Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A01N-043/54
A61K-031/505
출원번호
US-0138251
(2008-06-12)
등록번호
US-8367684
(2013-02-05)
발명자
/ 주소
Vernier, Jean-Michel
Ouk, Samedy
De La Rosa, Martha A.
출원인 / 주소
Valeant Pharmaceuticals International
인용정보
피인용 횟수 :
0인용 특허 :
52
초록▼
This invention provides potassium channel modulators which are compounds of formula I where at least one of W and Z is N; where the moiety is one of Groups A or B below A where Ar is a 1,2-fused, six membered ring aromatic group, bearing substituents R1 and R2 as defined below, and containing
This invention provides potassium channel modulators which are compounds of formula I where at least one of W and Z is N; where the moiety is one of Groups A or B below A where Ar is a 1,2-fused, six membered ring aromatic group, bearing substituents R1 and R2 as defined below, and containing zero or one ring nitrogen atom; and where other substituents are defined herein. The invention also provides a composition comprising a pharmaceutically acceptable carrier and at least one of the following: i) a pharmaceutically effective amount of a compound of formula I and ii) a pharmaceutically acceptable salt, ester, or prodrug thereof. The invention also provides a method of preventing or treating a disease or disorder which is affected by activities of potassium channels, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or a salt, ester, or prodrug thereof.
대표청구항▼
1. A compound of formula IA-1a wherein R5 is C3-C6 alkyl or CH2—C3—C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy;at least one of W and Z is N, and the other is C;R1 is H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—
1. A compound of formula IA-1a wherein R5 is C3-C6 alkyl or CH2—C3—C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy;at least one of W and Z is N, and the other is C;R1 is H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH—C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2)mC3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2)mC3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CH2)mAr1, phenyl, pyridyl, pyrrolyl, (CH2)mimidazolyl, (CH2)mpyrazyl, furyl, thienyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, or (CH2)mpyrimidyl, which cycloalkyl and said cycloalkenyl groups optionally contain one or two heteroatoms selected independently from O, N, and S, and which alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, imidazolyl, pyrazyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, phenyl, pyrrolyl, pyridyl, or pyrimidyl groups are optionally substituted with one or two groups selected, independently, from OH, halogen, cyano, methyl, ethyl, or trifluoromethyl, where m is zero, 1, or 2;R3 and R4 are, independently, H, halogen, methyl, methoxy, or trifluoromethyl;R′ and R2 are, independently, H, halogen, methyl, or trifluoromethyl;and pharmaceutically acceptable salts thereof. 2. The compound of claim 1 wherein R1 is H, F, methyl, or trifluoromethyl. 3. The compound of claim 1 wherein R3 and R4 are, independently, H, methyl, or methoxy. 4. A compound of formula IA-1b where at least one of W and Z is N, and the other is C;R1 and R2, are, independently, H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH—C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2)mC3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2)mC3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CH2)mAr1, phenyl, pyridyl, pyrrolyl, (CH2)mimidazolyl, (CH2)mpyrazyl, furyl, thienyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, or (CH2)mpyrimidyl, which cycloalkyl and said cycloalkenyl groups optionally contain one or two heteroatoms selected independently from O, N, and S, and which alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, imidazolyl, pyrazyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, phenyl, pyrrolyl, pyridyl, or pyrimidyl groups are optionally substituted with one or two groups selected, independently, from OH, halogen, cyano, methyl, ethyl, or