NUCLEOSIDE PHOSPHORAMIDATE PRODRUGS

Abstract

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure:

##STR00001##

Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Claims

1. A compound of formula IA: ##STR00061## or a stereoisomer thereof, wherein: R.sup.1 is naphthyl; R.sup.2 is H or C.sub.1-10 alkyl, or R.sup.2 together with R.sup.3a or R.sup.3b are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where n is 2 to 4; R.sup.3a and R.sup.3b are (i) independently selected from H, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms; (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3 is —OR′ or —N(R.sup.3′).sub.2; (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently H or alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2; R.sup.4 is H or C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)amino, or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, optionally substituted aryl or optionally substituted heteroaryl; R.sup.5 is CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3 or CH.sub.2N(CH.sub.3).sub.2; R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F or CN; X is H, OH, OCH.sub.3, halogen, NH.sub.2, or N.sub.3; Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen, NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2 or N(C.sub.1-4 acyl).sub.2; R.sup.7, R.sup.8 and R.sup.9 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 haloalkenyl, C.sub.2-6 alkynyl, C.sub.2-6 haloalkynyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, wherein R′ is an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted C.sub.2-6 alkynyl, an optionally substituted C.sub.2-6 alkenyl, or an optionally substituted acyl, or in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

2. The compound of claim 1 represented by formula IB: ##STR00062## or a stereoisomer thereof.

3. The compound of claim 2, wherein R.sup.2 is H or C.sub.1-10 alkyl.

4. The compound of claim 2, wherein one of R.sup.3a and R.sup.3b is H and the other is C.sub.1-10 alkyl.

5. The compound of claim 2, wherein R.sup.4 is C.sub.1-10 alkyl.

6. The compound of claim 2, wherein R.sup.6 is methyl.

7. The compound of claim 2, wherein each of R.sup.7 and R.sup.8 is H.

8. The compound of claim 2, wherein X is halogen.

9. The compound of claim 2, wherein Y is OH.

10. The compound of claim 2, wherein the compound is represented by formula IC: ##STR00063## or a stereoisomer thereof.

11. The compound of claim 10, wherein R.sup.2 is H.

12. The compound of claim 10 represented by formula ID: ##STR00064## or a stereoisomer thereof.

13. The compound of claim 12, wherein R.sup.4 is .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu or benzyl.

14. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.

15. A method of treating HCV comprising administering a therapeutically effective amount of a compound according to claim 1 to a human in need thereof.

16. The method of claim 15 further comprising administering to the human a therapeutically effective amount of a second antiviral agent.

17. The method of claim 16 wherein the second antiviral agent is an NS5A inhibitor.

18. The method of claim 16 wherein the second antiviral agent is an NS3 protease inhibitor.

19. The method of claim 15 further comprising administering to the human subject therapeutically effective amounts of an NS5A inhibitor and an NS3 protease inhibitor.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0065] An aspect of the invention is directed to a compound, its salts, hydrates, solvates, crystalline forms, and the like represented by formula I:

##STR00005## [0066] wherein

[0067] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0068] (b) R.sup.2 is hydrogen, C.sub.1-10 alkyl, R.sup.3a or R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, C(O)CR.sup.3aR.sup.3bNHR.sup.1, where n is 2 to 4 and R.sup.1, R.sup.3a, and R.sup.3b;

[0069] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0070] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0071] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0072] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0073] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0074] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0075] the base is a naturally occurring or modified purine or pyrimidine base represented by the following structures:

##STR00006## [0076] wherein

[0077] Z is N or CR.sup.12;

[0078] R.sup.7, R.sup.8, R.sup.9, R.sup.10, and R.sup.11 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkyl of C.sub.1-C.sub.6, lower alkenyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkenyl of C.sub.2-C.sub.6, lower alkynyl of C.sub.2-C.sub.6 such as C≡CH, halogenated (F, Cl, Br, I) lower alkynyl of C.sub.2-C.sub.6, lower alkoxy of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkoxy of C.sub.1-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0079] wherein R′ is an optionally substituted alkyl, which includes, but is not limited to, an optionally substituted C.sub.1-20 alkyl, an optionally substituted C.sub.1-10 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C.sub.2-C.sub.6, an optionally substituted lower alkenyl of C.sub.2-C.sub.6, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O)(C.sub.1-20 alkyl), C(O)(C.sub.1-10 alkyl), or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0080] R.sup.12 is H, halogen (including F, Cl, Br, I), OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2 lower alkyl of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkyl of C.sub.1-C.sub.6, lower alkenyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkenyl of C.sub.2-C.sub.6, lower alkynyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkynyl of C.sub.2-C.sub.6, lower alkoxy of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkoxy of C.sub.1-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R; with the proviso that when base is represented by the structure c with R.sup.11 being hydrogen, R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0081] As can be appreciated from the structure represented by formula I above, there are myriad ways to express the several embodiments and aspects of each embodiment of the present invention. As seen below, the inventors have disclosed certain embodiments directed to the compound of formula I, each having several aspects, based on the identity of the modified purine or pyrimidine base. This is not intended to be an explicit or implicit admission that the three embodiments are independent or distinct nor should it be interpreted as such. Rather, it is intended to convey information so that the full breadth of the present invention can be understood. Furthermore, the following embodiments, and aspects thereof, are not meant to be limiting on the full breadth of the invention as recited by the structure of formula I.

[0082] A first embodiment of the invention is directed to a compound represented by formula I-1:

##STR00007##

[0083] wherein

[0084] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0085] (b) R.sup.2 is hydrogen, C.sub.1-10 alkyl, R.sup.3a or R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, C(O)CR.sup.3aR.sup.3bNHR.sup.1, where n is 2 to 4 and R.sup.1, R.sup.3a, and R.sup.3b;

[0086] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0087] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)-amino, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0088] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0089] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0090] (g) X is H, OH, F, OMe, Cl, Br, I, NH.sub.2, or N.sub.3;

[0091] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0092] (i) R.sup.7, R.sup.8, R.sup.9 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C.sub.2-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl.

[0093] A first aspect of the first embodiment is directed to a compound represented by formula I-1

[0094] wherein

[0095] (a) R.sup.1 is hydrogen, n-alkyl or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl;

[0096] (b) R.sup.2 is hydrogen or CH.sub.3;

[0097] (c) R.sup.3a and R.sup.3b are independently (i) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), or CH.sub.2SH and R.sup.3b is H;

[0098] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0099] (e) R.sup.5 is H, CN, CH.sub.3, vinyl, OCH.sub.3, OCH.sub.2CH.sub.3, CH.sub.2OH, CH.sub.2(halo), such as CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3;

[0100] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0101] (g) X is H, OH, F, OMe, Cl, Br, I, NH.sub.2, or N.sub.3;

[0102] (h) Y is OH, H, C.sub.1-4 alkyl, vinyl, N.sub.3, CN, Cl, Br, F, I, O(C.sub.1-6 acyl), O(C.sub.1-4 alkyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-4 haloalkyl, O(aminoacyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2 (C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, or N(C.sub.1-4 acyl).sub.2;

[0103] (i) R.sup.7, R.sup.8, R.sup.9 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C.sub.2-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl.

[0104] A second aspect of the first embodiment is directed to a compound represented by formula I-1

[0105] wherein

[0106] (a) R.sup.1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a C.sub.1-3 alkyl, a C.sub.1-3 alkoxy, F, Cl, Br, I, nitro, cyano, and a C.sub.1-3 haloalkyl;

[0107] (b) R.sup.2 is hydrogen or CH.sub.3;

[0108] (c) R.sup.3a and R.sup.3b are independently (i) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), or CH.sub.2SH and R.sup.3b is H;

[0109] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl, or aminoacyl;

[0110] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2(halo), such as CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3;

[0111] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0112] (g) X is H, OH, F, OCH.sub.3, NH.sub.2, or N.sub.3;

[0113] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2, or O(aminoacyl);

[0114] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2; and

[0115] (j) R.sup.9 is selected from among OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2),CH.sub.3, NHC(O)(C1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2).sub.sCH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0116] A third aspect of the first embodiment is directed to a compound represented by formula I-1

[0117] wherein

[0118] (a) R.sup.1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH.sub.3, OCH.sub.3, F, Cl, Br, I, nitro, cyano, and a CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I, and q is 1-3;

[0119] (b) R.sup.2 is hydrogen or CH.sub.3;

[0120] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl or R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H;

[0121] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl, or aminoacyl;

[0122] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2(halo), such as CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3;

[0123] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0124] (g) X is H, OH, F, OCH.sub.3, NH.sub.2, or N.sub.3;

[0125] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2, or O(aminoacyl);

[0126] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl; and

[0127] (j) R.sup.9 is selected from among OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2),CH.sub.3, NHC(O)(C1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2),CH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0128] A fourth aspect of the first embodiment is directed to a compound represented by formula I-2

##STR00008##

[0129] wherein

[0130] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH.sub.3, OCH.sub.3, F, Cl, Br, I, nitro, cyano, and a CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I, and q is 1-3;

[0131] (b) R.sup.2 is hydrogen or CH.sub.3;

[0132] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl or R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H;

[0133] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0134] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3;

[0135] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0136] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0137] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2, or O(aminoacyl);

[0138] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl; and

[0139] (j) R.sup.9 is selected from among OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2),CH.sub.3, NHC(O)(C1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2),CH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0140] A fifth aspect of the first embodiment is directed to a compound represented by formula I-2

[0141] wherein

[0142] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0143] (b) R.sup.2 is hydrogen or CH.sub.3;

[0144] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0145] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, di(lower alkyl)amino-lower alkyl, or aminoacyl;

[0146] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I;

[0147] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0148] (g) X is H, OH, F, OCH.sub.3, NH.sub.2, or N.sub.3;

[0149] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, or O(aminoacyl);

[0150] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl; and

[0151] (j) R.sup.9 is selected from among OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C.sub.1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2).sub.sCH.sub.3, NHC(O)(C.sub.1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2).sub.sCH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0152] A sixth aspect of the first embodiment is directed to a compound represented by formula I-2

[0153] wherein

[0154] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0155] (b) R.sup.2 is hydrogen or CH.sub.3;

[0156] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0157] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0158] (e) R.sup.5 is H, OMe, CN, CH.sub.2F, F, Cl, Br, or I;

[0159] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0160] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, or N.sub.3;

[0161] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, or N.sub.3, OCH.sub.3, OC(O)CH.sub.3, or O(aminoacyl);

[0162] (i) R.sup.7 and R.sup.8 are independently H, F, Br, SCH.sub.3, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2; and

[0163] (j) R.sup.9 is selected from among OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C.sub.1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2).sub.sCH.sub.3, NHC(O)(C.sub.1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2).sub.sCH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0164] A seventh aspect of the first embodiment is directed to a compound represented by formula I-2

[0165] wherein

[0166] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0167] (b) R.sup.2 is hydrogen;

[0168] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0169] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0170] (e) R.sup.5 is H;

[0171] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0172] (g) X is H, OH, OCH.sub.3, F, or N.sub.3;

[0173] (h) Y is OH, OCH.sub.3, OC(O)CH.sub.3, or O(aminoacyl);

[0174] (i) R.sup.7 and R.sup.8 are independently H, F, Br, SCH.sub.3, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2; and

[0175] (j) R.sup.9 is selected from among OH, OCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C.sub.1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2),CH.sub.3, NHC(O)(C.sub.1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2),CH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from among 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0176] An eighth aspect of the first embodiment is directed to a compound represented by formula I-2

[0177] wherein

[0178] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0179] (b) R.sup.2 is hydrogen;

[0180] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0181] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0182] (e) R.sup.5 is H;

[0183] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0184] (g) X is H, OH, OCH.sub.3, F, or N.sub.3;

[0185] (h) Y is OH, OCH.sub.3, OC(O)CH.sub.3, or O(aminoacyl);

[0186] (i) R.sup.7 and R.sup.8 are independently H, F, Br, SCH.sub.3, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2;

[0187] (j) R.sup.9 is selected from among OH, OCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, OC(O)(C.sub.1-20 alkyl), which include but are not limited to OC(O)(CH.sub.2),CH.sub.3, NHC(O)(C.sub.1-20 alkyl), which include but are not limited to NHC(O)(CH.sub.2),CH.sub.3, and N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, which include but is not limited to N(C(O)(CH.sub.2).sub.sCH.sub.3).sub.2, where s is an integer selected from among 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0188] A second embodiment of the invention is directed to a compound represented by formula I in which the base is a structure represented by formula b above, wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, R.sup.6, X, Y, R.sup.7, and R.sup.8 are defined in the Summary of the Invention section above.

[0189] A first aspect of the second embodiment is directed to a compound represented by formula I-3

##STR00009##

[0190] wherein

[0191] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0192] (b) R.sup.2 is hydrogen or CH.sub.3;

[0193] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0194] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0195] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0196] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0197] (g) X is H, OH, F, OMe, Cl, Br, I, NH.sub.2, or N.sub.3;

[0198] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, or N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, or N(C.sub.1-4 acyl).sub.2;

[0199] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C.sub.2-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl.

[0200] The second aspect of the second embodiment is directed to a compound represented by formula I-3

[0201] wherein

[0202] (a) R.sup.1 is hydrogen, n-alkyl or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl;

[0203] (b) R.sup.2 is hydrogen or CH.sub.3;

[0204] (c) R.sup.3a and R.sup.3b are independently (i) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), or CH.sub.2SH and R.sup.3b is H;

[0205] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0206] (e) R.sup.5 is H, CN, CH.sub.3, vinyl, OCH.sub.3, OCH.sub.2CH.sub.3, CH.sub.2OH, CH.sub.2(halo), such as CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I;

[0207] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0208] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0209] (h) Y is OH, H, C.sub.1-4 alkyl, vinyl, N.sub.3, CN, Cl, Br, F, I, O(C.sub.1-6 acyl), O(C.sub.1-4 alkyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0210] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C.sub.2-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl.

[0211] The third aspect of the second embodiment is directed to a compound represented by formula I-3

[0212] wherein

[0213] (a) R.sup.1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a C.sub.1-3 alkyl, a C.sub.1-3 alkoxy, F, Cl, Br, I, nitro, cyano, and a C.sub.1-3 haloalkyl;

[0214] (b) R.sup.2 is hydrogen, CH.sub.3, R.sup.3a or R.sup.3b and R.sup.2 together are (CH.sub.2).sub.3 so as to form a cyclic ring that includes the adjoining N and C atoms, C(O)CR.sup.3aR.sup.3bNHR.sup.1, where n is 2 to 4 and R.sup.1, R.sup.3a, and R.sup.3b are as defined herein;

[0215] (c) R.sup.3a and R.sup.3b are independently (i) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 3 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H;

[0216] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0217] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2(halo), such as CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I;

[0218] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0219] (g) X is H, OH, F, OCH.sub.3, halogen, NH.sub.2, or N.sub.3

[0220] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2;

[0221] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2.

[0222] The fourth aspect of the second embodiment is directed to a compound represented by formula I-3

[0223] wherein

[0224] (a) R.sup.1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH.sub.3, OCH.sub.3, F, Cl, Br, I, nitro, cyano, and a CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I, and q is 1-3;

[0225] (b) R.sup.2 is hydrogen or CH.sub.3;

[0226] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl or R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H;

[0227] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0228] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2(halo), such as CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I;

[0229] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0230] (g) X is H, OH, F, OCH.sub.3, NH.sub.2, or N.sub.3;

[0231] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2;

[0232] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl.

