Claims for Patent: 6,632,829

Summary for Patent: 6,632,829

Title:	Sulfonamides and derivatives thereof that modulate the activity of endothelin
Abstract:	Thienyl-, furyl- and pyrrolyl-sulfonamides, formulations of pharmaceutically-acceptable salts thereof and methods for modulating or altering the activity of the endothelin family of peptides are provided. In particular, N-(isoxazolyl)thienylsulfonamides, N-(isoxazolyl)furylsulfonamides and N-(isoxazolyl)pyrrolylsulfonamides, formulations thereof and methods using these sulfonamides for inhibiting the binding of an endothelin peptide to an endothelin receptor by contacting the receptor with the sulfonamide are provided. Methods for treating endothelin-mediated disorders by administering effective amounts of one or more of these sulfonamides or prodrugs thereof that inhibit the activity of endothelin are also provided.
Inventor(s):	Wu; Chengde (Houston, TX), Raju; Bore Gowda (Sugarland, TX), Kogan; Timothy (Sugarland, TX), Blok; Natalie (Houston, TX), Woodard; Patricia (Sugarland, TX)
Assignee:	Texas Biotechnology Corp. (Houston, TX)
Application Number:	10/011,610
Patent Claims:	1. A lyophilized powder, comprising a salt of compound of formula (A): ##STR18## wherein: Ar.sup.1 is a substituted with one or more substituents or an unsubstituted monocyclic or polycyclic heteroaryl group in which each substituent is independently selected from the group consisting of H, NH.sub.2, halide, pseudohalide, alkyl, alkylcarbonyl, formyl, aryl, heteroaryl, alkoxyalkyl, alkylamino, alkylthio, arylcarbonyl, aryloxy, arylamino, arylthio, haloalkyl, and haloaryl, in which the aryl and alkyl portions are unsubstituted or substituted with any of the preceeding groups, and straight or branched chains of from about 1 up to about 12 carbons; A.sup.2 has the formula: ##STR19## in which M is (CH.sub.2).sub.m C(O)(CH.sub.2).sub.r, (CH.sub.2).sub.m C(O)NH(CH.sub.2).sub.r, (CH.sub.2).sub.m (CH.dbd.CH)(CH.sub.2).sub.r, (CH.sub.2).sub.m C(O)(CH.sub.2).sub.s NH(CH.sub.2).sub.r, (CH.sub.2).sub.m (CH.dbd.CH)(CH.sub.2).sub.r, C.dbd.N(OH)(CH.sub.2).sub.r, (CH.sub.2).sub.m C(O)(CH.dbd.CH).sub.s NH(CH.sub.2).sub.r, CH(OH)(CH.sub.2).sub.r, CH(CH.sub.3)C(O)(CH.sub.2).sub.r, CH(CH.sub.3)C(O)(CH.sub.2).sub.m (CH.dbd.CH)(CH.sub.2).sub.r, (CH.sub.2).sub.r, (CH.sub.2).sub.r O, (CH.sub.2)S(O).sub.n wherein n is 0-2, C(O)O, in which m, s and r are each independently 0 to 6; and R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from (i) or (ii) as follows: (i) R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are each independently selected from among H, OH, NHR.sup.38, CONR.sup.38 R.sup.39, NO.sub.2, cyano, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, haloalkyl, alkylsulfinyl, alkylsulfonyl, alkoxycarbonyl, alkylcarbonyl, alkenylthio, alkenylamino, alkenyloxy, alkenyl sulfinyl, alkenylsulfonyl, arylaminocarbonyl, alkylaminocarbonyl, aminocarbonyl, (alkylaminocarbonyl)alkyl, acetoxy, carboxyl, carboxyalkyl, carboxyalkenyl, alkylsulfonylaminoalkyl, cyanoalkyl, acetyl, acetoxyalkyl, hydroxyalkyl, alkyoxyalkoxy, (acetoxy)alkoxy, (hydroxy)alkoxy, formyl, sulfonyl chlorides, amino acids, hexoses, O-glycosides, riboses, lower alkyl, --(CH.sub.2).sub.x C(O)(CH.sub.2).sub.x, --(CH.sub.2).sub.x, (CH.sub.2).sub.x N-lower alkyl, --(CH.sub.2).sub.x C(O)NH.sub.2, a D-, L- or racemic amino acid, a primary or secondary amide, O-glycoside, a hexose or ribose, --S(O).sub.2 NH.sub.2, acetoxyalkyl, --(CH.sub.2).sub.x COOH, --(CH.sub.2).sub.x COOH--, CO.sub.2 -lower alkyl, --COC(O)(CH.sub.2).sub.x CH.sub.3, --(CH.sub.2).sub.x N(CH.sub.3).sub.2, a sulfonyl chloride, S(O).sub.2 NHR.sup.50, alkylaryl, alkylheteroaryl, C(O)NHR.sup.50, --(CH.sub.2).sub.x OH and --C(O)N(H)N(H)M, in which each x is 0-3, or; (ii) at least two of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5, which substitute adjacent carbons on the ring, together form alkylenedioxy, alkylenethioxyoxy or alkylenedithioxy, which is unsubstituted or substituted by replacing one or more hydrogens with halide, loweralkyl, loweralkoxy or halo loweralkyl, and the others of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are selected as in (i); and at least four of