Methods and compositions to inhibit edema factor and adenylyl cyclase

Abstract

Small molecules and their derivatives are described for the treatment and/or prevention of intestinal fluid loss. Also disclosed are methods of using said molecules and their derivatives to treat and/or prevent conditions associated with increased levels of 3′,5′-adenosine monophosphate. Specific compositions of the invention are also novel.

1 . A method of treating and/or preventing intestinal fluid loss in a subject, the method comprising administering to the subject a composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof wherein the general formula of the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and any combination thereof wherein,
 1) R is a cyclic or bicyclic ring structure; 
 2) R 1  is a hydrogen, cyclic or bicyclic ring structure; 
 3) R 2  is a hydrogen, alkyl, cyclic or bicyclic ring structure; 
 4) R 3  is a hydrogen, or alkyl; 
 5) R 5  is a hydrogen, alkyl, cyclic or bicyclic ring structure; 
 6) X is an alkyl, oxygen, an ester, an amine, or an amide 
 7) Z is selected from the group consisting of hydrogen, alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate; 
 8) W is selected from the group consisting of CO, NH, methylene, sulfur atom, oxygen atom and thionyl; and, 
 9) n is 0, 1, or more than 1. 
 
       
     
     
         2 . The method of  claim 1 , wherein R is substituted or unsubstituted and selected from the group consisting of phenyl, pyranonyl, pyridyl, imidazolyl, 1,8-napthyridinyl, and N-oxide pyridyl. 
     
     
         3 . The method of  claim 2 , wherein R is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         4 . The method of  claim 1 , wherein R 1  is substituted or unsubstituted and selected from the group consisting of phenyl, pyridyl, and furanyl. 
     
     
         5 . The method of  claim 4 , wherein R 1  is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         6 . The method of  claim 1 , wherein R 4  is a cyclic or bicyclic ring structure, substituted or unsubstituted and selected from the group consisting of phenyl, pyridyl, and furanyl. 
     
     
         7 . The method of  claim 6 , wherein R 4  is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         8 . The method of  claim 1 , wherein the compound is from the group consisting of FIV-50, FIV-1, FIV-29, FIV-31, FIV-34, FIV-35, FIV-39, FIV-40, FIV-46, FIII-1, FII-1, FI-3, FI-1, FI-2, FIV-49, FIV-54, FIV-58, FIV-55, FIV-53, FIV-67, FIV-70, FIV-65, FIV-68, FIV-66, FIV-61, FIV-60, FIV-64, FIV-71, FIV-46, FIV-72, FIV-73, FIV-75 and any combination thereof. 
     
     
         9 . The method of  claim 1 , wherein the method comprises inhibiting adenylyl cyclase, edema factor, CTA1, or any combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the intestinal fluid loss is the result of infection of a pathogen. 
     
     
         11 . The method of  claim 10 , wherein the pathogen is  B. anthracis, V. cholerae, E. coli , Pertussis,  Y. pestis , or any combination thereof. 
     
     
         12 . The method of  claim 1 , wherein the intestinal fluid loss is caused by an increase in 3′,5′-adenosine monophosphate levels in the subject's tissue. 
     
     
         13 . The method of  claim 1 , wherein the intestinal fluid loss is caused by cancer. 
     
     
         14 . The method of  claim 1 , wherein the composition is administered in combination with one or more other drugs. 
     
     
         15 . The method of  claim 1 , wherein the composition further comprises an antibiotic or an anti-inflammatory. 
     
     
         16 . The method of  claim 1 , wherein the composition comprises a pharmaceutically acceptable carrier. 
     
     
         17 . The method of  claim 1 , wherein the compound is delivered at dosages between 0.001 mM and 10 mM. 
     
     
         18 . The method of  claim 17 , wherein the compound is delivered at dosages between 0.1 mM and 1 mM. 
     
     
         19 . The method of  claim 1 , wherein the subject is a human. 
     
     
         20 . The method of  claim 1 , wherein the composition is administered through a route selected from the group consisting of alimentary, parenteral, topical, mucosal, inhalation and any combination thereof. 
     
     
         21 . A method of treating and/or preventing a condition associated with increased 3′-5′-adenosine monophosphate levels in a subject, the method comprising administering to the subject a composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof wherein the general formula of the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and combinations thereof wherein,
 1) R is a cyclic or bicyclic ring structure; 
 2) R 1  is a hydrogen, cyclic or bicyclic ring structure; 
 3) R 2  is a hydrogen, alkyl, cyclic or bicyclic ring structure; 
 ) R 3  is a hydrogen, or alkyl; 
 5) R 5  is a hydrogen, alkyl, cyclic or bicyclic ring structure; 
 6) X is an alkyl, oxygen, an ester, an amine, or an amide 
 7) Z is selected from the group consisting of hydrogen, alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate; 
 8) W is selected from the group consisting of CO, NH, methylene, sulfur atom, oxygen atom and thionyl; and, 
 9) n is 0, 1, or more than 1. 
 
