Patent ID: 6331529
Filing Date: 2001-12-18
Classification: A61K,A61P,Y10S

Abstract:
A method of stimulating mucosal hydration in a mammal in need thereof comprising administering an effective hydration increasing amount of a compound of Formulas I, II, III or IV: ##STR10##wherein:X.sub.1 and X.sub.2 are each independently either O.sup.- or S.sup.- ;R.sub.1 is O, imido, methylene or dihalomethylene;R.sub.2 is selected from the group consisting of H, halo, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, alkoxyl, nitro and azido; ##STR11##wherein:X is oxygen, methylene, difluoromethylene, or imido;B and B' are each independently a purine residue or a pyrimidine residue linked through the 9- or 1- position, respectively;Z=OH or N.sub.3 ;Z'=OH or N.sub.3 ;Y=H or OH;Y'=H or OH;provided that when Z is N.sub.3, Y is H or when Z' is N.sub.3, Y' is H; ##STR12##wherein:X=O;Z, Z', Y, and Y'=OH;B and B' are defined in Formulas IIc and IId;X=O;Z, Z', Y, and Y'=OH;B=uracil;B' is defined in Formulas IIc and IId; orX=O;Z, Y, and Y'=OH;Z'=H;B=uracil;B' is defined in Formulas IIc and IId; orX=O;Z and Y=OH;Z'=N.sub.3 ;Y'=H;B=uracil;B'=thymine; orX=O;Z and Z'=N.sub.3 ;Y and Y'=H;B and B'=thymine; orX=CH.sub.2, CF.sub.2, or NH;Z, Z', Y, and Y'=OH;B and B' are defined in Formulas IIc and IId; ##STR13##whereinR.sub.1 is hydrogen, C.sub.1-8 alkyl, C.sub.3-6 cycloalkyl, phenyl, or phenyloxy; wherein at least one hydrogen of said C.sub.1-8 alkyl, phenyl, phenyloxy, is optionally substituted with a moiety selected from the group consisting of halogen, hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.6-10 aryl, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C.sub.1-4 alkylamino, di-C.sub.1-4 alkylamino wherein said alkyl groups are optionally linked to form a heterocycle, .omega.-A(alkyl)CONH(alkyl)-, and .omega.-A(alkyl)NHCO(alkyl)-, wherein A is amino, mercapto, hydroxy or carboxyl;R.sub.2 is O or is absent; orR.sub.1 and R.sub.2 taken together form a 5-membered fused imidazole ring optionally substituted on the 4- or 5- positions of the etheno moiety with C.sub.1-4 alkyl, phenyl or phenyloxy , wherein at least one hydrogen of said C.sub.1-4 alkyl, phenyl, phenyloxy, is optionally substituted with a moiety selected from the group consisting of halogen, hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 alkyl, C.sub.6-10 aryl, C.sub.7-12 arylalkyl, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C.sub.1-4 alkylamino, and di-C.sub.1-4 alkylamino wherein said dialkyl groups are optionally linked to form a heterocycle; andR.sub.3 is hydrogen, NH.sub.2, C.sub.1-8 alkyl, C.sub.3-6 cycloalkyl, phenyl; or phenyloxy; wherein at least one hydrogen of said NH.sub.2, C.sub.1-8 alkyl, phenyl, or phenyloxy, is optionally substituted with a moiety selected from the group consisting of halogen, hydroxy, C.sub.1-4 alkyl, C.sub.6-10 aryl, C.sub.7-12 arylalkyl, C.sub.1-4 alkoxy, C7-12arylalkyloxy, C.sub.1-4 alkylthio, phenylthio C.sub.7-12 arylalkylthio, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C.sub.1-4 alkylamino, phenylamino, C.sub.7-12 arylalkyamino, di-C.sub.1-4 alkyl amino wherein said dialkyl groups are optionally linked to form a heterocycle, .omega.-A(alkyl)CONH(alkyl)B-, and .omega.-A(alkyl)NHCO(alkyl)B-, wherein A and B are independently amino, mercapto, hydroxy or carboxyl; ##STR14##wherein:R.sub.4 is hydrogen, hydroxy, mercapto, amino, cyano, C.sub.7-12 arylalkoxy, C.sub.1-6 alkylthio, C.sub.1-6 alkoxy, C.sub.1-6 alkylamino or diC.sub.1-4 alkylamino, wherein the alkyl groups are optionally linked to form a heterocycle;R.sub.5 is hydrogen, acetyl, benzoyl, C.sub.1-6 alkyl, phenyloxy, C.sub.1-5 alkanoyl, aroyl, or sulphonate;R.sub.6 is hydroxy, mercapto, C.sub.1-4 alkoxy, C.sub.7-12 arylalkoxy, C.sub.1-6 alkylthio, amino, S-phenyl, C.sub.1-5 disubstituted amino, triazolyl, C.sub.1-6 alkylamino, or di-C.sub.1-4 alkylamino wherein said dialkyl groups are optionally linked to form a heterocycle or linked to N.sup.3 to form a substituted ring; orR.sub.5 and R.sub.6 taken together form a 5-membered fused imidazole ring between positions 3 and 4 of the pyrimidine ring and form a 3,N.sup.4 -ethenocytosine derivative, wherein said etheno moiety is optionally substituted on the 4- or 5-positions with C.sub.1-4 alkyl; phenyl; or phenyloxy; wherein at least one hydrogen of said C.sub.1-4 alkyl; phenyl or phenyloxy is optionally substituted with a moiety selected from the group consisting of halogen, hydroxy, C.sub.1-4 alkoxy, C.sub.1-4 -alkyl, C.sub.6-10 aryl, C.sub.7-12 arylalkyl, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C.sub.1-4 alkylamino, and di-C.sub.1-4 alkylamino wherein said dialkyl groups are optionally linked to form a heterocycle;R.sub.7 is hydrogen, hydroxy, cyano, nitro, or C.sub.2-8 alkenyl; wherein said alkenyl moiety is optionally linked through an oxygen to form a ring, wherein at least one hydrogen of said alkenyl moiety on the carbon adjacent to said oxygen is optionally substituted with C.sub.1-6 alkyl, phenyl, substituted C.sub.2-8 alkynyl, halogen, substituted C.sub.1-4 alkyl, CF.sub.3, C.sub.2-3 alkenyl, C.sub.2-3 alkynyl, allylamino, bromovinyl, ethyl propenoate, or propenoic acid; orR.sub.6 and R.sub.7 together form a 5 or 6-membered saturated or unsaturated ring bonded through N or O at R.sub.6, such ring optionally contains substituents that themselves contain functionalities; provided that when R.sub.8 is amino or substituted amino, R.sub.7 is hydrogen; andR.sub.8 is hydrogen, amino or di-C.sub.1-4 alkylamino, C.sub.1-4 alkoxy, C.sub.7-12 arylalkoxy, C.sub.1-4 alkylthio, C.sub.7-12 arylalkylthio,carboxamidomethyl, carboxymethyl, methoxy, methylthio, phenoxy or phenylthio.