Sulfonyl amino cyclic derivatives and use thereof

1. A sulfonyl amino cyclic derivative according to the Formula:

wherein:

A is CR 4 R 5 ;

B is CR 4′ R 5′ ;

R 1 is selected from aryl, heteroaryl, C 3 -C 8 -cycloalkyl and heterocycloalkyl;

R 2 is selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

R 3 is selected from H, —Si(C 1 -C 6 -alkyl) 3 , amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, aryl, heteroaryl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and heterocycloalkyl;

R 4 , R 5 , R 4′ and R 5′ are independently selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

X is N;

Y is CH 2 ;

the group —X—Y— is —N—CH 2 —;

m is selected from 0, 1 and 2;

n is selected from 0 and 1; and

p is 1;

or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof.

2. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 1 is aryl.

3. A sulfonyl amino cyclic derivative according to claim 2 , wherein R 1 is phenyl.

4. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 1 is heteroaryl.

5. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 2 is H or methyl.

6. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 3 is selected from aryl and heteroaryl.

7. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 3 is selected from C 1 -C 6 -alkyl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl and heterocycloalkyl-C 1 -C 6 -alkyl.

8. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 3 is H.

9. A sulfonyl amino cyclic derivative according to claim 1 , wherein n is 0.

10. A sulfonyl amino cyclic derivative according to claim 1 , wherein m is 0.

11. A sulfonyl amino cyclic derivative according to claim 1 , wherein m and n are 1.

12. A sulfonyl amino cyclic derivative according to claim 1 , wherein R 1 is selected from aryl and heteroaryl; and R 2 is H or methyl.

13. A sulfonyl amino cyclic derivative according to claim 12 wherein A is C(CH 3 ) 2 ; B is CH 2 ; and both m and n are 1.

14. A sulfonyl amino cyclic derivative selected from the group consisting of:

3-(1,3-benzodioxol-5-yl)-1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-2-propynyl(hydroxy)formamide;

1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-3-(trimethylsilyl)-2-propynyl(hydroxy)formamide;

hydroxy[1-{[(4-pyridin-2-ylpiperazin-1-yl)sulfonyl]methyl}-3-(trimethylsilyl)prop-2-yn-1-yl]formamide;

1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-3-phenyl-2-propynyl(hydroxy)formamide;

1-[({4-[4-(benzyloxy)phenyl]-1-piperazinyl}sulfonyl)methyl]-2-octynyl(hydroxy)formamide;

1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-4-phenyl-2-butynyl(hydroxy)formamide;

1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-2-octynyl(hydroxy)formamide;

1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-3-(3-pyridinyl)-2-propynyl(hydroxy)formamide;

hydroxy[1-([{4-(4-methoxyphenyl)-1-piperazinyl]sulfonyl}methyl)-3-(3-pyridinyl)-2-propynyl]formamide;

hydroxy[3-(3-methoxyphenyl)-1-({[4-(4-methoxyphenyl)-1-piperazinyl]sulfonyl}methyl)-2-propynyl]formamide;

4-(diethylamino)-1-({[4-(4-methoxyphenyl)-1-piperazinyl]sulfonyl}methyl)-2-butynyl(hydroxy)formamide;

hydroxy(1-{[(4-pyridin-2-ylpiperazin-1-yl)sulfonyl]methyl}prop-2-yn-1-yl)formamide;

hydroxy(1-{[(4-pyridin-2-ylpiperazin-1-yl)sulfonyl]methyl}hex-2-yn-1-yl)formamide;

[1-({[4-(2-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

hydroxy(1-{[(4-pyridin-2-ylpiperazin-1-yl)sulfonyl]methyl}oct-2-yn-1-yl)formamide;

hydroxy{1-[({4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}sulfonyl)methyl]-oct-2-yn-1-yl}formamide;

{1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-3-[3-(methyloxy)phenyl]prop-2-yn-1-yl}hydroxyformamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)hex-2-yn-1-yl]hydroxy formamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-3-quinolin-3-ylprop-2-yn-1-yl]hydroxyformamide;

hydroxy(3-phenyl-1-{[(4-pyridin-2-ylpiperazin-1-yl)sulfonyl]methyl}prop-2-yn-1-yl)formamide;

hydroxy{3-phenyl-1-[({4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}sulfonyl)methyl]prop-2-yn-1-yl}formamide;

hydroxy{1-[({4-[4-(methyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]-3-phenylprop-2-yn-1-yl}formamide;

