Aminopiperidines

• US 20030176461A1
• Filed: 10/21/2002
• Published: 09/18/2003
• Est. Priority Date: 04/20/2000
• Status: Abandoned Application

• Current Assignee: NPS Allelix Corp.
• Original Assignee: NPS Allelix Corp.
• Inventors: Edwards, Louise G., Frey, Jennifer, Tse, Hoi Lun Allan, Isaac, Methvin B., Maddaford, Shewn P., Slass, Abdelmalik, Egle, Ian R., Begleiter, Leah E., Tehim, Ashok, Stefanac, Tomislav
• Application Number:
  US10/257,402
• Publication Number:
  US 20030176461A1
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 211/58 attached in position 4
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

Described herein are compounds having general formula (1), wherein groups R₁, R₂, R₃, Ar₁, Ar₂, Ar₃, X, Y, p and n are as defined in the specification, and a salt, solvate and hydrate thereof. Such compounds inhibit glycine transport (or reuptake) via the GlyT-1 transporter, or are precursors (for example, pro-drugs) of such compounds and, thus, are useful in the treatment of schizophrenia, as well as other CNS-related disorders such as dementia, Alzheimer'"'"'s disease, attention deficit disorder and depression.

Claims

1. A compound according to Formula I:

2. A compound according to claim 1 wherein X is SO₂.

3. A compound according to claim 2 wherein m is selected from the group consisting of 1 and 3;

5. A compound according to claim 3 wherein R₁, R₂ and R₃ are each H.

6. A compound according to claim 5 wherein Y is [CHR₁]-_m, m is 2 and R1 is H and Ar₁ is phenyl,

7. A compound according to claim 5 wherein Y is [CHR₁]-_m, m is 0 and Ar₁ is phenyl.

8. A compound according to claim 5 wherein Y is [CHR₁]_m, m is 1 and R₁ is H.

9. A compound according to claim 8 wherein the amino substituent attaches at the 3 position of the piperidine ring and p is 1.

10. A compound according to claim 8 wherein the amino substituent attaches at the 4 position of the piperidine ring.

11. A compound according to claim 10 wherein p is 0.

12. A compound according to claim 11 wherein n is 1 and Ar₂ is selected from the group consisting of phenyl and naphthyl.

13. A compound according to claim 11 wherein n is 2 and Ar₂ is phenyl.

14. A compound according to claim 11 wherein n is 0.

15. A compound according to claim 14 wherein Ar3 is selected from phenyl or naphthyl and is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkyloxy, heterocycloalkyl, heterocycloalkyloxy, alkanoyl, thioalkyl, aralkyl, aralkoxy, aryloxyalkyl, aryloxyalkoxy, cycloalkyl-substituted alkyl, cycloalkyloxy-substituted alkyl, cycloalkyl-substituted alkoxy, cycloalkyloxy-substituted alkoxy, heterocycloalkyl-substituted alkyl, heterocycloalkyloxy-substituted alkyl heterocycloalkyl-substituted alkoxy, heterocycloalkyloxy-substituted alkoxy, thioaryl, aralkylthio, thioaryl-alky, halo, NO₂, Ph, CF₃, OCF₃, CN, OH, methylenedioxy, ethylenedioxy, SO₂NRR′

, NRR′

, CO₂R (where R and R′

are independently selected from the group consisting of H and alkyl) and aryl. The aryl substituent may be further substituted with any substituent selected from the preceding list;

16. A compound of claim 15 wherein Ar₃ is optionally substituted phenyl wherein the substituent is selected from the group consisting of alkyl, alkoxy, halo, CN, CF₃, OCF₃, and OH.