[0233] The fifth aspect of the second embodiment is directed to a compound represented by formula I-4

##STR00010##

[0234] wherein

[0235] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH.sub.3, OCH.sub.3, F, Cl, Br, I, nitro, cyano, and a CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I, and q is 1-3;

[0236] (b) R.sup.2 is hydrogen or CH.sub.3;

[0237] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl or R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H;

[0238] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0239] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I;

[0240] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0241] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0242] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2;

[0243] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl,

[0244] The sixth aspect of the second embodiment is directed to a compound represented by formula I-4

[0245] wherein

[0246] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0247] (b) R.sup.2 is hydrogen or CH.sub.3;

[0248] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0249] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0250] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I;

[0251] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0252] (g) X is H, OH, F, OCH.sub.3, NH.sub.2, or N.sub.3;

[0253] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0254] (i) R.sup.7 and R.sup.8 are independently H, F, Cl, Br, I, OH, OCH.sub.3, SH, SCH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2H, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2, wherein R′ is a C.sub.1-20 alkyl; a C.sub.1-20 cycloalkyl; a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.6 alkynyl.

[0255] The seventh aspect of the second embodiment is directed to a compound represented by formula I-4

[0256] wherein

[0257] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0258] (b) R.sup.2 is hydrogen or CH.sub.3;

[0259] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0260] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0261] (e) R.sup.5 is H, OMe, CN, CH.sub.2F, F, Cl, Br, or I;

[0262] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0263] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0264] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH3, or OC(O)CH.sub.3;

[0265] (i) R.sup.7 and R.sup.8 are independently H, F, Br, SCH.sub.3, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2;

[0266] The eighth aspect of the second embodiment is directed to a compound represented by formula I-4

[0267] wherein

[0268] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0269] (b) R.sup.2 is hydrogen;

[0270] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0271] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0272] (e) R.sup.5 is H;

[0273] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0274] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0275] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0276] (i) R.sup.7 and R.sup.8 are independently H, F, Br, SCH.sub.3, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2.

[0277] The ninth aspect of the second embodiment is directed to a compound represented by formula I-4

[0278] wherein

[0279] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0280] (b) R.sup.2 is hydrogen;

[0281] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0282] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0283] (e) R.sup.5 is H;

[0284] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0285] (g) X is H, OH, OCH.sub.3, F, or N.sub.3;

[0286] (h) Y is OH, OCH.sub.3, or OC(O)CH.sub.3;

[0287] (i) R.sup.7 and R.sup.8 are independently H, F, Br, SCH.sub.3, CH.sub.3, CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO.sub.2CH.sub.3, CONH.sub.2, CONHCH.sub.3, or CON(CH.sub.3).sub.2.

[0288] A third embodiment of the invention is directed to a compound represented by formula I in which the base is a structure represented by formula c above, wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, R.sup.6, X, Y, Z, R.sup.10, R.sup.11, and R.sup.12 are defined in the Summary of the Invention section above; with the proviso that R.sup.11 is not H.

[0289] A first aspect of the third embodiment is directed to a compound represented by formula I-5

##STR00011##

[0290] wherein

[0291] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0292] (b) R.sup.2 is hydrogen or CH.sub.3;

[0293] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is from H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0294] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0295] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0296] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0297] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0298] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2 (C.sub.1-4 acyl), SO.sub.2 (C.sub.1-4 alkyl), SO.sub.2 (C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0299] (i) R.sup.10 and R.sup.11 are independently H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkyl of C.sub.1-C.sub.6, lower alkenyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkenyl of C.sub.2-C.sub.6, lower alkynyl of C.sub.2-C.sub.6 such as C≡CH, halogenated (F, Cl, Br, I) lower alkynyl of C.sub.2-C.sub.6, lower alkoxy of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkoxy of C.sub.1-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0300] wherein R′ is an optionally substituted alkyl, which includes, but is not limited to, an optionally substituted C.sub.1-20 alkyl, an optionally substituted C.sub.1-10 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C.sub.2-C.sub.6, an optionally substituted lower alkenyl of C.sub.2-C.sub.6, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O)(C.sub.1-20 alkyl), C(O)(C.sub.1-10 alkyl), or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0301] (j) Z is N or CR.sup.12; and

[0302] R.sup.12 is an H, halogen (including F, Cl, Br, I), OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2 lower alkyl of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkyl of C.sub.1-C.sub.6, lower alkenyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkenyl of C.sub.2-C.sub.6, lower alkynyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkynyl of C.sub.2-C.sub.6, lower alkoxy of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkoxy of C.sub.1-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0303] A second aspect of the third embodiment is directed to a compound represented by formula I-5

[0304] wherein

[0305] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0306] (b) R.sup.2 is hydrogen or CH.sub.3;

[0307] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0308] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0309] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H.

[0310] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0311] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0312] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0313] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0314] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0315] (j) Z is N or CR.sup.12; and

[0316] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0317] A third aspect of the third embodiment is directed to a compound represented by formula I-5

[0318] wherein

[0319] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0320] (b) R.sup.2 is hydrogen or CH.sub.3;

[0321] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0322] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0323] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I; with the proviso that X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0324] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0325] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0326] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0327] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0328] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0329] (j) Z is N or CR.sup.12; and

[0330] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0331] A fourth aspect of the third embodiment is directed to a compound represented by formula I-5

[0332] wherein

[0333] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0334] (b) R.sup.2 is hydrogen;

[0335] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0336] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0337] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0338] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0339] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0340] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0341] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0342] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0343] (j) Z is N or CR.sup.12; and

[0344] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0345] A fifth aspect of the third embodiment is directed to a compound represented by formula I-5

[0346] wherein

[0347] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0348] (b) R.sup.2 is hydrogen;

[0349] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0350] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0351] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0352] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0353] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0354] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0355] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0356] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0357] (j) Z is N or CR.sup.12; and

[0358] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0359] A sixth aspect of the third embodiment is directed to a compound represented by formula I-5

[0360] wherein

[0361] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0362] (b) R.sup.2 is hydrogen or CH.sub.3;

[0363] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0364] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0365] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H.

[0366] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0367] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0368] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0369] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0370] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0371] (j) Z is N or CR.sup.12; and

[0372] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0373] A seventh aspect of the third embodiment is directed to a compound represented by formula I-5

[0374] wherein

[0375] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0376] (b) R.sup.2 is hydrogen or CH.sub.3; [0377] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0378] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0379] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I; with the proviso that X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0380] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0381] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0382] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0383] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0384] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0385] (j) Z is N or CR.sup.12; and

[0386] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0387] An eighth aspect of the third embodiment is directed to a compound represented by formula I-5

[0388] wherein

[0389] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0390] (b) R.sup.2 is hydrogen;

[0391] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0392] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl;

[0393] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0394] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0395] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0396] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0397] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0398] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0399] (j) Z is N or CR.sup.12; and

[0400] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0401] A ninth aspect of the third embodiment is directed to a compound represented by formula I-5

[0402] wherein

[0403] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0404] (b) R.sup.2 is hydrogen;

[0405] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0406] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, or N-methyl-pyrrolidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0407] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0408] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0409] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0410] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0411] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′,

[0412] CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0413] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0414] (j) Z is N or CR.sup.12; and

[0415] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0416] A tenth aspect of the third embodiment is directed to a compound represented by formula I-6

##STR00012##

[0417] wherein

[0418] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0419] (b) R.sup.2 is hydrogen or CH.sub.3;

[0420] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0421] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0422] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0423] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0424] (g) X is H, OH, F, OMe, Cl, Br, I, NH.sub.2, or N.sub.3;

[0425] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2 (C.sub.1-4 acyl), SO.sub.2 (C.sub.1-4 alkyl), SO.sub.2 (C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0426] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0427] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0428] (j) Z is N or CR.sup.12; and

[0429] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0430] An eleventh aspect of the third embodiment is directed to a compound represented by formula I-6

[0431] wherein

[0432] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0433] (b) R.sup.2 is hydrogen or CH.sub.3;

[0434] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0435] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0436] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0437] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0438] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0439] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0440] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0441] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0442] (j) Z is N or CR.sup.12; and

[0443] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0444] A twelfth aspect of the third embodiment is directed to a compound represented by formula I-6

[0445] wherein

[0446] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0447] (b) R.sup.2 is hydrogen or CH.sub.3;

[0448] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0449] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0450] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I, with the provisos that when X is OH,

[0451] R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0452] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0453] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0454] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0455] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0456] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0457] (j) Z is N or CR.sup.12; and

[0458] R.sup.12 is a H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0459] A thirteenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0460] wherein

[0461] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0462] (b) R.sup.2 is hydrogen;

[0463] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0464] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0465] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0466] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0467] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0468] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0469] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0470] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0471] (j) Z is N or CR.sup.12; and

[0472] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0473] A fourteenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0474] wherein

[0475] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0476] (b) R.sup.2 is hydrogen;

[0477] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0478] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0479] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0480] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0481] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0482] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0483] (i) R.sup.10 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′, with the proviso that when R.sup.10 is OH and R.sup.11 is not NH.sub.2;

[0484] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0485] (j) Z is N or CR.sup.12; and

[0486] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0487] A fifteenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0488] wherein

[0489] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is OR′ or —N(R.sup.1′).sub.2);

[0490] (b) R.sup.2 is hydrogen or CH.sub.3;

[0491] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3u, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0492] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0493] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0494] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0495] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0496] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2 (C.sub.1-4 acyl), SO.sub.2 (C.sub.1-4 alkyl), SO.sub.2 (C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0497] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0498] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0499] (j) Z is N or CR.sup.12; and

[0500] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0501] An sixteenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0502] wherein

[0503] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0504] (b) R.sup.2 is hydrogen or CH.sub.3;

[0505] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0506] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0507] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0508] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0509] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0510] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0511] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0512] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0513] (j) Z is N or CR.sup.12; and

[0514] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0515] A seventeenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0516] wherein

[0517] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0518] (b) R.sup.2 is hydrogen or CH.sub.3;

[0519] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0520] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0521] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0522] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0523] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0524] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0525] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0526] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0527] (j) Z is N or CR.sup.12; and

[0528] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0529] An eighteenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0530] wherein

[0531] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0532] (b) R.sup.2 is hydrogen;

[0533] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0534] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0535] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0536] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0537] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0538] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0539] (i) R.sup.10 is NH.sub.2 and R.sup.11 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0540] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0541] (j) Z is N or CR.sup.12; and

[0542] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0543] A nineteenth aspect of the third embodiment is directed to a compound represented by formula I-6

[0544] wherein

[0545] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0546] (b) R.sup.2 is hydrogen;

[0547] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0548] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0549] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0550] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0551] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0552] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0553] (i) R.sup.10 is NH.sub.2 and R.sup.11 are independently H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′;

[0554] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0555] (j) Z is N or CR.sup.12; and

[0556] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0557] A fourth embodiment of the invention is directed to a compound represented by formula I in which the base is a structure represented by formula c above, where R.sup.11 is H and R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, R.sup.6, X, and Y are defined in the Summary of the Invention section above.

[0558] A first aspect of the fourth embodiment is directed to a compound represented by formula I-7

##STR00013##

[0559] wherein

[0560] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0561] (b) R.sup.2 is hydrogen or CH.sub.3;

[0562] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0563] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0564] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0565] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0566] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0567] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0568] (i) R.sup.10 is H, F, Cl, Br, I, OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, lower alkyl of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkyl of C.sub.1-C.sub.6, lower alkenyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkenyl of C.sub.2-C.sub.6, lower alkynyl of C.sub.2-C.sub.6 such as C≡CH, halogenated (F, Cl, Br, I) lower alkynyl of C.sub.2-C.sub.6, lower alkoxy of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkoxy of C.sub.1-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0569] wherein R′ is an optionally substituted alkyl, which includes, but is not limited to, an optionally substituted C.sub.1-20 alkyl, an optionally substituted C.sub.1-10 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C.sub.2-C.sub.6, an optionally substituted lower alkenyl of C.sub.2-C.sub.6, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(O)(C.sub.1-20 alkyl), C(O)(C.sub.1-10 alkyl), or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0570] (j) Z is N or CR.sup.12; and

[0571] R.sup.12 is H, halogen (including F, Cl, Br, I), OH, OR′, SH, SR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2 lower alkyl of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkyl of C.sub.1-C.sub.6, lower alkenyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkenyl of C.sub.2-C.sub.6, lower alkynyl of C.sub.2-C.sub.6, halogenated (F, Cl, Br, I) lower alkynyl of C.sub.2-C.sub.6, lower alkoxy of C.sub.1-C.sub.6, halogenated (F, Cl, Br, I) lower alkoxy of C.sub.1-C.sub.6, CO.sub.2H, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0572] A second aspect of the fourth embodiment is directed to a compound represented by formula I-7

[0573] wherein

[0574] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0575] (b) R.sup.2 is hydrogen or CH.sub.3;

[0576] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0577] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0578] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H.

[0579] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0580] (g) X is H, OH, F, OCH.sub.3, halogen, NH.sub.2, or N.sub.3;

[0581] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0582] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0583] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0584] (j) Z is N or CR.sup.12; and

[0585] R.sup.12 is H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0586] A third aspect of the third embodiment is directed to a compound represented by formula I-7

[0587] wherein

[0588] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0589] (b) R.sup.2 is hydrogen or CH.sub.3;

[0590] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0591] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0592] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I; with the proviso that X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0593] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0594] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0595] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0596] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0597] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0598] (j) Z is N or CR.sup.12; and

[0599] R.sup.12 is H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0600] A fourth aspect of the fourth embodiment is directed to a compound represented by formula I-7

[0601] wherein

[0602] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0603] (b) R.sup.2 is hydrogen;

[0604] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0605] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0606] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0607] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0608] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0609] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0610] (i) R.sup.10 and R.sup.11 H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0611] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0612] (j) Z is N or CR.sup.12; and

[0613] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0614] A fifth aspect of the fourth embodiment is directed to a compound represented by formula I-7

[0615] wherein

[0616] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0617] (b) R.sup.2 is hydrogen;

[0618] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0619] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0620] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0621] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0622] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0623] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0624] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0625] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0626] (j) Z is N or CR.sup.12; and

[0627] R.sup.12 is H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′.

[0628] A sixth aspect of the fourth embodiment is directed to a compound represented by formula I-8

##STR00014##

[0629] wherein

[0630] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0631] (b) R.sup.2 is hydrogen or CH.sub.3;

[0632] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0633] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0634] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0635] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0636] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0637] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2;

[0638] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0639] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0640] (j) Z is N or CR.sup.12; and

[0641] R.sup.12 is H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that when base is represented by the structure c with R.sup.11 being hydrogen, R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0642] A seventh aspect of the fourth embodiment is directed to a compound represented by formula I-8

[0643] wherein

[0644] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0645] (b) R.sup.2 is hydrogen or CH.sub.3;

[0646] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0647] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0648] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0649] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0650] (g) X is H, OH, F, OCH.sub.3, halogen, NH.sub.2, or N.sub.3;

[0651] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0652] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0653] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0654] (j) Z is N or CR.sup.12; and

[0655] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0656] An eighth aspect of the fourth embodiment is directed to a compound represented by formula I-8

[0657] wherein

[0658] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0659] (b) R.sup.2 is hydrogen or CH.sub.3;

[0660] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0661] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0662] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0663] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0664] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0665] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0666] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0667] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0668] (j) Z is N or CR.sup.12; and

[0669] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0670] A ninth aspect of the fourth embodiment is directed to a compound represented by formula I-8

[0671] wherein

[0672] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0673] (b) R.sup.2 is hydrogen;

[0674] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0675] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0676] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0677] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0678] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0679] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0680] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0681] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0682] (j) Z is N or CR.sup.12; and

[0683] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0684] A tenth aspect of the fourth embodiment is directed to a compound represented by formula I-8

[0685] wherein

[0686] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0687] (b) R.sup.2 is hydrogen;

[0688] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0689] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0690] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0691] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0692] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0693] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0694] (i) R.sup.10 is H, F, Br, I, OH, OR′, NH.sub.2, NHR′, NR′.sub.2, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′,

[0695] wherein R′ is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR′.sub.2, each R′ comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and

[0696] (j) Z is N or CR.sup.12; and

[0697] R.sup.12 is an H, halogen (including F, Cl, Br, I), OR′, NH.sub.2, NHR′, NR′.sub.2, NO.sub.2, lower alkyl of C.sub.1-C.sub.6, CO.sub.2R′, CONH.sub.2, CONHR′, CONR′.sub.2, CH═CHCO.sub.2H, or CH═CHCO.sub.2R′; with the proviso that R.sup.12 is not a: (i) —C≡C—H, (ii) —C═CH.sub.2, or (iii) —NO.sub.2.

