Heterocyclic arylsulphones suitable for treating disorders that respond to modulation of the serotonin 5HT6 receptor

1. A compound of the formula (I)

wherein

n is 1;

G is CH 2 or CHR 3 ;

R 1 is H, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl substituted by C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, fluorinated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 3 -C 6 -alkenyl, fluorinated C 3 -C 6 -alkenyl, formyl, acetyl, propionyl;

R 2 , R 3 and R 4 are, independently of each other, H, methyl, fluoromethyl, difluoromethyl, or trifluoromethyl;

A is 1,4-phenylene or 1,3-phenylene, which is optionally substituted by one, two, three or four substituents selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy;

E is NR 5 or CH 2 , wherein R 5 is H or C 1 -C 3 -alkyl;

Ar is a radical of the formula A, B, C, D, or E

wherein

R a is halogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, fluorinated C 2 -C 6 -alkenyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, phenylsulfonyl, benzyloxy, phenoxy, where the phenyl radical in the 3 last-mentioned radicals may be unsubstituted or may carry 1 to 3 substituents selected from the group consisting of C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl and halogen, CN, nitro, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, fluorinated C 1 -C 6 -alkylcarbonylamino, carboxy, NH—C(O)—NR 6 R 7 , NR 6 R 7 , NR 6 R 7 —C 1 -C 6 -alkylene, and O—NR 6 R 7 , where R 6 and R 7 are, independently of each other, H, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy or may form, together with N, a 4-, 5- or 6-membered saturated or unsaturated ring, or is a saturated or unsaturated aromatic or non-aromatic 3- to 7-membered heterocyclic ring comprising as ring members 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S, and/or 1, 2 or 3 heteroatom-containing groups selected from NR 8 , where R 8 is H, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkylcarbonyl or fluorinated C 1 -C 4 -alkylcarbonyl, SO, SO 2 , or CO, and where the heterocyclic ring may carry 1, 2 or 3 substituents selected from the group consisting of hydroxy, halogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, and C 1 -C 6 -alkoxy;

R b and R c , independently of each other, are H, CH 3 , OCH 3 , CHF 2 , OCHF 2 , CF 3 , or OCF 3 ;

with the proviso that R a is not F, CH 2 F, CHF 2 , CF 3 or OCF 3 if A is 1,4-phenylene, and R b and R c are H;

and

physiologically tolerated acid addition salts thereof.

2. The compound as claimed in claim 1 , wherein R 1 is hydrogen, methyl, ethyl, n-propyl, 2-fluoroethyl, 3-fluoropropyl, 3-hydroxypropyl, cyclopropylmethyl, or allyl.

3. The compound as claimed in claim 2 , wherein R 1 is hydrogen, n-propyl or allyl.

4. The compound as claimed in claim 1 , wherein R 2 , R 3 and R 4 are H.

5. The compound as claimed in claim 1 , wherein E is NH.

6. A compound of the formula (I)

wherein

n is 1;

G is CH 2 or CHR 3 ;

R 1 is H, C 1 -C 6 -alkyl, C 1 -C 6 -alkyl substituted by C 3 -C 6 -cycloalkyl, C 1 -C 6 -hydroxyalkyl, fluorinated C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 3 -C 6 -alkenyl, fluorinated C 3 -C 6 -alkenyl, formyl, acetyl, or propionyl;

R 2 , R 3 and R 4 are, independently of each other, H, methyl, fluoromethyl, difluoromethyl, or trifluoromethyl;

A is 1,4-phenylene or 1,3-phenylene, which is optionally substituted by one, two, three or four substituents selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy;

E is NR 5 or CH 2 , wherein R 5 is H or C 1 -C 3 -alkyl;

Ar is a radical of the formula A, B, C, D, or E

wherein

R a is selected from radicals of the formula R a′

wherein

Y is N, CH or CF, R a1 and R a2 are independently of each other selected from the group consisting of C 1 -C 2 -alkyl, fluorinated C 1 -C 2 -alkyl and C 1 -C 2 -alkoxy, provided for Y being CH or CF one of the radicals R a1 or R a2 may also be hydrogen or fluorine, or R a1 and R a2 together form a radical (CH 2 ) m wherein 1 or 2 of the hydrogen atoms may be replaced by fluorine, hydroxy, C 1 -C 2 -alkyl or C 1 -C 2 -alkoxy, wherein one CH 2 moiety may be replaced by O, S, SO, SO 2 or NR c , wherein R d is H or C 1 -C 2 -alkyl, and wherein m is 2, 3, 4, 5 or 6;

R b and R c , independently of each other, are H, CH 3 , OCH 3 , CHF 2 , OCHF 2 , CF 3 , or OCF 3 ;

and

physiologically tolerated acid addition salts thereof.