trifluoromethyl, where m is zero, 1, or 2; or R1 and R2, together with the ring carbon atoms to which they are attached, form a 5- or 6-member fused ring, which ring may be saturated, unsaturated, or aromatic, which optionally contains one or two heteroatoms selected independently from O, N, and S, and which is optionally substituted with halogen, CF3, or C1-C3 alkyl;R′ is H, halogen, CF3, or C1-C3 alkyl;R3 and R4 are, independently, H, CN, halogen, CF3, OCF3, OC1-C3 alkyl, or C1-C6 alkyl, all said C1-C3 alkyl groups and said C1-C6 alkyl groups optionally substituted with one or two groups selected, independently, from OH, halogen, C1-C3 alkyl, OC1-C3 alkyl, or trifluoromethyl;R5 is C1-C6 alkyl, (CHR6)wC3-C6 cycloalkyl, (CHR6)wCH2C3-C6 cycloalkyl, CH2(CHR6)wC3-C6 cycloalkyl, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6)wC5-C6 cycloalkenyl, CH2(CHR6)wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CHR6)wAr1, CH2(CHR6)wAr1, or (CHR6)wCH2Ar1, where w=0-3, Ar1 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 hydrogen or C1-C3 alkyl; where all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms selected independently from N, O, and S; where all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R1, R2, R3, R4, R5, R6, or Ar1 are optionally substituted with one or two substituents selected independently from C1-C3 alkyl, halogen, OH, OMe, SMe, CN, CH2F, and trifluoromethyl; where, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with either an exocyclic carbon-carbon double bond or a carbonyl group; and where, additionally, the alkenyl and alkynyl groups are also optionally substituted with phenyl or C3-C6 cycloalkyl; andpharmaceutically acceptable salts thereof. 5. The compound of claim 4 wherein R3 and R4 are, independently, H, halogen, methyl, methoxy, or trifluoromethyl. 6. The compound of claim 5 wherein R′ and R2 are, independently, H, halogen, methyl, or trifluoromethyl. 7. The compound of claim 6, wherein R5 is C3-C6 alkyl or CH2—C3-C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy. 8. The compound of claim 7 wherein R1 is H, F, methyl, or trifluoromethyl. 9. The compound of claim 4 wherein R3 and R4 are, independently, H, methyl, or methoxy. 10. A compound of formula IA2 where at least one of W and Z is N, and the other is C;R1 and R2, are, independently, H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH—C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C66 cycloalkyl, (CH2)mC3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2)mC3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CH2)mAr1, phenyl, pyridyl, pyrrolyl, (CH2)mimidazolyl, (CH2)mpyrazyl, furyl, thienyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, or (CH2)mpyrimidyl, which cycloalkyl and said cycloalkenyl groups optionally contain one or two heteroatoms selected independently from O, N, and S, and which alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, imidazolyl, pyrazyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, phenyl, pyrrolyl, pyridyl, or pyrimidyl groups are optionally substituted with one or two groups selected, independently, from OH, halogen, cyano, methyl, ethyl, or trifluoromethyl, where m is zero, 1, or 2; or R1 and R2, together with the ring carbon atoms to which they are attached, form a 5- or 6-member fused ring, which ring may be saturated, unsaturated, or aromatic, which optionally contains one or two heteroatoms selected independently from O, N, and S, and which is optionally substituted with halogen, CF3, or C1-C3 alkyl;R′ is H, halogen, CF3, or C1-C3 alkyl;R3 and R4 are, independently, H, CN, halogen, CF3, OCF3, OC1-C3 alkyl, or C1-C6 alkyl, all said C1-C3 alkyl groups and said C1-C6 alkyl groups optionally substituted with one or two groups selected, independently, from OH, halogen, C1-C3 alkyl, OC1-C3 alkyl, or trifluoromethyl;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, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6)wC5-C6 