| abstract |
Provided is a method of treating or ameliorating certain fibrotic diseases or other indications in an animal, including a human, comprising administering an effective amount of a compound of the formula I: n Y—Ar⊕·X — n wherein: n a. Ar is a five or six membered heteroaryl ring having a first ring nitrogen and optionally second or third ring nitrogens, with the remaining ring atoms being carbon, oxygen, or sulfur, provided the first nitrogen of Ar is a quaternary nitrogen and Ar is not thiazolium, oxazolium or imidazolium; n b. Y is substituted on the first ring nitrogen, with the proviso that if Ar is pyrazole, indazole, (1,2,3)-triazole, benzotriazole, or (1,2,4)-triazole, the second ring nitrogen is substituted n C. Y is: n 1 . a group of the formula —CH(R 5 )—R 6 [as preferred in one embodiment] n (a) wherein R 5 is hydrogen, alkyl, cycloalkyl-, alkenyl-, alkynyl-, aminoalkyl-, hydroxy[C 1 to C 6 ]alkyl, dialkylaminoalkyl-, (N-[C 6 or C 10 ]aryl)(N-alkyl)aminoalkyl-, piperidin-1-ylalkyl-, pyrrolidin-1-ylalkyl, azetidinylalkyl, 4-alkylpiperazin-1-ylalkyl, 4-alkylpiperidin-1-ylalkyl, 4-[C 6 or C 10 ]arylpiperazin-1-ylalkyl, 4-[C 6 or C 10 ]arylpiperidin-1-ylalkyl, azetidin-1-ylalkyl, morpholin-4-ylallcyl, thiomorpholin-4-ylalkyl, piperazin-1-ylalkyl, piperidin-1-ylalkyl, [C 6 or C 10 ]aryl, or independently the same as R 6 ; n (b) wherein R 6 is n (1) hydrogen, alkyl (which may be substituted by alkoxycarbonyl)-, alkenyl, alkynyl, cyano-, cyanoalkyl-, or Rs, wherein Rs is a [C 6 or C 10 ]aryl or a heterocycle containing 4-10 ring atoms of which 1-3 are heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur; or n (2) a group of the formula —W—R 7 [as preferred in one embodiment], wherein R 7 is alkyl, alkoxy, hydroxy, or Rs [as preferred in one embodiment], wherein W is —C(═O)— or —S(O) 2 —; n (3) a group of the formula —W—OR 8 wherein R 8 is hydrogen or alkyl, n (4) a group of the formula —CH(OH)Rs; or n (5) a group of the formula —W—N(R 9 )R 10 , wherein n (a) R 9 is hydrogen and R 10 is an alkyl or cycloalkyl, optionally substituted; or n (b) R 9 is hydrogen or alkyl and R 10 is Ar; or n (c) R 9 is hydrogen or alkyl, R 10 is a heterocycle containing 4-10 ring atoms of which 1-3 are heteroatoms are selected from the group consisting of oxygen, nitrogen and sulfur; or n (d) R 9 and R 10 are both alkyl groups; or n (e) R 9 and R 10 together with N form a heterocycle containing 4-10 ring atoms which can incorporate up to one additional heteroatom selected from the group of N, O or S in the ring, wherein the heterocycle is optionally substituted; or n (f) R 9 and R 10 are both hydrogen; or n 2 . —NH 2 , and n e. X is a pharmaceutically acceptable anion, which may be absent if the compound provides a neutralizing salt, or n (B) a pharmaceutically acceptable salt of the compound. |