17. A compound of claim 16 wherein Ar₁ is selected from optionally substituted phenyl, pyridine, thiophenyl, furan, quinoline optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkyloxy, heterocycloalkyl, heterocycloalkyloxy, alkanoyl, thioalkyl, aralkyl, aralkoxy, aryloxyalkyl, aryloxyalkoxy, cycloalkyl-substituted alkyl, cycloalkyloxy-substituted alkyl, cycloalkyl-substituted alkoxy, cycloalkyloxy-substituted alkoxy, heterocycloalkyl-substituted alkyl, heterocycloalkyloxy-substituted alkyl heterocycloalkyl-substituted alkoxy, heterocyc(oalkyloxy-substituted alkoxy, thioaryl, aralkylthio, thioaryl-alky, halo, NO₂, Ph, CF₃, OCF₃, CN, OH, methylenedioxy, ethylenedioxy, SO₂N RR′

, NRR′

, CO₂R (where R and R′

are independently selected from the group consisting of H and alkyl) and aryl. The aryl substituent may be further substituted with any substituent selected from the preceding list.

18. A compound of according to claim 17 wherein Ar₁ is optionally susbtituted phenyl wherein one or more substituents are selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkyloxy, heterocycloalkyl, heterocycloalkyloxy, alkanoyl, thioalkyl, aralkyl, aralkoxy, aryloxyalkyl, aryloxyalkoxy, cycloalkyl-substituted alkyl, cycloalkyloxy-substituted alkyl, cycloalkyl-substituted alkoxy, cycloalkyloxy-substituted alkoxy, heterocycloalkyl-substituted alkyl, heterocycloalkyloxy-substituted alkyl heterocycloalkyl-substituted alkoxy, heterocycloalkyloxy-substituted alkoxy, thioaryl, aralkylthio, thioaryl-alky, halo, NO₂, Ph, CF₃, OCF₃, CN, OH, methylenedioxy, ethylenedioxy, SO₂NRR′

, NRR′

, CO₂R (where R and R′

are independently selected from the group consisting of H and alkyl) and aryl.

The aryl substituent may be further substituted with any substituent selected form the preceding list.

19. A compound according to claim 18 wherein Ar₁ is phenyl.

20. A compound according to claim 18 wherein Ar₁ is optionally substituted phenyl wherein one or more substituents are selected from the group consisting of alkyl, alkoxy, halo, methylendioxy, NO₂, and CN.

21. A compound according to claim 20 wherein Ar₁ is phenyl optionally substituted with one or two substituents selected from, Cl, F, Me, methoxy, and ethoxy.

22. A compound according to claim 21 wherein Ar₁ is monosubstitueted phenyl and the substituent is located at the 2-position.

23. A compound according to claim 17 wherein Ar₂ is optionally substituted with one or more substituents and is selected from the group consisting of phenyl, thiophene, naphthalene and indane, wherein the substituents are selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkyloxy, heterocycloalkyl, heterocycloalkyloxy, alkanoyl, thioalkyl, aralkyl, aralkoxy, aryloxyalkyl, aryloxyalkoxy, cycloalkyl-substituted alkyl, cycloalkyloxy-substituted alkyl, cycloalkyl-substituted alkoxy, cycloalkyloxy-substituted alkoxy, heterocycloalkyl-substituted alkyl, heterocycloalkyloxy-substituted alkyl heterocycloalkyl-substituted alkoxy, heterocycloalkyloxy-substituted alkoxy, thioaryl, aralkylthio, thioaryl-alky, halo, NO₂, Ph, CF₃, OCF₃, CN, OH, methylenedioxy, ethylenedioxy, SO₂NRR′

, NRR′

, CO₂R (where R and R′

are independently selected from the group consisting of H and alkyl) and aryl. The aryl substituent may be further substituted with any substituent from the preceding list.

24. A compound according to claim 23 wherein Ar₂ is selected from optionally substituted phenyl wherein one or more substituents are selected from the group consisting of alkyl, alkoxy, halo, CF₃, and OCF₃.

25. A compound according to claim 24 wherein Ar₂ is phenyl substituted at the 3-position.

28. A composition comprising a compound of claim 1 and a carrier.

29. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and pharmaceutically acceptable carrier.

30. A method for treating a patient having a medical condition for which a glycine transport inhibitor is indicated, comprising the step of administering to the patient a pharmaceutical composition as defined in claim 29.

