Patent ID: 6436910
Filing Date: 2002-08-20
Classification: A61K,A61P,Y10S

Abstract:
A method of stimulating mucosal hydration in a tissue other than the lung of a mammal in need thereof, comprising administering an effective hydration increasing amount of a compound of Formula I, II, III, or IV: wherein:X1 and X2 are each independently either Oâˆ’ or Sâˆ’; R1 is O, imido, methylene or dihalomethylene; R2 is selected from the group consisting of: H, halo, alkyl, substituted alkyl, alkenyl and substituted alkenyl, alkynyl and substituted alkynyl, alkoxyl, nitro, and azido; wherein:X is oxygen, methylene, difluoromethylene, or imido; B and Bâ€² are each independently a purine residue or a pyrimidine residue as depicted in Formula IIc or IId, linked through the 9- or 1-position, respectively; Z=OH or N3; Zâ€²=OH or N3; Y=H or OH; Yâ€²=H or OH; provided that when Z is N3, Y is H or when Zâ€² is N3, Yâ€² is H; whereinR1 is hydrogen, C1-8alkyl, C3-6 cycloalkyl, phenyl, or phenyloxy; wherein at least one hydrogen of said C1-8alkyl, phenyl, phenyloxy, is optionally substituted with a moiety selected from the group consisting of: halogen, hydroxy, C1-4alkoxy, C1-4alkyl, C6-10aryl, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C1-4 alkylamino, and di-C1-4 alkylamino wherein said alkyl groups are optionally linked to form a heterocycle, &ohgr;-A(alkyl)CONH(alkyl)-, and &ohgr;-A(alkyl)NHCO(alkyl)-, wherein A is amino, mercapto, hydroxy, or carboxyl; R2 is O or is absent; or R1 and R2 taken together form a 5-membered fused imidazole ring optionally substituted on the 4- or 5- positions of the etheno moiety with C1-4alkyl, phenyl or phenyloxy, wherein at least one hydrogen of said C1-4alkyl, phenyl or phenyloxy, is optionally substituted with a moiety selected from the group consisting of: halogen, hydroxy, C1-4alkoxy, C1-4alkyl, C6-10aryl, C7-12arylalkyl, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C1-4 alkylamino, and di-C1-4 alkylamino wherein said dialkyl groups are optionally linked to form a heterocycle; and R3 is hydrogen, NH2, C1-8alkyl, C3-6 cycloalkyl, phenyl, or phenyloxy, wherein at least one hydrogen of said NH2, C1-8alkyl, phenyl, or phenyloxy, is optionally substituted with a moiety selected from the group consisting of: halogen, hydroxy, C1-4alkyl, C6-10aryl, C7-12arylalkyl, C1-4alkoxy, C7-12arylalkyloxy, C1-4alkylthio, phenylthio, C7-12arylalkylthio, carboxy, cyano, nito, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C1-4alkylamino, phenylamino, C7-12arylalkyamino, di-C1-4 alkyl amino, wherein said di-C1-4 alkyl groups are optionally linked to form a heterocycle, &ohgr;-A(alkyl)CONH(alkyl)Bâ€”, and &ohgr;-A(alkyl)NHCO(alkyl)Bâ€”, wherein A and B are independently amino, mercapto, hydroxy, or carboxyl; wherein:R4 is hydrogen, hydroxy, mercapto, amino, cyano, C7-12arylalkoxy, C1-6 alkylthio, C1-6 alkoxy, C1-6 alkylamino, or diC1-4alkylamino, wherein the alkyl groups are optionally linked to form a heterocycle; R5 is hydrogen, acetyl, benzoyl, C1-6 alkyl, phenyloxy, C1-5 alkanoyl, aroyl, or sulphonate; R6 is hydroxy, mercapto, C1-4alkoxy, C7-12arylalkoxy, C1-6alkylthio, amino, S-phenyl, C1-5 disubstituted amino, triazolyl, C1-6alkylamino, or di-C1-4alkylamino wherein said dialkyl groups are optionally linked to form a heterocycle or linked to N3 to form a substituted ring; or R5 and R6 taken together form a 5-membered fused imidazole ring between positions 3 and 4 of the pyrimidine ring and form a 3, N4-ethenocytosine derivative, wherein said etheno moiety is optionally substituted on the 4- or 5-positions with C1-4 alkyl, phenyl or phenyloxy, wherein at least one hydrogen of said C1-4alkyl, phenyl or phenyloxy is optionally substituted with a moiety selected from the group consisting of: halogen, hydroxy, C1-4alkoxy, C1-4alkyl, C6-10aryl, C7-12arylalkyl, carboxy, cyano, nitro, sulfonamido, sulfonate, phosphate, sulfonic acid, amino, C1-4 alkylamino, and di- C1-4 alkylamino, wherein said dialkyl groups are optionally linked to form a heterocycle; R7 is hydrogen, hydroxy, cyano, nitro, or C2-8alkenyl; 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 C1-6alkyl, phenyl, substituted C2-8galkynyl, halogen, substituted C1-4alkyl, CF3, C2-3 alkenyl, C2-3 alkenyl, allylamino bromovinyl, ethyl propenoate, or propenoic acid; or R6 and R7 together form a 5- or 6-membered saturated or unsaturated ring bonded through N or O at R6, such ring optionally contains substituents that themselves contain functionalities; provided that when R8 is amino or substituted amino, R7 is hydrogen; and R8 is hydrogen, amino or di-C1-4alkylamino, C1-4alkoxy, C7-12arylalkoxy, C1-4alkylthio, C7-12arylalkylthio,carboxarnidomethyl, carboxymethyl, methoxy, methylthio, phenoxy, or phenylthio; wherein:R1, X1 and X2 are defined as in Formula I; R5 and R6 are H while R7 is nothing and there is a double bond between N-3 and C-4, or R5, R6 and R7 taken together are â€”CH&boxH;CHâ€”, forming a ring from N-3 to N-4 with a double bond between N-4 and C-4 optionally substituted at the 4- or 5-position of the etheno ring; wherein:R1, X1 and X2 are defined as in Formula I; R3 and R4 are H while R2 is nothing and there is a double bond between N-1 and C-6, or R3 and R4 are H while R2 is O and there is a double bond between N-1 and C-6, or R3, R4, and R2 taken together are â€”CH&boxH;CHâ€”, forming a ring from N-6 to N-1 with a double bond between N-6 and C-6.