{1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-3-[4-(1,2,4-oxadiazol-3-yl)phenyl]prop-2-yn-1-yl}hydroxyformamide;

hydroxy{1-[({4-[4-(methyloxy)phenyl]piperazin-1-yl]sulfonyl)methyl}oct-2-yn-1-yl}formamide;

(1-{[(4-biphenyl-4-ylpiperazin-1-yl)sulfonyl]methyl}-3-phenylprop-2-yn-1-yl)hydroxy formamide;

[1-({[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

hydroxy(1-{[(4-pyrimidin-2-ylpiperazin-1-yl)sulfonyl]methyl}oct-2-yn-1-yl)formamide;

hydroxy(1-{[(4-phenylpiperazin-1-yl)sulfonyl]methyl}oct-2-yn-1-yl)formamide;

[1-({[4-(4-chlorophenyl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

hydroxy{1-[({4-[2-(methyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]oct-2-yn-1-yl}formamide;

hydroxy{1-[({4-[3-(methyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]oct-2-yn-1-yl}formamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-2,2-dimethyl-5-phenylpent-4-yn-1-yl]hydroxyformamide;

hydroxy{1-[({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}sulfonyl)methyl]oct-2-yn-1-yl}formamide;

hydroxy{1-[({4-[4-(phenyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]oct-2-yn-1-yl}formamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)hept-2-yn-1-yl]hydroxy formamide;

{1-[({4-[4-(ethyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]oct-2-yn-1-yl}hydroxy formamide;

[1-({[4-(5-bromopyridin-2-yl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-4-morpholin-4-ylbut-2-yn-1-yl]hydroxyformamide;

[1-({[4-(3-chlorophenyl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

[1-({[4-(1,3-benzodioxol-5-yl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

hydroxy{1-[({4-[3-(methyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]-3-phenylprop-2-yn-1-yl}formamide;

[1-({[4-(4-chlorophenyl)piperazin-1-yl]sulfonyl}methyl)-3-phenylprop-2-yn-1-yl]hydroxyformamide;

{1-[({4-[4-(ethyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]-3-phenylprop-2-yn-1-yl}hydroxyformamide;

[1-({[4-(5-bromopyridin-2-yl)piperazin-1-yl]sulfonyl}methyl)-2,2-dimethyl-5-phenylpent-4-yn-1-yl]hydroxyformamide;

{2,2-dimethyl-5-phenyl-1-[({4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}sulfonyl)methyl]pent-4-yn-1-yl}hydroxyformamide;

[1-({[4-(5-chloropyridin-2-yl)piperazin-1-yl]sulfonyl}methyl)hex-2-yn-1-yl]hydroxy formamide;

{1-[({4-[4-(ethyloxy)phenyl]piperazin-1-yl}sulfonyl)methyl]-2,2-dimethyl-5-phenylpent-4-yn-1-yl}hydroxyformamide;

[1-({[4-(3,4-dimethoxyphenyl)piperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxy formamide;

[1-({[(2R)-4-(4-fluorophenyl)-2-methylpiperazin-1-yl]sulfonyl}methyl)oct-2-yn-1-yl]hydroxyformamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-2,2-dimethylpent-4-yn-1-yl]hydroxyformamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-4-pyrrolidin-1-ylbut-2-yn-1-yl]hydroxyformamide;

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-2,2-dimethyl-6-morpholin-4-yl hex-4-yn-1-yl]hydroxyformamide; and

[1-({[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}methyl)-2,2-dimethyl hept-4-yn-1-yl]hydroxyformamide;

and an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

15. A method for treating inflammation in a mammal comprising administering to the mammal an effective amount of a sulfonyl amino cyclic derivative according to claim 1 .

16. A method for treating a mammal with a disease or disorder comprising administering to the mammal an effective amount of a sulfonyl amino cyclic derivative according to claim 1 , wherein the disease or disorder is selected from rheumatoid arthritis and multiple sclerosis.

17. A pharmaceutical composition comprising a sulfonyl amino cyclic derivative according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient thereof.

18. A process for the manufacture of a compound according to claim 1 , said process comprising the step of reacting a compound of Formula (II) with a formylating agent of Formula (FA):

and thereby forming a compound according to claim 1 ;

wherein A, B, R 1 , R 2 , R 3 , X, Y, m, n and p are as defined claim 1 ; and

LG 1 is a leaving group selected from the group consisting of —OH, —OAc, —OPiv, —OCH 2 CN, —OCH 2 CF 3 , —OPh and —OPfp.