       
     
     
         22 . The method of  claim 21 , wherein R is a substituted or unsubstituted and selected from the group consisting of: phenyl, pyranonyl, pyridyl, imidazolyl, 1,8-napthyridinyl, and N-oxide pyridyl. 
     
     
         23 . The method of  claim 22 , wherein R is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of: hydrogen, alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         24 . The method of  claim 21 , wherein R 1  is substituted or unsubstituted and selected from the group consisting of phenyl, pyridyl, and furanyl. 
     
     
         25 . The method of  claim 21 , wherein R 1  is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         26 . The method of  claim 21 , wherein R 4  is a cyclic or bicyclic ring structure, substituted or unsubstituted and selected from the group consisting of phenyl, pyridyl, and furanyl. 
     
     
         27 . The method of  claim 26 , wherein R 4  is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         28 . The method of  claim 21 , wherein the compound is from the group consisting of FIV-50, FIV-1, FIV-29, FIV-31, FIV-34, FIV-35, FIV-39, FIV-40, FIV-46, FIV-49, FIII-1, FII-1, FI-3, FI-1, FI-2, FIV-54, FIV-58, FIV-55, FIV-53, FIV-67, FIV-70, FIV-65, FIV-68, FIV-66, FIV-61, FIV-60, FIV-64, FIV-71, FIV-46, FIV-72, FIV-73, FIV-75 and any combination thereof. 
     
     
         29 . The method of  claim 21 , wherein the compound is inhibits adenylyl cyclase, edema factor, CTA1, or any combination thereof. 
     
     
         30 . The method of  claim 21 , wherein the condition is the result of infection with a pathogen. 
     
     
         31 . The method of  claim 26 , wherein the pathogen is  B. anthracis, V. cholere, E. coli , Pertussis,  Y. pestis , or any combination thereof. 
     
     
         32 . The method of  claim 27 , wherein the pathogen is  B. anthracis  and the method further comprises administration of a LT inhibitory drug. 
     
     
         33 . The method of  claim 28 , wherein the LT inhibitory drug is selected from the group consisting of bestatin, captopril, adefovir, and any combination thereof. 
     
     
         34 . The method of  claim 21 , wherein the composition comprises a pharmaceutically acceptable carrier. 
     
     
         35 . The method of  claim 21 , wherein the compound is delivered at dosages between 0.001 mM and 10 mM. 
     
     
         36 . The method of  claim 35 , wherein the compound is delivered at dosages between 0.1 mM and 1 mM. 
     
     
         37 . The method of  claim 21 , wherein the subject is a human. 
     
     
         38 . The method of  claim 21 , wherein the composition is administered through a route selected from the group consisting of alimentary, parenteral, topical, mucosal, inhalation and any combination thereof. 
     
     
         39 . A composition comprising a compound selected from the group consisting of FIV-1, FIV-29, FIV-31, FIV-34, FIV-35, FIV-39, FIV-40, FIV-46, FI-3, FI-1, FI-2, FIV-49, FIV-54, FIV-58, FIV-55, FIV-53, FIV-67, FIV-70, FIV-65, FIV-68, FIV-66, FIV-61, FIV-60, FIV-64, FIV-71, FIV-46, FIV-72, FIV-73, FIV-75 and combination thereof. 
     
     
         40 . The composition of  claim 39 , wherein the compound is FIV-1. 
     
     
         41 . The composition of  claim 39 , wherein the compound is FIV-29. 
     
     
         42 . The composition of  claim 39 , wherein the compound is FIV-31. 
     
     
         43 . The composition of  claim 39 , wherein the compound is FIV-34. 
     
     
         44 . The composition of  claim 39 , wherein the compound is FIV-35. 
     
     
         45 . The composition of  claim 39 , wherein the compound is FIV-39. 
     
     
         46 . The composition of  claim 39 , wherein the compound is FIV-40. 
     
     
         47 . The composition of  claim 39 , wherein the compound is FIV-46. 
     
     
         48 . The composition of  claim 39 , wherein the compound is FI-3. 
     
     
         49 . The composition of  claim 39 , wherein the compound is FI-1. 
     
     
         50 . The composition of  claim 39 , wherein the compound is FI-2. 
     
     
         51 . The composition of  claim 39 , wherein the compound is FIV-54. 
     
     
         52 . The composition of  claim 39 , wherein the compound is FIV-58. 
     
     
         53 . The composition of  claim 39 , wherein the compound is FIV-55. 
     
     
         54 . The composition of  claim 39 , wherein the compound is FIV-53. 
     
     
         55 . The composition of  claim 39 , wherein the compound is FIV-67. 
     