R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are not hydrogen, unless: (a) R.sup.1 and R.sup.3 are alkyl and R.sup.5 is R.sup.20, which is selected from the group consisting of aryl, heteroaryl, heterocyclyl, OH, CN, C(O)R.sup.16, CO.sub.2 R.sup.16, SH, S(O).sub.n R.sup.16 in which n is 0-2, a D, L or racemic amino acid, a ribose or hexose, an O-glycoside, a sulfonyl chloride, --(CH.sub.2).sub.x OH, NHOH, NR.sup.12 R.sup.16, NO.sub.2, N.sub.3, OR.sup.16, R.sup.12 NCOR.sup.16 and CONR.sup.12 R.sup.16, then R.sup.2 and R.sup.4 may be H; or (b) when M is --CONHC(R.sup.12)(R.sup.16)--, then R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 may all be H; (c) when M is --COCHR.sup.6 --, Ar.sup.1 is not an isoxazolyl, R.sup.1 is alkyl, and R.sup.3 and R.sup.4 form alkylenedioxy, then R.sup.2 and R.sup.5 may be H; R.sup.38 and R.sup.39 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, haloalkyl alkylaryl, heterocyclyl, arylalkyl, arylalkoxy, alkoxy, aryloxy, cycloalkyl, cycloalkenyl and cycloalkynyl; R.sup.6 is H, or substituted or unsubstituted alkyl or aryl; X is S, O or NR.sup.11, where R.sup.11 contains up to about 30 carbon atoms and is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R.sup.15 and S(O).sub.n R.sup.15 in which n is 0-2; R.sup.15 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, or cycloalkynyl; R.sup.11 and R.sup.15 are unsubstituted or are substituted with one or more substituents each selected independently from Z; Z is hydrogen, halide, pseudohalide, alkyl, alkoxy, alkenyl, alkynyl, aryl, amino acids, primary and secondary amides, O-glycosides, hexoses, riboses, alkylaryl, alkylheteroaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, OH, CN, C(O)R.sup.16, OC(O)R.sup.16, CO.sub.2 R.sup.16, OCO.sub.2 R.sup.16, SH, S(O).sub.n R.sup.16 in which n is 0-2, NHOH, NR.sup.12 R.sup.16, NO.sub.2, N.sub.3, OR.sup.16, R.sup.12 NCOR.sup.16 and CONR.sup.12 R.sup.16 ; R.sup.16 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, chloride, NHR.sup.50, alkylaryl, alkylheteroaryl, or --(CH.sub.2).sub.x OH in which each x is 0-3; R.sup.50 is hydrogen, lower alkyl, or lower alkoxy; R.sup.12, which is selected independently from R.sup.11 and Z, is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R.sup.17 and S(O).sub.n R.sup.17 in which n is 0-2; R.sup.17 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl or cycloalkynyl; R.sup.12 and R.sup.16 may together form alkylene; each of R.sup.12, R.sup.15 and R.sup.16 may be further substituted with any group those set forth for Z. 2. The lyophilized powder of claim 1 produced by a process, comprising: (a) dissolving a pharmaceutically-acceptable salt of the sulfonamide compound in a sodium phosphate buffer solution containing a sugar or carbohydrate; (b) sterile-filtering the resulting solution; and (c) lyophilizing the filtered solution under standard conditions to produce a sterile powder. 3. The powder of claim 2, wherein the sugar or carbohydrate is dextrose. 4. An article of manufacture, comprising packaging material and a powder of claim 1, contained within the packaging material, wherein the compound is effective for antagonizing the effects of endothelin, ameliorating the symptoms of an endothelin-mediated disorder, or inhibiting the binding of an endothelin peptide to an ET receptor with an IC.sub.50 of less than about 1 .mu.M, and the packaging material includes a label that indicates that the sulfonamide or salt thereof is used for antagonizing the effects of endothelin, inhibiting the binding of endothelin to an endothelin receptor or treating an endothelin-mediated disorder. 5. The combination comprising: a sterile vial containing the pharmaceutical formulation of claim 1. 6. The combination of claim 5, wherein the sterile vial contains an amount of the powder that is for single dose administration. 7. The combination of claim 5, wherein the sterile vial also contains an amount of sterile water for injection; and the final concentration of the sulfonamide sodium salt is between about 1 and 250 mg/mL. 8. The lyophylized powder of claim 1, wherein M is ##STR20## in which R.sup.40 is hydrogen, alkyl, alkoxy, alkoxyalkyl, haloalkyl. 