31. A method according to claim 30 in which the medical condition is schizophrenia.

32. A method according to claim 30 in which the medical condition is cognitive dysfunction.

33. A method according to claim 30 in which the medical condition is Alzheimer'"'"'s disease.

4. A compound according to 3 wherein R₁ and R3 are each H and R₂ is methyl.

26. A compound selected from the group consisting of:

N-Benzoyl-4-[(N-benzyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.1);

N-Phenyl-4-[(N-phenyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1. 11

     0);

N-Benzyl-4-[(N-2-methoxyphenyl-N-4-methoxyphenylsulphonylamino]-piperidine (1.2);

N-Benzyl-4-[(N-benzyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.3);

N-Benzyl-4-[(N-2-phenylethyl-N-(4-methoxyphenylsulphonyl)amino]-piperidine (1.4);

N-Benzyl-4-[(N-phenyl)-N-(4-methoxyphenyl)acetyl)amino]-piperidine (1.5);

N-Benzyl-4-[(N-phenyl)-N-(phenoxy)acetyl)amin6]-piperidine (1.6);

N-Benzyl-4-[(N-4-methoxybenzyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.9);

N-Benzyl-4-f(N-phenylJ-N-((2-benzo[b]thiophenyl)carbonyl)amino]-piperidine (1.7);

N-Benzyl-4-[(N-phenyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.8);

N-Benzyl-4-[(N-4-methoxybenzyl-N-phenylsulphonyl)amino]-piperidine (1.10);

N-Benzyl-4-[(N4-methoxybenzyi-N-4-chlorophenylsulphonylamino]-piperidine (1.11);

N-Benzyl-4-[(N-4-methoxybenzyl-N-4-methylphenylsulphonyl)amino]-piperidine (1.12);

N-Benzyl-4-[(N-4-methoxybenzyl-N-4-pheny/phenylsulphonyl)amino]-piperidine (1.13);

N-Benzyl-4-[(N4-methoxybenzyI-N-2, 5-dimethoxyphenylsulphonyl)amino]-piperidine (1.14);

N-Benzyl-4-[(N-2-phenylethyl-N-phenylsulphonyl)amino]-piperidine (1.15);

N-Benzyl-4-[(N-2-phenylethyl-N-(4-chloropheny11sulphonyl)amino;

-pipridine (1.16);

N-Benzyl4-[(N-2-phenylethyl-N-(4-methylphenyl)sulph;

nyl)amino]piperidine (1.17);

N-Benzyl-4-[(N-2-phenylethyl-N-(4-phenylphenyl)sulphonyl)amino]-piperidine (1.18);

N-Benzyl-4-[(N-2-phenylethyl-N-(2, 5-dimethoxyphenyl)sulphonyl)amino]-piperidine (1.19);

N-Benzyl4-[(N-phenyl-N-phenylsulphonyl)amino]-piperidine (1.20);

N-Benzyl-4-[(N-phenyl-N-(4-chlorophenyl)sulphonyl)amino]-piperidine (1.21);

N-Benzyl-4-[(N-phenyl-N-(4-methylphenyl)sulphonyl)amino]-piperidine (1.22);

N-Benzyl-4-[(N-phenyl-N-(4-phenylphenyl)sulphonyl)amino]-piperidine (1.23);

N-Benzyl-4-[(N-phenyl-N-(2,5-dimethoxyphenyl)sulphonyl)amino]-piperidine (1.24);

N-((2-fury)methyl)-4-[(N-benzyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.1112);

N-Benzyl-4-[(N-((2-fur)methylJ-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.25);

N-Benzyl4-[(N-(4-chlorobenzyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.26);

N-Benzyl-4-[(N-2-chlorobenzyl)-N-(4-methoxyphenyl)sulphonyl)amino]piperidine (1.27);

N-Benzyl4-[(N-(2-naphthyl)methyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.28);

N-Benzyl-4-[(N-1 -naphthylmethyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.29);

N-Benzyl4-[(N-(4-methoxypheny )-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.30);