[0698] A fifth embodiment of the invention is directed to a compound represented by formula I in which the base is a structure represented by formula d above, wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, R.sup.6, X, and Y are defined in the Summary of the Invention section above.

[0699] The first aspect of the fifth embodiment is directed to a compound represented by formula I-9

##STR00015##

[0700] wherein

[0701] (a) R.sup.1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C.sub.1-6 haloalkyl, —N(R.sup.1′).sub.2, C.sub.1-6 acylamino, —NHSO.sub.2C.sub.1-6 alkyl, —SO.sub.2N(R.sup.1′).sub.2, COR.sup.1″, and —SO.sub.2C.sub.1-6 alkyl; (R.sup.1′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.1″ is —OR′ or —N(R.sup.1′).sub.2);

[0702] (b) R.sup.2 is hydrogen or CH.sub.3;

[0703] (c) R.sup.3a and R.sup.3b are (i) independently selected from hydrogen, C.sub.1-10 alkyl, cycloalkyl, —(CH.sub.2).sub.c(NR.sup.3′).sub.2, C.sub.1-6 hydroxyalkyl, —CH.sub.2SH, —(CH.sub.2).sub.2S(O).sub.dMe, —(CH.sub.2).sub.3NHC(═NH)NH.sub.2, (1H-indol-3-yl)methyl, (1H-imidazol-4-yl)methyl, —(CH.sub.2).sub.eCOR.sup.3″, aryl and aryl C.sub.1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C.sub.1-10 alkyl, C.sub.1-6 alkoxy, halogen, nitro and cyano; (ii) R.sup.3a and R.sup.3b both are C.sub.1-6 alkyl; (iii) R.sup.3a and R.sup.3b together are (CH.sub.2).sub.f so as to form a spiro ring; (iv) R.sup.3a is hydrogen and R.sup.3b and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R.sup.3b is hydrogen and R.sup.3a and R.sup.2 together are (CH.sub.2).sub.n so as to form a cyclic ring that includes the adjoining N and C atoms, where c is 1 to 6, d is 0 to 2, e is 0 to 3, f is 2 to 5, n is 2 to 4, and where R.sup.3′ is independently hydrogen or C.sub.1-6 alkyl and R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2); (vi) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl; or (viii) R.sup.3a is CH.sub.3, —CH.sub.2CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H, where R.sup.3′ is independently hydrogen or alkyl, which includes, but is not limited to, C.sub.1-20 alkyl, C.sub.1-10 alkyl, or C.sub.1-6 alkyl, R.sup.3″ is —OR′ or —N(R.sup.3′).sub.2);

[0704] (d) R.sup.4 is hydrogen, C.sub.1-10 alkyl, C.sub.1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C.sub.1-10 haloalkyl, C.sub.3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl;

[0705] (e) R.sup.5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., —(CH.sub.2).sub.pOH, where p is 1-6, including hydroxyl methyl (CH.sub.2OH), CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R.sup.6 is H, R.sup.5 cannot be N.sub.3 and when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F and B is a purine base, R.sup.5 cannot be H;

[0706] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0707] (g) X is H, OH, F, OMe, halogen, NH.sub.2, or N.sub.3;

[0708] (h) Y is OH, H, C.sub.1-4 alkyl, C.sub.2-4 alkenyl, C.sub.2-4 alkynyl, vinyl, N.sub.3, CN, Cl, Br, F, I, NO.sub.2, OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.1-4 alkyl), OC(O)O(C.sub.2-4 alkynyl), OC(O)O(C.sub.2-4 alkenyl), OC.sub.1-10 haloalkyl, O(aminoacyl), O(C.sub.1-10 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-18 acyl).sub.2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N.sub.3, CN, one to three halogen (Cl, Br, F, I), NO.sub.2, C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.1-4 alkyl), C(O)O(C.sub.2-4 alkynyl), C(O)O(C.sub.2-4 alkenyl), O(C.sub.1-4 acyl), O(C.sub.1-4 alkyl), O(C.sub.2-4 alkenyl), S(C.sub.1-4 acyl), S(C.sub.1-4 alkyl), S(C.sub.2-4 alkynyl), S(C.sub.2-4 alkenyl), SO(C.sub.1-4 acyl), SO(C.sub.1-4 alkyl), SO(C.sub.2-4 alkynyl), SO(C.sub.2-4 alkenyl), SO.sub.2(C.sub.1-4 acyl), SO.sub.2(C.sub.1-4 alkyl), SO.sub.2(C.sub.2-4 alkynyl), SO.sub.2(C.sub.2-4 alkenyl), OS(O).sub.2(C.sub.1-4 acyl), OS(O).sub.2(C.sub.1-4 alkyl), OS(O).sub.2(C.sub.2-4 alkenyl), NH.sub.2, NH(C.sub.1-4 alkyl), NH(C.sub.2-4 alkenyl), NH(C.sub.2-4 alkynyl), NH(C.sub.1-4 acyl), N(C.sub.1-4 alkyl).sub.2, N(C.sub.1-4 acyl).sub.2.

[0709] A second aspect of the fifth embodiment is directed to a compound represented by formula I-9

[0710] wherein

[0711] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0712] (b) R.sup.2 is hydrogen or CH.sub.3;

[0713] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0714] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0715] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H.

[0716] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0717] (g) X is H, OH, F, OCH.sub.3, halogen, NH.sub.2, or N.sub.3;

[0718] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3;

[0719] A third aspect of the fifth embodiment is directed to a compound represented by formula I-9

[0720] wherein

[0721] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0722] (b) R.sup.2 is hydrogen or CH.sub.3;

[0723] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0724] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0725] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I; with the proviso that X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0726] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0727] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0728] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0729] A fourth aspect of the fifth embodiment is directed to a compound represented by formula I-9

[0730] wherein

[0731] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0732] (b) R.sup.2 is hydrogen;

[0733] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0734] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0735] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0736] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0737] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0738] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0739] A fifth aspect of the fifth embodiment is directed to a compound represented by formula I-9

[0740] wherein

[0741] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0742] (b) R.sup.2 is hydrogen;

[0743] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0744] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0745] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0746] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0747] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0748] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0749] A sixth aspect of the fifth embodiment is directed to a compound represented by formula I-10

##STR00016##

[0750] wherein

[0751] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH.sub.3, OCH.sub.3, F, Cl, Br, I, nitro, cyano, and a CH.sub.3-qX.sub.q, where X is F, Cl, Br, or I, and q is 1-3;

[0752] (b) R.sup.2 is hydrogen or CH.sub.3;

[0753] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl or R.sup.3a is CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl and R.sup.3b is H;

[0754] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0755] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, N.sub.3, CH.sub.2CN, CH.sub.2N.sub.3, CH.sub.2NH.sub.2, CH.sub.2NHCH.sub.3, CH.sub.2N(CH.sub.3).sub.2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0756] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0757] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3;

[0758] (h) Y is OH, H, CH.sub.3, vinyl, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3, NH.sub.2, NHCH.sub.3, NH(vinyl), NH(acetyl), NH(C(O)CH.sub.3), N(CH.sub.3).sub.2, N(C(O)CH.sub.3).sub.2;

[0759] A seventh aspect of the fifth embodiment is directed to a compound represented by formula I-10

[0760] wherein

[0761] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0762] (b) R.sup.2 is hydrogen or CH.sub.3;

[0763] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, CH.sub.2-indol-3-yl, —CH.sub.2CH.sub.2SCH.sub.3, CH.sub.2CO.sub.2H, CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2COOH, CH.sub.2CH.sub.2C(O)NH.sub.2, CH.sub.2CH.sub.2CH.sub.2CH.sub.2NH.sub.2, —CH.sub.2CH.sub.2CH.sub.2NHC(NH)NH.sub.2, CH.sub.2-imidazol-4-yl, CH.sub.2OH, CH(OH)CH.sub.3, CH.sub.2((4′-OH)-Ph), CH.sub.2SH, or lower cycloalkyl;

[0764] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0765] (e) R.sup.5 is H, CN, CH.sub.3, OCH.sub.3, CH.sub.2OH, CH.sub.2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0766] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, F, or CN;

[0767] (g) X is H, OH, F, OCH.sub.3, Cl, Br, I, NH.sub.2, or N.sub.3; and

[0768] (h) Y is OH, H, CH.sub.3, vinyl, NH.sub.2, N.sub.3, CN, Cl, Br, F, I, OC(O)CH.sub.3, OCH.sub.3.

[0769] An eighth aspect of the fifth embodiment is directed to a compound represented by formula I-10

[0770] wherein

[0771] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0772] (b) R.sup.2 is hydrogen or CH.sub.3;

[0773] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0774] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0775] (e) R.sup.5 is H, CN, CH.sub.2F, F, Cl, Br, or I, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0776] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0777] (g) X is H, OH, F, OCH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3;

[0778] (h) Y is H, OH, CH.sub.3, F, Cl, Br, I, NH.sub.2 or N.sub.3, OCH.sub.3, or OC(O)CH.sub.3;

[0779] A ninth aspect of the fifth embodiment is directed to a compound represented by formula I-10

[0780] wherein

[0781] (a) R.sup.1 is hydrogen, methyl, ethyl, n-propyl, i-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0782] (b) R.sup.2 is hydrogen;

[0783] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0784] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0785] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0786] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0787] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0788] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3;

[0789] A tenth aspect of the fifth embodiment is directed to a compound represented by formula I-10

[0790] wherein

[0791] (a) R.sup.1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;

[0792] (b) R.sup.2 is hydrogen;

[0793] (c) R.sup.3a is H and R.sup.3b is H, CH.sub.3, CH(CH.sub.3).sub.2, CH.sub.2CH(CH.sub.3).sub.2, CH(CH.sub.3)CH.sub.2CH.sub.3, CH.sub.2Ph, or lower cycloalkyl;

[0794] (d) R.sup.4 is hydrogen, CH.sub.3, Et, .sup.iPr, .sup.nPr, .sup.nBu, 2-butyl, .sup.tBu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl;

[0795] (e) R.sup.5 is H, with the provisos that when X is OH, R.sup.6 is CH.sub.3 or CH.sub.2F, R.sup.5 cannot be H;

[0796] (f) R.sup.6 is H, CH.sub.3, CH.sub.2F, CHF.sub.2, CF.sub.3, or F;

[0797] (g) X is H, OH, OCH.sub.3, F, NH.sub.2 or N.sub.3;

[0798] (h) Y is OH, NH.sub.2, OCH.sub.3, or OC(O)CH.sub.3.

[0799] The following tables contain numeric identifiers associated with various substituent designators that should be viewed in light of the accompanying structure. These structures are contemplated species of the various aspects of the disclosed embodiments and are not intended to be limiting on full breadth of the contemplated compound represented by the structure of formula I. However, it is contemplated that any one of the exemplified nucleoside bases can be used in combination with any one of contemplated species that specify a particular combination of R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, R.sup.6, X, and Y. In each of the presented tables, the phosphoramidate substituent containing the substituents R.sup.3a and R.sup.3b are depicted without reference to stereochemical structure (cf. structures I-1, I-3, I-5, I-7, and I-9 above). It is contemplated that the compounds recited below embody compounds in which R.sup.3a projects toward the viewer while R.sup.3b projects away from the viewer (cf. structures I-2, I-4, I-6, I-8, and I-10). Moreover, it is contemplated that the compounds recited below also embody compounds in which R.sup.3a projects away from the viewer while R.sup.3b projects towards the viewer. Not meant to be limiting, however, it is contemplated that preferred compounds are those in which R.sup.3a projects towards the viewer and R.sup.3b projects away from the viewer such that the natural L-amino acid (S)-configuration is presented. Additionally, the inventors recognize that the phosphorus atom of the phosphoramidate moiety is another source of chirality. Although the structures below do not specifically depict chirality at phosphorus, the inventors recognize that stereochemical configurations are possible such that in a staggered (or zig-zag) line structure the oxo-substitutent projects towards the viewer while the OR.sup.1 substitutent projects away from the viewer, and vice versa, i.e., where the Cahn-Ingold-Prelog stereochemical designation of phosphorous is either R or S. Therefore, the structures below include all possible stereochemical configurations possible for phosphorus.

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Dosage, Administration, and Use

[0800] A sixth embodiment of the present invention is directed to a composition for the treatment of any of the viral agents disclosed herein said composition comprising a pharmaceutically acceptable medium selected from among an excipient, carrier, diluent, and equivalent medium and a compound, that is intended to include its salts (acid or basic addition salts), hydrates, solvates, and crystalline forms can be obtained, represented by formula I.

[0801] It is contemplated that the formulation of the sixth embodiment can contain any of the compounds contemplated in any of the aspects of the first, second, third, fourth, and fifth embodiments or those specifically recited in the tables above or exemplified herein, either alone or in combination with another compound of the present invention.

[0802] The compounds of the present invention may be formulated in a wide variety of oral administration dosage forms and carriers. Oral administration can be in the form of tablets, coated tablets, hard and soft gelatin capsules, solutions, emulsions, syrups, or suspensions. Compounds of the present invention are efficacious when administered by suppository administration, among other routes of administration. The most convenient manner of administration is generally oral using a convenient daily dosing regimen which can be adjusted according to the severity of the disease and the patient's response to the antiviral medication.

[0803] A compound or compounds of the present invention, as well as their pharmaceutically acceptable salts, together with one or more conventional excipients, carriers, or diluents, may be placed into the form of pharmaceutical compositions and unit dosages. The pharmaceutical compositions and unit dosage forms may be comprised of conventional ingredients in conventional proportions, with or without additional active compounds and the unit dosage forms may contain any suitable effective amount of the active ingredient commensurate with the intended daily dosage range to be employed. The pharmaceutical compositions may be employed as solids, such as tablets or filled capsules, semisolids, powders, sustained release formulations, or liquids such as suspensions, emulsions, or filled capsules for oral use; or in the form of suppositories for rectal or vaginal administration. A typical preparation will contain from about 5% to about 95% active compound or compounds (w/w). The term “preparation” or “dosage form” is intended to include both solid and liquid formulations of the active compound and one skilled in the art will appreciate that an active ingredient can exist in different preparations depending on the desired dose and pharmacokinetic parameters.

[0804] The term “excipient” as used herein refers to a compound that is used to prepare a pharmaceutical composition, and is generally safe, non-toxic and neither biologically nor otherwise undesirable, and includes excipients that are acceptable for veterinary use as well as human pharmaceutical use. The compounds of this invention can be administered alone but will generally be administered in admixture with one or more suitable pharmaceutical excipients, diluents or carriers selected with regard to the intended route of administration and standard pharmaceutical practice.

[0805] A “pharmaceutically acceptable salt” form of an active ingredient may also initially confer a desirable pharmacokinetic property on the active ingredient which were absent in the non-salt form, and may even positively affect the pharmacodynamics of the active ingredient with respect to its therapeutic activity in the body. The phrase “pharmaceutically acceptable salt” of a compound as used herein means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as glycolic acid, pyruvic acid, lactic acid, malonic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, salicylic acid, muconic acid, and the like or (2) basic addition salts formed with the conjugate bases of any of the inorganic acids listed above, wherein the conjugate bases comprise a cationic component selected from among Na.sup.+, K.sup.+, Mg.sup.2+, Ca.sup.2+, and NH.sub.gR″.sub.4-g.sup.+, in which R″ is a C.sub.1-3 alkyl and g is a number selected from among 0, 1, 2, 3, or 4. It should be understood that all references to pharmaceutically acceptable salts include solvent addition forms (solvates) or crystal forms (polymorphs) as defined herein, of the same acid addition salt.

