DK2054411T3

DK2054411T3 - Hidtil ukendte forbindelser, isomer deraf, eller farmaceutisk acceptable salte deraf som vanilloid receptorantagonist og farmaceutiske sammensætninger indeholdende samme

Info

Publication number: DK2054411T3
Application number: DK07793254.9T
Authority: DK
Inventors: Sun-Young Kim; Jin Kwan Kim; Ki-Wha Lee; Byoung Young Woo; Song Seok Shin; Joo-Hyun Moh; Sung-Il Kim; Yeon Su Jeong; Kyung Min Lim; Jin Kyu Choi; Jun Yong Ha; Hyun-Ju Koh; Young-Ho Park; Young-Ger Suh; Hee-Doo Kim; Hyeung-Geun Park; Uh Taek Oh
Original assignee: Amorepacific Corp
Priority date: 2006-07-27
Filing date: 2007-07-26
Publication date: 2014-11-24
Also published as: TW200817332A; PT2054411E; ES2523191T3

Claims

1. Forbindelse med formlen (III), en optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf;

(lii) hvor Ri er hydrogen, halogen eller Cl-C5-alkyl; R2, R3, R4 og R5 uafhængigt er hydrogen, halogen, nitro, cyano, Cl-C5-alkyl, Cl-C5-alkoxy, halo (C1-C5) alkyl, C2-C5-alkenyl, C2-C5-alkynyl, carboxy, Cl-C5-alkoxycarbonyl eller Cl-C5-alkylthio; Re er hydroxy, halogen, nitro, carboxy, Cl-C10-alkyl, Cl-C10-alkoxy, C2-C10-alkenyl, C2-C10-alkynyl, Cl-C10-alkylthio, Cl-C10-alkylsulfonyl, Cl-C10-alkylcarbonyle, C1-C10-alkoxycarbonyl, C2-C10-alkenyloxy, Cl-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, piperidyl, piperazinyl, Cl-C5-alkoxy (C1-C5) alkylamino, C1-C10-alkylamino, di(Cl-C10-alkyl)amino, C3-C8-cycloalkyl, C3-C8-cycloalkylamino, C3-C8-cycloalkoxy, C3-C8-oxacycloalkyl-oxy, N-(Cl-C5)alkoxy (C1-C5) alkyl-N-(C1-C5) alkylamino, N-(C3-C8)cycloalkyl-N-(Cl-C5) alkylamino, N-aryl-N-(Cl-C5) alkylamino, fortrinsvis N-phenyl-N-(Cl-C5)alkylamino, aryl fortrinsvis phenyl, arylamino fortrinsvis phenylamino, arylthio fortrinsvis phenylthio, heteroaryl fortrinsvis thienyl, heteroarylamino, aryloxy fortrinsvis phenoxy, heteroaryloxy fortrinsvis pyridinyloxy, pyrrolidinyl eller morpholinyl; Rg og R9 uafhængigt er hydrogen, hydroxy, halogen, nitro, carboxy, Cl-C10-alkyl, C1-C10-alkoxy, C2-C10-alkenyl, C2-C10-alkynyl, Cl-C10-alkylthio, Cl-C10-alkylsulfonyl, C1-C10-alkylcarbonyl, Cl-C10-alkoxycarbonyl, C2-C10-alkenyloxy, Cl-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, piperidyl, piperazinyl, Cl-C5-alkoxy (C1-C5) alkylamino, Cl-C10-alkylamino, di(Cl-C10-alkyl)amino, C3-C8-cycloalkyl, C3-C8-cycloalkylamino, C3-C8-cycloalkoxy, C3-C8-oxacycloalkyl-oxy, N-(Cl-C5)alkoxy (C1-C5) alkyl-N-(Cl-C5) alkylamino, N-(C3-C8)cycloalkyl-N-(Cl-C5) alkylamino, N-aryl-N-(Cl-C5) alkylamino, fortrinsvis N-phenyl-N-(Cl-C5)alkylamino, aryl fortrinsvis phenyl, arylamino fortrinsvis phenylamino, arylthio fortrinsvis phenylthio, heteroaryl fortrinsvis pyridinyl eller thienyl, heteroarylamino, aryloxy fortrinsvis phenoxy, heteroaryloxy fortrinsvis pyridinyloxy, pyrrolidinyl eller morpholinyl, hvor hver alkyl, alkenyl og alkynyl, også som del af en gruppe, såsom i alkoxy, alkylsulfonyl, alkylcarbonyl, alkylamino eller alkenyloxy kan være uafhængigt ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, hydroxyl, ikke-substitueret eller halo-substitueret (C1-C5) alkoxy, (C3-C8) cycloalkyl, der kan være ikke-substitueret eller substitueret med én eller flere halogenradikaler og/eller methylgrupper, ikke-substitueret eller halo-substitueret (CICS) alkylamino, phenyl, der kan være ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, ikke-substitueret Cl-C3-alkyl eller halo (C1-C3) alkyl eller ikke-substitueret eller halo-substitueret di(Cl-C5) alkylamino, hver aryl eller heteroaryl, også en del af en gruppe, såsom i arylamino, aryloxy, heteroaryloxy eller heteroarylamino, kan være uafhængigt ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, ikke-substitueret Cl-C5-alkyl, ikke-substitueret Cl-C5-alkoxy eller halo (C1-C5) alkyl, hver cycloalkyl, også som del af en gruppe, såsom i cycloalkoxy eller cycloalkylamino kan være ikke-substitueret eller substitueret med én eller flere ikke-substituerede eller halo-substituerede Cl-C3-alkylgrupper, hydroxymethyl, hydroxy, methoxy eller amino og hver piperazinyl, piperidyl, morpholinyl og pyrrolidinyl kan være ikke-substitueret eller substitueret med én eller flere ikke-substituerede eller halo-substituerede C1-C3-alkylgrupper, hydroxy(Cl-C3)alkyl, Cl-C3-alkoxy, (Cl-C3)alkoxycarbonyl eller hydroxyl; R7 er halo(Cl-C5)alkyl; Rio er Cl-C5-alkyl, halo (C1-C5) alkyl eller C2-C5-alkenyl og Rn og R12 uafhængigt er hydrogen, Cl-C5-alkyl eller halogen.

2. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, fluoro, methyl, cyano, ethenyl eller ethynyl; R4 er hydrogen, fluoro eller methyl; R3 er hydrogen; R6 er n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, 2-phenylethyl, n-butoxy, isobutoxy, sec-butoxy, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, methoxyethylamino, ethoxyethylamino, benzylamino, N-ethyl-N-phenylamino eller N-methyl-N-phenylamino; R7 er trifluormethyl; Rg og R9 er hydrogen; Rio er methyl; og Ri 1 og R12 er hydrogen.

