IKK Inhibitors for the Treatment of Endometriosis
This invention relates to a method of treating and/or preventing endometriosis comprising administering an IKK inhibitor. The IKK inhibitor can also be administered combined with a hormonal suppressor. The invention further relates to the treatment of endometriosis-related infertility.
1 . A method of treating and/or preventing endometriosis in an individual comprising administering a therapeutically effective amount of an IKK inhibitor.
2 . The method according to claim 1 , wherein said IKK inhibitor is administered in combination with a hormonal suppressor.
3 . The method according to claim 1 , wherein said hormonal suppressor is selected from the group consisting of a GnRH antagonist, GnRH agonist, aromatase inhibitor, progesterone receptor modulator and an estrogen receptor modulator.
4 . The method according to claim 1 , wherein said IKK inhibitor is administered alone or in combination with drugs for the treatment of endometriosis-related infertility.
5 . The method according to claim 1 , wherein said IKK inhibitor is a compound according to Formula (I):
as well as its isomers, prodrugs and pharmaceutically acceptable salts and pharmaceutically active derivatives thereof, wherein
R 1 is either aryl or heteroaryl optionally substituted with one to four substituents independently selected from R 7 ;
R 2 is hydrogen;
R 3 is either hydrogen or lower alkyl;
R 4 is optionally substituted with one to four substituents, wherein each substituent is the same or different and is independently selected from the group consisting of halogen, hydroxy, lower alkyl and lower alkoxy;
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 19 , —(CH 2 ) a NR 9 C(═O)R 19 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 19 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
6 . The method according to claim 5 , wherein R 5 and R 6 , taken together with the nitrogen atom to which they are attached form an optionally substituted nitrogen-containing non-aromatic heterocycle.
7 . The method according to claim 5 , wherein the nitrogen-containing non-aromatic heterocycle is selected from the group consisting of morpholinyl, thiomorpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, homopiperazinyl, hydantoinyl, tetrahydropyrindinyl, tekahydropyrimidinyl, oxazolidinyl, thiazolidinyl, indolinyl, isoindolinyl, tetrahydroquinolinyl and tetrahydroisoquinolinyl.
8 . The method according to claim 5 , wherein R 1 is either aryl or heteroaryl.
9 . The method according to claim 5 , wherein R 1 is selected from the group consisting of aryl, furyl, benzofuranyl, thiophenyl, benzothiophenyl, quinolinyl, pyrrolyl, indolyl, oxazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isoxazolyl, 25 pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl and quinazolinyl.
10 . The method according to claim 5 , wherein R 1 is phenyl.
11 . The method according to claim 7 , wherein the nitrogen-containing heterocycle is piperazinyl.
12 . The method according to claim 7 , wherein the nitrogen-containing heterocycle is piperidinyl.
13 . The method according to claim 7 , wherein the nitrogen-containing heterocycle is morpholinyl.
14 . The method according to claim 1 , wherein said IKK inhibitor is a compound according to Formula (II):
as well as its isomers, prodrugs and pharmaceutically acceptable salts and pharmaceutically active derivatives thereof, wherein
R 1 is aryl or heteroaryl optionally substituted with one to four substituents independently selected from R 7 ;
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 10 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form a heterocycle or substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
15 . The method according to claim 14 , wherein R 5 and R 6 , taken together with the
nitrogen atom to which they are attached form an optionally substituted nitrogen-containing non-aromatic heterocycle.
16 . The method according to claim 15 , wherein the nitrogen-containing non-aromatic heterocycle is selected from the group consisting of morpholinyl, thiomorpholinyl, pyrrolidinonyl, pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, homopiperazinyl, hydantoinyl, tetrahydropyrindinyl, tekahydropyrimidinyl, oxazolidinyl, thiazolidinyl, indolinyl, isoindolinyl, tetrahydroquinolinyl and tetrahydroisoquinolinyl.
17 . The method according to claim 14 , wherein R 1 is either aryl or heteroaryl.
18 . The method according to claim 14 , wherein R 1 is selected from the group consisting of aryl, furyl, benzofuranyl, thiophenyl, benzothiophenyl, quinolinyl, pyrrolyl, indolyl, oxazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isoxazolyl, 25 pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, cinnolinyl, phthalazinyl and quinazolinyl.
19 . The method according to claim 14 , wherein R 1 is phenyl.
20 . The method according to claim 15 , wherein the nitrogen-containing heterocycle is piperazinyl.
21 . The method according to claim 15 , wherein the nitrogen-containing heterocycle is piperidinyl.
22 . The method according to claim 15 , wherein the nitrogen-containing heterocycle is morpholinyl.