[0806] Solid form preparations include powders, tablets, pills, capsules, suppositories, and dispersible granules. A solid carrier may be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material. In powders, the carrier generally is a finely divided solid which is a mixture with the finely divided active component. In tablets, the active component generally is mixed with the carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired. Suitable carriers include but are not limited to magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter, and the like. Solid form preparations may contain, in addition to the active component, colorants, flavors, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.

[0807] Liquid formulations also are suitable for oral administration include liquid formulation including emulsions, syrups, elixirs and aqueous suspensions. These include solid form preparations which are intended to be converted to liquid form preparations shortly before use. Emulsions may be prepared in solutions, for example, in aqueous propylene glycol solutions or may contain emulsifying agents such as lecithin, sorbitan monooleate, or acacia. Aqueous suspensions can be prepared by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, and other well known suspending agents.

[0808] The compounds of the present invention may be formulated for administration as suppositories. A low melting wax, such as a mixture of fatty acid glycerides or cocoa butter is first melted and the active component is dispersed homogeneously, for example, by stirring. The molten homogeneous mixture is then poured into convenient sized molds, allowed to cool, and to solidify.

[0809] The compounds of the present invention may be formulated for vaginal administration. Pessaries, tampons, creams, gels, pastes, foams or sprays containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

[0810] Suitable formulations along with pharmaceutical carriers, diluents and expcipients are described in Remington: The Science and Practice of Pharmacy 1995, edited by E. W. Martin, Mack Publishing Company, 19th edition, Easton, Pa., which is hereby incorporated by reference. The compounds of the present invention can also be encapsulated in liposomes, such as those disclosed in U.S. Pat. Nos. 6,180,134, 5,192,549, 5,376,380, 6,060,080, 6,132,763, each of which is incorporated by reference. A skilled formulation scientist may modify the formulations within the teachings of the specification to provide numerous formulations for a particular route of administration without rendering the compositions of the present invention unstable or compromising their therapeutic activity.

[0811] The modification of the present compounds to render them more soluble in water or other vehicle, for example, may be easily accomplished by minor modifications (e.g., salt formulation), which are well within the ordinary skill in the art. It is also well within the ordinary skill of the art to modify the route of administration and dosage regimen of a particular compound in order to manage the pharmacokinetics of the present compounds for maximum beneficial effect in patients.

[0812] A seventh embodiment of the present invention is directed to a use of the compound represented by formula I in the manufacture of a medicament for the treatment of any condition the result of an infection by any one of the following viral agents: hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus and Japanese encephalitis virus.

[0813] The term “medicament” means a substance used in a method of treatment and/or prophylaxis of a subject in need thereof, wherein the substance includes, but is not limited to, a composition, a formulation, a dosage form, and the like, comprising the compound of formula I. It is contemplated that the compound of the use of the compound represented by formula I in the manufacture of a medicament for the treatment of any of the antiviral conditions disclosed herein of the seventh embodiment can be any of the compounds contemplated in any of the aspects of the first, second, third, fourth, fifth embodiments or those specifically recited in the tables above or exemplified herein, either alone or in combination with another compound of the present invention. A medicament includes, but is not limited to, any one of the compositions contemplated by the sixth embodiment of the present invention.

[0814] A eighth embodiment of the present invention is directed to a method of treatment and/or prophylaxis in a subject in need thereof said method comprises administering a therapeutically effective amount of the compound represented by formula I to the subject.

[0815] A first aspect of the eighth embodiment is directed to a method of treatment and/or prophylaxis in a subject in need thereof said method comprises administering a therapeutically effective of at least two or more different compounds falling within the scope of the compound represented by formula I to the subject.

[0816] A second aspect of the eighth embodiment is directed to a method of treatment and/or prophylaxis in a subject in need thereof said method comprises alternatively or concurrently administering a therapeutically effective of at least two compounds falling within the scope of the compound represented by formula I to the subject.

[0817] It is intended that a subject in need thereof is one that has any condition the result of an infection by any of the viral agents disclosed herein, which includes, but is not limited to, hepatitis C virus, West Nile virus, yellow fever virus, dengue virus, rhinovirus, polio virus, hepatitis A virus, bovine viral diarrhea virus or Japanese encephalitis virus, flaviviridae viruses or pestiviruses or hepaciviruses or a viral agent causing symptoms equivalent or comparable to any of the above-listed viruses.

[0818] The term “subject” means a mammal, which includes, but is not limited to, cattle, pigs, sheep, chicken, turkey, buffalo, llama, ostrich, dogs, cats, and humans, preferably the subject is a human. It is contemplated that in the method of treating a subject thereof of the sixth embodiment can be any of the compounds contemplated in any of the aspects of the first, second, and third embodiments or those specifically recited in the tables above, either alone or in combination with another compound of the present invention.

[0819] The term “therapeutically effective amount” as used herein means an amount required to reduce symptoms of the disease in an individual. The dose will be adjusted to the individual requirements in each particular case. That dosage can vary within wide limits depending upon numerous factors such as the severity of the disease to be treated, the age and general health condition of the patient, other medicaments with which the patient is being treated, the route and form of administration and the preferences and experience of the medical practitioner involved. For oral administration, a daily dosage of between about 0.1 and about 10 g, including all values in between, such as 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, and 9.5, per day should be appropriate in monotherapy and/or in combination therapy. A preferred daily dosage is between about 0.5 and about 7.5 g per day, more preferred 1.5 and about 6.0 g per day. Generally, treatment is initiated with a large initial “loading dose” to rapidly reduce or eliminate the virus following by a decreasing the dose to a level sufficient to prevent resurgence of the infection. One of ordinary skill in treating diseases described herein will be able, without undue experimentation and in reliance on personal knowledge, experience and the disclosures of this application, to ascertain a therapeutically effective amount of the compounds of the present invention for a given disease and patient.

[0820] Therapeutic efficacy can be ascertained from tests of liver function including, but not limited to protein levels such as serum proteins (e.g., albumin, clotting factors, alkaline phosphatase, aminotransferases (e.g., alanine transaminase, aspartate transaminase), 5′-nucleosidase, γ-glutaminyltranspeptidase, etc.), synthesis of bilirubin, synthesis of cholesterol, and synthesis of bile acids; a liver metabolic function, including, but not limited to, carbohydrate metabolism, amino acid and ammonia metabolism. Alternatively the therapeutic effectiveness may be monitored by measuring HCV-RNA. The results of these tests will allow the dose to be optimized.

[0821] A third aspect of the eighth embodiment, is directed to a method of treatment and/or prophylaxis in a subject in need thereof said method comprises administering to the subject a therapeutically effective of a compound represented by formula I and a therapeutically effective amount of another antiviral agent; wherein the administration is concurrent or alternative. It is understood that the time between alternative administration can range between 1-24 hours, which includes any sub-range in between including, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours. Examples of “another antiviral agents” include, but are not limited to: HCV NS3 protease inhibitors (see WO 2008010921, WO 2008010921, EP 1881001, WO 2007015824, WO 2007014925, WO 2007014926, WO 2007014921, WO 2007014920, WO 2007014922, US 2005267018, WO 2005095403, WO 2005037214, WO 2004094452, US 2003187018, WO 200364456, WO 2005028502, and WO 2003006490); HCV NS5B Inhibitors (see US 2007275947, US20072759300, WO2007095269, WO 2007092000, WO 2007076034, WO 200702602, US 2005-98125, WO 2006093801, US 2006166964, WO 2006065590, WO 2006065335, US 2006040927, US 2006040890, WO 2006020082, WO 2006012078, WO 2005123087, US 2005154056, US 2004229840, WO 2004065367, WO 2004003138, WO 2004002977, WO 2004002944, WO 2004002940, WO 2004000858, WO 2003105770, WO 2003010141, WO 2002057425, WO 2002057287, WO 2005021568, WO 2004041201, US 20060293306, US 20060194749, US 20060241064, U.S. Pat. No. 6,784,166, WO 2007088148, WO 2007039142, WO 2005103045, WO 2007039145, WO 2004096210, and WO 2003037895); HCV NS4 Inhibitors (see WO 2007070556 and WO 2005067900); HCV NS5a Inhibitors (see US 2006276511, WO 2006120252, WO 2006120251, WO 2006100310, WO 2006035061); Toll-like receptor agonists (see WO 2007093901); and other inhibitors (see WO 2004035571, WO 2004014852, WO 2004014313, WO 2004009020, WO 2003101993, WO 2000006529).

[0822] A fourth aspect of the eighth embodiment, is directed to a method of treatment in a subject in need thereof said method comprises alternatively or concurrently administering a therapeutically effective of a compound represented by formula I and another antiviral agent to the subject. It is understood that the time between alternative administration can range between 1-24 hours, which includes any sub-range in between including, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours.

[0823] A fifth aspect of the eighth embodiment, is directed to a method of treatment and/or prophylaxis in a subject in need thereof said method comprises administering to the subject a therapeutically effective of at least one compound represented by formula I and a therapeutically effective amount of another antiviral agent; wherein the administration is concurrent or alternative. It is understood that the time between alternative administration can range between 1-24 hours, which includes any sub-range in between including, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours.

[0824] A sixth aspect of the eighth embodiment, is directed to a method of treatment in a subject in need thereof said method comprises alternatively or concurrently administering a therapeutically effective of at least one compound represented by formula I and another antiviral agent to the subject. It is understood that the time between alternative administration can range between 1-24 hours, which includes any sub-range in between including, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 hours.

[0825] It is contemplated that the another antiviral agent includes, but is not limited to interferon-α, interferon-β, pegylated interferon-α, ribavirin, levovirin, viramidine, another nucleoside HCV polymerase inhibitor, a HCV non-nucleoside polymerase inhibitor, a HCV protease inhibitor, a HCV helicase inhibitor or a HCV fusion inhibitor. When the active compound or its derivative or salt are administered in combination with another antiviral agent the activity may be increased over the parent compound. When the treatment is combination therapy, such administration may be concurrent or sequential with respect to that of the nucleoside derivatives. “Concurrent administration” as used herein thus includes administration of the agents at the same time or at different times. Administration of two or more agents at the same time can be achieved by a single formulation containing two or more active ingredients or by substantially simultaneous administration of two or more dosage forms with a single active agent.

[0826] It will be understood that references herein to treatment extend to prophylaxis as well as to the treatment of existing conditions. Furthermore, the term “treatment” of a HCV infection, as used herein, also includes treatment or prophylaxis of a disease or a condition associated with or mediated by HCV infection, or the clinical symptoms thereof.

Process for Preparation

[0827] An ninth embodiment of the present invention is directed to a process for preparing the compound of formula I, which comprises reacting a suitably substituted phosphochloridate compound 4 with a nucleoside analog 5

##STR00017##

[0828] wherein the substituents R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, X, Y, R.sup.6, and base have their meanings as disclosed in the Detailed Description of the Invention and X′ is a leaving group, such as Cl, Br, I, tosylate, mesylate, trifluoroacetate, trifluorosulfonate, pentafluorophenoxide, p-NO.sub.2-phenoxide, or other commonly used leaving groups as disclosed in Advanced Organic Chemistry by March, Fourth Edition. Leaving groups and methods that can be used to effect the formation of a phosphoramidate nucleoside conjugate are found in US 20060142238 and WO 2007095269. Preferably, the leaving group is Cl.

[0829] This reaction is performed in an anhydrous aprotic solvent such tetrahydrofuran, dioxane, or both tetrahydrofuran and dioxane, or any functional equivalent thereof, with tetrahydrofuran being the preferred solvent. The reaction is typically initiated at a temperature range from −78° C. to 40° C. with the preferred reaction temperature being between 0° C. and room temperature. The nucleoside is first stirred with a base (5 to 12 equivalents) such as N-methylimidazole, collidine, pyridine, 2,6-lutidine, 2, 6-.sup.tBu-pyridine, etc. a tertiary amine base, such as triethylamine, diisopropylethylamine, etc., or an alkyl Grignard reagent, such as tBuMgCl, tBuMgBr, MeMgCl, MeMgBr, etc. The phosphorochloridate (3-10 equivalents) is dissolved in the reaction solvent and added to the mixture of the nucleoside and base. The reaction is then allowed to stir over a period of time at a temperature between room temperature and 40° C. for a period of 30 min to 24 hr. with the preferred reaction temperature being room temperature and time being 24 hr. The solvent is removed from the reaction mixture and the product is purified by chromatography on silica gel.

[0830] A tenth embodiment of the present invention is directed to a product obtained by a process which comprises reacting a suitably substituted phosphochloridate compound 4 with a nucleoside analog 5

##STR00018##

[0831] wherein the substituents R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, X, Y, R.sup.6, X′, and base have their meanings as disclosed in the Detailed Description of the Invention.

[0832] This reaction can be performed in an anhydrous aprotic solvent or other suitable solvent, such as tetrahydrofuran, dioxane, or a mixture of tetrahydrofuran and dioxane, with tetrahydrofuran being the preferred solvent. The reaction is typically initiated at a temperature range from −78° C. to 40° C. with the preferred reaction temperature being between 0° C. and room temperature. The nucleoside is first stirred with a base (5 to 12 equivalents) such as N-methylimidazole, a tertiary amine base or tButyl Magnesium Chloride. A phosphorochloridate (3-10 equivalents (or suitable “phosphoro-(leaving group)-date”)) is dissolved in the reaction solvent and added to the mixture of the nucleoside and base. The reaction is then allowed to stir over a period of time at a temperature between room temperature and 40° C. for a period of 30 min to 24 hr. with the preferred reaction temperature being room temperature and time being 24 hr. The solvent is removed from the reaction mixture and the product is purified by chromatography on silica gel.

Compounds and Preparation

[0833] Phosphoramidate compounds of the present invention can be prepared by condensation of a nucleoside analog 5 with a suitably substituted phosphochloridate compound 4 (Scheme 1). The nucleoside analog is made by conventional procedures disclosed in any one of U.S. Published Application Nos. 2005/0009737, 2006/0199783, 2006/0122146, and 2007/0197463, each of which is incorporated by reference in its entirety.

[0834] Disclosed 1H-NMR values were recorded on a Varian AS-400 instrument. Mass spectral data were obtain using either a Micromass-Quattromicro API or a Waters Acquity.

[0835] Thus, by way of example only, a suitably substituted phenol can be reacted with phosphorus oxychloride (1) to afford an aryloxy phosphorodichloridate 2 (see Example 1) which is subsequently treated with a acid addition salt of an a-amino acid ester in the presence of TEA to afford an aryloxy phosphorochloridate 4. This arylalkoxy-amino acid phosphoramidate is reacted with the nucleoside analog to provide the product I (for procedure see, e.g., C. McGuigan et al. Antiviral Res. 1992 17:311-321; D. Curley et al. Antiviral Res. 1990 14:345-356; McGuigan et al. Antiviral Chem. Chemother 1990 1(2):107-113).

##STR00019##

[0836] The preparation of nucleoside phosphoramidates requires reacting an appropriately substituted phosphochloridate with a nucleoside containing a free 5′-hydroxyl moiety. In cases where only one hydroxyl group is present, preparation of the phosphoramidate usually proceeds smoothly when the phosphochloridate is reacted with the desired nucleoside. In cases where the nucleoside contains more than one free hydroxyl group, preparation of the appropriately protected nucleoside might be required. Silyl, acetonide or other alcohol protecting groups known in the art might be warranted for protection of the sugar moiety. For protection of the nucleoside base, protecting a free amino group may require amidine protection strategy.

[0837] Condensation of the phosphochloridate can be carried out on the unprotected nucleoside. Since the 5′-OH group of a nucleoside is much less hindered than the 3′-OH group, selective phosphoramidation is possible under carefully controlled conditions. After condensation to form a protected phosphoramidate nucleoside, deprotection to obtain the free phosphoramidate nucleoside can be carried out using standard protocols for nucleic acid chemistry. In many cases, the desired product is readily separated from the starting material using column chromatography on silica gel. The synthetic scheme is summarized in Scheme 1.

[0838] A further understanding of the disclosed embodiments will be appreciated by consideration of the following examples, which are only meant to be illustrative, and not limit the disclosed invention.