cycloalkenyl, CH2(CHR6)wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CHR6)wAr1, CH2(CHR6)wAr1, or (CHR6)wCH2Ar1, where w=0-3, Ar1 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 hydrogen or C1-C3 alkyl; where all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms selected independently from N, O, and S; where all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R1, R2, R3, R4, R5, R6, or Ar1 are optionally substituted with one or two substituents selected independently from C1-C3 alkyl, halogen, OH, OMe, SMe, CN, CH2F, and trifluoromethyl; where, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with either an exocyclic carbon-carbon double bond or a carbonyl group; and where, additionally, the alkenyl and alkynyl groups are also optionally substituted with phenyl or C3-C6 cycloalkyl; andpharmaceutically acceptable salts thereof. 11. The compound of claim 10 wherein X is O, Y is O, and q is 0 or 1. 12. The compound of claim 11 wherein R3 and R4 are, independently, H, halogen, methyl, methoxy, or trifluoromethyl. 13. The compound of claim 12 wherein R′ and R2 are, independently, H, halogen, methyl, or trifluoromethyl. 14. The compound of claim 13, wherein R5 is C3-C6 alkyl or CH2—C3-C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy. 15. The compound of claim 14 wherein R1 is H, F, methyl, or trifluoromethyl. 16. The compound claim 11 wherein R3 and R4 are, independently, H, methyl, or methoxy. 17. A compound of formula IA3 where at least one of W and Z is N, and the other is C;R1 and R2, are, independently, H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH—C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2)mC3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2)mC3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CH2)mAr1, phenyl, pyridyl, pyrrolyl, (CH2)mimidazolyl, (CH2)mpyrazyl, furyl, thienyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, or (CH2)mpyrimidyl, which cycloalkyl and said cycloalkenyl groups optionally contain one or two heteroatoms selected independently from O, N, and S, and which alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, imidazolyl, pyrazyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, phenyl, pyrrolyl, pyridyl, or pyrimidyl groups are optionally substituted with one or two groups selected, independently, from OH, halogen, cyano, methyl, ethyl, or trifluoromethyl, where m is zero, 1, or 2; or R1 and R2, together with the ring carbon atoms to which they are attached, form a 5- or 6-member fused ring, which ring may be saturated, unsaturated, or aromatic, which optionally contains one or two heteroatoms selected independently from O, N, and S, and which is optionally substituted with halogen, CF3, or C1-C3 alkyl;R′ is H, halogen, CF3, or C1-C3 alkyl;R3 and R4 are, independently, H, CN, halogen, CF3, OCF3, OC1-C3 alkyl, or C1-C6 alkyl, all said C1-C3 alkyl groups and said C1-C6 alkyl groups optionally substituted with one or two groups selected, independently, from OH, halogen, C1-C3 alkyl, OC1-C3 alkyl, or trifluoromethyl;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, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6)wC5-C6 cycloalkenyl, CH2(CHR6)wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CHR6)wAr1, CH2(CHR6)wAr1, or (CHR6)wCH2Ar1, where w=0-3, Ar1 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 hydrogen or C1-C3 alkyl; where all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms selected independently from N, O, and S; where all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R1, R2, R3, R4, R5, R6, or Ar1 are optionally substituted with one or two substituents selected independently from C1-C3 alkyl, halogen, OH, OMe, SMe, CN, CH2F, and trifluoromethyl; where, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with either an exocyclic carbon-carbon double bond or a carbonyl group; and where, additionally, the alkenyl and alkynyl groups are also optionally substituted with phenyl or C3-C6 cycloalkyl; andpharmaceutically acceptable salts thereof. 