)pyrrolidin-1-yl]pyridin-3-yl}methyl)-1H-tetraazol-5-amine;

1-[3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)pyridin-2-yl]pyrrolidin-3-ol;

1-(2,3-dichlorophenyl)-N-{[2-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2-methylpyrrolidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(2,5-dimethylpyrrolidin-1-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(1,4-oxazepan-4-yl)pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-{[2-(4-methyl-1,4-diazepan-1-yl)-pyridin-3-yl]methyl}-1H-tetraazol-5-amine;

tert-butyl 4-[3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)yridin-2-yl]-1,4-diazepane-1-carboxylate;

N-{[2-(1,4-diazepan-1-yl)pyridin-3-yl]methyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

tert-butyl 3-[3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)pyridin-2-yl]-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate;

N-{[2-(3,6-diazabicyclo[3.2.0]hept-3-yl)pyridin-3-yl]methyl}-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

benzyl (1S,5S)-6-[3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)pyridin-2-yl]-3,6-diazabicyclo[3.2.0]heptane-3-carboxylate;

N-({2-[(1R,5S)-3,6-diazabicyclo[3.2.0]hept-6-yl]pyridin-3-yl}methyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

benzyl (1R,5R)-6-[3-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)pyridin-2-yl]-3,6-diazabicyclo[3.2.0]heptane-3-carboxylate;

N-({2-[(1S,5R)-3,6-diazabicyclo[3.2.0]hept-6-yl]pyridin-3-yl}methyl)-1-(2,3-dichlorophenyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-({2-[(3aR,7aS)-octahydro-2H-4,7-epoxyisoindol-2-yl]pyridin-3-yl}methyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(7,8-dimethoxy-1,2,3,4-tetrahydro-1,4-methanonaphthalen-2-yl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(5-methoxy-2,3-dihydro-1H-inden-1-yl)methyl]-1H-tetraazol-5-amine;

1-({[1-(2,3-dichlorophenyl)-1H-tetraazol-5-yl]amino}methyl)indan-4-ol;

1-(2,3-dichlorophenyl)-N-[(6,7-dimethoxy-2,3-dihydro-1H-inden-1-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[(4-methoxy-2,3-dihydro-1H-inden-1-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[4-(3-fluoropiperidin-1-yl)-2,3-dihydro-1H-inden-1-yl]-1H-tetraazol-5-amine;

[1-(2,3-Dichloro-phenyl)-1H-tetrazol-5-yl]-(6′-fluoro-[2,3′]bipyridinyl-3-ylmethyl)-amine;

1-(2,3-dichlorophenyl)-N-[(2,4-dimethylpyridin-3-yl)methyl]-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-(quinolin-8-ylmethyl)-1H-tetraazol-5-amine;

1-(2,3-dichlorophenyl)-N-[2-(4-methylphenoxy)benzyl]-1H-tetraazol-5-amine; and

1-(2,3-dichlorophenyl)-N-{2-[(1-methylpiperidin-3-yl)oxy]benzyl}-1H-tetraazol-5-amine.

11. The compound of claim 2 having Formula (II),

or a therapeutically acceptable salt thereof, in which

Z is —H;

A is CR 6 ;

B is CR 7 ;

E is CR 8 ;

R 3 is —NH 2 , —R 3a , —OR 3a , —NHR 3a , —N(R 3a ) 2 , —NHC(O)R 3f , —N(R 3d )C(O)R 3f , —R 3c , —OR 3e , —SR 3e , —NH(R 3e ), or —N(R 3d )(R 3e );

R 3a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or R 3b ;