3. Forbindelse of formlen (I), optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf:

(i) hvor X er CRu=CR12 eller C=C; hvor Ru og R12, hvis til stede, uafhængigt er hydrogen, halogen eller Cl-C5-alkyl; Z er N; Y er CR6; Ri er hydrogen, halogen eller Cl-C5-alkyl; R2, R3, R4 og R5 uafhængigt er hydrogen, halogen, nitro, cyano, Cl-C5-alkyl, Cl-C5-alkoxy, halo (C1-C5) alkyl, C2-C5-alkenyl, C2-C5-alkynyl, carboxy, Cl-C5-alkoxycarbonyl eller Cl-C5-alkylthio; R6 er hydroxy, halogen, nitro, carboxy, Cl-C10-alkyl, Cl-C10-alkoxy, C2-C10-alkenyl, C2-C10-alkynyl, Cl-C10-alkylthio, Cl-C10-alkylsulfonyl, Cl-C10-alkylcarbonyl, C1-C10-alkoxycarbonyl, C2-C10-alkenyloxy, Cl-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, piperidyl, piperazinyl, Cl-C5-alkoxy (C1-C5) alkylamino, C1-C10-alkylamino, di(Cl-C10-alkyl)amino, C3-C8-cycloalkyl, C3-C8-cycloalkylamino, C3-C8-cycloalkoxy, C3-C8-oxacycloalkyloxy, N-(C1-C5) alkoxy (C1-C5) alkyl-N-(C1-C5) alkylamino, N-(C3-C8) cycloalkyl-N-(Cl-C5) alkylamino, N-aryl-N-(Cl-C5) alkylamino fortrinsvis N-phenyl-N-(Cl-C5)alkylamino, aryl fortrinsvis phenyl, arylamino fortrinsvis phenylamino, arylthio fortrinsvis phenylthio, heteroaryl fortrinsvis pyridinyl eller thienyl, heteroarylamino, aryloxy fortrinsvis phenoxy, heteroaryloxy fortrinsvis pyridinyloxy, pyrrolidinyl eller morpholinyl, Rg og R9 uafhængigt er hydrogen, hydroxy, halogen, nitro, carboxy, Cl-C10-alkyl, C1-C10-alkoxy, C2-C10-alkenyl, C2-C10-alkynyl, Cl-C10-alkylthio, Cl-C10-alkylsulfonyl, C1-C10-alkylcarbonyl, Cl-C10-alkoxycarbonyl, C2-C10-alkenyloxy., Cl-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, piperidyl, piperazinyl, Cl-C5-alkoxy (C1-C5) alkylamino, Cl-C10-alkylamino, di(Cl-C10-alkyl)amino, C3-C8-cycloalkyl, C3-C8-cycloalkylamino, C3-C8-cycloalkoxy, C3-C8-oxacycloalkyloxy, N-(C1-C5) alkoxy (C1-C5) alkyl-N-(C1-C5) alkylamino, N-(C3-C8) cycloalkyl-N-(Cl-C5) alkylamino, N-aryl-N-(Cl-C5) alkylamino, fortrinsvis N-phenyl-N-(Cl-C5)alkylamino, aryl fortrinsvis phenyl, arylamino fortrinsvis phenylamino, arylthio fortrinsvis phenylthio, heteroaryl fortrinsvis pyridinyl eller thienyl, heteroarylamino, aryloxy fortrinsvis phenoxy, heteroaryloxy fortrinsvis pyridinyloxy, pyrrolidinyl eller morpholinyl, hvor hver alkyl, alkenyl og alkynyl, også som del af en gruppe, såsom i alkoxy, alkylsulfonyl, alkylcarbonyl, alkylamino eller alkenyloxy kan være uafhængigt ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, hydroxyl, ikke-substitueret eller halo-substitueret (C1-C5) alkoxy, (C3-C8) cycloalkyl, der kan være ikke-substitueret eller substitueret med én eller flere halogenradikaler og/eller methylgrupper, ikke-substitueret eller halo-substitueret (CICS) alkylamino, phenyl, der kan være ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, ikke-substitueret Cl-C3-alkyl eller halo (C1-C3) alkyl eller ikke-substitueret eller halo-substitueret di(Cl-C5) alkylamino, hver aryl eller heteroaryl, også som en del af en gruppe såsom i arylamino, aryloxy, heteroarylamino eller heteroaryloxy, kan være uafhængigt ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, ikke-substitueret Cl-C5-alkyl, ikke-substitueret Cl-C5-alkoxy eller halo (C1-C5) alkyl, hver cycloalkyl, også som del af en gruppe, såsom i cycloalkoxy eller cycloalkylamino kan være ikke-substitueret eller substitueret med én eller flere ikke-substituerede eller halo-substituerede Cl-C3-alkylgrupper, hydroxymethyl, hydroxy, methoxy eller amino og hver piperazinyl, piperidyl, morpholinyl og pyrrolidinyl kan være ikke-substitueret eller substitueret med én eller flere ikke-substituerede eller halo-substituerede C1-C3-alkylgrupper, hydroxy(Cl-C3)alkyl, Cl-C3-alkoxy, (Cl-C3)alkoxycarbonyl eller hydroxyl; R7 er halo(Cl-C5)alkyl; og Rio er Cl-C5-alkyl, halo (C1-C5) alkyl eller C2-C5-alkenyl.

4. Forbindelse ifølge krav 3, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor X er -CH=CH-, -C(CHr)=CH-, -CH=C(CH3)-, -C(CH3)-C(CH3)-, -C(C2H5)=CH-, -CH=C(C2H5)-, -C1==CH-, -CH=CF- eller C=C; Ri er hydrogen, fluoro, methyl eller ethyl; R2, R3, R4 og R5 uafhængigt er hydrogen, fluoro, chloro, bromo, nitro, cyano, methyl, ethyl, ethenyl, ethynyl, trifluormethyl, methoxy, ethoxy eller methoxycarbonyl; Re er hydroxy, fluoro, bromo, chloro, hydroxymethyl, Cl-C6-alkyl, Cl-C6-alkoxy, C2-C6-alkenyl, C2-C6-alkynyl, halo (C1-C6) alkyl, halo (C1-C6) alkoxy, C2-C6-alkenyloxy, C1-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, di(Cl-C6-alkyl)amino, Cl-C6-alkylamino, C1-C3-alkoxy (C1-C5) alkylamino, C3-C6-cycloalkyl, der kan være ikke-substitueret eller substitueret med én eller flere methylgrupper, C3-C6-cycloalkylamino, der kan være ikke-substitueret eller substitueret med én eller flere methylgrupper, C3-C6-cycloalkoxy, C3-C6-oxacycloalkoxy, N-(C1-C2) alkoxy (C1-C3) alkyl-N-(Cl-C3) alkylamino, N-(C3-C6) cycloalkyl-N-(Cl-C3) alkylamino, piperidyl, pyrrolidinyl, halophenyl, phenyl, phenoxy, phenylamino, halophenoxy, morpholinyl: C1-C2 alkoxy (C1-C3) alkyl, phenyl(Cl-C3)alkyl, phenyl(C2-C3)alkenyl, Cl-C3-alkoxyalkynyl, di(Cl-C3)alkylaminoalkynyl, (Cl- C3)alkoxyphenyl, thienyl, (C3-C6) cycloalkyl (C1-C3) alkoxy, phenyl (C1-C3) alkoxy, C1-C5-alkylthio, phenyl (C1-C3) alkylamino, arylamino, N-phenyl-N-(Cl-C3) alkylamino, (Cl-C3)alkoxycarbonyl eller piperidyl; R7 er halo (Cl-C5) alkyl; R8 og R9 uafhængigt er hydrogen, halogen eller trifluormethyl og Rio er Cl-C5-alkyl, halo (C1-C5) alkyl eller C2-C5-alkenyl.

