Indole-containing quaternary ammonium compounds
AssigneeCardiome Pharma Corp.
InventorsGregory N. Beatch, Lewis S. L. Choi, Clive P. Page, Bertrand M. C. Plouvier, Yuzhong Liu
Life of this patent
Estimating the term…
Abstract
Compounds and pharmaceutical compositions containing such compounds and possessing anti-tussive activity, and a method of administering the same to warm-blooded animals, including humans.
Claims24
A compound of the following formula (I), or a solvate or pharmaceutically acceptable salt thereof:
- wherein Y and E are independently selected from —CH2—R16 or a group represented by the following formula (II):
- wherein R, R1, R2, R3, R4, R5, and R16 are independently selected from hydrogen, C1-C8 alkyl, C3-C8 alkoxyalkyl and C7-C12 aralkyl;
- m is an integer of from 1 to 8 and n is an integer of from 0 to 8;
- A is selected from C5-C12 alkyl, a C3-C13 carbocyclic ring, and ring systems selected from formulae (III), (IV), (V), (VI), (VII), (VIII), (IX) and (X):
- where R7, R8, R9 R10, R11 and R12 are independently selected from bromine, chlorine, fluorine, carboxy, hydrogen, hydroxy, hydroxymethyl, methanesulfonamido, nitro, sulfamyl, trifluoromethyl, C2-C7 alkanoyloxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxycarbonyl, C1-C6 thioalkyl, aryl and N(R13,R14) where R13 and R14 are independently selected from hydrogen, acetyl, methanesulfonyl and C1-C6 alkyl, and Z is selected from CH, CH2, O, N and S, where Z may be directly bonded to X when Z is CH, or X may be a direct bond to Z when Z is N, or Z may be directly bonded to R15 when Z is N and X is not a direct bond to Z, R15 is selected from hydrogen, C1-C6 alkyl, C3-C8 cyclocalkyl, aryl and benzyl;
- and X is N—R6 except when Z in A is nitrogen and X is a direct bond to Z;
- An− is the acid addition salt of a pharmaceutically acceptable acid or the anion from a pharmaceutically acceptable salt, and isolated enantiomeric, diastereomeric and geometric isomers thereof, and mixtures thereof, with the proviso that E is represented by formula (II) wherein A is either formula (VI) or formula (IX) and Z is N.
A method for the treatment and/or prevention of cough in warm-blooded animals including human, which comprises administering to a warm-blooded animal in need thereof a therapeutically effective amount of an anti-tussive comprising as the anti-tussive effective ingredient a modulator/blocker of cation channel, wherein said modulator/blocker is a quaternary ammonium compound of the following Formula I, or a pharmaceutically acceptable salt thereof:
- wherein Y and E are independently selected from —CH2—R16 or a group represented by the following formula (II):
- wherein R, R1, R2, R3, R4, R5, and R16 are independently selected from hydrogen, C1-C8 alkyl, C3-C8 alkoxyalkyl and C7-C12 aralkyl;
- m is an integer of from 1 to 8 and n is an integer of from 0 to 8;
- A is selected from C5-C12 alkyl, a C3-C13 carbocyclic ring, and ring systems selected from formulae (III), (IV), (V), (VI), (VII), (VIII), (IX) and (X):
- where R7, R8, R9 R10, R11 and R12 are independently selected from bromine, chlorine, fluorine, carboxy, hydrogen, hydroxy, hydroxymethyl, methanesulfonamido, nitro, sulfamyl, trifluoromethyl, C2-C7 alkanoyloxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C7 alkoxycarbonyl, C1-C6 thioalkyl, aryl and N(R13,R14) where R13 and R14 are independently selected from hydrogen, acetyl, methanesulfonyl and C1-C6 alkyl, and Z is selected from CH, CH2, O, N and S, where Z may be directly bonded to X when Z is CH, or X may be a direct bond to Z when Z is N, or Z may be directly bonded to R15 when Z is N and X is not a direct bond to Z, R15 is selected from hydrogen, C1-C6 alkyl, C3-C8 cyclocalkyl, aryl and benzyl;
- and X is N—R6 except when Z in A is nitrogen and X is a direct bond to Z;
- An− is the acid addition salt of a pharmaceutically acceptable acid or the anion from a pharmaceutically acceptable salt, and isolated enantiomeric, diastereomeric and geometric isomers thereof, and mixtures thereof, with the proviso that E is represented by formula (II) wherein A is either formula (VI) or formula (IX) and Z is N.
Dependencies are inferred from the claim text.