Example 1

General Procedure for Preparation of Phosphorodichloridates

[0839] ##STR00020##

[0840] A solution of the appropriate phenol R.sup.1—OH (1 eq) and triethylamine (1 eq.) in anhydrous ether was added dropwise to a stirred solution of phosphoryl trichloride 1 (1 eq) at 0° C. over a period of 3 hours under nitrogen. Then the temperature was warmed to room temperature, and the reaction was stirred overnight. The triethylamine salt was quickly removed with suction filtration and the filtrate concentrated in vacuo to dryness to afford 2 as an oil which was used without further purification.

Example 2

General Procedure for Preparation of Phosphorochloridates

[0841] ##STR00021##

[0842] A solution of triethylamine (2 eq) in anhydrous dichloromethane was added dropwise to a solution of aryloxy-phosphodichloridate 2 (1 eq) and the appropriate amino ester 3 (1 eq) in anhydrous dichloromethane with vigorous stirring at −78° C. over a period of 30 to 120 minutes. Then the reaction temperature was allowed to warm to room temperature and stirred over night. Solvent was removed. The residue was washed with ethyl ether and filtered, the filtrate was dried over reduced pressure to give 4.

Example 3

General Procedures for Nucleoside Phosphoramidate Derivatives

[0843] ##STR00022##

[0844] A solution of the appropriate phosphorochloridate 4 (6.5 equivalents) in anhydrous tetrahydrofuran (THF) was added to a mixture of nucleoside 5 (1 equivalent) and N-methylimidazole (8 equivalents) in anhydrous THF with vigorous stirring at room temperature and the reaction mixture was stirred overnight. The solvent was removed in vacuo and the crude was purified by column chromatography and/or preparative thin layer chromatography to give I.

Example 4

Preparation of 2′-deoxy-2′-fluoro-2′-C-methyluridine

[0845] ##STR00023##

[0846] 2′-Deoxy-2′-fluoro-2′-C-methylcytidine (1.0 g, 1 eq) (Clark, J., et al., J. Med. Chem., 2005, 48, 5504-5508) was dissolved in 10 ml of anhydrous pyridine and concentrated to dryness in vacuo. The resulting syrup was dissolved in 20 ml of anhydrous pyridine under nitrogen and cooled to 0° C. with stirring. The brown solution was treated with benzoyl chloride (1-63 g, 3 eq) dropwise over 10 min. The ice bath was removed and stirring continued for 1.5h whereby thin-layer chromatography (TLC) showed no remaining starting material. The mixture was quenched by addition of water (0.5 ml) and concentrated to dryness. The residue was dissolved in 50 mL of dichloromethane (DCM) and washed with saturated NaHCO.sub.3 aqueous solution and H.sub.2O. The organic phase was dried over NaSO.sub.4 and filtered, concentrated to dryness to give N.sup.4,3′,5′-tribenzoyl-2′-Deoxy-2′-fluoro-2′-C-methylcytidine (2.0 g, Yield: 91%).

[0847] N.sup.4,3′,5′-tribenzoyl-2′-Deoxy-2′-fluoro-2′-C-methylcytidine (2.0 g, 1 eq) was refluxed in 80% aqueous AcOH overnight. After cooling and standing at room temperature (15° C.), most of the product precipitated and then was filtered through a sintered funnel. White precipitate was washed with water and co-evaporated with toluene to give a white solid. The filtrate was concentrated and co-evaporated with toluene to give additional product which was washed with water to give a white solid. Combining the two batches of white solid gave 1.50 g of 3′,5′-dibenzoyl-2′-Deoxy-2′-fluoro-2′-C-methyluridine (Yield: 91%).

[0848] To a solution of 3′,5′-dibenzoyl-2′-Deoxy-2′-fluoro-2′-C-methyluridine (1.5 g, 1 eq) in MeOH (10 mL) was added a solution of saturated ammonia in MeOH (20 mL). The reaction mixture was stirred at 0° C. for 30 min, and then warmed to room temperature slowly. After the reaction mixture was stirred for another 18 hours, the reaction mixture was evaporated under reduced pressure to give the residue, which was purified by column chromatography to afford pure compound 2′-deoxy-2′-fluoro-2′-C-methyluridine (500 mg, Yield: 60%).

Example 5

Preparation of 2′-Deoxy-2′-fluoro-2′-C-methyluridine 5′-(phenyl methoxy-alanyl phosphate)

[0849] ##STR00024##

[0850] Phenyl methoxyalaninyl phosphorochloridate (1 g, 6.5 eq) dissolved in 3 mL of THF was added to a mixture of 2′-Deoxy-2′-fluoro-2′-C-methyluridine (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 8 eq) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed under reduced pressure to give the desired product (50.1 mg, 15.6%). .sup.1H NMR (DMSO-d.sub.6) δ 1.20-1.27 (m, 6H), 3.58 (d, J=16.0 Hz, 3H), 3.75-3.92 (m, 2H), 4.015-4.379 (m, 2H), 5.54 (t, J=10.2 Hz, 1H), 5.83-5.91 (m, 1H), 6.00-6.16 (m, 1H), 7.18 (d, J=8.0 Hz, 2H), 7.22 (s, 1H), 7.35 (t, J=4.4 Hz, 2H), 7.55 (s, 1H), 11.52 (s, 1H); MS, m/e 502 (M+1).sup.+.

Example 6

Preparation of 2′-Deoxy-2′-fluoro-2′-C-methyluridine 5′-(phenyl methoxy-valyl phosphate)

[0851] ##STR00025##

[0852] Phenyl methoxy-valyl phosphorochloridate (0.6 g, 3.6 eq) dissolved in 3 mL of THF was added to a mixture of 2′-Deoxy-2′-fluoro-2′-C-methyluridine (0.15 g, 1 eq) and N-methylimidazole (0.44 g, 9 eq) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed under reduced pressure to give the desired product (60 mg, 20%). .sup.1H NMR (DMSO-d.sub.6) δ 0.74-0.847 (m, 6H), 1.20-1.28 (m, 3H), 1.89-1.92 (m, 1H), 3.50-3.54 (m, 1H), 3.58 (d, J=10.4 Hz, 3H), 3.72-3.95 (m, 1H), 4.03-4.05 (m, 1H), 4.23-4.43 (m, 2H), 5.56 (t, J=16.0 Hz, 1H), 5.85-5.92 (m, 1H), 6.01-6.07 (m, 1H), 7.16-7.21 (m, 3H), 7.37 (t, J=8 Hz, 2H), 7.55-7.60 (m, 1H), 11.52 (s, 1H); MS, m/e 530 (M+1).sup.+.

Example 7

Preparation of 2′-Deoxy-2′-fluoro-2′-C-methyluridine 5′-(4-bromophenyl methoxy-valyl phosphate)

[0853] ##STR00026##

[0854] 4-Bromophenyl methoxy-valyl phosphorochloridate (1 g, 3.4 eq) dissolved in 3 mL of THF was added to a mixture of 2′-deoxy-2′-fluoro-2′-C-methyluridine (0.2 g, 1 eq) and N-methylimidazole (0.35 g, 6 eq) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed reduced pressure to give the desired product (120 mg, 26%). .sup.1H NMR (DMSO-d.sub.6) δ 0.72-0.82 (m, 6H), 1.19-1.26 (m, 3H), 1.86-1.92 (m, 1H), 3.48-3.50 (m, 1H), 3.56 (d, J=12.0 Hz, 3H), 3.72-3.89 (m, 1H), 3.96-4.03 (m, 1H), 4.22-4.37 (m, 2H), 5.54-5.60 (m, 1H), 5.85-5.91 (m, 1H), 5.98-6.13 (m, 1H), 7.15 (d, J=8.0 Hz, 2H), 7.49-7.56 (m, 3H), 11.53 (s, 1H); MS, m/e 608 (M+1).sup.+.

Example 8

Preparation of 2′-Deoxy-2′-fluoro-2′-C-methyluridine 5′-(4-bromophenyl methoxy-alanyl phosphate)

[0855] ##STR00027##

[0856] 4-Bromophenyl methoxy-alanyl phosphorochloridate (0.6 g, 5 eq) dissolved in 3 mL of THF was added to a mixture of 2′-deoxy-2′-fluoro-2′-C-methyluridine (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 7.8 eq) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed under reduced pressure to give the desired product (40 mg, 12%); .sup.1H NMR (DMSO-d.sub.6) δ 1.20-1.26 (m, 6H), 3.57 (d, J=2.8 Hz, 3H), 3.84 (s, 1H), 3.97-4.03 (m, 1H), 4.21-4.25 (m, 1H), 4.33-4.37 (m, 2H), 5.54-5.60 (m, 1H), 5.83-5.89 (m, 1H), 5.98-6.19 (m, 1H), 7.16 (t, J=10.2 Hz, 2H), 7.52-7.57 (m, 3H), 11.52 (s, 1H); MS, m/e 580(M+1).sup.+.

Example 9

Preparation of N.SUP.4.-(N,N-dimethylformamidinyl)-2′-deoxy-2′-fluoro-2′-C-methylcytidine

[0857] ##STR00028##

[0858] 2′-Deoxy-2′-fluoro-2′-C-methylcytidine (500 mg, 1.9 mmol) was stirred with dimethylformamide dimethyl acetal in DMF (10 mL). The resulting mixture was stirred at room temperature overnight. After solvent removal the crude product was used for next step without further purification.

Example 10

Preparation of 2′-Deoxy-2′-fluoro-2′-C-methylcytidine 5′-(phenyl methoxy-alanyl phosphate)

[0859] ##STR00029##

[0860] Phenyl methoxyalaninyl phosphorochloridate (0.6 g, 6 eq) dissolved in 3 mL of THF was added to a mixture of N.sup.4-(N,N-dimethylformamidinyl)-2′-deoxy-2′-fluoro-2′-C-methylcytidine (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 7.8 eq) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed under reduced pressure to give the desired product (62 mg, 20.6%). .sup.1H NMR (DMSO-d.sub.6) δ 1.16 (d, J=23.2 Hz, 3H), 1.22 (d, J=7.2 Hz, 3H), 3.56 (S, 3H), 3.69-3.75 (d, J=25.6 Hz, 1H), 3.82-3.86 (m, 1H), 3.96-3.98 (m, 1H), 4.21-4.34 (m, 2H), 5.68 (d, J=7.2 Hz, 1H), 5.75-5.77 (m, 1H), 6.07-6.16 (m, 1H), 7.15-7.19 (m, 3H), 7.2 (d, J=9.2 Hz, 2H), 7.39 (t, J=7.8 Hz, 2H), 7.48 (d, J=9.2 Hz, 1H); MS, m/e 501(M+1).sup.+.

Example 11

Preparation of 2′-Deoxy-2′-fluoro-2′-C-methylcytidine 5′-(4-bromophenyl methoxy-valyl phosphate)

[0861] ##STR00030##

[0862] 4-Bromophenyl methoxy-valyl phosphorochloridate (1.0 g, 3.4 eq.) dissolved in 3 mL of THF was added to a mixture of N.sup.4-(N,N-dimethylformamidinyl)-2′-deoxy-2′-fluoro-2′-C-methylcytidine (0.2 g, 1 eq.) and N-methylimidazole (0.35 g, 6 eq.) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure. The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed under reduced pressure to give the desired product as a white solid (59 mg, 13%); .sup.1H NMR (DMSO-d.sub.6) δ 0.74-0.83 (m, 6H), 1.12-1.20 (m, 3H), 1.89-1.92 (m, 1H), 3.49-3.51 (m, 1H), 3.55 (s, 3H), 3.59-3.68 (m, 1H), 3.72-3.83 (m, 1H), 4.21-4.39 (m, 2H), 5.70-5.72 (m, 1H), 5.76-5.83 (m, 1H), 6.04-6.16 (m, 1H), 7.15 (d, J=13.0 Hz, 2H), 7.26 (s, 1H), 7.33 (s, 1H), 7.46-7.55 (m, 1H), 7.56 (d, J=4.4 Hz, 2H); MS, m/e 607 (M+1).sup.+.

Example 12

Preparation of 2′-deoxy-2′-fluoro-2′-C-methylcytidine 5′-(phenyl methoxy-valyl phosphate)

[0863] ##STR00031##

[0864] Phenyl methoxy-valyl phosphorochloridate (0.6 g, 6 eq) dissolved in 3 mL of THF was added to a mixture of N.sup.4-(N,N-dimethylformamidinyl)-2′-deoxy-2′-fluoro-2′-C-methylcytidine (0.15 g, 1 eq) and N-methylimidazole (0.3 g, 7.8 eq) in 3 mL THF with vigorous stirring at room temperature, then the reaction was stirred overnight. Solvent was removed by reduced pressure The resulting crude product was dissolved in methanol purified by prep-HPLC on a YMC 25×30×2 mm column using a water/acetonitrile gradient elution mobile phase. The acetonitrile and water were removed under reduced pressure to give the desired product as a white solid (86 mg, 42.9%). .sup.1H NMR (DMSO-d.sub.6) δ 0.72-0.80 (m, 6H), 1.09-1.18 (m, 3H), 1.87-1.92 (m, 1H), 3.47-3.51 (m, 1H), 3.58 (s, 3H), 3.71-3.75 (m, 1H), 3.97 (t, J=11.2 Hz, 1H), 4.22-4.37 (m, 2H), 5.70 (d, J=8.0 Hz, 1H), 5.76-5.84 (m, 1H), 6.01-6.15 (m, 1H), 7.13-7.18 (m, 3H), 7.27 (s, 2H), 7.34 (d, J=4.0 Hz, 2H), 7.46-7.50 (m, 1H); MS, m/e 529 (M+1).sup.+.