5. Sammensætning ifølge krav 3, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor X er CR11-CR12, hvor Ru og R12, uafhængigt er hydrogen, halogen eller Cl-C3-alkyl; Ri er hydrogen eller Cl-C3-alkyl; R2, R3, R4 og R5 uafhængigt er hydrogen, halogen, nitro, cyano, methyl, ethyl, ethenyl, ethynyl, trifluormethyl, methoxy, ethoxy eller methoxycarbonyl; R6 er hydroxy, halogen, nitro, carboxy, Cl-C5-alkyl, Cl-C5-alkoxy, hydroxy (C1-C5) alkyl, C2-C5-alkenyl, C2-C5-alkynyl, halo (C1-C5) alkyl, halo (C1-C5) alkoxy, Cl-C5-alkythio, Cl-C5-alkylsulfonyl, Cl-C5-alkylcarbonyl, Cl-C5-alkoxycarbonyl, C2-C5-alkenyloxy, C1-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, piperidyl, Cl-C5-alkoxy (C1-C5) alkylamino, C1-C7 alkylamino, di(Cl-C3-alkyl)amino, C3-C6-cycloalkyl, der kan være ikke-substitueret eller substitueret med én eller flere methylgrupper, pyrrolidinyl, phenyl eller morpholinyl, hvor phenyl kan være ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, Cl-C5-alkyl og halo (C1-C5) alkyl Rg og R9 uafhængigt er hydrogen, hydroxy, halogen, nitro, carboxy, Cl-C5-alkyl, C1-C5-alkoxy, hydroxy (C1-C5) alkyl, C2-C5-alkenyl, C2-C5-alkynyl, halo (C1-C5) alkyl, halo (CICS) alkoxy, Cl-C5-alkylthio, C1 -C5-alkylsulfonyl, Cl-C5-alkylcarbonyl, C1-C5-alkoxycarbonyl, C2-C5-alkenyloxy, Cl-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, Cl-C3-alkylpiperazinyl, piperidyl, C1-C5-alkoxy (C1-C5) alkylamino, C1-C7 alkylamino, di(Cl-C3-alkyl)amino, C3-C6-cycloalkyl, der kan være ikke-substitueret eller substitueret med én eller flere methylgrupper, pyrrolidinyl, phenyl eller morpholinyl, hvor phenyl kan være ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, Cl-C5-alkyl og halo (C1-C5) alkyl; R7 er halo(Ci-C4)alkyl og Rio er Cl-C3-alkyl eller C2-C3-alkenyl.

6. Forbindelse ifølge et hvilket som helst af kravene 3 til 5, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor R7 er trifluormethyl.

7. Forbindelse ifølge krav 1 eller 3, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen, methyl eller ethyl; R2, R3, R4 og R5 uafhængigt er hydrogen, fluoro, chloro, bromo, nitro, cyano, methyl, ethyl, ethenyl, ethynyl, trifluormethyl, methoxy, ethoxy eller methoxycarbonyl; R6 er hydroxy, fluoro, bromo, chloro, hydroxymethyl, Cl-C5-alkyl, Cl-C5-alkoxy, C2-C5-alkenyl, C2-C5-alkynyl, halo (C1-C5) alkyl, halo (C1-C5) alkoxy, C2-C5-alkenyloxy, C1-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, di(Cl-C3-alkyl)amino, Cl-C3-alkylpiperazinyl, piperidyl, pyrrolidinyl, halophenyl, phenyl eller morpholinyl; R7 er halo (C1-C4) alkyl; R8 og R9 uafhængigt er hydrogen, halogen eller trifluormethyl; Rio er Cl-C5-alkyl, halo (C1-C5) alkyl eller C2-C5-alkanyl og Ru og R12, hvis til stede, uafhængigt er hydrogen eller methyl.

8. Forbindelse ifølge et hvilket som helst af kravene 1 og 3 til 7, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri, R2 og R5 er hydrogen; R3 er hydrogen, fluoro, chloro, cyano, methyl, ethenyl, ethynyl eller trifluormethyl; R4 er hydrogen, fluoro, chloro, cyano, methyl, ethyl eller trifluormethyl; Rg er hydroxy, fluoro, bromo, chloro, methyl, hydroxymethyl, methoxy, trifluormethyl, diethylamino, piperidyl, pyrrolidinyl, trifluorphenyl, phenyl eller morpholinyl; R7 er trifluormethyl; Rg er hydrogen; Ru og R12, hvis til stede, er hydrogen, R9 er hydrogen eller trifluormethyl og Rio er methyl.

9. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri, R2 og R5 er hydrogen; R3 er hydrogen, fluoro, chloro, cyano, methyl, ethenyl, ethynyl eller trifluormethyl; R4 er hydrogen, fluoro, chloro, cyano, methyl, ethyl eller trifluormethyl; R6 er hydroxy, fluoro, bromo, chloro, methyl, propyl, butyl, pentyl, hydroxymethyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, methoxymethoxy, methoxyethoxy, methoxypropoxy, trifluormethyl, diethylamino, methoxymethylamino, methoxyethylamino, methoxypropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, ethylamino, propylamino, butylamino, pentylamino, Ν,Ν-dimethylamino, N-methyl-N-ethylamino Ν,Ν-diethylamino, N-methyl-N-propylamino, N-ethyl-N-propylamino, Ν,Ν-dipropylamino, N-methyl-N-butylamino, N-ethyl-N-butylamino, N-methyl-N-methoxymethylamino, N-methyl-N-methoxyethylamino, N-methyl-N-methoxypropylamino, N-methyl-N-cyclobutylamino, N-methyl-N-cyclopentylamino, N-methyl-N-cyclohexylamino, phenoxy, halophenoxy, piperidyl, pyrrolidinyl, trifluorphenyl, phenyl eller morpholinyl; R7 er trifluormethyl, Rs er hydrogen; Ru og R12 er hydrogen; R9 er hydrogen eller trifluormethyl og Rio er methyl.

10. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, ethenyl, ethynyl eller trifluormethyl; R4 og R5 uafhængigt er hydrogen, fluoro, chloro, cyano, methyl, ethyl eller trifluormethyl; R6 er fluoro, chloro, bromo, methyl, n-butyl, methoxy, n-butyloxy, isobutyloxy, sec-butyloxy, methoxyethoxy, methoxyethylamino, diethylamino, n-butylamino, cyclopentylamino, phenoxy, N-pyrrolidinyl, N-piperidyl eller N-morpholinyl; R7 er trifluormethyl; R8 er hydrogen; Ru og R12 er hydrogen; R9 er hydrogen eller trifluormethyl og Rio er methyl.

11. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, ethenyl eller ethynyl; R4 er hydrogen eller fluoro; R5 er hydrogen; Rg er hydroxy, fluoro, bromo, chloro, methyl, propyl, butyl, pentyl, hydroxymethyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, methoxymethoxy, methoxyethoxy, methoxypropoxy, ethoxyethoxy, trifluormethyl, Ν,Ν-dimethylamino, N-methyl-N-ethylamino N,N-diethylamino, N-methyl-N-propylamino, N-ethyl-N-propylamino, Ν,Ν-dipropylamino, N-methyl-N-butylamino, N-ethyl-N-butylamino, methoxymethylamino, methoxyethylamino, methoxypropylamino, N-methyl-N-methoxymethylamino, N-methyl-N-methoxyethylamino, N-methyl-N-methoxypropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, N-methyl-N-cyclobutylamino, N-methyl-N-cyclopentylamino, N-methyl-N-cyclohexylamino, ethylamino, propylamino, butylamino, pentylamino, phenoxy, halophenoxy, N-piperidyl, N-pyrrolidinyl, trifluorphenyl, phenyl eller N-morpholinyl; R7 er trifluormethyl: Rg er hydrogen; Rg er hydrogen eller trifluormethyl; Rio er methyl og Ru og R12 er hydrogen.

12. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen; R2 er hydrogen; R3 er hydrogen, ethenyl eller ethynyl; R4 er hydrogen eller fluoro; R5 er hydrogen; Rg er bromo, chloro, n-butyl, methoxy, isobutyloxy, sec-butyloxy, methoxyethoxy, diethylamino, N-pyrrolidinyl, N-piperidyl, N-morpholinyl, cyclopentylamino, n-butylamino, phenoxy, n-butyloxy, methoxyethylamino; R7 er trifluormethyl; Rg er hydrogen; R9 er hydrogen eller trifluormethyl; Rio er methyl og Ru og R12 er hydrogen.

13. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, fluoro, methyl, ethyl, cyano, ethenyl, ethynyl eller trifluormethyl; R4 er hydrogen, fluoro, chloro eller methyl; R5 er hydrogen; R-6 er fluoro, chloro, bromo, methyl, ethyl, propyl, butyl, pentyl, trifluormethyl, ethoxymethyl, methoxypropyl, phenylethyl, phenylethenyl, ethynyl, methoxypropynyl, diethylaminopropynyl, phenyl, halophenyl, methoxyphenyl, thienyl, pyridinyl, halopyridinyl, methoxy, ethoxy, propoxy, butoxy, pentoxy, trifluorethoxy, cyclopentoxy, cyclopropylmethoxy, methoxyethoxy, tetrahydropyranyloxy, phenoxy, halophenoxy, benzyloxy, pyridinyloxy, ethylthio, propylthio, butylthio, pentylthio, ethylamino, propylamino, butylamino, pentylamino, methoxyethylamino, ethoxyethylamino, methoxypropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, benzylamino, phenylamino, Ν,Ν-dimethylamino, N-methyl-N-propylamino, N-ethyl-N-propylamino, Ν,Ν-dipropylamino, N-methyl-N-butylamino, N-ethyl-N-butylamino, N-ethyl-N-phenylamino, N-methyl-N-phenylamino, N-pyrrolidinyl, methoxy N-pyrrolidinyl, hydroxymethyl N-pyrrolidinyl; N-pipendyl, ethoxycarbonyl N-piperidyl, piperazinyl eller N-morpholinyl; R7 er trifluormethyl; Rg er hydrogen; R9 er hydrogen eller trifluormethyl, Rio er methyl og Ru og R12 er hydrogen

14. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, fluoro, chloro, bromo, cyano, methyl, ethyl, ethenyl, ethynyl eller trifluormethyl, R4 og R5 uafhængigt er hydrogen, fluoro, chloro, cyano, methyl eller ethyl; R6 er n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, 2-phenylethyl, n-butoxy, isobutoxy, sec-butoxy, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, methoxyethylamino, ethoxyethylamino, benzylamino, phenylamino, N-ethyl-N-phenylamino eller N-methyl-N-phenylamino; R7 er trifluormethyl; Rg er hydrogen eller chloro; R9 er hydrogen eller trifluormethyl; Rio er methyl og Ru og R12 er hydrogen.

15. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor Ri er hydrogen eller methyl; R2 er hydrogen; R4 er hydrogen, fluoro, chloro eller methyl; R3 er hydrogen, fluoro, methyl, cyano, ethenyl, ethynyl eller trifluormethyl; R5 er hydrogen; R6 er ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, ethoxymethyl, 2-phenylethyl, phenylethenyl, phenyl, fluorphenyl, thienyl, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, 3-metylbutoxy, 2,2,2-trifluorethoxy, cyclopentoxy, cyclopropylmethoxy, phenoxy, ethylthio, propylthio, isopropylthio, phenylthio, ethylamino, n-propylamino isopropylamino, n-butylamino, isobutylamino, sec-butylamino, methoxymethylamino, methoxyethylamino, ethoxyethylamino, cyclopentylamino, benzylamino, phenylamino, N-ethyl-N-phenylamino, N-methyl-N-phenylamino, N-methyl-N-propylamino, N-pyrrolidinyl, methoxy N-pyrrolidinyl, N-pipendyl eller ethoxycarbonyl N-piperidyl; R7 er trifluormethyl; Rg er hydrogen eller chloro; R9 er hydrogen eller trifluormethyl; Rio er methyl og Ru og R12 er hydrogen.

16. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, fluoro, chloro, methyl, cyano, ethenyl eller ethynyl; R4 er hydrogen; R5 er fluoro, chloro eller methyl; R6 er ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, ethoxymethyl, 2-phenylethyl, phenylethenyl, phenyl, fluorphenyl, thienyl, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, 3-metylbutoxy, 2,2,2-trifluorethoxy, cyclopentoxy, cyclopropylmethoxy, phenoxy, ethylthio, propylthio, isopropylthio, ethylamino, n-propylamino isopropylamino, n-butylamino, isobutylamino, sec-butylamino, methoxymethylamino, methoxyethylamino, ethoxyethylamino, cyclopentylamino, benzylamino, phenylamino, N-ethyl-N-phenylamino, N-methyl-N-phenylamino, N-methyl-N-propylamino, N-pyrrolidinyl, N-piperidyl eller ethoxycarbonyl N-piperidyl; R7 er halo(Cl-C3)alkyl; Rg og R9 uafhængigt er hydrogen, halogen eller trifluormethyl; Rio er methyl og Ru og R12 er hydrogen.

17. Forbindelse ifølge krav 1, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf; hvor Ri er hydrogen eller methyl; R2 er hydrogen; R3 er hydrogen, fluoro, chloro, methyl, cyano, ethenyl eller ethynyl; R4 er hydrogen; R5 er fluoro; Rs er n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, 2-phenylethyl, n-butoxy, isobutoxy, sec-butoxy, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, methoxyethylamino, ethoxyethylamino, benzylamino, N-ethyl-N-phenylamino eller N-methyl-N-phenylamino; R7 er trifluormethyl; Rx er hydrogen eller chloro; R9 er hydrogen; Rio er methyl og Ru og R12 er hydrogen.