18. The compound of claim 17 wherein X is O, Y is O, and q is 0 or 1. 19. The compound of claim 18 wherein R3 and R4 are, independently, H, halogen, methyl, methoxy, or trifluoromethyl. 20. The compound of claim 19 wherein R′ and R2 are, independently, H, halogen, methyl, or trifluoromethyl. 21. The compound of claim 20, wherein R5 is C3-C6 alkyl or CH2—C3-C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy. 22. The compound of claim 21 wherein R1 is H, F, methyl, or trifluoromethyl. 23. The compound of claim 17 wherein R3 and R4 are, independently, H, methyl, or methoxy. 24. A compound of formula IA4 where at least one of W and Z is N, and the other is C;R1 and R2, are, independently, H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH—C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2)mC3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2)mC3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CH2)mAr1, phenyl, pyridyl, pyrrolyl, (CH2)mimidazolyl, (CH2)mpyrazyl, furyl, thienyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, or (CH2)mpyrimidyl, which cycloalkyl and said cycloalkenyl groups optionally contain one or two heteroatoms selected independently from O, N, and S, and which alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, imidazolyl, pyrazyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, phenyl, pyrrolyl, pyridyl, or pyrimidyl groups are optionally substituted with one or two groups selected, independently, from OH, halogen, cyano, methyl, ethyl, or trifluoromethyl, where m is zero, 1, or 2; or R1 and R2, together with the ring carbon atoms to which they are attached, form a 5- or 6-member fused ring, which ring may be saturated, unsaturated, or aromatic, which optionally contains one or two heteroatoms selected independently from O, N, and S, and which is optionally substituted with halogen, CF3, or C1-C3 alkyl;R′ is H, halogen, CF3, or C1-C3 alkyl;R3 and R4 are, independently, H, CN, halogen, CF3, OCF3, OC1-C3 alkyl, or C1-C6 alkyl, all said C1-C3 alkyl groups and said C1-C6 alkyl groups optionally substituted with one or two groups selected, independently, from OH, halogen, C1-C3 alkyl, OC1-C3 alkyl, or trifluoromethyl;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, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6)wC5-C6 cycloalkenyl, CH2(CHR6)wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CHR6)wAr1, CH2(CHR6)wAr1, or (CHR6)wCH2Ar1, where w=0-3, Ar1 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 hydrogen or C1-C3 alkyl; where all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms selected independently from N, O, and S; where all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R1, R2, R3, R4, R5, R6, or Ar1 are optionally substituted with one or two substituents selected independently from C1-C3 alkyl, halogen, OH, OMe, SMe, CN, CH2F, and trifluoromethyl; where, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with either an exocyclic carbon-carbon double bond or a carbonyl group; and where, additionally, the alkenyl and alkynyl groups are also optionally substituted with phenyl or C3-C6 cycloalkyl; andpharmaceutically acceptable salts thereof. 25. The compound of claim 24 wherein X is O, Y is O, and q is 0 or 1. 26. The compound of claim 25 wherein R3 and R4 are, independently, H, halogen, methyl, methoxy, or trifluoromethyl. 27. The compound of claim 26 wherein R′ and R2 are, independently, H, halogen, methyl, or trifluoromethyl. 28. The compound of claim 27, wherein R5 is C3-C6 alkyl or CH2—C3-C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy. 29. The compound of claim 28 wherein R1 is H, F, methyl, or trifluoromethyl. 30. The compound of claim 24 wherein R3 and R4 are, independently, H, methyl, or methoxy. 