Importance

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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.sym..multidot.X.sup.-- wherein: 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; 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.sup.5)--R.sup.6 [as preferred in one embodiment] (a) wherein R.sup.5 is hydrogen, alkyl, cycloalkyl-, alkenyl-, alkynyl-, aminoalkyl-, hydroxy[C.sub.1 to C.sub.6]alkyl, dialkylaminoalkyl-, (N-[C.sub.6 or C.sub.10]aryl)(N-alkyl)aminoalkyl-, piperidin-1-ylalkyl-, pyrrolidin-1-ylalkyl, azetidinylalkyl, 4-alkylpiperazin-1-ylalkyl, 4-alkylpiperidin-1-ylalkyl, 4-[C.sub.6 or C.sub.10]arylpiperazin-1-ylalky-l, 4-[C.sub.6 or C.sub.10]arylpiperidin-1-ylalkyl, azetidin-1-ylalkyl, morpholin-4-ylallcyl, thiomorpholin-4-ylalkyl, piperazin-1-ylalkyl, piperidin-1-ylalkyl, [C.sub.6 or C.sub.10]aryl, or independently the same as R.sup.6; (b) wherein R.sup.6 is (1) hydrogen, alkyl (which may be substituted by alkoxycarbonyl)-, alkenyl, alkynyl, cyano-, cyanoalkyl-, or Rs, wherein Rs is a [C.sub.6 or C.sub.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 (2) a group of the formula --W--R.sup.7 [as preferred in one embodiment], wherein R.sup.7 is alkyl, alkoxy, hydroxy, or Rs [as preferred in one embodiment], wherein W is --C(.dbd.O)-- or --S(O).sub.2--; (3) a group of the formula --W--OR.sup.8 wherein R.sup.8 is hydrogen or alkyl, (4) a group of the formula --CH(OH)Rs; or (5) a group of the formula --W--N(R.sup.9)R.sup.10, wherein (a) R.sup.9 is hydrogen and R.sup.10 is an alkyl or cycloalkyl, optionally substituted; or (b) R.sup.9 is hydrogen or alkyl and R.sup.10 is Ar; or (c) R.sup.9 is hydrogen or alkyl, R.sup.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.sup.9 and R.sup.10 are both alkyl groups; or (e) R.sup.9 and R.sup.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.sup.9 and R.sup.10 are both hydrogen; or 2. --NH.sub.2, and e. X is a pharmaceutically acceptable anion, which may be absent if the compound provides a neutralizing salt, or (B) a pharmaceutically acceptable salt of the compound.

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First Claim