N-Benzyl4-[(N-4-chlorophanyl)-N-(4-methoxyphenyf)sutphonyl)amino]-piperidine (1.31);

N-(2-phenethyl)-4-[(Nphenyl-N-(4-methoxyphenyl)sulphonyf)amino]-piperidine (1.111);

N-Benzyl-4-[(N-4-phenylphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.32);

N-Benzyl-4-[(N-(2-naphthyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.33);

N-Benzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.34);

N-Benzyl-4-[(N-3-chlorophenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.35);

N-Benzyl-4-[(N-4-methylphenylJ-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.36);

N-Benzyl-4-[(N-4-isopropylphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]piperidine (1.37);

N-Benzyl-4-[(N-4-trifluoromethoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.38);

N-Benzyl-4-[(N-(I-naphthyl))-N-(4-methoxyphenyfsutphonyl)amino]-piperdine (1.39);

N-Benzyl-4-[(N-3-methylphenyl)-N-(4-methoxyphenyl)suiphonyl)amino]-piperidine (1.40);

N-Benzyl-4-[(N-(5-indanyl))-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.41);

N-Benzyl-4-[(N-3, 4-dichlorophenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.42);

N-Benzyl-4-[(N-3-chloro-4-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.43);

N-Benzyl-4-[(N-3, 4-methylendioxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.44);

N-(2-furylmethyl)-4-[(N-3-mothoxyphenyl)-N-(4-mothoxyphenylpsulphonylpamino]-piperidine (1.45);

N-3-chlorobenzyl-4-[(N-3-methoxyphenyl-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.46);

N-(2-Chlorobenzyl)-4-[(N-3-methoxybenzyl)-N-(4-methoxyphenyI)sulphonyl)amino]-piperidine (1.47);

N-2-methylbenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.48);

N-2-methoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.49);

N-3-methoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.50);

N-4-methoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)suiphonyluamina]-piperidine (1.51);

N-3-methylbenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.52);

N4-methylbenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.53);

N-4-chlorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyqamino] piperidine (1.54);

N-benzyl-4-[(N-3, 5-dimethoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.55);

N-benzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-mothoxyphenylsulphonyl)amino]-piperidine (1.56);

N-benzyl-4-[(N-3-isopropylphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.57);

N-benzyl-4-[(N-3-ethoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]piperidine (1.58);

N-benzyl-4-[(N-3-isopropoxyphenyl)-N-(4-methoxyphenyl)sulphonyluamino]-piperidine (1.59);

N-benzyl-4-[(N-3-phenoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino] piperidine (1.60);

N-α

-methylbenzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)amino]-piperidine (1.61);

N-2-methylbenzyf-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)amino]-piperidine (1.62);

N-2-methoxylbenzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)-amino]piperidine (1.63);

N-2-ethoxybenzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)amino]-piperidine (1.64);

(R,S)-(trans)-N-Benzyl-3-methyl-4-[(N-phenyl-N-(4-methoxyphenyl)sulphonyl) amino]-piperidine (1.66);

(R, S)-(cis)-N-Benzyl-3-methyl-4-[(N-(3-methoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)-amino]piperidine (1.67);

N-Benzyl-3-[(N-3-methoxyphenyl-N-4-methoxyphenylsulphonyl)amino] piperidine (1.70);

N-Benzyl-3-[(N-3-methoxyphenyt-N-phenylsulphonyl)aminomethyllpiperidine (1.71);

N-Benzyl-3-[(N-3-methoxyphenyl-N-4-methoxyphenylsulphonyl)aminomethyll piperidine(1 .72);

N-2-Cyanobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.73);

N-2-Nitrobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.74);

N-2-Fluorobenzyl4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphony1) amino]piperidine (1.75);

N-3-Fluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.76);

N-4-Fluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.77);

N-3, 5-Difluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.78);

N-2, 6-Difluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.79);

N-Cinnamyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.80);

N-2-Phenylethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.81);

N-2-Pyridylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.82);

N-2-QuinoIylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.83);

