Substituted sulfonamide compounds

• US 8,580,965 B2
• Filed: 10/16/2007
• Issued: 11/12/2013
• Est. Priority Date: 10/16/2006
• Status: Expired due to Fees

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Oberboersch, Stefan, Reich, Melanie, Schunk, Stefan, Hees, Sabine, Jostock, Ruth, Engels, Michael, Kless, Achim, Christoph, Thomas, Schiene, Klaus, Germann, Tieno, Bijsterveld, Edward
• Primary Examiner(s): CHANG, CELIA C
• Application Number:
  US11/873,065
• Publication Number:
  US 20080249128A1
• Time in Patent Office: 2,219 Days
• Field of Search: 514/318, 514/324, 514/326, 514/327, 546/194, 546/202, 546/212, 546/213, 546/217
• US Class Current: 546/217
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/38 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 211/52 having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links

Abstract

Substituted sulfonamide compounds with bradykinin receptor (B1R) modulating activity; processes for the preparation thereof, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat or inhibit pain and/or other disorders and/or disease states.

Claims

1. A substituted sulfonamide derivative of the general formula I

2. A compound according to claim 1, wherein said compound is in the form of a pure enantiomer or diastereomer.

3. A compound according to claim 1, wherein said compound is in the form of a racemic mixture.

4. A compound according to claim 1, wherein

m represents 1, 2 or 3

n represents 1 or 2

p represents 1,

R¹ represents thienyl, phenyl, benzyl, phenethyl, pyridyl, or pyridyl linked via a —

CH₂—

or —

CH₂—

CH₂- chain, in each case unsubstituted or mono- or poly-substituted,

R² represents OH, OC_1-6-alkyl or F,

R³ represents aryl or heteroaryl, in each case unsubstituted or mono- or poly-substituted;

R⁴ and R^4a independently of one another represent H, C_1-6-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted;

F;

Cl;

aryl, in each case unsubstituted or mono- or poly-substituted;

or aryl linked via a C_1-3-alkyl chain and in each case unsubstituted or mono- or poly-substituted;

Z represents O;

R⁵ and R^5a independently of one another represent H;

or C_1-6-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted;

OH, OC_1-6-alkyl, F, Cl, phenoxy or benzyloxy;

R⁶ represents H;

C_1-6-alkyl, in each case saturated or unsaturated, branched or unbranched, unsubstituted or mono- or poly-substituted;

C_3-8-cycloalkyl, saturated or unsaturated, unsubstituted or mono- or poly-substituted;

aryl or heteroaryl, unsubstituted or mono- or poly-substituted;

aryl or C_3-8-cycloalkyl linked via a C_1-3-alkyl chain;

or Cl_1-6-alkyl;

Q denotes —

CH₂—

, —

CH₂—

CH₂—

, or

5. A compound according to claim 1, wherein R³ denotes phenyl, naphthyl, thienyl or benzothiophene, in each case unsubstituted or mono- or poly-substituted.

6. A compound according to claim 1, wherein

R⁶ denotes H, methyl, ethyl, n-propyl, isobutyl, cyclopropyl, cyclopropyl linked via a C_1-3-alkyl chain, or benzyl.

7. A compound according to claim 1, wherein R⁴ and R^4a each represent H.

8. A compound according to claim 1, wherein R⁵ and R^5a each represent H.

9. A compound according to claim 1, wherein

m represents 1,

n represents 1 or 2

R⁴, R^4a, R⁵ and R^5a each represent H, and

Z represents O;

or

m represents 2,

Z represents O,

n represents 1, and

R⁴ and R^4a, R⁵ and R^5a each represent H.

10. A compound according to claim 1, wherein R² denotes OH.

11. A compound according to claim 1, wherein R³ denotes 2,6-dimethyl-4-methoxyphenyl.

12. A compound according to claim 1, selected from the group consisting of:

1 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-N-ethyl-4-methoxy-2,3,6-trimethyl-phenylsulfonamide

2 2,4,6-trichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

3 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide hydrochloride

4 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,6,N-trimethyl-phenylsulfonamide

5 2,4,6-trichloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylphenylsulfonamide hydrochloride

6 2,4,6-trichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

7 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-pyrrolidin-3-yloxy]-ethanone

8 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-4-yloxy]-ethanone

9 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-2,4,6-trichloro-N-methyl-phenylsulfonamide

10 2,6-dichloro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

11 1-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-[1-(4-methoxy-2,3,6-trimethyl-phenylsulfonyl)-piperidin-3-yloxy]-ethanone

12 2-[1-(3,4-dichloro-phenylsulfonyl)-piperidin-2-ylmethoxy]-1-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-ethanone

13 N-benzyl-N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,3,6-trimethyl-phenylsulfonamide

16 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-3,4-dimethoxy-N-methyl-phenylsulfonamide

20 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-4-trifluoromethoxy-phenylsulfonamide

28 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-N-methyl-phenylsulfonamide

38 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-3-trifluoromethyl-phenylsulfonamide

39 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

41 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-3,4-dimethoxy-N-methyl-phenylsulfonamide

42 N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-N-methyl-phenylsulfonamide

43 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-cyclohexyl}-3,4-dichloro-N-methyl-phenylsulfonamide