23 . The method according to claim 1 , wherein said IKK inhibitor is a compound according to Formula (III):
wherein
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 19 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 21 SO c R 9 and —(CH 2 ) a SO c NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form a heterocycle or substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
24 . The method according to claim 1 , wherein said IKK inhibitor is a compound according to Formula (IV):
wherein
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) 4 C(═O)NR 9 (CH 2 ) b C(═O)R 10 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH)NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 .
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form a heterocycle or substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
25 . The method according to claim 1 , wherein said IKK inhibitor is 1-(4-{4-[4-(4-Chloro-phenyl)-pyrimidin-2-ylamino]-benzoyl}-piperazin-1-yl)-ethanone.
26 . A pharmaceutical composition comprising an IKK inhibitor, a hormonal suppressor and a pharmaceutically acceptable excipient.
27 . The pharmaceutical composition according to claim 26 , wherein said hormonal suppressor is selected from the group consisting of a GnRH antagonist, GnRH agonist, aromatase inhibitor, progesterone receptor modulator and an estrogen receptor modulator.
28 - 29 . (canceled)
30 . The pharmaceutical composition according to claim 26 , wherein said IKK inhibitor is a compound according to Formula (I):
as well as its isomers, prodrugs and pharmaceutically acceptable salts and pharmaceutically active derivatives thereof, wherein
R 1 is either aryl or heteroaryl optionally substituted with one to four substituents independently selected from R 7 ;
R 2 is hydrogen;
R 3 is either hydrogen or lower alkyl;
R 4 is optionally substituted with one to four substituents, wherein each substituent is the same or different and is independently selected from the group consisting of halogen, hydroxy, lower alkyl and lower alkoxy;
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 10 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO c R 8 , —SO c NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
31 . The pharmaceutical composition according to claim 26 , wherein said IKK inhibitor is a compound according to Formula (II):
as well as its isomers, prodrugs and pharmaceutically acceptable salts and pharmaceutically active derivatives thereof, wherein
R 1 is aryl or heteroaryl optionally substituted with one to four substituents independently selected from R 7 ;
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 10 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form a heterocycle or substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
32 . The pharmaceutical composition according to claim 26 , wherein said IKK inhibitor is a compound according to Formula (III):
wherein
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 10 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form a heterocycle or substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
33 . The pharmaceutical composition according to claim 26 , wherein said IKK inhibitor is a compound according to Formula (IV):
wherein
R 5 and R 6 are the same or different and are independently selected from the group consisting of —R 8 , —(CH 2 ) a C(═O)R 9 , —(CH 2 ) a C(═O)OR 9 , —(CH 2 ) a C(═O)NR 9 R 10 , —(CH 2 ) a C(═O)NR 9 (CH 2 ) b C(═O)R 10 , —(CH 2 ) a NR 9 C(═O)R 10 , —(CH 2 ) a NR 11 C(═O)NR 9 R 10 , —(CH 2 ) a NR 9 R 10 , (CH 2 ) a OR 9 , —(CH 2 ) a SO c R 9 and —(CH 2 ) a SO 2 NR 9 R 10 ;
or R 5 and R 6 taken together with the nitrogen atom to which they are attached to form a heterocycle or substituted heterocycle;
R 7 is at each occurrence independently selected from the group consisting of halogen, hydroxy, cyano, nitro, carboxy, alkyl, alkoxy, haloalkyl, acyloxy, sulfanylalkyl, sulfinylalkyl, sulfonylalkyl, hydroxyalkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl, substituted alkylheterocycloalkyl, —C(═O)OR 8 , —OC(═O)R 8 , —C(═O)NR 8 R 9 , —C(═O)NR 8 OR 9 , —SO C R 8 , —SO C NR 8 R 9 , —NR 8 SO C R 9 —NR 8 R 9 , —NR 8 C(═O)R 9 , —NR 8 C(═O)(CH 2 ) b OR 9 , —NR 8 C(═O)(CH 2 ) b R 9 , —O(CH 2 ) b NR 8 R 9 and heterocycloalkyl fused to phenyl;
R 8 , R 9 , R 10 and R 11 are the same or different and are at each occurrence independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, heterocycloalkyl, substituted heterocycloalkyl, alkylheterocycloalkyl and substituted alkylheterocycloalkyl;
or R 8 and R 9 taken together with the atom or atoms to which they are attached to form an optionally substituted heterocycle;
a and b are the same or different and are at each occurrence independently selected from the group consisting of 0, 1, 2, 3 and 4; and
c is at each occurrence 0, 1 or 2.
34 . The pharmaceutical composition according to claim 26 , wherein said IKK inhibitor is 1-(4-{4-[4-(4-Chloro-phenyl)-pyrimidin-2-ylamino]-benzoyl}-piperazin-1-yl)-ethanone.