R 3c is cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, azetidinyl, naphthyl, quninolinyl, isoquinolinyl, phenyl, furyl, imidazolyl, isothiazolyl, oxazolyl, oxazolinyl, isoxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolinyl, tetrahydrofuryl, tetrahydrothienyl, thiazolyl, thienyl, pyrrolidinyl, dioxolanyl, pyrazolinyl, pyrazolidinyl, pyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, 2-azabicyclo[2.2.2]octyl, 2-oxa-5-azabicyclo[2.2.2]octyl, 2,5-diazabicyclo[2.2.2]octyl, 2-azabicyclo[2.2.1]heptyl, 2-oxa-5-azabicyclo[2.2.1]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, 2-azabicyclo[2.1.1]hexyl, 5-azabicyclo[2.1.1]hexyl, 3-azabicyclo[3.2.0]heptyl, 3,6-diazabicyclo[3.2.0]heptyl, octahydrocyclopenta[c]pyrrolyl, hexahydro-1H-furo[3,4-c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, 3-azabicyclo[3.1.1]heptyl, 6-oxa-3-azabicyclo[3.1.1]heptyl, octahydro-1H-4,7-methanoisoindolyl, octahydro-1H-4,7-epoxyisoindolyl, 8-azabicyclo[3.2.1]octyl, 3-oxa-8-azabicyclo[3.2.1]octyl, 1,4-diazepanyl, 1,4-diazabicyclo[3.2.2]nonyl, 1,4-diazatricyclo[4.3.1.1 3,8 ]undecyl, 3,10-diazabicyclo[4.3.1]decyl, or 8-oxa-3-azabicyclo[3.2.1]octyl, each of which is unsubstituted or substituted with one, two, three, or four substituents independently selected from the group consisting of —Cl, —F, —Br, —I, —OH, —R 3aa —NH 2 , —OR 3aa , —SR 3aa , —NHR 3aa , and —N(R 3aa ) 2 ;

R 3d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 3aa is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, or —R 3bb ;

R 3f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, or R 3g ;

v is one, two, or three, and when v is two or three, R 3 may be the same or different;

R 4 is —Cl;

R 5 is Cl;

R 6 is —H;

R 7 is —H;

R 8 is —H.

12. The compound of claim 11 , or a therapeutically acceptable salt thereof, in which

R 3 is —NH 2 , —R 3a , —OR 3a , —NH(R 3a ), —N(R 3a ) 2 , —NHC(O)R 3f , or —N(R 3d )C(O)R 3f ;

R 3a is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl or R 3b ;

R 3b is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl, each of which is substituted with one or two or three substituents independently selected from the group consisting —NH 2 , —CN, —OH, —OR 3d , —N(R 3d ) 2 , and —NHR 3d ;

R 3d is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, or —C 6 -alkyl;

R 3f is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl, —C 6 -alkyl, aryl, heteroaryl, or R 3g ;

v is one, two, or three, and when v is two or three, R 3 may be the same or different.

13. The compound of claim 11 , or a therapeutically acceptable salt thereof, in which

R 3 is —C 1 -alkyl, —C 2 -alkyl, —C 3 -alkyl, —C 4 -alkyl, —C 5 -alkyl or —C 6 -alkyl; and

v is one.

14. The compound of claim 11 , or a therapeutically acceptable salt thereof, in which

R 3 is —C 1 -alkyl; and v is one.

15. The compound of claim 13 , or a therapeutically acceptable salt thereof, is 1-(2,3-dichlorophenyl)-N-(2-methylphenyl)-1H-tetraazol-5-amine.

16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

17. A method for alleviating or inhibiting the progress of chronic inflammatory pain, neurodegeneration, spinal cord injury, depression or neuropathic pain comprising administering to a patient in need thereof a pharmaceutical composition of claim 16 .

18. A method for alleviating or inhibiting the progress of chronic inflammatory pain or neuropathic pain comprising administering to a patient in need thereof a therapeutically effective amount a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

19. A method for inhibiting P2X7 activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

20. A medicament for alleviating or inhibiting the progress of chronic inflammatory pain or neuropathic pain in a patient, said medicament comprising a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

21. A method for alleviating or inhibiting the progress of inflammation and inflammatory pain comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

22. A method for alleviating or inhibiting the progress of neurodegeneration comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

23. A method for alleviating or inhibiting the progress of depression comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

24. A method for alleviating or inhibiting the progress of spinal cord injury comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 or 2 , or a therapeutically acceptable salt thereof.

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 9, 2013

From: ABBOTT LABORATORIES

To: ABBVIE INC.

Reel/Frame 030182/0547 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 20, 2013

From: ABBOTT LABORATORIES

To: ABBVIE INC.

Reel/Frame 029838/0299 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 18, 2013

From: CARROLL, WILLIAM A.; PEREZ-MEDRANO, ARTURO; FLORJANCIC, ALAN S.; NELSON, DEREK W.; PEDDI, SRIDHAR; LI, TONGMEI; BUNNELLE, ERIC M.; HIRST, GAVIN; LI, BIQIN C.

To: ABBOTT LABORATORIES

Reel/Frame 029824/0761 →