EXAMPLES

[0865] Example numbers 13-54 and 56-66 are prepared using similar procedures described for examples 5-8. The example number, compound identification, and NMR/MS details are shown below:

TABLE-US-00032 [00032] Ex. R.sup.1 R.sup.2 R.sup.3a R.sup.3b R.sup.4 NMR/MS 13 Ph H H Me Et 1H NMR (DMSO-d.sub.6) δ 1.12-1.16 (m, 3H), 1.20-1.28 (m, 6H), 3.70-3.90 (m, 2H), 4.00-4.08 (m, 3H), 4.18-4.45 (m, 2H), 5.52-5.58 (m, 1H), 5.85-5.98 (m, 1H), 6.00-6.20 (m, 2H), 7.16-7.23 (m, 3H), 7.37-7.40 (m, 2H), 7.54-7.60 (m, 1H), 11.54 (s, 1H); MS, m/e 516.1 (M + 1)+ 14 1-Napth H H Me Bn 1H NMR (DMSO-d.sub.6) δ 1.18-1.30 (m, 6H), 3.78-4.10 (m, 3H), 4.38- 4.49 (m, 2H), 4.99-5.11 (m, 2H), 5.28-5.40 (m, 1H), 5.85-6.10 (m, 2H), 6.30-6.41 (m, 1H), 7.28-7.32 (m, 5H), 7.41-7.60 (m, 5H), 7.73- 7.76 (m, 1H), 7.94-8.11 (m, 1H), 8.13-8.15 (m, 1H), 11.50 (s, 1H); MS, m/e 628.4 (M + 1)+ 15 Ph H H H Me 1H NMR (DMSO-d.sub.6) δ 1.22 (d, J = 22.4 Hz, 3H), 3.59 (s, 3H), 3.63-3.69 (m, 2H), 3.74-3.8 (m, 1H), 4.02 (d, J = 11.2 Hz, 1H), 4.23-4.28 (m, 1H), 4.40-4.43 (m, 1H), 5.57-5.60 (m, 1H), 5.89 (d, J = 6.8 Hz, 1H), 6.00- 6.06 (m, 2H), 7.15-7.23 (m, 3H), 7.35-7.39 (m, 2H), 7.52 (d, J = 8 Hz, 1H), 11.52 (s, 1H); MS, m/e 487.97 (M + 1)+ 16 2,4-Cl—Ph H H Me Me 1H NMR (DMSO-d.sub.6) δ 1.22-1.28 (m, 6H), 3.57-3.60 (m, 3H), 3.84- 3.92 (m, 2H), 4.00-4.04 (m, 1H), 4.31-4.44 (m, 2H), 5.54-5.61 (m, 1H), 5.85-6.10 (m, 2H), 6.32-6.43 (m, 1H), 7.44-7.54 (m, 3H), 7.72- 7.75 (m, 1H), 11.54 (s, 1H); MS, m/e 570.2 (M + 1)+ 17 1-Napth H H Me Me 1H NMR (DMSO-d.sub.6) δ 1.15-1.27 (m, 6H), 3.51-3.55 (d, 3H), 3.85- 3.96 (m, 2H), 4.00-4.10 (m, 1H), 4.30-4.46 (m, 2H), 5.31-5.39 (m, 1H), 5.89-6.05 (m, 2H), 6.22-6.34 (m, 1H), 7.44-7.60 (m, 5H), 7.73-7.77 (m, 1H), 7.93-7.96 (m, 1H), 8.12-8.14 (m, 1H), 11.50 (s, 1H); MS, m/e 552.1 (M + 1)+ 18 Ph * H * Me 1H NMR (DMSO-d.sub.6) δ 1.19 (d, J = 22.8 Hz, 3H), 1.69-1.84 (m, 3H), 1.99-2.04 (m, 1H), 3.16-3.21 (m, 2H), 3.58 (s, 3H), 3.68-3.8 (m, 1H), 4.00 (m, 1H), 4.01-4.13 (m, 1H), 4.22-4.25 (m, 1H), 4.5 (d, J = 11.2 Hz, 1H), 5.54 (d, J = 8.0 Hz, 1H), 5.86 (s, 1H), 5.6 (d, J = 19.6 Hz, 1H), 7.15-7.2 (m, 3H), 7.34 (t, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 1H), 11.38 (s, 1H); MS, m/e 527.93 (M + 1)+ 19 Ph H H Me n-Bu 1H NMR (DMSO-d.sub.6) δ 0.80-0.90 (m, 3H), 1.20-1.35 (m, 8H), 1.48- 1.55 (m, 2H), 3.78-3.88 (m, 2H), 3.95-4.08 (m, 3H), 4.22-4.45 (m, 2H), 5.55-5.57 (t, 1H), 5.85-6.18 (m, 3H), 7.14-7.23 (m, 3H), 7.35-7.40 (m, 2H), 7.51-7.60 (d, 1H), 11.50 (s. 1H); MS, m/e 544.2 (M + 1)+ 20 Ph H H Me Bn 1H NMR (DMSO-d.sub.6) δ 1.20-1.30 (m, 6H), 3.72-4.05 (m, 3H), 4.23- 4.27 (m, 1H), 4.32-4.45 (m, 1H), 5.07-5.10 (t, 2H), 5.52-5.56 (t, 1H), 5.86-6.10 (m, 2H), 6.13-6.21 (m, 1H), 7.15-7.21 (m, 3H), 7.29-7.40 (m, 7H), 7.51-7.56 (d, 1H), 11.50 (s, 1H); MS, m/e 578.2 (M + 1)+ 21 4-F—Ph H H Me Me 1H NMR (DMSO-d.sub.6) δ 1.28-1.34 (m, 6H), 3.65 (d, J = 4 Hz, 3H), 3.85- 3.96 (m, 2H), 4.06-4.12 (m, 1H), 4.30-4.34 (m, 1H), 4.40-4.47 (m, 1H), 5.62-5.67 (m, 1H), 5.94-6.01 (m, 1H), 6.09 (d, J = 18.8 Hz, 1H), 6.17- 6.26 (m, 1H), 7.27-7.33 (m, 4H), 7.62 (d, J = 7.6 Hz, 1H), 11.61 (s, 1H); MS, m/e 519.94 (M + 1)+ 22 4-Cl—Ph H H Me Me 1H NMR (DMSO-d.sub.6) δ 1.22-1.28 (m, 6H), 3.58 (d, 2H), 3.70- 3.95 (m, 2H), 3.95-4.08 (m, 1H), 4.23-4.45 (m, 2H), 5.55-5.61 (t , 1H), 5.85-6.10 (m, 2H), 6.15-6.23 (m, 1H), 7.20-7.26 (m, 2H), 7.43-7.46 (m, 2H), 7.54-7.57 (d, 1H), 11.50 (s, 1H); MS, m/e 536.1 (M + 1)+ 23 3,4-C1—Ph H H Me Me 1H NMR (DMSO-d.sub.6) δ 1.13 (m, 6H), 3.49 (s, 3H), 3.61-3.85 (m, 2H), 3.90-3.93 (m, 1H), 4.16-4.22 (m, 1H), 4.27-4.31 (m, 1H), 5.47-5.52 (m, 1H), 5.82 (d, J = 11.6 Hz, 1H), 5.93 (d, J = 19.2 Hz, 1H), 6.15-6.25 (m, 1H), 7.13 (t, J = 9.6 Hz, 1H), 7.43 (d, J = 12 Hz, 2H), 7.57 (d, J = 6.0 Hz, 1H), 11.43 (s, 1H); MS, m/e 569.85 (M + 1)+ 24 Ph H H Me 2-Bu 1H NMR (DMSO-d.sub.6) δ 0.83 (d, J = 6.8 Hz, 6H), 1.20-1.26 (m, 6H), 1.79-1.86 (m, 1H), 3.73-3.90 (m, 4H), 4.01 (t, J = 11.2 Hz, 1H), 4.21- 4.28 (m, 1H), 4.33-4.42 (m, 1H), 5.54 (t, J = 7.6 Hz, 1H), 5.85-5.92 (m, 1H), 5.99-6.13 (m, 2H), 7.19 (t, J = 8 Hz, 3H), 7.36 (t, J = 7.6 Hz, 2H), 7.53 (d, J = 7.6 Hz, 1H), 11.52 (s, 1H); MS, m/e 544.00 (M + 1)+ 25 Ph H H Me i-Pr 1H NMR (DMSO-d.sub.6) δ 1.13-1.28 (m, 12H), 3.74-3.81 (m, 2H), 3.95- 4.08 (m, 1H), 4.20-4.45 (m, 2H), 4.83-4.87 (m, 1H), 5.52-5.58 (m, 1H), 5.84-6.15 (m, 3H), 7.17-7.23 (m, 3H), 7.35-7.39 (m, 2H), 7.54-7.57 (m, 1H), 11.50 (s, 1H); MS, m/e 530.2 (M + 1)+ 26 4-MeO—Ph H H Me n-Bu 1H NMR (400 MHz, DMSO-d.sub.6): δ = 0.78-0.82 (m, 3H), 1.29-1.47 (m, 8H), 1.49-1.54 (m, 2H), 3.66-3.87 (m, 5H), 3.96-4.02 (m, 3H), 4.21- 4.39 (m, 2H), 5.57 (t, J = 12.0 Hz, 1H), 5.84-6.05 (m, 3H), 6.90 (dd, J1 = 8.0 Hz, J2 = 4.0 Hz, 2H), 7.09-7.14 (dd, J1 = 16.0 Hz, J2 = 4.0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1H), 11.48-11.62 (s, 1H) 27 4-F—Ph H H Me Et 1H NMR (DMSO-d.sub.6) δ 1.12-1.28 (m, 9H), 3.72-3.94 (m, 2H), 3.98-4.10 (m, 3H), 4.21-4.42 (m, 2H), 5.55-5.61 (t, 1H), 5.85-6.20 (m, 3H), 7.18- 7.25 (m, 4H), 7.55-7.58 (d, 1H), 11.50 (s, 1H); MS, m/e 533.90 (M + 1)+ 28 4-F—Ph H H Me i-Pr 1H NMR (DMSO-d.sub.6) δ 1.13-1.30 (m, 12H), 3.74-3.85 (m, 2H), 3.98- 4.06 (m, 1H), 4.23-4.41 (m, 2H), 4.83-4.87 (m, 1H), 5.55-5.61 (t, 1H), 5.85-6.12 (m, 3H), 7.18-7.24 (m, 4H), 7.55-7.58 (d, 1H), 11.50 (s, 1H); MS, m/e 547.91 (M + 1)+ 29 4-F—Ph H H Me Bn 1H NMR (DMSO-d.sub.6) δ 1.10-1.23 (m, 6H), 3.65-3.89 (m, 3H), 4.10-4.30 (m, 2H), 4.96-5.00 (m, 2H), 5.46-5.50 (t, 1H), 5.75-5.96 (m, 2H), 6.04- 6.12 (m, 1H), 7.05-7.11 (m, 4H), 7.20-7.24 (d, 5H), 7.42-7.45 (d, 1H), 11.50 (s, 1H); MS, m/e 595.94 (M + 1)+ 30 4-MeO—Ph H H Me i-Pr 1H NMR (400 MHz, DMSO-d.sub.6): δ = 1.15-1.27 (m, 12H), 3.71-3.89 (m, 5H), 3.98-4.02 (m, 1H), 4.22-4.25 (m, 1H), 4.33-4.39 (m, 1H), 4.84- 4.87 (m, 1H), 5.57 (t, J = 12.0 Hz, 1H), 5.91-6.03 (m, 3H), 6.90 (d, J = 8.0 Hz, 2H), 7.09-7.14 (m, 2H), 7.55 (d, J = 8.0 Hz, 1H), 11.51 (s, 1H) 31 2-Cl—Ph H H Me Bn 1H NMR (DMSO-d.sub.6) δ 1.23 (m, 6 H), 3.93-4.00 (m, 3 H), 4.27-4.40 (m, 2H), 5.0 (t, J = 7.2 Hz, 2 H), 5.53 (m, 1 H), 5.80-6.0 (m, 2 H), 6.30 (m, 1H), 7.15 (d, J = 2.4 Hz, 1 H), 7.27 (m, 6 H), 7.51 (m, 3 H), 11.5 (s, 1 H); MS, m/e 579.87 (M + 1)+ / 596.78 (M + 18)+ 32 2,4-Cl—Ph H H Me n-Bu 1H NMR (DMSO-d.sub.6) δ = 0.82 (m, 3 H), 1.23 (m, 8 H), 1.47 (m, 2 H), 3.86 (m, 2 H), 3.84 (m, 3 H), 4.27-4.43 (m, 2H), 5.5 (m, 1 H), 6.02 (m, 2 H), 6.35 (m, 1H), 7.44 (m, 3 H), 7.77 (m, 1 H), 11.5 (s, 1 H); MS, m/e 611.87 (M + 1)+ 33 4-Me—Ph H H Me i-Pr 1H NMR (DMSO-d.sub.6) δ 1.14-1.27 (m, 12H), 2.17-2.26 (m, 3H), 3.73- 3.82 (m, 1H), 3.99-4.02 (m, 1H), 4.23-4.26 (m, 1H), 4.37-4.40 (m, 1H), 4.82-4.88 (m, 1H), 5.52-5.58 (m, 1H), 5.85-6.07 (m, 3H), 7.01- 7.20 (m, 4H), 7.55 (d, J = 16 Hz, 1H), 11.51 (s, 1H); MS, m/e 543.98 (M + 1)+; 1108.86 (2M + 23)+ 34 4-F—Ph H H Me n-Bu 1H NMR (DMSO-d.sub.6) δ 0.82-0.89 (m, 3H), 1.20-1.31 (m, 8H), 1.48- 1.53 (m, 2H), 3.77-3.90 (m, 2H), 3.95-4.10 (m, 3H), 4.21-4.45 (m, 2H), 5.56-5.61 (t, 1H), 5.83-6.20 (m, 3H), 7.18-7.25 (m, 4H), 7.55-7.58 (d, 1H), 11.50 (s, 1H); MS, m/e 584.1 (M + 23)+ 35 3,4-diCl—Ph H H Me Et 1H NMR (DMSO-d.sub.6) δ 1.12-1.31 (m, 9H), 3.77-3.92 (m, 2H), 3.95-4.08 (m, 3H), 4.21-4.45 (m, 2H), 5.56-5.62 (t, 1H), 5.80-6.11 (m, 2H), 6.18- 6.33 (m, 1H), 7.18-7.25 (m, 1H), 7.49-7.56 (d, 2H), 7.62-7.67 (m, 1H), 11.50 (s, 1H); MS, m/e 606.1 (M + 23)+ 36 2-Cl—Ph H H Me i-Pr 1H NMR (400 MHz, DMSO-d.sub.6): δ = 1.12-1.16 (m, 6H), 1.21-1.27 (m, 6H), 3.79-3.85 (m, 2H), 4.00-4.07 (m, 1H), 4.28-4.32 (m, 1H), 4.38- 4.43 (m, 1H), 4.83-4.87 (m, 1H), 5.56 (dd, J1 = 16.0 Hz, J2 = 8.0 Hz, 1H), 5.85-6.12 (m, 2H), 6.20-6.33 (m, 1H), 7.19-7.22 (m, 1H), 7.33 (t, J = 16.0 Hz, 1H), 7.48-7.55 (m, 3H), 11.55 (s, 1H) 37 4-MeO—Ph H H Me Bn 1H NMR (400 MHz, DMSO-d.sub.6): δ = 1.19-1.26 (m, 6H), 3.69-3.70 (s, 3H), 3.87 (m, 2H), 3.99 (m, 1H), 4.20-4.21 (m, 1H), 4.35 (m, 1H), 5.07-5.09 (m, 2H), 5.54 (t, J = 16.0 Hz, 1H), 5.85-5.92 (m, 1H), 6.04- 6.10 (m, 2H), 6.86 (d, J = 8.0 Hz, 2H), 7.09 (dd, J1 = 16.0 Hz, J2 = 4.0 Hz, 2H), 7.30-7.34 (m, 5H), 7.53 (s, 1H), 11.52 (s, 1H) 38 Ph H H Me n-Pen 1H NMR (DMSO-d.sub.6) δ 0.79-0.81 (m, 3H), 1.17-1.23 (m, 10H), 3.74- 3.81 (m, 2H), 3.94-3.96 (m, 3H), 4.19-4.36 (m, 2H), 5.49-5.54 (m, 1H), 5.87-6.08 (m, 3H), 7.14-7.33 (m, 3H), 7.31-7.35 (m, 2H), 7.51 (d, J = 8 Hz, 1H), 11.51 (s, 1H); MS, m/e 557.9 (M + 1)+; 1136.88 (2M + 23)+ 39 4-Cl—Ph H H Me i-Pr 1H NMR (DMSO-d.sub.6) δ 1.04-1.19 (m, 12H), 3.76-3.80 (m, 2H), 3.98- 4.08 (m, 1H), 4.42-4.42 (m, 2H), 4.82-4.85 (m, 1H), 5.55-5.60 (m, 1H), 5.80-6.20 (m, 3H), 7.20-7.25 (m, 2H), 7.43 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8 Hz, 1H), 11.51 (s, 1H); MS, m/e 563.88 (M + 1)+; 1148.73 (2M + 23)+ 40 4-Cl—Ph H H Me n-Bu 1H NMR (DMSO-d.sub.6) δ 0.85 (t, J = 7.2 Hz, 3H), 1.22-1.33 (m, 8H), 1.45-1.53 (m, 2H), 3.80-3.87 (m, 2H), 3.96-4.04 (m, 3H), 4.24- 4.27 (m, 1H), 4.35-4.39 (m, 1H), 5.56-5.61 (m, 1H), 5.82-6.11 (m, 2H), 6.15-6.18 (m, 1H), 7.20-7.56 (m, 4H), 7.51-7.57 (m, 1H), 11.54 (s, 1H); MS, m/e 577.95 (M + 1)+ 41 4-Cl—Ph H H Me Et 1H NMR (DMSO-d.sub.6) δ 1.14 (t, J = 7.0 Hz, 3H), 1.20-1.28 (m, 6H), 3.77-3.88 (m, 2H), 3.99-4.07 (m, 3H), 4.24-4.28 (m, 1H), 4.34- 4.43 (m, 1H), 5.56-5.61 (m, 1H), 5.86-6.13 (m, 2H), 6.15-6.24 (m, 1H), 7.20-7.26 (m, 2H), 7.44 (d, J = 7.6 Hz, 2H), 7.55 (d, J = 7.6 Hz, 1H), 11.55 (s, 1H); MS, m/e 549.11 (M + 1)+ 42 4-Me—Ph H H Me n-Bu 1H NMR (DMSO-d.sub.6) δ 0.79-0.83 (m, 3H), 1.17-1.28 (m, 8H), 1.45- 1.47 (m, 2H), 2.22 (d, J = 2.8 Hz, 1H), 3.70-3.90 (m, 2H), 3.95-3.98 (m, 3H), 4.10-4.40 (m, 2H), 5.51 (t, 1H), 5.80-5.90 (m, 1H), 5.95-6.05 (m, 2H), 7.02-7.06 (m, 2H), 7.51 (t, J = 4.2 Hz, 4H), 7.51 (d, 1H), 11.51 (s, 1H); MS, m/e 557.99 (M + 1)+; 1136.84 (2M + 23)+ 43 4-Me—Phe H H Me Bn 1H NMR (DMSO-d.sub.6) δ 1.16-1.24 (m, 6H), 2.22 (s, 3H), 3.65-4.03 (m, 3H), 4.11-4.38 (m, 2H), 5.04-5.05 (m, 2H), 5.48-5.50 (m, 1H), 5.77-5.87 (m, 1H), 5.90-6.11 (m, 2H), 6.98-7.10 (m, 4H), 7.28-7.32 (m, 5H), 7.50 (t, 1H), 11.48 (s, 1H); MS, m/e 592.00 (M + 1)+. 