N-3-Thienylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.85);

N-2-Furylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.85);

N-3-pyridylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.86);

N-2-ethoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.87);

N-2, 3-methylendioxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]piperidine (1.88);

N-2-Methoxybenzyl-4-[(N-3-methoxyphenyl-N-2, 5dimethoxy-4-nitrophenylsulphonyl)amino]piperidine (1.89);

N-benzyl-4-[N-(3-(trifluoromethoxy)phenyl)-N-(4-fluorophenylsulphonyl) amino]-piperidine (1.90);

N-benzyl-4-[N-(phenyl)-N-(3-methoxyphenylsulphonyl)amino]-piperidine (1.91);

N-benzyl-4-[N-(phenyl)-N-(4-(trifluoromethoxy)pheny1sulphonyl)amino]-piperidine (1.92);

N-benzyl-4-[N-(4-methylphenyl)-N-(3-methoxyphenylsulphonyl)amino]-piperidine (1.93);

N-benzyl-4-[N-(4-methylphenyl)-N-(4-(trifluoromethoxy)phenylsulphonyl) amino]-piperidine (1.94);

N-benzyl-4-[N-(4-methylphenyl)-N-(2-naphthylsulphonyl)amino]-piperidine (1.95);

N-benzyl-4-[N-(3-(trifluoromethoxy)phenyt)-N-(3-methoxyphenylsulphonyl) amino]-piperidine (1.96);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyf)-N-(2-cyanophenylsufphonyl) amino]-piperidine (1.97);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(3-cyanophenylsulphonyl) amino]-piperidine (1.98);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(2-naphthylsulphonyl)amino]-piperidine (1.99);

N-(pytidin-4-ylmethyl)-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-methoxyphenylsulphonyl)amino]-piperidine (1.100);

N-(2-chlorobenzyl)-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-methoxyphenylsulphonyl)amino]-piperidine (1.101);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-methylphenylsulphonyl) amino]-piperidine (1.102);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl]-N-(4-tert-butylphenylsulphony-) amino]-piperidine (1.103);

N-benzyl-4-[(4-t-butylphenyl-N-4-methoxyphenylsulphonyl)amino]piperidine (1.105);

N-benzyl-4-[(4-trifluoromethyl-N-4-methoxyphenylsulphonyl)amino] piperidine (1.106);

N-benzyl-4-[(3-trifluoromethyl-N-4- methoxyphenylsuiphonyl)amino] piperidine (1.107);

N-benzyl-4-[(4-propylphenyl-N-4- methoxyphenylsulphonyl)amino]piperidine (1.108);

N-benzyl-4[(N-3trifluoromethoxyphenyl-N-4-hydroxyphenylsulphonyl) amino]piperidine (1.109);

27. A compound selected from the group consisting of:

N-Benzoyl-4-[(N-benzyf-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.1);

N-Phenyl-4-[(N-phenyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.110);

N-Benzyl-4-[(N-2-methoxyphenyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.2);

N-Benzyl-4-[(N-benzyl-N-4methoxyphenylsulphonyl)amino]-piperidine (1.3);

N-Benzyl-4-[(N-2-phenylethyl-N-(4-methoxyphenylsulphonyl)amino]-piperidine (1.4);

N-Benzyl-4-[(N-phenyl)-N-(4-methoxyphenyl)acetyl)amino]-piperidine (1.5);

>

N-Benzyl-4-[(N-phenyl)-N-(phenoxy)acetyl)amino]-piperidine (1.6);

N-Benzyl-4-[(N-4-methoxybenzyl-N-4-methoxyphenylsulphonyl)amino;

-piperidine (1.9);

N-Benzyl-4-[(N-phenyl)-N-((2-benzo[b]thiophenylucarbonyl)amino]-piperidine (1.7);

N-Benzyl-4-[(N-phenyl-N-4-methoxyphenylsulphonyl)amino]-piperidine (1.8);

N-Benzyl-4-[(N-4-methoxybenzyl-N-4-chlarophenylsulphonyl)amino]-piperidine (1.11);

