2' and 3'- substituted cyclobutyl nucleoside analogs for the treatment of viral infections and abnormal cellular proliferation

A cyclobutyl nucleoside of the formula (I)-(IV):

• or a pharmaceutically acceptable salt, ester, salt of an ester, prodrug, salt of a prodrug, enantiomer, diastereomer, or tautomer thereof, wherein;
• Base is a purine or pyrimidine base;
• Z is independently H;
• phosphate, P(O)Z′Z″, CH2P(O)Z′Z″, acyl, alkyl, sulfonate ester, sulfonyl and benzyl, wherein the phenyl group of the benzyl is optionally substituted, a lipid, an amino acid, a carbohydrate, a peptide, a cholesterol, or other pharmaceutically acceptable leaving group which when administered in vivo is capable of providing a compound wherein Z is independently H or phosphate;
• Z′ and Z″ each independently is OH, OAlkyl, OAryl, alkyl, aryl, SH, SAlkyl, SAryl, NH2, mono or di-alkylamino, mono- or di-arylamino, or a residue of an amino acid;
• A is O, S, or CH2;
• or alternatively
• A can be a covalent bond when Z is P(O)Z′Z″ or CH2P(O)Z′Z″;
• R1, R2, and R3 are independently hydrogen, lower alkyl, halogenated lower alkyl, CF3, 2-Br-ethyl, lower alkenyl, halogenated lower alkenyl, Br-vinyl, lower alkynyl, halogenated lower alkynyl, halo, cyano, azido, NO2, NH2, —NH(lower alkyl), NH(acyl), N(lower alkyl)2, —N(acyl)2, hydroxy, OZ, O(lower acyl), O(lower alkyl), O(alkenyl), C(O)O(alkyl), C(O)O(lower alkyl);
• or alternatively,
• R1 and R2 together are ═CH2 or ═CHY;
• or alternatively
• R1 and R2 can come together to form a three-membered carbocyclic or heterocyclic ring, such as an epoxide ring;
• such that if R1 is H, then R2 is not CH2OH, and if R2 is H, then R1 is not CH2OH;
• X is CH2, CHY, or S;
• and
• Y is independently H, methyl, halogenated methyl, CF3, halogen, N3, cyano, or NO2.