| abstract |
A method is provided for treating or improving certain fibrotic diseases or other indications in an animal, including a human, which comprises administering an effective amount of a compound of the farmulg I: Y-Ar + .X where: a) Ar is a chain heteroaryl five or six members having a first nitrogen chain and optionally nitrogens chain, second or third, with the atoms in remaining chain being carbon, oxygen or sulfur, provided that the first nitrogen of Ar is a quaternary nitrogen and Ar other than thiazolium, oxazolium imidazolium; b) And it is substituted in the first chain nitrogen, with the proviso that if Ar is pyrazole, indazole, (1,2,3) -triazole, benzotriazole, or (1,2,4) -triazole, the second nitrogen chain is substituted, c) Y is a group of the formula -CH (R5) -R6 (as preferred in one embodiment), (a) wherein R5 is hydrogen, alkyl-, cycloalkyl-, alkenyl-, alkynyl- , aminoalkyl, hydroxy [C1 to C6] alkyl, dialkylaminoalkyl, (N- [C6 or C10] aryl) (N-alkyl) aminoalkyl, piperidiri-1- ilalquil-, pyrrolidin-1-ylalkyl, azetidinilalquilo, 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- ilalkyl, thiomorpholin-4-ylalkyl, piperazin-1-ylalkyl, piperidin-1-ylalkyl, [C6 or C10] aryl or independently the same as R6; (B) wherein R6 is (1) hydrogen, (which may be substituted by alkoxycarbonyl) -, alkenyl, alkynyl, cyano, cianoalquil-, or Rs, Rs is where [C6 or C10] aryl or heterocycle it contains 4-10 chain atoms of which 1-3 are heteroatoms selected from the group consisting of an oxygen, nitrogen and sulfur; or (2) a group of the formula -W-R7 (as preferred in one embodiment), wherein R7 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-OR8 wherein R8 is hydrogen or alkyl, (4) a group of the formula -CH (OH) R5; or (5) a group of the formula -W-N (R9) R10, wherein (a) R9 is hydrogen and R10 is an optionally substituted alkyl or cycloalkyl; or (b) R9 is hydrogen or alkyl and R10 is Ar *; or (c) R9 is hydrogen to alkyl, R10 is a heterocycle containing 4-10 chain atoms of which 1-3 are heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur; or (d) R9 and R10 are both alkyl groups; or (e) R9 and R10 together with N form a heterocycle containing 4-10 chain atoms that can be incorporated to an additional heteroatom selected from the group of N, O or S in the chain, wherein the heterocycle is optionally substituted; or (f) R9 and R10 are both hydrogen 2-NH2, and d) X is a pharmaceutically acceptable anion that may be absent if the compound provides a neutralizing salt, or a pharmaceutically acceptable salt of the compound. |