Substituted arylamino-1,2,3,4-tetrahydro naphthalenes and -2,3-dihydro-1H-indenes as potassium channel modulators
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07C-235/16
A61K-031/16
출원번호
US-0098176
(2011-04-29)
등록번호
US-8338487
(2012-12-25)
발명자
/ 주소
Chen, Huanming
Vernier, Jean-Michel
출원인 / 주소
Valeant Pharmaceuticals International, Inc.
대리인 / 주소
Jones Day
인용정보
피인용 횟수 :
0인용 특허 :
51
초록▼
This invention provides compounds of formula I where Ar1 is a 5- to 10-member mono- or bicyclic aromatic group, optionally substituted; where the —NR3R4 group is situated ortho to the NHC(═X) group; n=1 or 2; X=O or S; Y is O or S; and q=1 or 0. The invention also provides pharmaceutical compositio
This invention provides compounds of formula I where Ar1 is a 5- to 10-member mono- or bicyclic aromatic group, optionally substituted; where the —NR3R4 group is situated ortho to the NHC(═X) group; n=1 or 2; X=O or S; Y is O or S; and q=1 or 0. The invention also provides pharmaceutical compositions comprising compounds of formula I and/or salts, esters, and prodrugs thereof. These compounds modulate the activation and inactivation of potassium channels. The compounds are useful for the treatment and prevention of diseases and disorders—such as seizure disorders—which are affected by modulation of potassium ion channels.
대표청구항▼
1. A method of treating seizure disorders which are affected by modulation of potassium channels, comprising administering to a patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula I or a salt or ester thereof: where Ar1 is a 5- to 10-member
1. A method of treating seizure disorders which are affected by modulation of potassium channels, comprising administering to a patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula I or a salt or ester thereof: where Ar1 is a 5- to 10-member mono- or bicyclic aromatic group, optionally containing 1-4 heteroatoms selected independently from N, O, and S; R1 and R2 are selected, independently, from H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, OR8, C(═O)R9, C(═O)OR10, OC(═O)R11, SR12, NR13C(═O)R14, C(═O)NR15R16, CH2C(═O)NR15R16, NR17R18, SO2R19, N(R20)SO2R21, SO2NR22R23, C3-C6 cycloalkyl, C5-C6 cycloalkenyl, C2-C6 alkenyl, or C2-C6 alkynyl; where the —NR3R4 group is situated ortho to the NHC(═X) group and R3 and R4 are, independently, H or C1-6 alkyl, which C1-6 alkyl group optionally substituted with 1 or 2 groups selected, independently, from methyl, halogen, methoxy, and hydroxy, or R3 and R4 together form a 5- or 6-membered ring, optionally substituted with halogen, methyl, methoxy, or hydroxy and optionally containing one or two double bonds; n=1 or 2; X=O or S; Y is O or S; q=1 or 0; R5 is C1-C6 alkyl, (CHR6)wC3-C6 cycloalkyl, (CHR6)wCH2C3-C6 cycloalkyl, CH2(CHR6)wC3-C6 cycloalkyl, (CHR6)wC5-C6 cycloalkenyl, CH2(CHR6)wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar2, (CHR6)wAr2, CH2(CHR6)wAr2, or (CHR6)wCH2Ar2, where w=0-3, Ar2 is a 5- to 10-member mono- or bicyclic aromatic group, optionally containing 1-4 ring heteroatoms selected independently from N, O, and S; R6 is C1-C3 alkyl; and R8-R23 are, independently, H, C1-C6 alkyl, C3-C6 cycloalkyl, (CHR6)wC3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, where all said alkyl, cycloalkyl, alkenyl, alkynyl, aryl, groups are optionally substituted with one or two substituents selected independently from C1-C3 alkyl, halogen, OH, OMe, CN, CH2F, and trifluoromethyl; where, additionally, said alkenyl and alkynyl groups are optionally substituted with phenyl or C3-C6 cycloalkyl; and where all said cycloalkyl groups optionally contain one or two ring heteroatoms selected independently from N, O, and S. 2. The method of claim 1, where NH—C(═X)—(Y)q—R5 is NHC(═O)R5 or NHC(═O)OR5. 3. The method of claim 2, where Ar1 is 4. The method of claim 3, where R1 is F, CH2F, CHF2, or CF3. 5. The method of claim 4, where n is 1 and R1 is para. 6. The method of claim 4, where R2 is H, C1-C3 alkyl, or halogen. 7. The method of claim 4, where n is 1 and R1 is meta. 8. The method of claim 7, where R2 is H, C1-C3 alkyl, or halogen. 9. The method of claim 1, where the compound of formula I is a compound of formula IA where Q=CR7 or N, where R7 is H or C1-C6 alkyl. 10. The method of claim 9, where the compound of formula IA is a compound of formula IA-1 or a compound of formula IA-2 11. The method of claim 9, where the compound of formula IA is a compound of formula IA-3 or a compound of formula IA-4 12. The method of claim 10, where Q is N; R2, R3, and R4 are, independently, H or CH3; and R5 is C1-C6 alkyl or (CHR6)wC3-C6 cycloalkyl, where R6 is H or CH3 and w is 1 or 2. 13. The method of claim 10, where Q is CH; R2, R3, and R4 are, independently, H, CH3 or CH2CH3; and R5 is C1-C6 alkyl or (CHR6)wC3-C6 cycloalkyl, where R6 is H or CH3 and w is 1 or 2. 14. The method of claim 11, where Q is N, R2 and R3 are H, R4 is H or CH3, and R5 is C1-C6 alkyl or (CHR6)wC3-C6 cycloalkyl, where R6 is H or CH3 and w is 1 or 2. 15. The method of claim 11, where Q is CH, R2 and R3 are H, R4 is H or CH3, and R5 is C1-C6 alkyl, or (CHR6)wC3-C6 cycloalkyl, where R6 is H or CH3 and w is 1 or 2. 16. The method of claim 12, where R1 is meta or para to NH and is halogen or methyl or ethyl, said methyl or ethyl optionally substituted with 1-3 fluorine atoms. 17. The method of claim 13, where R1 is meta or para to NH and is halogen or methyl or ethyl, said methyl or ethyl optionally substituted with 1-3 fluorine atoms. 18. The method of claim 14, where R1 is meta or para to NH and is halogen or methyl or ethyl, said methyl or ethyl optionally substituted with 1-3 fluorine atoms. 19. The method of claim 15, where R1 is meta or para to NH and is halogen or methyl or ethyl, said methyl or ethyl optionally substituted with 1-3 fluorine atoms. 20. The method of claim 1, wherein the compound is one of the following:
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