Patent ID: 6555675
Filing Date: 2003-04-29
Classification: A61K,A61P,C07H

Abstract:
A compound of Formula I: whereinX is oxygen, inethylene, dihalornethylene, or imido; n=0, 1 or 2; m=0, 1 or 2; n+m=0, 1, 2, 3 or 4; Z=OH or H; Zâ€²=OH or H; Y=OH or H; Yâ€²=OH or H; and B and Bâ€² are each independently a purina residue or a pyrimidine residue, as defined in Formula Ia or Ib, linked through the 9- or 1-position, respectively: wherein: R1 is hydrogen, chlorine, amino, monosubstituted amino, disubstituted amino, alkylthio, arylthio, or aralkylthio, wherein the substituent on sulfur contains up to a maximum of 20 carbon atoms, with or without unsaturation; R2 is hydroxy, alkenyl, oxo, amino, mercapto, thione, alkylthio, arylthio, aralkylthio, acylthio, alkyloxy, aryloxy, aralkyloxy, acyloxy, monosubstituted alkylamino, heterocyclic, monosubstituted cycloalkylamino, monosubstituted aralkylamino, monosubstituted arylamino, diaralkylamino, diarylamino, dialkylamino, acylamino, or diacylamino; Rx is O, H or is absent; R2 and Rx are optionally taken together to form a 5-membered fused imidazole ring of 1,N6-etheno adenine derivatives, optionally substituted on the 4- or 5-positions of the etheno moiety with alkyl, aryl or aralkyl moieties; R3 is hydrogen, azido, alkoxy, aryloxy, aralkyloxy, alkylthio, arylthio, or aralkylthio as defined below; or T(C1-6alkyl)OCONH(C1-6 alkyl)W, wherein T and W are independently amino, mercapto, hydroxy or carboxyl; or pharmaceutically acceptable esters, amides or salts thereof; or absent; J is carbon or nitrogen, with the provision that when J is nitrogen, R3 is not present; wherein the alkyls are straight-chain, branched or cyclic; wherein the aryl groups are optionally substituted with lower alkyl, aryl, amino, mono- or dialkylamino, NO2, N3, cyano, carboxylic, amido, sulfonamido, suiphonic acid, phosphate, or halo group; wherein: R4 is hydroxy, oxo, mercapto, thione, amino, cyano, C7-12 arylalkoxy, C1-6 alkylthio, C1-6 alkoxy, C1-6 alkylamino or diC1-4alkylaniino, wherein the alkyl groups are optionally linked to form a heterocycle;R5 is hydrogen, acetyl, benzoyl, C1-6 alkyl, C1-5 alkanoyl, aroyl, or absent; R6 is hydroxy, oxo, mercapto, thione, C1-4alkoxy, C7-12arylakoxy, C1-6alkylthio, S-phenyl, arylthio, arylalkylthio, triazolyl amino, C1-6 alkylamino, C1-5 disubstituted amino, or di-C1-4alkylamino, wherein said dialkyl groups are optionally linked to form a heterocycle or linked to form a substituted ring such as morpholino, pyrrolo; or R5 and R6 taken together form a 5-membered fused imidazole ring of 3,N4-ethenocytosine derivatives between positions 3 and 4 of the pyrimidine ring, 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 C1-4 alkyl, phenyl or phenyloxy is optionally substituied with a moiety selected from the group consisting of halogen, hydroxy, C1-4 alkoxy, C1-4 alkyl, C6-10 aryl, C7-12 arylalkyl, 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 selected from the group consisting of hydrogen, hydroxy, cyano, nitro, C1-6 alkyl or phenyl; substituted C2-8 alkynyl, halogen, substituted C1-4 alkyl, CF3, C2-3 alkenyl, C2-3 alkynyl, allylamino, bromovinyl, ethyl propenoate or propenoic acid and C2-8 alkenyl; or R6 and R7 together form a 5 or 6-membered saturated or unsaturated ring bonded through N or O or S at R6, such ring optionally contains substituents that themselves contain functionalities; R8 is selected from the group consisting of hydrogen, amino, di-C1-4alkylamino, C1-4alkoxy, C1-12arylalkoxy, C1-4alkylthio, C7-12arylalkylthio, carboxamidomethyl, carboxymethyl, methoxy, methylthio, phenoxy, and phenylthio; provided that when R8 is amino or substituted amino, R7 is hydrogen; and one or both of the furanosyl sugar moieties of Formula I is selected from the group consisting of 2â€²,3â€²-dideoxyribofuranosyl, 3â€²-deoxyarabinofuranosyl, xylofuranosyl, 2â€²-deoxyxylofuranosyl, and lyxofuranosyl.