Sulfonamides

A compound of formula II

• wherein
• R1 is aryl or is heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl, each of which is unsubstituted or substituted by one or more substituents selected from the group consisting of halogen, CF3, OCF3, NO2 and CN;
• R2, R3, R4, R2′, R3′, and R4′ are each independently hydrogen, lower alkyl or CF3;
• R5 is cycloalkyl, aryl or heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl, wherein cycloalkyl, aryl or heteroaryl are unsubstituted or substituted by one or more substituents selected from the group consisting of
• halogen,
• lower alkyl,
• CHO,
• CN,
• hydroxy,
• lower alkyloxy,
• lower alkinyloxy,
• —OCF3,
• OCHF2,
• OCH2F,
• —OC(O)-lower alkyl,
• —OC(O)—NR′R″,
• —O—(CH2)n-heterocycloalkyl wherein heterocycloalkyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl,
• —O—(CH2)n-heteroaryl wherein heteroaryl is selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl which is unsubstituted or substituted by lower alkyl,
• —O—(CH2)n-aryl,
• —(CH2)n—C(O)NR′R″,
• —(CH2)n—C(O)O-lower alkyl,
• —(CH2)n—C(O)OH,
• —(CH2)n—C(O)O-lower alkinyl,
• —C(O)-heterocycloalkyl wherein heterocycloalkyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl optionally substituted by COOH,
• —C(O)-cycloalkyl,
• —C(O)-aryl,
• —NR′R″,
• nitro,
• —S(O)2-lower alkyl,
• —S(O)2-cycloalkyl,
• —S(O)2-heterocycloalkyl wherein heterocycloalkyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl,
• —S(O)2-aryl, and
• —S(O)2—NR′R″,
• or is
• R′ and R″ are each independently hydrogen,
• lower alkyl,
• cycloalkyl,
• heterocycloalkyl selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl,
• heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl,
• di-lower alkylamino,
• —CH2CF3,
• —CH2CHF2,
• —CH2CH2F,
• —C(O)-lower alkyl,
• —C(O)O-lower alkyl or
• —C(O)-cycloalkyl;
• X is a bond, lower alkyl or lower alkenyl;
• and
• n is 0, 1, 2 or 3;
• or a pharmaceutically acceptable acid addition salt, optically pure enantiomer, racemate or diastereomeric mixture thereof.

A pharmaceutical composition comprising a compound of formula I

• wherein
• R1 is aryl or is heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl, each of which is unsubstituted or substituted by one or more substituents selected from the group consisting of
• halogen,
• lower alkyl,
• lower alkyl substituted by halogen,
• —O-lower alkyl substituted by halogen,
• NO2, and
• CN;
• R2, R3, R4, R2′, R3′, and R4′ are each independently hydrogen, lower alkyl, phenyl or lower alkyl substituted by halogen;
• R5 is aryl or is heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl, each of which is unsubstituted or substituted by one or more substituents, selected from the group consisting of
• halogen,
• lower alkyl,
• lower alkoxy,
• CN,
• nitro,
• amino,
• hydroxy,
• lower alkyl substituted by hydroxy, and
• lower alkyl substituted by halogen,
• or is aryl or is heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl, each of which is substituted by
• —C(O)—NR″2,
• —(CR2)m—C(O)—R′,
• —(CH2)m-heterocycloalkyl,
• —(CH2)m-heteroaryl wherein heteroaryl is selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl which is unsubstituted or substituted by —(CH2)m-lower alkoxy, lower alkyl, —(CH2)m—O-benzyl or CH2OH,
• —O—C(O)-lower alkyl,
• —O—C(O)—NR2,
• —O—(CH2)m—C(O)OH,
• —O-lower alkinyl,
• —O-lower alkyl substituted by halogen,
• —O—(CH2)m-heterocyclyl,
• —O—(CH2)m-phenyl which is unsubstituted or substituted by hydroxy,
• —O—(CH2)m-heteroaryl wherein heteroaryl is selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl which is unsubstituted or substituted by lower alkyl,
• —(CH2)m—NH—C(O)R′,
• —(CH2)m—NH—S(O)2—R′,
• —S(O)2-lower alkyl,
• —S(O)2-heterocyclyl, or
• —S(O)2NH-cycloalkyl,
• or is cycloalkyl;
• R′ is hydrogen,
• lower alky,
• lower alkinyloxy,
• hydroxy,
• cycloalkyl,
• heterocycloalkyl selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl, which is unsubstituted or substituted by one or more substituents selected from COOH, —C(O)O-lower alkyl, —CH2C(O)O-lower alky, halogen and lower alkyl,
• or is phenyl,
• benzyl,
• heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl,
• —(CH2)m-lower alkoxy or
• —(CHR)m—C(O)O-lower alkyl;
• R″ is hydrogen,
• cycloalkyl, which is unsubstituted or substituted by one or more halogen atoms,
• lower alkyl,
• lower alkyl substituted by halogen,
• lower alkyl substituted by hydroxy,
• —(CH2)m-heterocycloalkyl wherein heterocycloalkyl is selected from the group consisting of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl,
• —NR2,
• heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, tetrazolyl, [1,2,4]triazolyl, [1,2,4]oxadiazolyl, oxazolyl, indanyl, benzo[1,3]dioxolyl, benzofuranyl and isoxazolyl,
• benzyl or
• —(CHR)m—C(O)O-lower alkyl;
• R is hydrogen or lower alkyl;
• R6 is hydrogen or lower alkyl;
• X is —CHR—;
• and
• m is 0, 1, 2 or 3;
• or a pharmaceutically acceptable acid addition salt, optically pure enantiomer, racemate or diastereomeric mixture thereof
• and a pharmaceutically acceptable carrier.