31. A compound of formula IA5 where at least one of W and Z is N, and the other is C;R1 and R2, are, independently, H, CN, halogen, CH2CN, OH, NO2, CH2F, CHF2, CF3, CF2CF3, C1-C6 alkyl, C(═O)C1-C6 alkyl, NH—C1-C6 alkyl, NHC(═O)C1-C6 alkyl, C(═O)N(CH3)2, C(═O)N(Et)2, C(═O)NH—C1-C6 alkyl, C(═O)OC1-C6 alkyl, OC(═O)C1-C6 alkyl, OC1-C6 alkyl, SC1-C6 alkyl, C3-C6 cycloalkyl, (CH2)mC3-C6 cycloalkyl, C3-C6 cycloalkenyl, (CH2)mC3-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CH2)mAr1, phenyl, pyridyl, pyrrolyl, (CH2)mimidazolyl, (CH2)mpyrazyl, furyl, thienyl, (CH2)moxazolyl, (CH2)misoxazolyl, (CH2)mthiazolyl, (CH2)misothiazolyl, (CH2)mphenyl, (CH2)mpyrrolyl, (CH2)mpyridyl, or (CH2)mpyrimidyl, which cycloalkyl and said cycloalkenyl groups optionally contain one or two heteroatoms selected independently from O, N, and S, and which alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, imidazolyl, pyrazyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, phenyl, pyrrolyl, pyridyl, or pyrimidyl groups are optionally substituted with one or two groups selected, independently, from OH, halogen, cyano, methyl, ethyl, or trifluoromethyl, where m is zero, 1, or 2; or R1 and R2, together with the ring carbon atoms to which they are attached, form a 5- or 6-member fused ring, which ring may be saturated, unsaturated, or aromatic, which optionally contains one or two heteroatoms selected independently from O, N, and S, and which is optionally substituted with halogen, CF3, or C1-C3 alkyl;R′ is H, halogen, CF3, or C1-C3 alkyl;R3 and R4 are, independently, H, CN, halogen, CF3, OCF3, OC1-C3 alkyl, or C1-C6 alkyl, all said C1-C3 alkyl groups and said C1-C6 alkyl groups optionally substituted with one or two groups selected, independently, from OH, halogen, C1-C3 alkyl, OC1-C3 alkyl, or trifluoromethyl;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, CR6═CH—C3-C6 cycloalkyl, CH═CR6—C3-C6 cycloalkyl, (CHR6)wC5-C6 cycloalkenyl, CH2(CHR6)wC5-C6 cycloalkenyl, C2-C6 alkenyl, C2-C6 alkynyl, Ar1, (CHR6)wAr1, CH2(CHR6)wAr1, or (CHR6)wCH2Ar1, where w=0-3, Ar1 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 hydrogen or C1-C3 alkyl; where all cycloalkyl and cycloalkenyl groups optionally contain one or two ring heteroatoms selected independently from N, O, and S; where all alkyl, cycloalkyl, alkenyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, alkynyl, aryl, and heteroaryl groups in R1, R2, R3, R4, R5, R6, or Ar1 are optionally substituted with one or two substituents selected independently from C1-C3 alkyl, halogen, OH, OMe, SMe, CN, CH2F, and trifluoromethyl; where, additionally, all cycloalkyl and heterocycloalkyl groups are optionally substituted with either an exocyclic carbon-carbon double bond or a carbonyl group; and where, additionally, the alkenyl and alkynyl groups are also optionally substituted with phenyl or C3-C6 cycloalkyl; andpharmaceutically acceptable salts thereof. 32. The compound of claim 31 wherein X is O, Y is O, and q is 0 or 1. 33. The compound of claim 32 wherein R3 and R4 are, independently, H, halogen, methyl, methoxy, or trifluoromethyl. 34. The compound of claim 33 wherein R′ and R2 are, independently, H, halogen, methyl, or trifluoromethyl. 35. The compound of claim 34, wherein R5 is C3-C6 alkyl or CH2—C3-C6-cycloalkyl and where R5 is optionally substituted with halogen, hydroxy, or methoxy. 36. The compound of claim 35 wherein R1 is H, F, methyl, or trifluoromethyl. 37. The compound of claim 31 wherein R3 and R4 are, independently, H, methyl, or methoxy. 38. A pharmaceutical composition comprising a compound of claim 1 with a pharmaceutically acceptable carrier. 39. A pharmaceutical composition comprising a compound of claim 4 with a pharmaceutically acceptable carrier. 40. A pharmaceutical composition comprising a compound of claim 10 with a pharmaceutically acceptable carrier. 41. A pharmaceutical composition comprising a compound of claim 17 with a pharmaceutically acceptable carrier. 42. A pharmaceutical composition comprising a compound of claim 24 with a pharmaceutically acceptable carrier. 43. A pharmaceutical composition comprising a compound of claim 31 with a pharmaceutically acceptable carrier.