N-Benzyl-4-[(N-2-phenylethyl-N-phenylsulphonyl)amino]-piperidine (1.15);

N-Benzyl-4-[(N-2-phenylethyl-N-(4-chlorophenyl)sulphonyl)amino]-piperidine (1.16);

N-Benzyl-4-[(N-2-phenylethyl-N-(4-methylphenyl)sulphonyl)amino]-piperidine (1.17);

N-Benzyl-4-[(N-2-phenylethyl-N-(2,5-dimethoxyphenyl)sulphonyl)amino]-piperidine (1.19);

N-Benzyl-4-[(N-phenyl-N-(4-chlorophenyl)sulphonyl)amino]-piperidine (1.21);

N-Benzyl-4-[(N-phenyl-N-(4-methylphenyl)sulphonyl)amino]-piperidine (1.22);

N-((2-fu(yl)methyl)-4-[(N-benzyl-N-4-methoxyphenylsulphonylwamino]-piperidine (1.112);

N-Benzyl-4-[(N-(2-naphthyl)methyl)-N-(4-methoxypheny)sulphonyl)amino-piperidine (1.28);

N-Benzyl-4-[(N-1-naphthylmethyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.29);

N-Benzyl-4-[(N-(4-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyluamino]-piperidine (1.30);

N-Benzyl-4-[(N-4-chlorophenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.31);

N-(2phonethyl)-4-[(N-phenyl-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.111);

N-Benzyl-4-[(N-(2-naphthyl)-N-(4-methoxyphenylusulphonyl)amino]-piperidine (1.33);

N-Benzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.34);

N-Benzyl-4-[(N-3-chlorophenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.35);

N-Benzyl-4-[(N-4-methylphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.36);

N-Benzyl-4-[(N-4-isopropylphenyl)-N-(4-methoxyphenyl)sulphonyf)amino]-piperidine (1.37);

N-Benzyl-4-[(N-4-trifruoromethoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.38);

N-Benzyl-4-[(N-3-mothylphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.40);

N-Benzyl-4-[(N-15-indanyl))-N-(4-methoxyphenyl)sulphanyl;

amino]-piperidine (1.41);

N-Benzyl-4-[(N-3,4-dichlorophenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.42);

N-Benzyl-4-[(N-3-chloro-4-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.43);

N-Benzyl-4-[(N-3,4-methylendioxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.44);

N-(2-furylmethyl)-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.45);

N-3-chlorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyI)amino]-piperidine (1.46);

N-(2-Chlorobenzyl)-4-[(N-3-methoxybenzyl)-N-(4-methoxyphenyI)sulphonyl)amino]-piperidine (1.47);

N-2-methylbenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.48);

N-2-methoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.49);

N-3-methoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.50);

N-4-methoxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.51);

N-3-methylbenzyl-4-[(N-3-methoxyphonyl)-N-(4-mothoxyphenyl)sulphonyl)amino]-piperidine (1.52);

N-4-methylbenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.53);

N-4-chlorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonylpamino]-piperidine (1.54);

N-benzyl-4-[(N-3, 5-dimethoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.55);

N-benzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.56);

N-benzyl-4-[(N-3-isopropyfphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]-piperidine (1.57);

N-benzyl-4-[(N-3-ethoxyphenyl)-N-(4-methoxyphenyl)sulphonylvamino]-pipeiidine (1.58);

N-benzyl-4-[(N-3-isopropoxyphenyl)-N-(4-methoxyphenylpsulphonylpamino]-piperidine (1.59);

N-α

-methylbenzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)amino]-piperidine (1.61);

N-2-methylbenzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)amino]-piperidine (1.62);

N-2-methoxylbenzyl-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)-amino]piperidine (1.63);

N-2-ethoxybenzyf-4-[(N-3-trifluoromethoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)amino]-piperidine (1.64);

(R,S)-(trans)-N-Benzyl-3-methyl-4-[(N-phenyl-N-(4-methoxyphenyl)sulphonyl) amino]-piperidine (1.66);