9. The lyophylized powder of claim 1, wherein M is C(O)CH.sub.2, C(O)NH, --CH.dbd.CH--, CH.sub.2 CH.sub.2 C(O)(CH).sub.2, CH.sub.2 CHC(O)CH.sub.2. 10. The lyophylized powder of claim 1, wherein M is selected from among: ##STR21## 11. The lyophilized powder of claim 1, wherein the compound has the formula (I): ##STR22## wherein: Ar.sup.1 is a substituted with one or more substituents or an unsubstituted monocyclic or polycyclic heteroaryl group in which each substituent is independently selected from the group consisting of H, NH.sub.2, halide, pseudohalide, alkyl, alkylcarbonyl, formyl, aryl, heteroaryl, alkoxyalkyl, alkylamino, alkylthio, arylcarbonyl, aryloxy, arylamino, arylthio, haloalkyl, and haloaryl, in which the aryl and alkyl portions are unsubstituted or substituted with any of the preceeding groups, and straight or branched chains of from about 1 up to about 12 carbons; X is S; W is .dbd.C(halo).sub.2, --(CH.sub.2).sub.x --, .dbd.N(lower alkyl), --C(O)--, .dbd.C(lower alkyl).sub.2, --NH--, .dbd.NCOR.sup.16, --NHC(R.sup.12)(R.sup.16)--, .dbd.NCO.sub.2 R.sup.16, --CH.sub.2 -- or .dbd.CHR.sup.6 ; and each x is 0-3. 12. The lyophilized powder of claim 1, wherein the compounds of formula (A) are of formula (II): ##STR23## wherein: Ar.sup.1 is a substituted or unsubstituted monocyclic or polycyclic heteroaryl group with one or more substituents, selected from the group consisting of H, NH.sub.2, halide, pseudohalide, alkyl, alkylcarbonyl, formyl, aryl, heteroaryl, alkoxyalkyl, alkylamino, alkylthio, arylcarbonyl, aryloxy, arylamino, arylthio, haloalkyl, and haloaryl, in which the aryl and alkyl portions are unsubstituted or substituted with any of the preceeding groups, and straight or branched chains of from about 1 up to about 10-12 carbons; R.sup.7 is R.sup.1, R.sup.8 is R.sup.3, R.sup.9 is R.sup.4 and R.sup.10 is R.sup.5. 13. The lyophylized powder of claim 12, wherein R.sup.7, R.sup.8 and R.sup.10 are alkyl, haloalkyl, polyhaloalkyl, alkenyl containing 1 to 2 double bonds, alkynyl containing 1 to 2 triple bonds, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl. 14. The lyophylized powder of claim 13, wherein R.sup.7, R.sup.8 and R.sup.10 are lower alkyl, lower alkenyl, lower alkynyl, or aryl. 15. The lyophylized powder of claim 14, wherein R.sup.7, R.sup.8 and R.sup.10 are methyl. 16. The lyophylized powder of claim 12, wherein R.sup.7, R.sup.8, R.sup.9 and R.sup.10 do not contain cyano groups, and W is not --CH.sub.2 --. 17. The lyophylized powder of claim 12, wherein: Ar.sup.1 is benzo-2,1,3-thiadiazol-5-yl, benzo-2,1,3-oxadiazol-5-yl, 3-methoxy-2-pyrazinyl, 3,4-dimethyl-5-isoxazolyl, 4-chloro-3-methyl-5-isoxazolyl or 4-chloro-5-methyl-3-isoxazolyl; W is --NH--, .dbd.NCO.sub.2 R.sup.16, or is --CH.sub.2 -- when R.sup.9 is hydroxyl; R.sup.7, R.sup.8 and R.sup.10 are methyl; and R.sup.9 is selected from the group consisting of Z-substituted and unsubstituted alkyl, hydroxyl, substituted and unsubstituted alkoxy, OC(0)R.sup.16, OCO.sub.2 R.sup.16, NR.sup.12 R.sup.16 and S(O).sub.n R.sup.16 in which n is 0-2. 18. The lyophylized powder of claim 17, wherein R.sup.9 is selected from the group consisting of methoxy, methoxycarbonylmethoxy, 2-(2-methoxyethoxy)ethoxyacetoxy 2-hydroxyethoxy, N,N-dimethylthiocarbonyloxy, N,N-dimethylthiocarbonyloxymethyl, dimethylamino, pyrrolidinyl, acetoxy, hydroxy, cyanomethyl, acetoxymethyl, hydroxymethyl, carboxylmethyl, methanesulfonylamino, N,N-dimethylaminomethyl, SO.sub.2 NH.sub.2, and methoxycarbonylmethyl. 19. The lyophylized powder of claim 17, wherein R.sup.9 does not contain a cyano group. 20. The lyophylized powder of claim 17, wherein R.sup.9 is selected from the group consisting of methoxy, methoxycarbonylmethoxy, 2-(2-methoxyethoxy)ethoxyacetoxy, 2-hydroxyethoxy, N,N-dimethylthiocarbonyloxy N,N-dimethylthiocarbonyloxymethyl, dimethylamino, pyrrolidinyl, acetoxymethyl, methoxycarbonylmethyl, hydroxy and acetoxy. 