61 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-5-fluoro-N,2-dimethylphenylsulfonamide

62 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-5-fluoro-2,N-dimethyl-phenylsulfonamide

69 N-benzyl-N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxymethyl]-thiophen-3-yl}-3,4-dichloro-phenylsulfonamide

70 3,5-difluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

71 2,5-difluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-N-methyl-phenylsulfonamide

86 N-{2-[2-(4-hydroxy-4-thiophen-2-yl-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,6,N-trimethyl-phenylsulfonamide

88 N-{2-[2-(4-hydroxy-3,4,5,6-tetrahydro-2H-[4,4′

]bipyridinyl-1-yl)-2-oxo-ethoxy]-ethyl}-4-methoxy-2,6,N-trimethyl-phenylsulfonamide

93 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-3,5-difluoro-N-methylphenylsulfonamide

97 5-fluoro-N-{2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-2,N-dimethyl-phenylsulfonamide

102 5-chloro-thiophene-2-sulfonic acid {2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[3,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-methyl-amide

103 5-chloro-thiophene-2-sulfonic acid {2-[2-(4′

-hydroxy-3′

,4′

,5′

,6′

-tetrahydro-2′

H-[2,4′

]bipyridinyl-1′

-yl)-2-oxo-ethoxy]-ethyl}-methyl-amide

104 2,4-dichloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,6-dimethylphenylsulfonamide

105 2,4-dichloro-N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-N,6-dimethylphenylsulfonamide

106 N-{2-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-2-oxo-ethoxy]-ethyl}-2,4-dichloro-6,N-dimethyl-phenylsulfonamide

130 N-benzyl-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,6-dimethylphenylsulfonamide

132 N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

133 N-(2-(3-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

136 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

137 N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

139 N-cyclopropyl-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,6-dimethylphenylsulfonamide

140 N-(2-(2-(4-hydroxy-4-(2-(pyridin-3-yl)ethyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

141 N-(2-(2-(4-(3-fluorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

143 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

148 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2-dimethylnaphthalene-1-sulfonamide

149 4-chloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

150 4-chloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

151 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-chloro-N,2,5-trimethylphenylsulfonamide

152 4-chloro-N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

153 N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-chloro-N,2,5-trimethylphenylsulfonamide

154 4-chloro-N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylphenylsulfonamide

191 N-benzyl-N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

198 2,4-dichloro-N-(2-(2-(4-hydroxy-4-(pyridin-2-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,6-dimethylphenylsulfonamide

199 2,4-dichloro-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,5-dimethylphenylsulfonamide

205 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-(cyclopropylmethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

206 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-phenylpiperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

207 N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-(cyclopropylmethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

208 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)-piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenyl-sulfonamide

209 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

210 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

211 N-(2-(2-(4-benzyl-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

212 N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

237 N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-(cyclopropylmethyl)-4-methoxy-2,3,6-trimethylphenyl-sulfonamide

238 N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

240 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

241 N-(2-(2-(4-hydroxy-4-(pyridin-3-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

256 N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

257 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

258 N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

259 N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N,2,5-trimethylthiophene-3-sulfonamide

260 2,5-dichloro-N-(2-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylthiophene-3-sulfonamide

261 N-(2-(2-(4-(4-bromophenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-2,5-dichloro-N-methylthiophene-3-sulfonamide

262 2,5-dichloro-N-(2-(2-(4-hydroxy-4-(3-(trifluoromethyl)phenyl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylthiophene-3-sulfonamide

263 2,5-dichloro-N-(2-(2-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-2-oxoethoxy)ethyl)-N-methylthiophene-3-sulfonamide

268 N-(cyclopropylmethyl)-N-(2-(2-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-4-methoxy-2,3,6-trimethylphenylsulfonamide

269 N-(2-(2-(4-hydroxy-4-(thiophen-2-yl)piperidin-1-yl)-2-oxoethoxy)ethyl)-N-isobutyl-4-methoxy-2,3,6-trimethylphenylsulfonamide

275 N-(2-(3-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

276 N-(2-(3-(4-hydroxy-4-phenylpiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

277 N-(2-(3-(4-benzyl-4-hydroxypiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide

278 N-(2-(3-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4-hydroxypiperidin-1-yl)-3-oxopropoxy)ethyl)-4-methoxy-N,2,6-trimethylphenylsulfonamide.

13. A process for preparing a substituted sulfonamide compound according to claim 1, said process comprising:

reacting a carboxylic acid corresponding to formula G with a primary or secondary amine corresponding to formula S;

14. A method according to claim 13, wherein the dehydrating agent is selected from the group consisting of sodium sulfate, magnesium sulfate and phosphorus oxide;

the coupling agent is CDI or polymer-bonded DCC, TBTU, EDCI, PyBOP or PFPTFA;

HOAt or HOBt is added;

the organic base is selected from the group consisting of DIPEA and pyridine, and the organic solvent is selected from the group consisting of THF, methylene chloride, diethyl ether, dioxane, DMF and acetonitrile.

15. A pharmaceutical composition comprising a compound according to claim 1 and at least one pharmaceutically acceptable carrier, additive or auxiliary substance.