| 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 : Y-Ar<+>.X<-> wherein : a) Ar is a five or six membered heteroaryl ring having a first ring nitrogen an 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; 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, c) Y is 1- a group of the formula -CH(R<5>)-R<6> (as preferred in one embodiment), (a) wherein R<5> is hydrogen, alkyl-, cycloalkyl-, alkenyl-, alkynyl-, aminoalkyl-, hydroxy[C1 to C6]alkyl, dialkylaminoalkyl-, (N-[C6 or C10]aryl)(N-alkyl)aminoalkyl-, piperidin-1-ylalkyl-, pyrrolidin-1-ylalkyl, azetidinyalkyl, 4-alkylpiperazin-1-ylalkyl, 4-alkylpiperidin-1-ylalkyl, 4-[C6 or C10]arylpiperazin-1-ylalkyl, 4-[C6 or C10]arylpiperidin-1-ylalkyl, azetidin-1-ylalkyl, morpholin-4-ylalkyl, thiomorpholin-4-ylalkyl, piperazin-1-ylalkyl, piperidin-1-ylalkyl, [C6 or C10]aryl, or independently the same as R<6>; (b) wherein R<6> is (1) hydrogen, alkyl (which may be substituted by alkoxycarbonyl)-, alkenyl, alkynyl, cyano-, cyanoalkyl-, or Rs, wherein Rs is a [C6 or C10]aryl or a heterocycle containing 4-10 ring atoms of which 1-3 are heteroatoms selected from the group consisting of a oxygen, nitrogen and sulfur; or (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-; (3) a group of the formula -W-OR<8> wherein R<8> is hydrogen or alkyl, (4) a group of the formula -CH(OH)Rs; or (5) a group of the formula -W-N(R<9>)R<10>, wherein (a) R<9> is hydrogen and R<10> is an alkyl or cycloalkyl, optionally substituted; or (b) R<9> is hydrogen or alkyl and R<10> is Ar*; or (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 (d) R<9> and R<10> are both alkyl groups; or (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 (f) R<9> and R<10> are both hydrogen; or 2- NH2; and d) X is a pharmaceutically acceptable anion, which may be absent if the compound provides a neutralizing salt, or a pharmaceutically acceptable salt of the compound. |