18. Forbindelse ifølge krav 3, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor forbindelsen er repræsenteret ved formlen (VI):

hvor W er hydrogen eller fluoro; X er -CRn=CRi2- eller -OC-; Ri er udvalgt blandt hydrogen og Cl -C3-alkyl; Rd er hydroxy, halogen, nitro, carboxy, Cl-C10-alkyl, Cl-C10-alkoxy, C2-C10-alkenyl, C2-C10-alkynyl, Cl-C10-alkylthio, Cl-C10-alkylsulfonyl, Cl-C10-alkylcarbonyl, C1-C10-alkoxycarbonyl, C2-C10-alkenyloxy, Cl-C5-alkoxy (C1-C5) alkoxy, Cl-C5-alkoxy (C1-C5) alkoxy (C1-C5) alkyl, piperidyl, Cl-C5-alkoxy (C1-C5) alkylamino, Cl-C10-alkylamino, di(Cl-C10-alkyl)amino, C3-C8-cycloalkyl, C3-C8-cycloalkylamino, C3-C8-cycloalkoxy, C3-C8-oxacycloalkyl-oxy, N-(Cl-C5)alkoxy (C1-C5) alkyl-N-(Cl-C5) alkylamino, N-(C3-C8)cycloalkyl-N-(Cl-C5) alkylamino, N-aryl-N-(Cl-C5) alkylamino, fortrinsvis N-phenyl-N- (Cl-C5)aLkylamino, aryl fortrinsvis phenyl, arylamino fortrinsvis phenylamino, heteroaryl fortrinsvis thienyl, heteroarylamino, aryloxy fortrinsvis phenoxy, pyrrolidinyl eller morpholinyl; Ri i og R12, hvis til stede, uafhængigt er udvalgt blandt hydrogen og propyl; R7 er CF3, CF2C1 eller CF2CF3; R8 og R9 uafhængigt er udvalgt blandt hydrogen, halogen eller CF3; hvor hver alkyl, alkenyl og alkynyl også som del af en gruppe, såsom i alkoxy, alkylsulfonyl, alkylcarbonyl, alkylamino eller alkenyloxy kan være uafhængigt ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, hydroxyl, ikke-substitueret eller halo-substitueret (C1-C5) alkoxy, (C3-C8) cycloalkyl, der kan være ikke-substitueret eller substitueret med én eller flere halogenradikaler og/eller methylgrupper, ikke-substitueret eller halo-substitueret (C1-C5) alkylamino, phenyl, der kan være ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, ikke-substitueret Cl-C3-alkyl eller halo (C1-C3) alkyl eller ikke-substitueret eller halo-substitueret di(Cl-C5) alkylamino, hver aryl eller heteroaryl, også som en del af en gruppe såsom i arylamino, aryloxy, heteroaryloxy eller heteroarylamino, kan være uafhængigt ikke-substitueret eller substitueret med én eller flere substituenter, der er udvalgt blandt halogen, ikke-substitueret Cl-C5-alkyl, ikke-substitueret Cl-C5-alkoxy eller halo (C1-C5) alkyl, hver cycloalkyl, også som del af en gruppe, såsom i cycloalkoxy eller cycloalkylamino kan være ikke-substitueret eller substitueret med én eller flere ikke-substituerede eller halo-substituerede Cl-C3-alkylgrupper, hydroxymethyl, hydroxy, methoxy eller amino og hver piperidyl eller morpholinyl kan være ikke-substitueret eller substitueret med én eller flere ikke-substituerede eller halo-substituerede Cl-C3-alkylgrupper, hydroxy(Cl-C3)alkyl, Cl-C3-alkoxy, (Cl-C3)alkoxycarbonyl eller hydroxyl.

19. Forbindelse ifølge krav 18, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor R8 og R9 begge er hydrogen.

20. Forbindelse ifølge krav 18 eller 19, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor X er -CH=CH-,

21. Forbindelse ifølge krav 18 eller 20, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor X er -CH=CH- og W, R8 og R9 alle er hydrogen.

22. Forbindelse ifølge et hvilket som helst af kravene 18 til 21, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor R6 er udvalgt blandt C2-C6-alkyl, di (Cl-C6-alkyl)amino, 2,2,2-trifluoro(Cl-C3)alkoxy, Cl-C3-alkoxy (C1-C5) alkylamino, Cl-C6-alkylamino, C3-C6-cycloalkylamino, phenyl, phenylamino, phenyl(Cl-C3)alkylamino, phenyl(Cl-C3)alkyl eller N-phenyl-N-(Cl-C5)alkylamino, hvor hver phenyl kan substitueres med ét eller flere halogener og R7 er CF3.

23. Forbindelse ifølge et hvilket som helst af kravene 18 til 22, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor R6 er udvalgt blandt C2-C5-alkyl, C1-C4 alkylamino eller methoxyethylamino; R7 er CF3 og R12 er hydrogen.

24. Forbindelse ifølge et hvilket som helst af kravene 18 til 23, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor R6 er -NH-(C1-C4) alkyl eller lineær eller forgrenet C2-C5-alkyl og R7 er CF3.

25. Forbindelse ifølge et hvilket som helst af kravene 18 til 24, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor R[ er hydrogen eller methyl.

26. Forbindelse ifølge et hvilket som helst af kravene 1 til 7, 10, 11, 13 til 24, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor hvis Ri er methyl eller ethyl, det atom, hvortil Ri er forbundet, er i (Rekonfiguration.