Tibes Ulrich (Frankfurt am Main DEX) Weischer Carl H. (Bonn DEX) Hettche Helmut (Offenbach am Main DEX) Breuel Hans-Peter (Mainz DEX) Gunesch Dietmar (Offenbach am Main DEX), Combination of flupirtin and anticholinergic acting spasmolytic.
Piyasena Hewawasam ; Pierre Dextraze CA; Valentin K. Gribkoff ; Gene G. Kinney ; Steven I. Dworetzky, Fluoro oxindole derivatives as modulators if KCNQ potassium channels.
Aberg A. K. Gunnar (Lawrenceville NJ) Ogletree Martin L. (Newtown PA) O\Keefe Eugene H. (Newtown PA), Method for the prophylaxis and/or treatment of ulcerative gastrointestinal conditions using a potassium channel activato.
Lobisch Michael (Ober-Ramstadt DEX) Venhaus Ralph (Heppenheim DEX) Nickel Bernd (Mhltal DEX) Szelenyi Istvan (Schwaig DEX) Engel Jrgen (Alzenau DEX) Emig Peter (Niederdorfelden DEX), Pharmaceutical composition comprising flupirtine and its use to combat Parkinson disorders.
Lobisch Michael (Ober-Ramstadt DEX) Venhaus Ralph (Heppenheim DEX) Nickel Bernd (Mhltal DEX) Szelenyi Istvan (Schwaig DEX) Engel Jrgen (Alzenau DEX) Emig Peter (Niederdorfelden DEX), Pharmaceutical composition comprising flupirtine and its use to combat muscular tension.
Dieter Hans-Reinhold (Darmstadt DEX) Engel Jurgen (Alzenau DEX) Kutscher Bernhard (Maintal DEX) Polymeropoulos Emanuel (Frankfurt DEX) Szelenyi Stefan (Schwaig DEX) Nickel Bernd (Muhltal DEX), Pharmaceutically active 1,2,4-triamino-benzene derivatives, processes for their preparation and pharmaceutical compositi.
Carroll, William A.; Chen, Yiyuan; Holladay, Mark W.; Kort, Michael E.; Kym, Philip R.; Sullivan, James P.; Tang, Rui; Yi, Lin; Zhang, Henry Q.; Drizin, Irene, Potassium channel openers.
Tibes Ulrich (Am Sandberg 102 D-6000 Frankfurt am Main 70 DEX) Weischer Carl H. (Schmidtbonnstrasse 8 D-5300 Bonn 1 DEX) Hettche Helmut (Buchrainweg 65 D-6050 Offenbach am Main DEX) Breuel Hans-Peter, Synergistic combination of flupirtin and non-steroidal antiphlogistic.
Rostock Angelika,DEX ; Rundfeldt Chris,DEX ; Tober Christine,DEX ; Bartsch Reni,DEX, Use of 2-4-amino-4-(4-fluorobenzylamino) (-1-ethoxy-carbonylaminobenzene for the prophylaxis and treatment of the neurod.
Rostock Angelika,DEX ; Rundfeldt Chris,DEX ; Tober Christine,DEX ; Bartsch Reni,DEX, Use of 4-amino-4-(4-fluorobenzylamino)-1-ethoxy-carbonylaminobenzene for the prophylaxis and treatment of reduced cerebr.
Rundfeldt Chris,DEX ; Bartsch Reni,DEX ; Rostock Angelika,DEX ; Tober Christine,DEX ; Dost Rita,DEX, Use of retigabine for the treatment of neuropathic pain.
Rundfeldt,Chris; Kuss,Hildegard; Draheim,Regina; Bernoester,Katrin, Use of the non-opiate analgesic drug flupirtine for the treatment of overactive bladder and associated diseases including urge incontinence, urinary flow problems as a result of prostate hyperplasia and irritable bowel syndrome.
Demopulos Gregory A. ; Pierce Pamela A. ; Herz Jeffrey M., Vascular irrigation solution and method for inhibition of pain, inflammation, spasm and restenosis.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.