44 Ph H H Et Me 1H NMR (DMSO-d.sub.6) δ 0.70-0.80 (m, 3H), 1.11-1.26 (m, 3H), 1.42- 1.61 (m, 2H), 3.50-3.54 (m, 3H), 3.58-3.80 (m, 2H), 3.91-4.02 (m, 1H), 4.12-4.38 (m, 2H), 5.47-5.52 (m, 1H), 5.90-6.03 (m, 2H), 7.08- 7.16 (m, 3H), 7.26-7.35 (m, 2H), 7.48 (t, 1H), 11.45 (s, 1H); MS, m/e 515.95 (M + 1)+; 1052.82 (2M + 23)+ 45 Ph H H Me 4-F—Bn .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 1.20-1.26 (m, 6H), 3.80-3.93 (m, 2H), 3.98 (s, 1H), 4.25-4.26 (m, 1H), 4.36-4.37 (m, 1H), 5.07 (s, 2H), 5.52-5.55 (m, 1H), 5.86-5.87 (m, 1H), 5.98-6.04 (m, 1H), 6.14-6.17 (m, 1H), 7.15-7.20 (m, 5H), 7.36 (dd, J = 20.0, 8.0 Hz, 4H), 7.54 (s, 1H), 11.55 (s, 1H) 46 4-Cl—Ph H H Me n-Bu .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 1.21-1.28 (m, 6H), 3.71-3.88 (m, 1H), 3.91-3.98 (m, 1H), 4.00-4.01 (m, 1H), 4.23-4.27 (m, 1H), 4.35- 4.38 (m, 1H), 5.08 (d, J = 4.0 Hz, 2H), 5.57 (dd, J = 12.0, 8.0 Hz, 1H), 5.91 (d, J = 8.0 Hz, 1H), 6.01 (d, J = 8.0 Hz, 1H), 6.22-6.24 (m, 1H), 7.17-7.23 (m, 2H), 7.31-7.40 (m, 7H), 7.53 (s, 1H), 11.50 (s, 1H) 47 Ph H H Me 3-Me-1-Bu .sup.1H NMR (DMSO-d.sub.6) δ 0.80-0.82 (m, 6H), 1.18-1.40 (m, 8H), 1.50- 1.58 (m, 1H), 3.71-3.82 (m, 3H), 3.97-3.4.01 (m, 3H), 4.21-4.40 (m, 2H), 5.30 (t, J = 8.6 Hz, 1H), 5.81-6.10 (m, 3H), 7.15-7.20 (m, 3H), 7.32-7.36 (m, 2H), 7.48 (d, J = 8.4 Hz, 1H), 11.38 (s, 1H); MS, m/e 557.98 (M + 1).sup.+; 1136.88 (2M + 23).sup.+ 48 3,4-diCl—Ph H H Me Bn .sup.1H NMR (DMSO-d.sub.6) δ 1.05-1.37 (m, 6H), 3.71-3.82 (m, 1H), 3.87- 4.02 (m, 2H), 4.28-4.29 (m, 1H), 4.36-4.38 (m, 1H), 5.04 (d, J = 5.2 Hz, 2H), 5.55-5.64 (m, 1H), 5.85-5.94 (m, 1H), 6.00-6.05 (m, 1H), 6.29- 6.40 (m, 1H), 7.17-7.24 (m, 1H), 7.30-7.41 (m, 5H), 7.45-7.58 (m, 2H), 7.61 (d, J = 4.0 Hz, 1H), 11.53 (s, 1H); MS, m/e 545.80 (M + 1).sup.+; 49 Ph H H Me c-Hex .sup.1H NMR (DMSO-d.sub.6) δ 1.18-1.41 (m, 12H), 1.59-1.67 (m, 4H), 3.74- 13.80 (m, 1H), 3.96-4.02 (m, 1H), 4.19-4.26 (m, 1H), 4.31-4.39 (m, 1H), 4.60 (s, 1H), 5.52 (t, J = 7.8 Hz, 1H), 5.80-6.09 (m, 3H), 7.15- 7.20 (m, 3H), 7.32-7.36 (m, 2H), 7.52 (d, J = 8 Hz, 1H), 11.50 (s, 1H); MS, m/e 569.98 (M + 1).sup.+; 592.14 (M + 23).sup.+ 50 Ph H Me H n-Bu 1H NMR (DMSO-d.sub.6) δ 0.76 (t, J = 7.2 Hz, 3H), 1.10-1.22 (m, 8H), 1.38-1.43 (m, 2H), 3.72-3.75 (m, 2H), 3.87-3.93 (m, 3H), 4.14-4.21 (m, 1H), 4.23-4.33 (m, 1H), 5.46-5.54 (m, 1H), 5.84-6.11 (m, 3H), 7.09-7.14 (m, 2H), 7.27-7.32 (m, 2H), 7.34-7.51 (m, 1H), 11.47 (s, 1H); MS, m/e 543.98 (M + 1)+ 51 Ph H Me H i-Pr 1H NMR (DMSO-d.sub.6) δ 1.39 (d, J = 7.2 Hz, 6H), 1.19-1.29 (m, 6H), 3.65-3.75 (m, 2H), 3.95-4.05 (m, 1H), 4.20-4.22 (m, 1H), 4.31-4.33 (m, 1H), 4.79-4.82 (m, 1H), 5.48-5.57 (m, 1H), 5.84-5.91 (m, 1H), 5.96-6.07 (m, 2H), 7.12-7.35 (m, 5H), 7.44-7.54 (m, 1H), 11.49 (s, 1H); MS, m/e 529.96 (M + 1)+ 52 Ph H Me H Bn .sup.1H NMR (DMSO-d.sub.6) δ 1.18-1.28 (m, 6H), 3.70-3.83 (m, 1H), 3.87- 3.94 (m, 1H), 3.99-4.01 (m, 1H), 4.23-4.26 (m, 1H), 4.33-4.37 (m, 1H), 5.03-5.12 (m, 2H), 5.51-5.59 (m, 1H), 5.87-5.90 (m, 1H), 5.95- 6.07 (m, 1H), 6.10-6.27 (m, 1H), 7.15-7.23 (m, 3H), 7.31-7.38 (m, 7H), 7.47-7.56 (m, 1H), 11.50 (s, 1H); MS, m/e 577.99 (M + 1)+ 53 2-Cl—Ph H H Me n-Bu .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 0.81-0.86 (m, 3H), 1.21-1.31 (m, 8H), 1.46-1.52 (m, 2H), 3.84-3.90 (m, 2H), 3.97-4.04 (m, 3H), 4.27- 4.41 (m, 2H), 5.53-5.58 (m, 1H), 5.82-5.95 (m, 1H), 5.96-6.10 (m, 1H), 6.27-6.31 (m, 1H), 7.19-7.22 (m, 1H), 7.34 (dd, J = 8.0, 4.0 Hz, 1H), 7.47-7.55 (m, 3H), 11.55 (s, 1H) 54 4-Br—Ph H H Me i-Pr .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 1.10-1.14 (m, 6H), 1.20-1.27 (m, 6H), 3.74-3.81 (m, 2H), 3.99-4.01 (m, 1H), 4.21-4.25 (m, 1H), 4.37- 4.38 (m, 1H), 4.81-4.85 (m, 1H), 5.58 (dd, J = 8.0, 4.0 Hz, 1H), 5.82- 5.95 (m, 1H), 5.96-6.09 (m, 1H), 6.10-6.13 (m, 1H), 7.18 (dd, J = 12.0, 8.0 Hz, 2H), 7.53-7.57 (m, 3H), 11.52 (s, 1H) 55 4-F—Ph H H Me c-Hex .sup.1H NMR (DMSO-d.sub.6) δ 1.20-1.44 (m, 12H), 1.60-1.71 (m, 4H), 3.75- 4.02 (m, 2H), 3.94-4.02 (m, 1H), 4.19-4.26 (m, 2H), 4.59-4.61 (m, 1H), 5.57 (t, J = 8.4 Hz, 1H), 5.85-6.06 (m, 3H), 7.17-7.23 (m, 4H), 7.54 (d, J = 8.4 Hz, 1H), 11.50 (s, 1H); MS, m/e 587.92 (M + 1).sup.+ 56 4-Br—Ph H H Me c-Hex .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ = 1.18-1.46 (m, 12H), 1.61-1.69 (m, 4H), 3.75-3.82 (m, 2H), 3.95-4.08 (m, 1H), 4.25-4.28 (m, 1H), 4.38 (s, 1H), 4.60-4.62 (m, 1H), 5.56-5.60 (m, 1H), 5.82-5.95 (m, 1H), 6.02- 6.20 (m, 2H), 7.09-7.20 (m, 2H), 7.53-7.57 (m, 3H), 11.52 (s, 1H) MS, m/e 650.0 (M + 3).sup.+ 57 Ph H H Et i-Pr .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ = 0.75-0.82 (m, 3H), 1.12-1.26 (m, 9H), 1.52-1.59 (m, 2H), 3.55-3.68 (m, 1H), 3.72-3.85 (m, 1H), 3.95- 4.08 (m, 1H), 4.18-4.28 (m, 1H), 4.32-4.41 (m, 1H), 4.83-4.86 (m, 1H), 5.55 (m, J = 7.6 Hz, 1H), 5.99-6.04 (m, 2H), 6.05-6.10 (m, 1H), 7.14-7.21 (m, 3H), 7.33-7.37 (m, 2H), 7.52-7.54 (m, 1H), 11.53 (s, 1H); MS, m/e 566.07 (M + 23).sup.+ 58 Ph H H Et c-Hex .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 0.75-0.88 (m, 3H), 1.26-1.46 (m, 9H), 1.52-1.69 (m, 6H), 3.60-3.63 (m, 1H), 3.72-3.90 (m, 1H), 4.02- 4.03 (m, 1H), 4.24-4.27 (m, 1H), 4.37-4.38 (m, 1H), 4.63-4.65 (m, 1H), 5.55 (dd, J = 8.0 Hz, 4.4 Hz, 1H), 5.80-5.95 (m, 1H), 6.00-6.07 (m, 2H), 7.15-7.22 (m, 3H), 7.34-7.38 (m, 2H), 7.54 (d, J = 8.0 Hz, 1H), 11.55 (s, 1H); MS, m/e 584.01 (M + 1).sup.+, 606.17 (M + 23).sup.+ 59 4-F—Ph H H Et c-Hex .sup.1H NMR (DMSO-d.sub.6) δ 0.75-0.84 (m, 3H), 1.24 (d, J = 22.8 Hz, 3H), 1.29-1.47 (m, 6H), 1.51-1.70 (m, 6H), 3.59-3.66 (m, 1H), 3.77-3.84 (m, 1H), 3.98-4.04 (m, 1H), 4.21-4.27 (m, 1H), 4.34-4.41 (m, 1H), 4.60-4.65 (m, 1H), 5.56-5.60 (m, 1H), 5.84-5.90 (m, 1H), 6.00-6.08 (m, 2H), 7.20-7.24 (m, 4H), 7.56 (d, J = 8.0 Hz, 1H), 11.49 (s, 1H); MS, m/e 602.00 (M + 1).sup.+ 60 Ph H H Me F—CH.sub.2—CH.sub.2 .sup.1H NMR (DMSO-d.sub.6) δ 1.18-1.25 (m, 6H), 3.71-3.89 (m, 2H), 3.92-3.99 (m, 1H), 4.19-4.27 (m, 4H), 4.48-4.61 (m, 2H), 3.94-3.98 (m, 2H), 4.11-4.23 (m, 4H), 5.47-5.52 (m, 1H), 6.01-6.11 (m, 1H), 5.90-6.14 (m, 2H), 7.15-7.21 (m, 3H), 7.32-7.36 (m, 2H), 7.46-7.57 (m, 1H), 11.49 (s, 1H); MS, m/e 533.86 (M + 1).sup.+ 61 Ph H H Me F.sub.2CH—CH.sub.2— .sup.1H NMR (DMSO-d.sub.6) δ 1.17-1.24 (m, 6H), 3.67-3.81 (m, 1H), 3.89- 3.98 (m, 2H), 4.21-4.36 (m, 4H), 5.48-5.53 (m, 1H), 5.82-6.05 (m, 2H), 6.18-6.22 (m, 2H), 7.15-7.20 (m, 3H), 7.32-7.36 (m, 2H), 7.51 (s, 1H), 11.50 (s, 1H); MS, m/e 551.92 (M + 1).sup.+; 62 Ph H H Me (CF.sub.3).sub.2—CH— .sup.1H NMR (DMSO-d.sub.6) δ 1.13-1.29 (m, 6H), 3.67-3.81 (m, 1H), 3.94- 4.32 (m, 4H), 5.47 (t, J = 8 Hz 1H), 5.82-6.01 (m, 2H), 6.33-6.36 (m, 1H), 6.70-6.78 (m, 1H), 7.09-7.15 (m, 3H), 7.28-7.32 (m, 2H), 7.43- 7.46 (m, 1H), 11.44 (s, 1H); MS, m/e 637.90 (M + 1).sup.+ 63 Ph H H Me (CH.sub.2F).sub.2—CH— .sup.1H NMR (DMSO-d.sub.6) δ 1.20-1.29 (m, 6H), 3.70-3.90 (m, 1H), 3.91- 4.12 (m, 2H), 4.20-4.33 (m, 1H), 4.35-4.48 (m, 1H), 4.52-4.55 (m, 2H), 4.63-4.67 (m, 2H), 5.20-5.35 (m, 1H), 5.56 (t, J = 8.4 Hz, 1H), 5.80-5.95 (m, 1H), 5.95-6.10 (m, 1H), 6.18-6.21 (m, 1H), 7.18-7.23 (m, 3H), 7.35-7.39 (m, 2H), 7.54 (s, 1H), 11.55 (s, 1H); MS, m/e 565.98 (M + 1).sup.+ 64 Ph H H Me c-Pr—CH.sub.2— .sup.1H NMR (DMSO-d.sub.6) δ 0.20-0.24 (m, 2H), 0.47-0.48 (m, 2H), 0.76- 0.84 (m, 3H), 1.03-1.05 (m, 1H), 1.23 (dd, J = 22.4 6.8 Hz 3H), 1.55- 1.60 (m, 2H), 3.61-3.68 (m, 1H), 3.81-3.89 (m, 3H), 3.98-4.03 (m, 1H), 4.23-4.29 (m, 1H), 4.35-4.41 (m, 1H), 5.56-6.00 (m, 1H), 5.88-5.91 (m, 1H), 6.04-6.10 (m, 2H), 7.20-7.24 (m, 4H), 7.55 (d, J = 7.6 Hz 1H), 11.53 (s, 1H); MS, m/e 573.17 (M + 1).sup.+ 65 Ph H H Et c-Pen .sup.1H NMR (DMSO-d.sub.6) δ 0.75-0.83 (m, 3H), 1.20-1.28 (m, 3H), 1.49- 1.63 (m, 8H), 1.76-1.80 (m, 2H), 3.58-3.60 (m, 1H), 3.70-3.82 (m, 1H), 3.98-4.05 (m, 1H), 4.24-4.26 (m, 1H), 4.37-4.42 (m, 1H), 5.03 (s, 1H), 5.54-5.57 (m, 1H), 5.90-6.00 (m, 1H), 6.02-6.07 (m, 2H), 7.15- 7.22 (m, 3H), 7.35-7.39 (m, 2H) 7.55 (d, J = 8.0 Hz, 1H), 11.55 (s, 1H); MS, m/e 570.03 (M + 1).sup.+ *R.sup.2 and R.sup.3b together are —(CH.sub.2).sub.3— as derived from L-proline