     
         56 . The composition of  claim 39 , wherein the compound is FIV-70. 
     
     
         57 . The composition of  claim 39 , wherein the compound is FIV-65. 
     
     
         58 . The composition of  claim 39 , wherein the compound is FIV-68. 
     
     
         59 . The composition of  claim 39 , wherein the compound is FIV-66. 
     
     
         60 . The composition of  claim 39 , wherein the compound is FIV-61. 
     
     
         61 . The composition of  claim 39 , wherein the compound is FIV-60. 
     
     
         62 . The composition of  claim 39 , wherein the compound is FIV-64. 
     
     
         63 . The composition of  claim 39 , wherein the compound is FIV-71. 
     
     
         64 . The composition of  claim 39 , wherein the compound is FIV-46. 
     
     
         65 . The composition of  claim 39 , wherein the compound is FIV-72. 
     
     
         66 . The composition of  claim 39 , wherein the compound is FIV-73. 
     
     
         67 . The composition of  claim 39 , wherein the compound is FIV-49. 
     
     
         68 . The composition of  claim 39 , wherein the compound is FIV-75. 
     
     
         69 . The composition of  claim 39 , formulated in a pharmaceutical composition. 
     
     
         70 . A kit for the treatment intestinal fluid loss in a subject, said kit comprising a composition comprising a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof wherein the general formula of the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and any combination thereof wherein,
 1) R is a cyclic or bicyclic ring structure; 
 2) R 1  is a hydrogen, cyclic or bicyclic ring structure; 
 3) R 2  is a hydrogen, alkyl, cyclic or bicyclic ring structure; 
 4) R 3  is a hydrogen, or alkyl; 
 ) R 5  is a hydrogen, alkyl, cyclic or bicyclic ring structure; 
 6) X is an alkyl, oxygen, an ester, an amine, or an amide 
 7) Z is selected from the group consisting of hydrogen, alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate; 
 8) W is selected from the group consisting of CO, NH, methylene, sulfur atom, oxygen atom and thionyl; and, 
 9) n is 0, 1, or more than 1. 
 
       
     
     
         71 . The kit of  claim 70 , wherein R is substituted or unsubstituted and selected from the group consisting of phenyl, pyranonyl, pyridyl, imidazolyl, 1,8-napthyridinyl, and N-oxide pyridyl. 
     
     
         72 . The kit of  claim 71 , wherein R is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         73 . The kit of  claim 70 , wherein R 1  is substituted or unsubstituted and selected from the group consisting of phenyl, pyridyl, and furanyl. 
     
     
         74 . The kit of  claim 73 , wherein R 1  is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         75 . The kit of  claim 70 , wherein R 4  is a cyclic or bicyclic ring structure, substituted or unsubstituted and selected from the group consisting of phenyl, pyridyl, and furanyl. 
     
     
         76 . The kit of  claim 75 , wherein R 4  is mono, di, tri, tetra, or appropriately penta substituted with a functional group selected form the group consisting of alkenyl, alkynyl, phenyl, benzyl, halo, fluoro, chloro, bromo, iodo, hydroxy, keto, oxo, aldo, carbonate, carboxy, alkoxy, ester, carboxamido, amino, ammonio, imino, imido, azido, azo, cyanato, isocyano, isocyanato, isothiocyanato, nitroxy, cyano, nitrosooxy, nitro, nitroso, 4-pyridyl, 3-pyridyl, 2-pyridyl, thioether, sulfonyl, sulfo, sulfinyl, mercapto, sulfanyl, sulfhydryl, sulfonamino, thiocyanato, alkyl amino, hydroxyamic acid, methyl, ethyl, 1,3-dioxylanyl, propyl, iso-propyl, butyl, tert-butyl, unsubstantiated or substituted branched or unbranched alkyl, (C1-C3) alkenyl, unsubstantiated or substituted branched or unbranched aryl, unsubstantiated or substituted branched or unbranched alkylaryl, unsubstantiated or substituted branched or unbranched carbohydrate and any combination thereof. 
     
     
         77 . The kit of  claim 70 , wherein the compound is from the group consisting of FIV-50, FIV-1, FIV-29, FIV-31, FIV-34, FIV-35, FIV-39, FIV-40, FIV-46, FIII-1, FII-1, FI-3, FI-1, FI-2, FIV-54, FIV-58, FIV-55, FIV-53, FIV-67, FIV-70, FIV-65, FIV-68, FIV-66, FIV-61, FIV-60, FIV-64, FIV-49, FIV-75 and any combination thereof. 
     
     
         78 . The kit of  claim 70 , further comprising a drug selected from the group consisting of an antibiotic, an antidiarrheal, and a LT inhibitory drug. 
     
     
         79 . The kit of  claim 70 , further comprising a pharmaceutically acceptable carrier.