19. A compound according to the Formula:

wherein:

A is CR 4 R 5 ;

B is CR 4′ R 5′ ;

R 1 is selected from aryl, heteroaryl, C 3 -C 8 -cycloalkyl and heterocycloalkyl;

R 2 is selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

R 3 is selected from H, —Si(C 1 -C 6 -alkyl) 3 , amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, aryl, heteroaryl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and heterocycloalkyl;

R 4 , R 5 , R 4′ and R 5′ are independently selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

X is N;

Y is CH 2 ;

the group —X—Y— is —N—CH 2 —;

m is selected from 0, 1 and 2;

n is selected from 0 and 1; and

p is 1;

or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof.

20. A compound selected from the group consisting of:

N-[3-(1,3-benzodioxol-5-yl)-1-({[4-(4-fluorophenyl)-1-piperazinyl]sulfonyl}methyl)-2-propynyl]hydroxylamine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-4-(trimethylsilyl)-3-butynyl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)-4-(trimethylsilyl)-3-butynyl]sulfonyl}-4-(2-pyridinyl)piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-4-phenyl-3-butynyl]sulfonyl}piperazine;

1-[4-(benzyloxy)phenyl]-4-{[2-(hydroxyamino)-3-nonynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-5-phenyl-3-pentynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-3-nonynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-4-(3-pyridinyl)-3-butynyl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)-4-(3-pyridinyl)-3-butynyl]sulfonyl}-4-(4-methoxyphenyl)piperazine;

1-{[2-(hydroxyamino)-4-(3-methoxyphenyl)-3-butynyl]sulfonyl}-4-(4-methoxyphenyl)piperazine;

N,N-diethyl-4-(hydroxyamino)-5-{[4-(4-methoxyphenyl)-1-piperazinyl]sulfonyl}-2-pentyn-1-amine;

1-{[2-(hydroxyamino)but-3-yn-1-yl]sulfonyl}-4-pyridin-2-ylpiperazine;

1-{[2-(hydroxyamino)hept-3-yn-1-yl]sulfonyl}-4-pyridin-2-ylpiperazine;

1-(2-fluorophenyl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-pyridin-2-ylpiperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-[4-(trifluoromethyl)phenyl]piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-4-(3-methoxyphenyl)but-3-yn-1-yl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)hept-3-yn-1-yl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}-4-[4-(trifluoromethyl)phenyl]piperazine;

3-[4-{[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}-3-(hydroxyamino)but-1-yn-1-yl]quinoline;

1-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}-4-pyridin-2-ylpiperazine;

1-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}-4-(4-methoxyphenyl)piperazine;

1-(4-fluorophenyl)-4-({2-(hydroxyamino)-4-[4-(1,2,4-oxadiazol-3-yl)phenyl]but-3-yn-1-yl}sulfonyl)piperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-(4-methoxyphenyl)piperazine;

1-biphenyl-4-yl-4-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}piperazine;

1-(5-chloropyridin-2-yl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

2-(4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazin-1-yl)pyrimidine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-phenylpiperazine;

1-(4-chlorophenyl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-(2-methoxyphenyl)piperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-(3-methoxyphenyl)piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-3,3-dimethyl-6-phenylhex-5-yn-1-yl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine;

1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-4-(4-phenoxyphenyl)piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)oct-3-yn-1-yl]sulfonyl}piperazine;

1-(4-ethoxyphenyl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

1-(5-bromopyridin-2-yl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

4-[5-{[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}-4-(hydroxyamino)pent-2-yn-1-yl]morpholine;

1-(3-chlorophenyl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

1-(1,3-benzodioxol-5-yl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}-4-(3-methoxyphenyl)piperazine;

1-(4-chlorophenyl)-4-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}piperazine;

1-(4-ethoxyphenyl)-4-{[2-(hydroxyamino)-4-phenylbut-3-yn-1-yl]sulfonyl}piperazine;

1-(5-bromopyridin-2-yl)-4-{[2-(hydroxyamino)-3,3-dimethyl-6-phenylhex-5-yn-1-yl]sulfonyl}piperazine;

1-{[2-(hydroxyamino)-3,3-dimethyl-6-phenylhex-5-yn-1-yl]sulfonyl}-4-[4-(trifluoromethyl)phenyl]piperazine;

1-(5-chloropyridin-2-yl)-4-{[2-(hydroxyamino)hept-3-yn-1-yl]sulfonyl}piperazine;

1-(4-ethoxyphenyl)-4-{[2-(hydroxyamino)-3,3-dimethyl-6-phenylhex-5-yn-1-yl]sulfonyl}piperazine;