27. Forbindelse ifølge krav 1 eller 3, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor forbindelsen er udvalgt fra gruppen bestående af; 3-((2-Diethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Chlor-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-methoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Diethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Fbror-4-methansulfonylamino-benzyl)-3-(2-pyrrc>lidin-l-yl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3 -Fluor-4-methansulfonylamino-benzyl)-3 -(2-methoxy-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-[2-(2-hydroxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-pyrrolidin-l-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamlde, N-(3-Ethynyl-5-fluor-4-methansulfc>nylamino-benzyl)-3-(2-methyl-6-trifluormethyl-pyridin-3- yl)-acryamid, N-(3-Fluor-4-methansulfc>nylamino-benzyl)-3-(2-methyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, 3-((2-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansufc>nylamino-benzyl)-acrylamid, 3-((2-Cyclopentylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4- methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethoxy)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3 -((2-Butyl-5 -chlor-6-trifluormethyl-pyridin-3 -yl)-N-(3 -ethynyl-5 -fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-sec-Butoxy-6-trifluormethyo-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino- benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-phenoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-Isopropyloxy-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isobutoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-[2-(tetrahydro-furan-3-yloxy)-6-trifluormethyl-pyridin-3-yl]-N-(3-ethynyl-5-fluor-4- methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(fluor-phenoxy)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-(2-morpholm-4-yl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(4-Methansulfonylamino-3-vmyl-benzyl)-3-(2-morpholin-4-yl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3 -Chlor-4-methansulfonylamino-benzyl)-3 -(2-morpholin-4-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-morpholin-4-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-morpholin-4-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-morpholin-4-yl-6-trifluormethym-pyridin- 3-yl)-acrylamid. N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-piperid-l-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3 -Fluor-4-methansulfonylamino-benzyl)-3 -(2-piperid-1 -yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2,2,2-trifluor-ethoxy)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(3-methoxy-pyrrolidin-l-yl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Cyclopentylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino- benzyl)-acrylamid, N-(3 -Fluor-4-methansulfonylamino-benzyl)-3 -[2-(3 -methoxy-pyrrolidin-1 -yl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Cyclopropylmethoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4- methansulfonylamino-benzyl)-acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-(2-pyrrolidin-l-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-cyan-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-cyan-5-fluor-4-methansulfonylamino- benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-phenyl-6-trifluormethyl-pyridm-3- yl)-acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfc>nylamino-benzyl)-3-(2-phenylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(3-ethoxycarbony-piperid-l-yl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(3-ethoxycarbony-piperid-l-yl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3 -((2-sec-Butylamino-6-trifluormethyl-pyridin-3 -yl)-N-(3 -ethynyl-5 -fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(3-methyl-butoxy)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-thien-3-yl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(3-fluor-phenyl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropylamin-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino- benzyl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-cyan-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-(2-phenylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, 3 -((2-sec-Butylamino-6-trifluormethyl-pyridin-3 -yl)-N-(3,5 -difluor-methansulfonylamino-benzyl)-acrylamid, 3 -((2-sec-Butylamino-6-trifluormethyl-pyridin-3 -yl)-N-(3 -fluor-A-methansulfonylamino-5 -methyl-benzyl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-vinyl-benzyl)-3-(2-phenoxy-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-phenylthio-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3 -Fluor-4-methansulfonylamino-benzyl)-3 -(2-phenethyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3 -Fluor-4-methansulfonylamino-benzyl)-3 -(2-isobutyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isobutyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-phenylamino-B-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-Ethyl-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3 -Fluor-4-methansulfonylamino-benzyl)-3 -[2-(2-methyl-butyl)-6-trifluormethyl-pyridin-3 -yl]-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methyl-butyl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-styryl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-[2-(methyl-propyl-amino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(methyl-propyl-amino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-sec-Butoxy-6-trifluormethyl-pyridin.3-yl)-N-(4methansulfonylamino-3-methyl-benzyl)- acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isobutyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-isobutyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, (i?)-N-[l-(3-Fluor-4-mathanesulfonylamino-phenyl)-ethyl]-3-[2-(methyl-phenyl-amino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(methyl-phenyl-amino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-[2-(methyl-phenyl-amino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, (Æ)-3-(2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-[l-(3-fluor-4-methansulfc>nylamino-phenyl)-ethyl] -acrylamid, 3-((2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, 3-((2-Ethyhhio-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfc>nylamino-benzyl)-acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridm-3-yl)- acrylamid, N-(3-Fhror-4-methansulfonylamino-5-methyl-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-isobutyl-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, (/?)-N-[ 1 -(3-Fluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-(2-isobutyl-6-trifluorincthyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyndin-3-yl)-N-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropylthio-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-[2-(3-fluor-phenyl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-[2-(3-fluor-phenyl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3 - [2-(3 -F luor-phenyl) -6 -trifluormethyl-pyridin-3 -yl] -N-(4 -methansulfonylamino-3 -methylbenzyl)-acrylamid, (/?)-N-[ 1 -(3-Fluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-[2-pipcrid-l -yl-6-trifluormcthyl-pyridin-3 -yl] -acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-[2-piperid-l-yl-6-trifluormethyl-pyridin-3-yl]- acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-propylthio-6-trifluoromethyl-pyridin-3 -yl)-acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-propylthio-6-trifluormethyl-pyridin-3-yl)- acrylamid, 3-((2-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, 3-((2.Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-5-methyl-benzyl)-acrylamid, N-(3 -F luor-4 -methansulfonylamino-5 -trifluormethyl-b enzyl) -3 -(2-phenethyl-6 -trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-Benzylamino-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl-acryl)amid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfanylamino-5-methyl-benzyl)-acrylamid, (R)-3 -(2-Butyl-6-trifluormethyl-pyridin-3 -yl)-N-[ 1 -(3 -fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, (i?)-3-(2-Benzylamino-6-trifluormethyl-pyridin-3-yl)-N-[l-(3-fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, 3-((2-Benzylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-methansrdfonylamino-benzyl)-3-[2-(3-fbiorphenyl)-6-trifluormethyl-pyridin-3- yl]-acrylemide, 3-((2·-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3,5-difluor-4-methansulfc>nylamino-benzyl)-acrylamid, N-(3 ,5-Difluor-4-methansulfc>nylamino-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridin-3-yl)-acrylamid, N-(3,5-Difluor-4-methansrdfonylamino-benzyl)-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3,5-difluor-4-methansulfonylammo-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-propyl-6-trifluormethyl-pyridm-3- yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-propyl-6-trifluormethyl-pyridln-3-yl)- acrylamid, N-(4-Methansulfc>nylamino-3-methyl-benzyl)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, (/?)-N-(1 -(3-Fluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-(2-propyl-6-trifluormcthyl-pyridin-3-yl)-acrylamid, (i?)-3-(2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-[l-(3-fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, (Æ)-N-[ 1 -(3-Fluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-[2-(2-mcthy 1-butyl )-6- trifluormethyl-pyridin-3 -yl] -acrylamid, (Æ)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, (R)-3 -(2-Butylamino-8 -trifluormethyl-pyridin-3 -yl)-N - [ 1 -(3 -fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, (Æ)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-pentyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin- 3-yl)-acrylamid, (Λ’)-Ν-[ 1 -(3-Fluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl) -acrylamid, 3-((2-Isopropylamino-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (/?)-N-[ 1 -(3-Fluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-(2-propylamino-6-trifluormcthyl-pyridin-3 -yl)-acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-isobutyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, (Æ)-N-[l-(3,5-Difluor-4-methansulfbnylamino-phenyl)-ethyl]-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl) -acrylamid, (i?)-3-(2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-[l-(3,5-difluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, (R)- N - [ 1 -(3,5 -Difluor-4 -methansulfonylamino-phenyl) -ethyl] -3-(2 -propylamino -6 -trifluormethyl-pyridin-3 -yl) -acrylamid, (Æ)-N-[l-(3,5-Difluor-4-methansulfbnylamino-phenyl)-ethyl]-3-(2-propyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansufonylamino-benzyl)-3-(2-isopropyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-isopropyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, 3-((2-Isopropyl-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)- acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-isopropyl-5-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3,5-difluor-4-methansulfonylamino-benzyl)- acrylamid, (i?)-N-[l-(3,5-Difluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-phenethyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-phenethyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (R)-3-(2-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-[l-(3,5-difluor-4-methansulfc>nylamino-phenyl)-ethyl] -acrylamid, (R)-N-[l-(3,5-Difluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-piperid-l-yl-6-trifluormethyl-pyridin-3 -yl) -acrylamid, (5)-3-(2-Butylamino-6-trifluomethyl-pyridin-3-yl)-N-[l-(3,5-difluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, (R)-3-(2-sec-Butyl-6-trifluormethyl-pyridin-3-yl)-N-l-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, (R)-N-[l-(3,5-Difluor-4-methansulfbnylamino-phenyl)-ethyl]-3-(2-isopropyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, (R)-3-(2-sec-Butyl-6-trifluormethyl-pyridin-3-yl)-N-[l-(3-fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, (R)-N- [ 1 -(3,5 -Difluor-4-methansulfonylamino-phenyl)-ethyl] -3 -(2-ethylamino-6-trifluormethyl-pyridin-3 -yl) -acrylamid, (R)-N- [ 1 -(3,5 -Difluor-4-methansulfonylamino-phenyl)-ethyl] -3 -(2-isobutyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (R)-3 -(2-Ethylamino-6-trifluormethyl-pyridin-3 -yi)-N - [ 1 -(3 -fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, 3-((2-Ethylamino-6-trifluormethyl-pyridin-3-yl)-N-l-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, N-(2,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, 3-((2-Ethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Ethylamino-6-trifluormethyl-pyridln-3-yl)-N-(3-ethenyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(4-Methansulfonylamino-benzyl)-3-(2-propyl-6-trifluormethyl-pyndin-3-yl)-acrylamid, N-(3-Chlor-4-methansulfonylamino-benzyl)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3-Chlor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(2,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifbiormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Cono-5-fluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-propynsyre 3,5-difluor-4-methansulfonylamino-benzylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-propynsyre [l-(3,5-difluor-4-methansulfonylamino-phenyl)-ethyl] -amid, N-(4-Methansulfonylamino-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridin-3-yl)-acrylamid, N-(4-Ethensulfonylamino-benzyl)-3-(2-isoproylamino-6-trifluormethyl-pyridin-3-yl)-acrylamid. (Z)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)-hex-2-ensyre 3-ethynyl-5-fluor-4-methansulfonylamino-benzylamid, (E)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)-hex-2-ensyre 3-ethynyl-5-fluor-4-methansulfonylamino-benzyilamid, (Z)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)-hex-2-ensyre [l-(3,5-difluor-4-methansulfonylamino-phenyl)-ethyl]-amid, (E)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)-hex-2-ensyre [l-(3,5-difluor-4-methansulfonylamino-phenyl)ethyl]-amid og N-(3-Ethenyl-5-fluor-4-methansulfbnylamino-benzyl)-3-(2-morpholin-l-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid.