(R,S)-(cis)-N-Benzyl-3-methyl-4-[(N-(3-methoxyphenyl)-N-(4-methoxyphenyl) sulphonyl)-amino]piperidine (1.67);

N-Benzyl-3-[(N-3-methoxyphenyl-N-4-methoxyphenylsulphonyl)amino] piperidine (1.70);

N-Benzyl-3-[(N-3-methoxyphenyl-N-phenylsulphonyl)aminomethy]piperidine (1.71);

N-2-Cyanobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.73);

N-2-Nitrobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.74);

N-2-Fluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.75);

N-3-Fluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.76);

N-4-Fluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.77);

N-3, 5-Difluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.78);

N-2, 6-Difluorobenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.79);

N-Cinnamyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphony1) amino]piperidine (1.80);

N-2-Phenylethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.81);

N-2-Pyridyfmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.82);

N-2-Quinolylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.83);

N-3-Thienylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.85);

N-2-Furylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.85);

N-3-pyridylmethyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.86);

N-2-ethoxybenzyl-4-[(N-3-methoxyphenyt)-N-(4-methoxyphenyl)sulphonyl) amino]piperidine (1.87);

N-2,3-methylendioxybenzyl-4-[(N-3-methoxyphenyl)-N-(4-methoxyphenyl)sulphonyl)amino]piperidine (1.88);

N-2-Methoxybenzyl-4-[(N-3-methoxyphenyl-N-2, 5-dimethoxy-4-nitrophenylsulphonyl)amino]piperidine (1.89);

N-benzyl-4-[N-(3-(trifluoromethoxy)phenyl)-N-(4-fluorophenylsulphonyl) amino]-piperidine (1.90);

N-benzyl-4-[N-(phenyl)-N-(3-methoxyphenylsulphonyl)amino]-piperidine (1.91);

N-benzyl-4-[N-(phenyl)-N-(4-(trifluoromethoxy);

phenysulphonyI)amino]-piperidine (1.92);

N-benzyl-4-[N-(4-methylph1nyl)-N-(3-methoxyphenylsulphonyl)amino-piperidine (1.93);

N-benzyl-4-[N-(4-methylphenyl)-N-(4-(trifluoromethoxy)phenylsulphonyl) amino]-piperidine (1.94);

N-benzyl-4-[N-(4-methylphenyl)-N-(2-naphthylsulphonyl)amino]-piperidine (1.95);

N-benzyl-4-[N-(3-(trifluoromethoxy)phenyl)-N-(3-methoxyphenylsulphonyl) amino]-piperidine (1.96);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(2-cyanophenylsulphonyl) amino]-piperidine (1.97);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(3-cyanophenylsulphonyl) amino]-piperidine (1.98);

N-benzyl4-[N-(3-trifluoromethoxy)phenyl)-N-(2-naphthyisulphonyl)amino]-piperidine (1.99);

N-(pyridin-4-ylmethyl)-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-methoxyphenylsulphonyl)amino]-piperidine (1.100);

N-(2-chlorobenzyl)-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-methoxyphenylsulphonyl)amino]-piperidine (1.101);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-methylphenylsulphonyl) amino]-pipendine (1.102);

N-benzyl-4-[N-(3-trifluoromethoxy)phenyl)-N-(4-tert-butylphenylsulphony1) amino]-piperidine (1.103);

N-benzyi-4-[(4-t-butylphenyl-N-4-methox henylsulphonyl)amino]piperidine (1.105);

N-benzyl-4-[(4-trifluoromethyl-N-4-methoxyphenylsulphonyl)amino]pipetidine (1.106);

N-benzyl-4-[(3-trifluoromethyl-N-4- methoxyphenylsulphonyl)amino] piperidine (1.107);

N-benzyl-4-[(4-propylphenyl-N-4- methoxyphenylsulphonyl)amino] piperidine (1.

     108);

N-benzyl-4[(N-3trifluoromethoxyphenyl-N-4-hydroxyphenylsulphonyl) amino]piperidine (1.109);