21. The lyophylized powder of claim 12, wherein the compound is selected from the group consisting of: N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-carboxylmethyl-2,4,6-trimethylpheny laminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-acetoxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-pyrrolidinyl-2,4,6-trimethylphenyla minocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-dimethylamino-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(N,N-dimethylthiocarbonyloxymethyl- 2,4,6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(N,N-dimethylthiocarbonyloxy)-2,4,6 -trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(2-hydroxyethoxy)-2,4,6-trimethylph enylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(2-(2-methoxyethoxy)ethoxy)acetoxy- 2,4,6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methoxycarbonylmethoxy-2,4,6-trimet hylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methoxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methoxycarbonylmethyl-2,4,6-trimeth ylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-acetoxymethyl-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-hydroxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-dimethylaminomethyl-2,4,6-trimethyl phenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methanesulfonylamino-2,4,6-trimethy lphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-sulfamoyl-2,4,6-trimethylphenylamin ocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-cyanomethyl-2,4,6-trimethylphenylam inocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-methoxycarbonylmethyl-2,4,6-trimeth ylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-carboxylmethyl-2,4,6-trimethylpheny laminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-acetoxymethyl-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-hydroxymethyl-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-dimethylaminomethyl-2,4,6-trimethyl phenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-methanesulfonylamino-2,4,6-trimethy lphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-hydroxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-carboxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-cyano-2,4,6-trimethylphenylaminocar bonyl)thiophene-3-sulfonamide; N-(4-chloro-5-methyl-3-isoxazolyl)-2-(3-sulfamoyl-2,4,6-trimethylphenylamin ocarbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-cyanomethyl-2,4,6-trimethylphenylaminoca rbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-methoxycarbonylmethyl-2,4,6-trimethylphe nylaminocarbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-carboxylmethyl-2,4,6-trimethylphenylamin ocarbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-acetoxymethyl-2,4,6-trimethylphenylamino carbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-hydroxymethyl-2,4, 6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-dimethylaminomethyl-2,4,6-trimethylpheny laminocarbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-methanesulfonylamino-2,4,6-trimethylphen ylaminocarbonyl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-hydroxy-2,4,6-trimethylphenylaminocarbon yl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-carboxy-2,4,6-trimethylphenylaminocarbon yl)thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-cyano-2,4,6-trimethylphenylaminocarbonyl )thiophene-3-sulfonamide; N-(3,4-dimethyl-5-isoxazolyl)-2-(3-sulfamoyl-2,4,6-trimethylphenylaminocarb onyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-cyanomethyl-2,4,6-trimethylphenylamino carbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-methoxycarbonylmethyl-2,4,6-trimethylp henylaminocarbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-carboxylmethyl-2,4,6-trimethylphenylam inocarbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-acetoxymethyl-2,4,6-trimethylphenylami nocarbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-hydroxymethyl-2,4,6-trimethylphenylami nocarbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-dimethylaminomethyl-2,4,6-trimethylphe nylaminocarbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-methanesulfonylamino-2,4,6-trimethylph enylaminocarbonyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-hydroxy-2,4,6-trimethylphenylaminocarb onyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-carboxy-2,4,6-trimethylphenylaminocarb onyl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-cyano-2,4,6-trimethylphenylaminocarbon yl)thiophene-3-sulfonamide; N-(benzo-2,1,3-thiadiazol-5-yl)-2-(3-sulfamoyl-2,4,6-trimethylphenylaminoca rbonyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-cyanomethyl-2,4,6-trimethylphenylaminocarbon yl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-methoxycarbonylmethyl-2,4,6-trimethylphenyla minocarbonyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-carboxylmethyl-2,4,6-trimethylphenylaminocar bonyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-acetoxymethyl-2,4,6-trimethylphenylaminocarb onyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-hydroxymethyl-2,4,6-trimethylphenylaminocarb onyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-dimethylaminomethyl-2,4,6-trimethylphenylami nocarbonyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-methanesulfonylamino-2,4,6-trimethylphenylam inocarbonyl)thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-hydroxy-2,4,6-trimethylphenylaminocarbonyl)t hiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-carboxy-2,4,6-trimethylphenylaminocarbonyl)t hiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-cyano-2,4,6-trimethylphenylaminocarbonyl)thi ophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(3-sulfamoyl-2,4,6-trimethylphenylaminocarbonyl )thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(1-methyl-1-phenyl-1-ethylaminocarbony l)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-((R)-1-phenyl-1-ethylaminocarbonyl)thi ophene-3-sulfonamide; and N-(4-chloro-3-methyl-5-isoxazolyl)-2-((S)-1-phenyl-1-ethylaminocarbonyl)thi ophene-3-sulfonamide; and pharmaceutically acceptable salts, acids and esters thereof. 22. The lyophylized powder of claim 12, wherein the compound is selected from the group consisting of: N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methoxycarbonylmethyl-2,4,6-trimeth ylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-acetoxymethyl-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-hydroxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methoxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-methoxycarbonylmethoxy-2,4,6-trimet hylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(2-(2-methoxyethoxy)ethoxy)acetoxy- 2,4,6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(2-hydroxyethoxy)-2,4,6-trimethylph enylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(N,N-dimethylthiocarbonyloxy)-2,4,6 -trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-(N,N-dimethylthiocarbonyloxymethyl- 2,4,6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-dimethylamino-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-pyrrolidinyl-2,4,6-trimethylphenyla minocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-acetoxy-2,4,6-trimethylphenylaminoc arbonyl)thiophene-3-sulfonamide; and pharmaceutically acceptable salts, acids and esters thereof. 23. The lyophylized powder of claim 1, wherein Ar.sup.1 has the formula: ##STR24## in which R.sup.A and R.sup.B are either (i), (ii) or (iii) as follows: (i) R.sup.A and R.sup.B are each independently selected from H, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, except that R.sup.2 is not halide or pseudohalide; or, (ii) R.sup.A and R.sup.B together form --(CH.sub.2).sub.n, where n is 3 to 6; or, (iii) R.sup.A and R.sup.B together form 1,3-butadienyl. 24. The lyophylized powder of claim 23, wherein R.sup.A and R.sup.B are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.B is not halide. 25. The lyophylized powder of claim 1, wherein the compound is a thiophene-3-sulfonamide. 26. The lyophylized powder of claim 12, wherein Ar.sup.1 had the formula: ##STR25## in which R.sup.A and R.sup.B are either (i), (ii) or (iii) as follows: (i) R.sup.A and R.sup.B are each independently selected from H, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, except that R.sup.2 is not halide or pseudohalide; or, (ii) R.sup.A and R.sup.B together form --(CH.sub.2).sub.n, where n is 3 to 6; or, (iii) R.sup.A and R.sup.B together form 1,3-butadienyl. 27. The lyophylized powder of claim 26, wherein R.sup.A and R.sup.B are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.B is not halide. 28. The lyophylized powder of claim 12, wherein the compound is a thiophene-3-sulfonamide. 