1-(3,4-dimethoxyphenyl)-4-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}piperazine;

(2R)-4-(4-fluorophenyl)-1-{[2-(hydroxyamino)non-3-yn-1-yl]sulfonyl}-2-methyl piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-3,3-dimethylhex-5-yn-1-yl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-5-pyrrolidin-1-ylpent-3-yn-1-yl]sulfonyl}piperazine;

4-[7-{[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}-6-(hydroxyamino)-5,5-dimethyl hept-2-yn-1-yl]morpholine; and

1-(4-fluorophenyl)-4-{[2-(hydroxyamino)-3,3-dimethyloct-5-yn-1-yl]sulfonyl}piperazine;

and an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

21. A process for the manufacture of a compound, according to claim 19 , said process comprising the step of reacting a compound of Formula (III) with an aqueous solution of hydroxylamine of Formula (HA):

and thereby forming a compound according to claim 19 ;

wherein A, B, R 1 , R 2 , R 3 , X, Y, m, n and p are as in claim 19 ; and

W is selected from H, Benzyl, TMS, TBDMS and THP.

22. A compound according to the Formula:

wherein:

A is CR 4 R 5 ;

B is CR 4′ R 5′ ;

R 1 is selected from aryl, heteroaryl, C 3 -C 8 -cycloalkyl and heterocycloalkyl;

R 2 is selected from H, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

R 3 is selected from H, —Si(C 1 -C 6 -alkyl) 3 , amino-C 1 -C 6 -alkyl, C 1 -C 6 -alkyl, aryl, heteroaryl, aryl-C 1 -C 6 -alkyl, heteroaryl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, heterocycloalkyl-C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl and heterocycloalkyl;

R 4 , R 5 , R 4′ and R 5′ are independently selected from H, halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl and C 2 -C 6 -alkynyl;

X is N;

Y is CH 2 ;

the group —X—Y— is —N—CH 2 —;

m is selected from 0, 1 and 2;

n is selected from 0 and 1; and

p is 1;

or an enantiomer, diastereomer, or a pharmaceutically acceptable salt thereof.

23. A compound selected from the group consisting of:

1-{[(1E)-4-(1,3-benzodioxol-5-yl)-1-buten-3-ynyl]sulfonyl}-4-(4-fluorophenyl)piperazine;

1-{[(1Z)-4-(1,3-benzodioxol-5-yl)-1-buten-3-ynyl]sulfonyl}-4-(4-fluorophenyl)piperazine;

1-(4-fluorophenyl)-4-{[(1E)-4-(trimethylsilyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[(1Z)-4-(trimethylsilyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(2-pyridinyl)-4-{[(1E)-4-(trimethylsilyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(2-pyridinyl)-4-{[(1Z)-4-(trimethylsilyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[(1E)-4-phenyl-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[(1Z)-4-phenyl-1-buten-3-ynyl]sulfonyl}piperazine;

benzyl 4-{4-[(1E)-1-nonen-3-ynylsulfonyl]-piperazinyl}phenyl ether;

benzyl 4-{4-[(1Z)-1-nonen-3-ynylsulfonyl]-1-piperazinyl}phenyl ether;

1-(4-fluorophenyl)-4-{[(1E)-5-phenyl-1-penten-3-ynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[(1Z)-5-phenyl-1-penten-3-ynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-[(1E)-1-nonen-3-ynylsulfonyl]piperazine;

1-(4-fluorophenyl)-4-[(1Z)-1-nonen-3-ynylsulfonyl]piperazine;

1-(4-fluorophenyl)-4-{[(1E)-4-(3-pyridinyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-{[(1Z)-4-(3-pyridinyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-methoxyphenyl)-4-{[(1E)-4-(3-pyridinyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-methoxyphenyl)-4-{[(1Z)-4-(3-pyridinyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-methoxyphenyl)-4-{[(1E)-4-(3-methoxyphenyl)-1-buten-3-ynyl]sulfonyl}piperazine;

1-(4-methoxyphenyl)-4-{[(1Z)-4-(3-methoxyphenyl)-1-buten-3-ynyl]sulfonyl}piperazine;

N,N-diethyl-N-((4E)-5-{[4-(4-methoxyphenyl)-1-piperazinyl]sulfonyl}-4-penten-2-ynyl)amine;

N,N-diethyl-N-((4Z)-5-{[4-(4-methoxy phenyl)-1-piperazinyl]sulfonyl}-4-penten-2-ynyl)amine;