7. The compound as claimed in claim 1 , wherein the radical R a is selected from the group consisting of halogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 6 -alkoxy, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, CN, nitro, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, fluorinated C 1 -C 6 -alkylcarbonylamino, or a saturated or unsaturated 3- to 7-membered heterocyclic ring comprising as ring members 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S and/or 1, 2 or 3 heteroatom-containing groups selected from NR 8 , where R 8 is as defined in claim 1 , SO, SO 2 and CO, and where the heterocyclic ring may carry 1, 2 or 3 substituents selected from the group consisting of hydroxy, halogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy.

8. The compound as claimed in claim 1 , wherein the absolute configuration at the carbon atom carrying the group A is (S).

9. The compound as claimed in claim 1 , wherein A is 1,3-phenylene, which is optionally substituted by one or more substituents selected from halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy.

10. The compound as claimed in claim 1 , wherein A is 1,4-phenylene which is optionally substituted by one or more substituents selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkyl and fluorinated C 1 -C 4 -alkoxy.

11. The compound as claimed in claim 10 , wherein R a is C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkyl, C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, C 1 -C 6 -alkenyl, fluorinated C 1 -C 6 -alkenyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxy-C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, fluorinated C 1 -C 6 -alkylthio, C 1 -C 6 -alkylsulfinyl, fluorinated C 1 -C 6 -alkylsulfinyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfonyl, phenylsulfonyl, benzyloxy, phenoxy, where the phenyl radical in the 3 last-mentioned radicals may be unsubstituted or may carry 1 to 3 substituents selected from the group consisting of C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl and halogen, CN, nitro, C 1 -C 6 -alkylcarbonyl, fluorinated C 1 -C 6 -alkylcarbonyl, C 1 -C 6 -alkylcarbonylamino, fluorinated C 1 -C 6 -alkylcarbonylamino, carboxy, NH—C(O)—NR 6 R 7 , NR 6 R 7 , NR 6 R 7 —C 1 -C 6 -alkylene, and O—NR 6 R 7 , where R 6 and R 7 are, independently of each other, H, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl or C 1 -C 4 -alkoxy or may form, together with N, a 4-, 5- or 6-membered saturated or unsaturated ring, or is a saturated or unsaturated 3- to 7-membered heterocyclic ring comprising as ring members 1, 2, 3 or 4 heteroatoms selected from the group consisting of N, O and S and/or 1, 2 or 3 heteroatom-containing groups selected from NR 8 , where R 8 is as defined in claim 1 , SO, SO 2 , and CO, and where the heterocyclic ring may carry 1, 2 or 3 substituents selected from the group consisting of hydroxy, halogen, C 1 -C 6 -alkyl, fluorinated C 1 -C 6 -alkyl and C 1 -C 6 -alkoxy.

12. The compound as claimed in claim 1 , wherein the saturated or unsaturated 3- to 7-membered heterocyclic ring R a is selected from the group consisting of azetidinyl, pyrrolidinyl, oxopyrrolidinyl, oxo-oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-oxothiomorpholinyl, 1,1-dioxothiomorpholinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, furazanyl, thiadiazolyl, and tetrazolyl, where the heterocyclic radical may be unsubstituted or may carry 1 to 3 substituents selected from the group consisting of halogen, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy.

13. The compound as claimed in claim 12 , wherein the saturated or unsaturated 3- to 7-membered heterocyclic ring R a is selected from the group consisting of azetidinyl, pyrrolidinyl, oxopyrrolidinyl, oxo-oxazolidinyl, piperidinyl, morpholinyl, furanyl, thienyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl and thiadiazolyl, where the heterocyclic radical may be unsubstituted or may carry 1 to 3 substituents selected from the group consisting of halogen and C 1 -C 4 -alkyl.

14. The compound as claimed in any of claim 12 or 13 , wherein the saturated or unsaturated 3- to 7-membered heterocyclic ring comprises as ring member at least one nitrogen atom or at least one group NR 8 .

15. The compound as claimed in claim 1 , wherein R a is selected from the group consisting of halogen, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, CN, a 5-membered heteroaromatic ring comprising as ring members one nitrogen atom or one group NR 8 , where R 8 is H or C 1 -C 4 -alkyl, and optionally one or two further heteroatoms selected from N, O, S, and where the heteroaromatic ring may carry 1, 2 or 3 substituents selected from halogen, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy, and a 5- or 6-membered saturated heterocyclic ring bound via a nitrogen atom optionally containing, apart this nitrogen atom one further heteroatom or heteroatom-containing group selected from O and NR 8 , where R 8 is H or C 1 -C 4 -alkyl, where the heterocyclic radical may carry 1, 2 or 3 substituents selected from halogen, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and hydroxy.

16. A pharmaceutical composition comprising at least one compound as claimed in claim 1 , optionally together with at least one physiologically acceptable carrier or auxiliary substance.

17. A method for treating a medical disorder susceptible to treatment with a 5-HT 6 receptor ligand, said method comprising administering an effective amount of at least one compound as claimed in claim 1 to an individual having said medical disorder wherein said medical disorder is a cognitive dysfunction associated with Alzheimer's disease or schizophrenia.