28. Forbindelse ifølge krav 27, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, hvor forbindelsen er udvalgt fra gruppen bestående af: 3-((2-Diethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-methoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Diethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-pyrrolidin-l-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Cyclopentylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4- methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethoxy)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3 -((2-Butyl-5 -chlor-6-trifluormethyl-pyridin-3 -yl)-N-(3 -ethynyl-5 -fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-sec-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino- benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-phenoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-Isopropyloxy-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4- methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isobutoxy-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-[2-(Tetrahydro-furan-3 -yloxy)-6-trifluormethyl-pyridin-3 -yl] -N-(3 -ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-6-fluor-4-methansulfonylamino-benzyl)-3-[2-(4-fluor-phenoxy)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(4-Methansulfonylamino-3-vmyl-benzyl)-3-(2-morpholin-4-yl-6-influormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-morpholin-4-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-morpholin-4-yl-6-trifluormethyl-pyridin-3 -yl) -acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-piperid-l-yl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butoxy-6-trifluormethyl-pyridin-3-yl)-N-(3-cyan-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3 -((2-sec-Butylamino-6-trifluormethy l-pyridin-3 -yl)-N-(3 -ethynyl-5 -fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Cyan-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfbnylamino-benzyl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-cyan-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3,5-difluor-4-methansulfonylamino- benzyl)-acrylamid, 3 -((2-sec-Butylamino-6-trifluormethyl-pyridin-3 -yl)-N-(3 -fluor-4-methansulfonylamino-5 -methyl-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isobutyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(2-methyl-butyl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-isobutyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, M-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-[2-(methyl-phenyl-amino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridm-3-yl)- acrylamid, 3-((2-Isobutyl-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)- acrylamid, (Æ)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-isobutyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-sec-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, 3-((2-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, 3-((2 -Butylammo-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-methansulfonylamino-5-methylbenzyl)-acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3-fluor-4-methansulfonylamino-5-methyl-benzyl)-acrylamid, (R)-3 -(2-Butyl-6-trifluormethyl-pyridin-3 -yl)-N-[ 1 -(3 -fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, (i?)-3-(2-Benzylamino-6-trifluormethyl-pyridin-3-yl)-N-[l-(3-fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, 3-((2·-Benzylarmino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-4-methansulfonylammo-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, 3-((2·-Butylamino-6-trifluormethyl-pyridin-3-yl)-N-(3,5-difluor-4-methansulfc>nylamino-benzyl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-phenethyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-[2-(2-methoxy-ethylamino)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-N-(3,5-difluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-F-thynyl-5-fluor-4-methansrdfc>nylamino-benzyl)-3-(2-propyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-propyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, (2^-3-(2-sec-Butylammo-6-trifluormethyl-pyridin-3-yl)-N-[l-(3-fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-[2-(2-methyl-butyl)-6-trifluormethyl-pyridin-3 -yl] -acrylamid, (/?)-3-(2-Butylamino-6-trifluormcthyl-pyridin-3-yl)-N - [ 1 -(3 -fbror-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, N-(3-Fluor-4-methansulfc>nylamino-5-methyl-benzyl)-3-(2-pentyl-6-trifluormethyl-pyridin-3- yl)-acrylamid, (Æ)-N-[l-(3-Fluor-4-methansulfc>nylamino-phenyl)-ethyl]-3-(2-pentyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, (i?)-N-[l-(3-Fluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl) -acrylamid, 3-((2-isopropylamino-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)-acrylamid, N-(3-Fluor-4-methansulfc>nylamino-5-methyl-benzyl)-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfc>nylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (/?)-N-[ 1 -(3 -Fluor-methansulfonylamino-phenyl)-ethyl] -3 -(2-propylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, N-(4-Methansulfonylamino-3-methyl-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, (R)-N-[l-(3,5-Difluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-isopropylamino-6-trifluormethyl-pyridin-3 -yl) -acrylamid, (R)-3-(2-Butyl-6-trifluorumethyl-pyridin-3-yl)-N-[l-(3,5-difluor-4-methansulfbnylamino-phenyl)-ethyl] -acrylamid, (R)-N-[l-(3,5-Difluor-4-methansulfbnylarnino-phenyl)-ethyl]-3-(2-propylamino-6-trifluormethyl-pyridin-3 -yl) -acrylamid, (7?)-N-[l -(3,5-Difluor-4-mcthansulfonylamino-phcnyl)-cthyl]-3-(2-propyl-6-trifluormcthyl-pyridin-3 -yl)-acrylamid, N-(3-Ethynyl-5-fluor-4-methansulfonylamino-benzyl)-3-(2-isopropyl-6-trifluormethyl-pyridin- 3-yl)-acrylamid, 3-((2-Isopropyl-6-trifluormethyl-pyridin-3-yl)-N-(4-methansulfonylamino-3-methyl-benzyl)- acrylamid, (R)-N-[ 1 -(3 -Fluor-4-methansulfonylamino-phenyl)ethyl] -3 -(2-isopropyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (R)-N-[l-(3,5-Difluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-phenethyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (/? )-3-(2-Butylamino-6-trifluormcthyl-pyridin-3-yl)-N - [ 1 -(3,5-difluor-4-mcthansulfonylamino-phenyl)-ethyl] -acrylamid, (R)-3-(2-sec-Butyl-6-trifluormethyl-pyridm-3-yl)-N-l-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, (R)-N-[l-(3,5-Difluor-4-methansulfonylamino-phenyl)-ethyl]-3-(2-isopropyl-6-trifluormethyl-pyridin-3-yl)- acrylamid, (R)-3-(2-sec-Butyl-6-trifluorrnethyl-pyridin-3-yl)-N-[l(3-fluor-4-rnethansulfbnylammo-phenyl)-ethyl] -acrylamid, (R)-N- [ 1 -(3,5 -Difluor-4-methansulfonylamino-phenyl)-ethyl] -3 -(2-ethylamino-trifluormethyl-pyridin-3 -yl)-acrylamid, (R)-N- [ 1 -(3,5 -Difluor-4-methansulfonylamino-phenyl)-ethyl] -3 -(2-isobutyl-6-trifluormethyl-pyridin-3 -yl)-acrylamid, (R)-3 -(2-Ethylamino-6-trifluormethyl-pyridin-3 -yl)-N - [ 1 -(3 -fluor-4-methansulfonylamino-phenyl)-ethyl] -acrylamid, 3-((2-Ethylamino-6-trifluormethyl-pyridin-3-yl)-N-l-(4-methansulfonylamino-3-methyl- benzyl)-acrylamid, N-(2,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, 3-((2-Ethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethynyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, 3-((2-Ethylamino-6-trifluormethyl-pyridin-3-yl)-N-(3-ethenyl-5-fluor-4-methansulfonylamino-benzyl)-acrylamid, N-(3-Chlor-4-methansulfonylamino-benzyl)-3-(2-propylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(2,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3-yl)- acrylamid, N-(3,5-Difluor-4-methansulfonylamino-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3- yl)-acrylamid, N-(3-Fluor-4-methansulfonylamino-5-methyl-benzyl)-3-(2-ethylamino-6-trifluormethyl-pyridin-3 -yl)-acrylamid, 3-((2-Butyl-6-trifluormethyl-pyridin-3-yl)-propynsyre [l-(3,5-difluor-4-methansulfonylamino)-phenyl)-ethyl]-amid og (E)-3-(2-propyl-6-trifluormethyl-pyridin-3-yl)-hex-2-ensyre [l-(3,5-difluor-4-methansulfonylamino-phenyl)-ethyl]amid.