29. The lyophylized powder of claim 1, wherein the compound has formula III: ##STR26## wherein: X is S, O or NR.sup.11 ; each G and R is independently selected from lower alkyl, CN, --(CH.sub.2).sub.x C(O)(CH.sub.2).sub.x, --(CH.sub.2).sub.x, (CH.sub.2).sub.x N-lower alkyl, --(CH.sub.2).sub.x C(O)NH.sub.2, a D-, L- or racemic amino acid, a primary or secondary amide, O-glycoside, a hexose or ribose, --S(O).sub.2 NH.sub.2, hydroxy, alkoxy, alkoxycarbonyl, acetoxyalkyl, --(CH.sub.2).sub.x COOH; --(CH.sub.2).sub.x COOH--, CO.sub.2 -lower alkyl, CN, heteroaryl, --COC(O)(CH.sub.2).sub.x CH.sub.3, --(CH.sub.2).sub.x N(CH.sub.3).sub.2, a sulfonyl chloride, S(O).sub.2 NHR.sup.50, alkylaryl, alkylheteroaryl, C(O)NHR.sup.50, --(CH.sub.2).sub.x OH, --C(O)N(H)N(H)M; R.sup.50 is hydrogen, lower alkyl, or lower alkoxy; M is H or R.sup.50 ; R' is independently selected from hydrogen, G and R; W is .dbd.C(halo).sub.2, .dbd.N(H), --(CH.sub.2).sub.x --, .dbd.N(lower alkyl), --C(O)--, .dbd.C(lower alkyl).sub.2 ; and each x is independently is 0-3. 30. The lyophylized powder of claim 29, wherein Ar.sup.1 is an isoxazolyl, a thiazolyl, a pyrimidinyl, or a pyridazinyl group. 31. The lyophylized powder of claim 29, wherein Ar.sup.1 is an isoxazolyl. 32. The lyophylized powder of claim 29, wherein R, G and R' are selected where the amino acid is L-Asp or L-Glu; the hexose is D-mannose, the heteroaryl is triazolyl, and X is S. 33. The lyophylized powder of claim 31, wherein R, G and R' are selected where the amino acid is L-Asp or L-Glu; the hexose is D-mannose, the heteroaryl is triazolyl, and X is S. 34. The lyophylized powder of claim 29, wherein: W is .dbd.CH.sub.2, .dbd.NH, .dbd.NCH.sub.3, .dbd.NCH.sub.2 CH.sub.3, .dbd.C(CH.sub.3).sub.2 or CF.sub.2 ; and G is --CH.sub.3, --CN, --COCH.sub.3, --CH.sub.2 CH.sub.3, --(CH.sub.2).sub.x CO.sub.2 H. 35. The lyophylized powder of claim 30, wherein: W is .dbd.CH.sub.2, .dbd.NH, .dbd.NCH.sub.3, .dbd.NCH.sub.2 CH.sub.3, .dbd.C(CH.sub.3).sub.2 or CF.sub.2 ; and G is --CH.sub.3, --CN, --COCH.sub.3, --CH.sub.2 CH.sub.3, --(CH.sub.2).sub.x CO.sub.2 H . 36. The lyophylized powder of claim 31, wherein: W is .dbd.CH.sub.2, .dbd.NH, .dbd.NCH.sub.3, .dbd.NCH.sub.2 CH.sub.3, .dbd.C(CH.sub.3).sub.2 or CF.sub.2 ; and G is --CH.sub.3, --CN, --COCH.sub.3, --CH.sub.2 CH.sub.3, --(CH.sub.2).sub.x CO.sub.2 H . 37. The lyophylized powder of claim 29, wherein the compound is selected from the group consisting of: N.sup.2 -(3-cyanomethyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazolylsu lfamoyl)-2-thiophenecarboxamide; methyl-2-(3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxami do)-2,4,6-trimethylphenyl)acetate; 2-(3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-2,4 ,6-trimethylphenyl)acetic acid; N.sup.2 -(3-acetyloxymethyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazol ylsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-hydroxymethyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazolyl sulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-dimethylaminomethyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isox azolylsulfamoyl)-2-thiophenecarboxamide trifluoroacetate; N.sup.2 -(3-(4,5-dihydro-1,3-oxazol-2-yl)-2,4,6-trimethylphenyl)-3-(4-chloro-3-met hyl-5-isoxazolylsulfamoyl)-2-thiophenecarboxamide; 3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-2,4,6 -trimethylbenzoic acid; N-[3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-2,4 ,6-trimethylbenzoyl]glutamic acid; N-[3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-2,4 ,6-trimethylbenzoyl]aspartic acid; N-[2-(3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)- 2,4,6-trimethylphenyl)acetyl]glutamic acid; N-[2-(3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)- 2,4,6-trimethylphenyl)acetyl]aspartic acid; N.sup.2 -(3-cyano-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazolylsulfamoy l)-2-thiophenecarboxamide; 2-(3-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-2,4 ,6-trimethylphenoxy)acetic acid; N.sup.2 -(3-alkylsulfonamido-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazo lylsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-arylsulfonamido-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazol ylsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-sulfamoyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazolylsulf amoyl)-2-thiophenecarboxamide; N.sup.2 -(3-alkylsulfamoyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazoly lsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-arylsulfamoyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazolyl sulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-(1H-1,2,3,4-tetraazol-5-ylmethyl)-2,4,6-trimethylphenyl)-3-(4-chloro-3 -methyl-5-isoxazolylsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-(2-pyridylmethyl)-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxaz olylsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-hydrazinocarbonyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxaz olylsulfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-aminomethyl-2,4,6-trimethylphenyl)-3-(4-chloro-3-methyl-5-isoxazolylsu lfamoyl)-2-thiophenecarboxamide; N.sup.2 -(3-(a-D-mannopyranosyloxymethyl)-2,4,6-trimethylphenyl)-3-(4-chloro-3-met hyl-5-isoxazolylsulfamoyl)-2-thiophenecarboxamide; 5-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-cyan o-6-methylbenzo[d][1,3]dioxole; 5-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-6-cyan o-4-methylbenzo[d][1,3]dioxole; 2-(5-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-m ethylbenzo[d][1,3]dioxole)-6-acetic acid; 5-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-acet yl-6-methylbenzo[d][1,3]dioxole; 5-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-6-acet yl-4-methylbenzo[d][1,3]dioxole; 5-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-7-cyan o-4,6-dimethylbenzo[d][1,3]dioxole; 6-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-5,7-di methylbenzo[d][1,3]dioxole-4-carboxylic acid; 7-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-5,6-di methylbenzo[d][1,3]dioxole-4-carboxylic acid; 7-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-cyan o-5,6-dimethylbenzo[d][1,3]dioxole; 7-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-acet yl-5,6-dimethylbenzo[d][1,3]dioxole; 7-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-carb oxamido-5,6-dimethylbenzo[d][1,3]dioxole; 7-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-amin omethyl-5,6-dimethylbenzo[d][1,3]dioxole; 7-(3-(4-chloro-3-methyl-5-isoxazolylsulfamoyl)-2-thienylcarboxamido)-4-dime thylaminomethyl-5,6-dimethylbenzo[d][1,3]dioxole; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-cyanomethyl-2,4,6-trimethylphenylam inocarbonyl)thiophene-3-sulfonamide, N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-carboxymethyl-2,4,6-trimethylpheny laminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-acetoxymethyl-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-hydroxymethyl-2,4,6-trimethylphenyl aminocarbonyl)thiophene-3-sulfonamide; and pharmaceutically acceptable salts, esters and acids thereof. 38. The lyophylized powder of claim 37, wherein the compound is a sodium salt. 39. The lyophylized powder of claim 29, wherein Ar.sup.1 has formula: ##STR27## in which R.sup.A and R.sup.B are either (i), (ii) or (iii) as follows: (i) R.sup.A and R.sup.B are each independently selected from H, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, except that R.sup.2 is not halide or pseudohalide; or, (ii) R.sup.A and R.sup.B together form --(CH.sub.2).sub.n, where n is 3 to 6; or, (iii) R.sup.A and R.sup.B together form 1,3-butadienyl. 40. The lyophylized powder of claim 39, wherein R.sup.A and R.sup.B are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.B is not halide. 41. The lyophylized powder of claim 29, wherein the compound is a thiophene-3-sulfonamide. 42. The lyophylized powder of claim 1, wherein the compounds of formula (A) are of formula (IV): ##STR28## wherein: Ar.sup.1 is selected with the proviso that Ar.sup.1 is not 4-chloro-3-methyl-5-isoxazolyl, 4-chloro-5-methyl-3-isoxazolyl or 3,4-dimethyl-5-isoxazolyl when R.sup.6 is H; and R.sup.6 is H, or substituted or unsubstituted alkyl or aryl. 43. The lyophylized powder of claim 42, wherein: Ar.sup.1 is benzo-2,1,3-oxadiazol-5-yl or 2-methoxy-3-pyrazinyl; and R.sup.6 is H, or substituted or unsubstituted alkyl. 44. The lyophylized powder of claim 42, wherein R.sup.6 is methyl or carboxymethyl. 