1-[(1E)-but-1-en-3-yn-1-ylsulfonyl]-4-pyridin-2-ylpiperazine;

1-[(1Z)-but-1-en-3-yn-1-ylsulfonyl]-4-pyridin-2-ylpiperazine;

1-[-hept-1-en-3-yn-1-ylsulfonyl]-4-pyridin-2-ylpiperazine;

1-(2-fluorophenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-[-non-1-en-3-yn-1-ylsulfonyl]-4-pyridin-2-ylpiperazine;

1-[-non-1-en-3-yn-1-ylsulfonyl]-4-[4-(trifluoromethyl)phenyl]piperazine;

1-(4-fluorophenyl)-4-{[-4-(3-methoxyphenyl)but-1-en-3-yn-1-yl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-[-hept-1-en-3-yn-1-ylsulfonyl]piperazine;

1-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}-4-[4-(trifluoromethyl)phenyl]piperazine;

3-((3E)-4-{[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}but-3-en-1-yn-1-yl)quinoline;

1-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}-4-pyridin-2-ylpiperazine;

1-(4-methoxyphenyl)-4-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}piperazine;

1-(4-fluorophenyl)-4-({-4-[4-(1,2,4-oxadiazol-3-yl)phenyl]but-1-en-3-yn-1-yl}sulfonyl)piperazine;

1-(4-methoxyphenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-biphenyl-4-yl-4-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}piperazine;

1-(5-chloropyridin-2-yl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

2-{4-[-non-1-en-3-yn-1-ylsulfonyl]piperazin-1-yl}pyrimidine;

1-[-non-1-en-3-yn-1-ylsulfonyl]-4-phenylpiperazine;

1-(4-chlorophenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-(2-methoxyphenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-(3-methoxyphenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-{[-3,3-dimethyl-6-phenylhex-1-en-5-yn-1-yl]sulfonyl}-4-(4-fluorophenyl)piperazine;

1-[-non-1-en-3-yn-1-ylsulfonyl]-4-[5-(trifluoromethyl)pyridin-2-yl]piperazine;

1-[-non-1-en-3-yn-1-ylsulfonyl]-4-(4-phenoxyphenyl)piperazine;

1-(4-fluorophenyl)-4-[-oct-1-en-3-yn-1-ylsulfonyl]piperazine;

1-(4-ethoxyphenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-(5-bromopyridin-2-yl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

4-(-5-{[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}pent-4-en-2-yn-1-yl)morpholine;

1-(3-chlorophenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-(1,3-benzodioxol-5-yl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-(3-methoxyphenyl)-4-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}piperazine;

1-(4-chlorophenyl)-4-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}piperazine;

1-(4-ethoxyphenyl)-4-{[-4-phenylbut-1-en-3-yn-1-yl]sulfonyl}piperazine;

1-(5-bromopyridin-2-yl)-4-{[-3,3-dimethyl-6-phenylhex-1-en-5-yn-1-yl]sulfonyl}piperazine;

1-{[-3,3-dimethyl-6-phenylhex-1-en-5-yn-1-yl]sulfonyl}-4-[4-(trifluoromethyl)phenyl]piperazine;

1-(5-chloropyridin-2-yl)-4-[-hept-1-en-3-yn-1-ylsulfonyl]piperazine;

1-{[-3,3-dimethyl-6-phenylhex-1-en-5-yn-1-yl]sulfonyl}-4-(4-ethoxyphenyl)piperazine;

1-(3,4-dimethoxyphenyl)-4-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

(2R)-4-(4-fluorophenyl)-2-methyl-1-[-non-1-en-3-yn-1-ylsulfonyl]piperazine;

1-{[-3,3-dimethylhex-1-en-5-yn-1-yl]sulfonyl}-4-(4-fluorophenyl)piperazine;

1-(4-fluorophenyl)-4-{[-5-pyrrolidin-1-ylpent-1-en-3-yn-1-yl]sulfonyl}piperazine;

4-(7-{[4-(4-fluorophenyl)piperazin-1-yl]sulfonyl}-5,5-dimethylhept-6-en-2-yn-1-yl)morpholine; and

1-{[-3,3-dimethyloct-1-en-5-yn-1-yl]sulfonyl}-4-(4-fluorophenyl)piperazine;

and an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof.

24. A method for treating a mammal with a disease or disorder comprising administering to the mammal an effective amount of a sulfonyl amino cyclic derivative according to claim 1 , wherein the disease or disorder is Chronic Obstructive Pulmonary Disease.