29. Farmaceutisk sammensætning omfattende en forbindelse ifølge et hvilket som helst af kravene 1 til 28, en optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf, som en aktiv bestanddel og et farmaceutisk acceptabelt bærestof.

30. Farmaceutisk sammensætning til forebyggelse eller behandling af en tilstand, der er forbundet med den patologiske stimulering og/eller afvigende ekspression af vanilloide receptorer, hvor sammensætningen omfatter forbindelsen ifølge et hvilket som helst af kravene 1 til 28, optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf og et farmaceutisk acceptabelt bærestof.

31. Farmaceutisk sammensætning ifølge krav 29 eller 30, til behandling af en tilstand, der er udvalgt fra gruppen bestående af smerte, inflammatorisk ledsmerte, neuropatier, HIV-relateret neuropati, nerveskade, neurodegeneration, apopleksi, hypersensitiv urinblære herunder urininkontinens, cystitis, gastroduodenalt ulcus, irritabelt tarmsyndrom (IBS) og inflammatorisk tarmsygdom (IBD), fækal urgency, gastro-øsophagus refluxsygdom (GERD), Crohns sygdom, astma, kronisk obstruktiv lungesygdom, hoste, neurotisk / allergisk / inflammatorisk hudsygdom, psoriasis, pruritus, prurigo, irritation af hud, øjne eller slimhinde, hyperacusis, tinnitus, vestibular hypersensitivity, episodisk svimmelhed, hjertesygdomme såsom myokardiel iskæmi, hårvækstrelaterede forstyrrelser såsom effluvium, alopeci, Rhinitis og pancreatitis.

32. Farmaceutisk sammensætning ifølge krav 31 hvor smerten er eller er forbundet med en tilstand, der er udvalgt fra gruppen bestående af osteoarthritis, rheumatoid arthntis, ankylosing spondylitis, diabetisk neuropatisk smerte, post-operativ smerte, dental smerte, ikke-inflammatorisk smerte i muskel eller skelet (herunder fibromyalgi, myofascielt smertesyndrom og rygsmerte), migræne og andre typer af hovedpine

33. Farmaceutisk sammensætning ifølge et hvilket som helst af kravene 29 til 32 kendetegnet ved, at den er tilpasset til oral administration.

34. Anvendelse af forbindelsen ifølge et hvilket som helst af kravene 1 til 28, en optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf i fremstilling af et medikament til forebyggelse eller behandling af en tilstand, der er forbundet med den afvigende ekspression og/eller afvigende aktivering af en vanilloid receptor.

35. Anvendelse af forbindelsen ifølge et hvilket som helst af kravene 1 til 28, en optisk isomer, geometrisk isomer, tautomer eller et farmaceutisk acceptabelt salt deraf i fremstilling af et medikament til forebyggelse eller behandling af en tilstand, der er udvalgt fra gruppen bestående af smerte, inflammatorisk ledsmerte, neuropatier, HIV-relateret neuropati, nerveskade, neurodegeneration, apopleksi, hypersensitiv urinblære herunder urininkontinens, cystitis, gastroduodenalt ulcus, irritabelt tarmsyndrom (IBS) og inflammatorisk tarmsygdom (IBD), fækal urgency, gastro-øsophagus refluxsygdom (GERD), Crohns sygdom, astma, kronisk obstruktiv lungesygdom, hoste, neurotisk / allergisk / inflammatorisk hudsygdom, psoriasis, pruritus, prurigo, irritation af hud, øjne eller slimhinde, hyperacusis, tinnitus, vestibulær hypersensitivitet, episodisk svimmelhed, hjertesygdomme såsom myokardiel iskæmi, hårvækstrelaterede forstyrrelser såsom effluvium, alopeci, rhinitis og pancreatitis.

36. Anvendelse af forbindelsen ifølge krav 35, hvor tilstanden er smerte, der er eller ikke er forbundet med en tilstand, der er udvalgt fra gruppen bestående af osteoarthritis, rheumatoid arthritis, ankyloserende spondylitis, diabetisk neuropatisk smerte, post-operativ smerte, dental smerte, ikke-inflammatorisk smerte i muskel eller skelet (herunder fibromyalgi, myofascielt smertesyndrom og rygsmerte), migræne og andre typer af hovedpine.

37. Fremgangsmåde til fremstilling af en forbindelse repræsenteret ved formlen (III)

·: m der omfatter at lade en forbindelse repræsenteret ved formlen (Illa);

(I«a) reagere med en forbindelse repræsenteret ved formlen (Illb);

(lllb) hvor Ri, R2, R3, R4, R5 R6, R7, Rs, R9, Rio, R11 og R12 er som beskrevet i et hvilket som helst af de foregående krav.

38. Fremgangsmåde ifølge krav 37, hvor reaktionen sker i nærvær af et koblingsmiddel udvalgt fra gruppen bestående af DCC (Ν,Ν-dicyclcohexylcarbodidimid), EDCI {l-(3-dimethylaminopropyl)-3-ethylcarbodidimidhydrochlorid(EDCI)} og DMTMM {4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholiniumchlorid}.