45. The lyophylized powder of claim 42, wherein Ar.sup.1 has the formula: ##STR29## in which R.sup.A and R.sup.B are either (i), (ii) or (iii) as follows: (i) R.sup.A and R.sup.B are each independently selected from H, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, except that R.sup.2 is not halide or pseudohalide; or, (ii) R.sup.A and R.sup.B together form --(CH.sub.2).sub.n, where n is 3 to 6; or, (iii) R.sup.A and R.sup.B together form 1,3-butadienyl. 46. The lyophylized powder of claim 45, wherein R.sup.A and R.sup.B are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.B is not halide. 47. The lyophylized powder of claim 42, wherein the compound is a thiophene-3-sulfonamide. 48. The lyophylized powder of claim 42, wherein the compound is selected from the group consisting of: N-(benzo-2,1,3-oxadiazol-5-yl)-2-(2-methyl-4,5-methylene-dioxyphenylacetyl) thiophene-3-sulfonamide; N-(3-methoxy-2-pyrazinyl)-2-(2-methyl-4,5-methylene-dioxyphenylacetyl)thiop hene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(2-(2-methyl-4,5-methylene-dioxyphenyl )propanoyl)thiophene-3-sulfonamide; N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-carboxyl-2-2-methyl-4,5-methylenedi oxyphenyl)propanoyl)thiophene-3-sulfonamide; and pharmaceutically acceptable salts, esters and acids thereof. 49. The lyophylized powder of claim 48, wherein the compound is a sodium salt. 50. The lyophylized powder of claim 1, wherein the compounds of formula (A) are of formula (V): ##STR30## wherein: W is --NH--; and R.sup.20 is selected from the group consisting of aryl, heteroaryl, heterocyclyl, OH, CN, C(O)R.sup.16, CO.sub.2 R.sup.16, SH, S(O).sub.n R.sup.16 in which n is 0-2, a D, L or racemic amino acid, a ribose or hexose, an O-glycoside, a sulfonyl chloride, --(CH.sub.2).sub.x OH, NHOH, NR.sup.12 R.sup.16, NO.sub.2, N.sub.3, OR.sup.16, R.sup.12 NCOR.sup.16 and CONR.sup.12 R.sup.16 ; R.sup.16 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl or cycloalkynyl; R.sup.12 is selected from hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl, cycloalkynyl, C(O)R.sup.17 and S(O).sub.n R.sup.17 in which n is 0-2; R.sup.17 is hydrogen, alkyl, alkenyl, alkynyl, aryl, alkylaryl, heterocyclyl, aralkyl, aralkoxy, cycloalkyl, cycloalkenyl or cycloalkynyl; and each of R.sup.12, R.sup.15 and R.sup.16 may be further substituted with the any of the groups set forth for Z. 51. The lyophylized powder of claim 50, wherein Ar.sup.1 has the formula: ##STR31## in which R.sup.A and R.sup.B are either (i), (ii) or (iii) as follows: (i) R.sup.A and R.sup.B are each independently selected from H, NH.sub.2, NO.sub.2, halide, pseudohalide, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, alkoxy, alkylamino, alkylthio, alkyloxy, haloalkyl, alkylsufinyl, alkylsulfonyl, aryloxy, arylamino, arylthio, arylsufinyl, arylsulfonyl, haloalkyl, haloaryl, alkoxycarbonyl, alkylcarbonyl, aminocarbonyl, arylcarbonyl, formyl, substituted or unsubstituted amido, substituted or unsubstituted ureido, in which the alkyl, alkenyl and alkynyl portions contain from 1 up to about 14 carbon atoms and are either straight or branched chains or cyclic, and the aryl portions contain from about 4 to about 16 carbons, except that R.sup.2 is not halide or pseudohalide; or, (ii) R.sup.A and R.sup.B together form --(CH.sub.2).sub.n, where n is 3 to 6; or, (iii) R.sup.A and R.sup.B together form 1,3-butadienyl. 52. The lyophylized powder of claim 51, wherein R.sup.A and R.sup.B are each selected independently from among alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, halide, pseudohalide or H, except that R.sup.B is not halide. 53. The lyophylized powder of claim 50, wherein the compound is a thiophene-3-sulfonamide. 54. The lyophylized powder of claim 40, wherein: Ar.sup.1 is 4-chloro-3-methyl-5-isoxazolyl; W is --NH--; and R.sup.20 is CONH.sup.2, COOH, or phenyl. 55. The lyophylized powder of claim 1, wherein the compound is N.sup.2 -(3-hydroxy-2,4,6-trimethyl)phenyl-3-(4-chloro-3-methyl-5-isoxazolyl)sulfa moyl-2-thiophenecarboxamide or a pharmaceutically acceptable salt thereof.

Details for Patent 6,632,829

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	ZOSTAVAX	zoster vaccine live	For Injection	125123	05/25/2006		2013-05-20