The Purification Procedure by Prep-HPLC:

[0866] Crude products were dissolved in methanol. Injection volumes of these solutions were 5 mL.

[0867] The preparative HPLC system including 2 sets of Gilson 306 pumps, a Gilson 156 UV/Vis detector, a Gilson 215 injector & fraction collector, with Unipoint control software. A Ymc 25×30×2 mm column was used. The mobile phase was HPLC grade water (A), and HPLC grade acetonitrile (B). Fractions were collected into 100*15 mm glass tubes.

[0868] HPLC gradient is shown in Table 1. Once the gradient was selected, acetonitrile solution was injected into HPLC system, and then fractions collected according to UV peaks. After the separation, each glass tubes were run MS test to collect the desired compounds. The fractions with target MS were combined in a well-weighted flask. Most of acetonitrile was removed under reduce pressure and the remaining solution was freeze-dried to give desired compound.

TABLE-US-00033 TABLE 1 Preparative HPLC gradient Time (min) Flow rate (mL/min) % A % B 0 15 90 10 30 15 60 40

Preparation of Example 66

[0869] ##STR00033## ##STR00034##

Preparation of Compound (b)

[0870] To a solution of compound a (1 g, 2.69 mmol) in anhydrous THF (30 mL) was added dropwise 1 M solution of LiAl(OBu-t).sub.3H in THF (2.69 mL, 2.69 mmol) at −20° C. The reaction mixture was stirred for 2-3 h at the same temperature. EtOAc (100 mL) was added followed by saturated NH.sub.4Cl solution (10 mL) and reaction mixture was slowly brought to room temperature. Reaction mixture was extracted with EtOAc and washed with 1N HCl and water. Combined organic phase was evaporated to give 0.8 g of crude compound b as transparent oil, which was used directly for next reaction.

Preparation of Compound (d)

[0871] To a solution of compound b (0.8 g, 2.1 mmol), compound c (0.45 g, 2.5 mmol) and Ph.sub.3P (0.56 g, 2.1 mmol) in anhydrous THF (20 mL) under nitrogen atmosphere was added DEAD (1.8 mL). The reaction mixture was stirred at room temperature overnight. The reaction solution was concentrated under reduce pressure. The residue was separated by preparative layer chromatography (hexanes:EtOAc=3:1) to give crude compound d (0.8 g). The crude compound d was used to the next step without further purification.

Preparation of Compound (e)

[0872] Compound d (0.8 g, 1.57 mmol) was dissolved in THF (2 mL) and THF saturated with ammonia (5 mL) was then added to this solution. The reaction mixture was heated to 90° C. overnight. After 18 hours, the solution was cooled to room temperature by ice water, then the solvent was removed under reduced pressure and the residue was purified by column to give compound e (0.75 g) for the next step.

Preparation of Compound (f)

[0873] Compound e (0.5 g, 1.01 mmol) was dissolved in methanol (2 mL) and methanol was saturated with ammonia (5 mL) was then added to this solution. The reaction mixture was stirred at room temperature overnight. After 18 hours, the solvent was removed under reduced pressure and the residue was purified by column to give crude compound f (0.15 g) for the next step.

Preparation of Compound (i)

[0874] A solution of triethylamine (1.07 g, 10.6 mmol) in anhydrous dichloromethane (15 mL) was added dropwise to a solution of compound g (1.16 g, 5.3 mmol) and compound h (1.31 g, 5.3 mmol) in dichloromethane (10 mL) with vigorous stirring at −78° C. over a period of 2 hours. After completion of addition, the reaction temperature was allowed to warm to room temperature gradually and stirred over night. Then the solvent was removed under vacuum and anhydrous ether 20 mL was added and the precipitated salt was filtered and the precipitate was washed with ether. The combined organic phase was concentrated to give the colorless oil of compound i (1.0 g).

Preparation of Compound 66

[0875] To a solution of compound j (0.1 g, 0.35 mmol) dissolved in 10 mL of anhydrous THF, stirred and added 0.4 g NMI till the solution became clear, added compound i (0.8 g, 2.89 mmol) in 10 mL THF dropwise, stirred at r.t. overnight. Compound purity and identification was confirmed by LCMS. The solvent was evaporated and purified by Prep-HPLC to afford 66. (25 mg, Yield: 13.6%). .sup.1H NMR (DMSO-d.sub.6) δ 1.08 (d, J=22.8 Hz, 3H), 1.17-1.24 (m, 3H), 3.50-3.52 (m, 3H), 3.78-3.83 (m, 1H), 4.10-4.13 (m, 1H), 4.24-4.44 (m, 2H), 5.85-5.92 (m, 1H), 6.01-6.11 (m, 1H), 6.2.-6.27 (m, 1H), 7.08-7.19 (m, 4H), 7.31-7.38 (m, 3H), 8.15 (s, 1H), 8.26 (s, 1H); MS, m/e 525 (M+1).sup.+.

Example numbers 67-74, identified below, were prepared using similar procedures disclosed for Example 66, above.

TABLE-US-00034 [00035] Example R.sup.11 R.sup.10 NMR/MS 67 OH NH.sub.2 .sup.1H NMR(DMSO-d.sub.6) δ 1.06-1.13 (m, 3H), 1.20-1.24 (m, 3H), 3.27-3.33 (m, 3H), 3.56 (s, 1H), 3.82-3.88 (m, 1H), 4.07-4.13 (m, 1H), 4.25-4.40 (m, 2H), 5.85-5.87 (m, 1H), 5.98-6.09 (m, 2H), 6.59 (s, 32H), 7.14-7.37 (m, 3H), 7.35-7.37 (m, 2H), 7.79 (d, J = 7.2 Hz, 1H), 10.69 (s, 1H); MS, m/e 541 (M + 1).sup.+; 68 NH.sub.2 NH.sub.2 .sup.1H NMR (DMSO-d.sub.6) δ 1.07 (d, J = 22.8 Hz, 3H), 1.19 (d, J = 7.2 Hz, 3H), 3.51 (s, 3H), 3.62 (s, 1H), 3.75-3.81 (m, 1H), 4.05-4.11 (m, 1H), 4.27-4.42 (m, 2H), 5.79-5.83 (m, 1H), 5.92 (s, 2H), 6.00-6.09 (m, 2H), 6.75 (s, 2H), 7.08-7.17 (m, 3H), 7.31-7.35 (m, 2H), 7.78 (s, 1H); MS, m/e 540 (M + 1).sup.+; 69 NH.sub.2 c-Pentyl-NH— .sup.1H NMR (DMSO-d.sub.6) δ 1.05 (d, J = 22.8 Hz, 3H), 1.09-1.19 (m, 3H), 1.48 (s, 4H), 1.66 (s, 1H), 1.86 (s, 1H), 3.54 (d, J = 14 Hz, 3H), 3.65 (s, 1H), 4.25-4.43 (m, 4H), 5.71-5.82 (m, 1H), 5.94-6.04 (m, 4H), 7.11-7.24 (m, 3H), 7.26-7.34 (m, 2H), 7.77 (d, J = 3.6 Hz, 1H); MS, m/e 608 (M + 1).sup.+ 70 NH.sub.2 [00036] .sup.1H NMR (DMSO-d.sub.6) δ 1.07 (d, J = 22.4 Hz, 3H), 2.35-2.38 (m, 2H), 3.54 (d, J = 9.2 Hz, 3H), 3.59-3.62 (m, 2H), 3.65 (s, 1H), 3.75-3.82 (m, 1H), 4.01-4.13 (m, 2H), 4.22-4.40 (m, 6H), 5.75-5.85 (m, 1H), 6.00-6.07 (m, 4H), 7.15-7.21 (m, 3H), 7.32-7.35 (m, 2H), 7.79 (d, J = 4.0 Hz, 1H); MS, m/e 580 (M + 1).sup.+ 71 NH.sub.2 Et.sub.2N— .sup.1H NMR (DMSO-d.sub.6) δ 1.06-1.28 (m, 12H), 3.55 (d, J = 4.8 Hz, 3H), 3.79-3.87 (m, 4H), 4.07-4.12 (m, 2H), 4.29-4.42 (m, 3H), 5.75-5.82 (m, 1H), 5.94 (s, 2H), 6.04-6.10 (m, 2H), 7.14-7.22 (m, 3H), 7.31-7.37 (m, 2H), 7.82 (d, J = 4.4 Hz, 1H); MS, m/e 596 (M + 1).sup.+ 72 NH.sub.2 n-Propyl-NH— .sup.1H NMR (DMSO-d.sub.6) δ 0.84 (t, J = 7.2 Hz, 3H), 1.01-1.01 (m, 3H), 1.09-1.12 (m, 3H), 1.51-1.56 (m, 2H), 3.48 (d, J = 15.2 Hz, 3H), 3.79-3.82 (m, 1H), 4.04-4.05 (m, 1H), 4.27-4.38 (m, 3H), 5.72-5.79 (m, 1H), 5.98-6.04 (m, 4H), 7.13-7.20 (m, 3H), 7.26-7.32 (m, 2H), 7.76 (d, J = 5.2 Hz, 1H); MS, m/e 582 (M + 1).sup.+ 73 NH.sub.2 c-Butyl-NH— .sup.1H NMR (DMSO-d.sub.6) δ 1.02-1.08 (m, 3H), 1.18 (d, J = 4.8 Hz, 3H), 1.44-1.61 (m, 2H) , 2.02-2.17 (m, 4H), 3.51 (d, J = 10.8 Hz, 3H), 3.78-3.83 (m, 1H), 4.03-4.06 (m, 1H), 4.27-4.38 (m, 2H), 4.53-4.62 (m, 1H), 5.68-5.79 (m, 1H), 5.95-6.04 (m, 4H), 7.11-7.18 (m, 3H), 7.29-7.35 (m, 2H), 7.51-7.58 (m, 1H), 7.78 (d, J = 5.2 Hz, 1H); MS, m/e 594 (M + 1).sup.+ 74 NH.sub.2 [00037] .sup.1H NMR (DMSO-d.sub.6) δ 0.97-1.20 (m, 6H), 2.18 (s, 3H), 2.19 (s, 4H), 3.43-3.47 (m, 3H), 3.75 (s, 1H), 4.01-4.06 (m, 4 H), 4.22-4.35 (m, 3H), 5.69-5.75 (m, 1H), 5.98-6.05 (m, 3H), 7.09-7.15 (m, 3H), 7.25-7.29 (m, 2H), 7.77 (d, J = 3.6 Hz, 1H); MS, m/e 623 (M + 1).sup.+

[0876] Example numbers 75-80 are prepared using similar procedures disclosed for Example 66, above.

TABLE-US-00035 [00038] Example R.sup.11 R.sup.10 75 H n-propyl—NH— 76 H c-Butyl—NH— 77 H c-Pentyl—NH— 78 H [00039] 79 H [00040] 80 H [00041]

Example 81

[0877] Certain exemplified compounds were obtained as mixture of diastereomers because of the chirality at phosphorous. The diastereomers were separated on a Chiralpak-AS-H (2×25 cm) column under Supercritical Fluid Chromatography (SFC) conditions using 20% methanol in carbon dioxide as solvent. The absolute stereochemistry of the P-chiral center of the diastereromers were not determined. However, chromatographic resolution of these two diastereomers provides for isomers that are characterized as fast eluting and slow eluting isomers. Some examples are shown below.

TABLE-US-00036 Compound EC90 (uM) Example 15 (Diastereomeric mixture) 0.86 Fast Moving isomer of Example 15 1.35 Slow Moving isomer of Example 15 0.26 Example 39 (Diastereomeric mixture) 0.47 Fast Moving isomer of Example 39 0.78 Slow Moving isomer of Example 39 0.02 Example 49 (Diastereomeric mixture) 0.126 Fast Moving isomer of Example 49 0.03 Slow Moving isomer of Example 49 5.78

Example 82

[0878] HCV Replicon Assay.

[0879] HCV replicon RNA-containing Huh7 cells (clone A cells; Apath, LLC, St. Louis, Mo.) were kept at exponential growth in Dulbecco's modified Eagle's medium (high glucose) containing 10% fetal bovine serum, 4 mM L-glutamine and 1 mM sodium pyruvate, lx nonessential amino acids, and G418 (1,000 μg/ml). Antiviral assays were performed in the same medium without G418. Cells were seeded in a 96-well plate at 1,500 cells per well, and test compounds were added immediately after seeding. Incubation time 4 days. At the end of the incubation step, total cellular RNA was isolated (RNeasy 96 kit; Qiagen). Replicon RNA and an internal control (TaqMan rRNA control reagents; Applied Biosystems) were amplified in a single-step multiplex RT-PCR protocol as recommended by the manufacturer. The HCV primers and probe were designed with Primer Express software (Applied Biosystems) and covered highly conserved 5′-untranslated region (UTR) sequences (sense, 5′-AGCCATGGCGTTAGTA(T)GAGTGT-3′, and antisense, 5′-TTCCGCAGACCACTATGG-3′; probe, 5′-FAM-CCTCCAGGACCCCCCCTCCC-TAMRA-3′).

[0880] To express the antiviral effectiveness of a compound, the threshold RT-PCR cycle of the test compound was subtracted from the average threshold RT-PCR cycle of the no-drug control (ΔCt.sub.HCV). A ΔCt of 3.3 equals a 1-log 10 reduction (equal to the 90% effective concentration [EC.sub.90]) in replicon RNA levels. The cytotoxicity of the test compound could also be expressed by calculating the ΔCt.sub.rRNA values. The ΔΔCt specificity parameter could then be introduced (ΔCt.sub.HCV−ΔCt.sub.rRNA), in which the levels of HCV RNA are normalized for the rRNA levels and calibrated against the no-drug control.

TABLE-US-00037 Log10 Reduction at EC90 Ex # Compound 50 μM (μM)  5 [00042] −1.21 3.0  6 [00043] −0.45 ND  7 [00044] 0.31 ND  8 [00045] −1.48 2.11 10 [00046] −1.25 19.15 11 [00047] −0.55 ND 12 [00048] 0.31 ND 15 [00049] ND 0.86 25 [00050] −2.22 0.39 27 [00051] −2.25 0.66 28 [00052] −2.16 0.75 36 [00053] −1.64 21.9 39 [00054] −1.78 0.47 49 [00055] −2.69 0.126 53 [00056] −1.33 <0.3 54 [00057] −1.55 0.57 55 [00058] −2.38 <0.3 69 [00059] −2.25 <0.3 70 [00060] −2.25 <0.3 .sup.1(4-BrPh): 4-bromo—phenyl.

[0881] The entire contents of U.S. Provisional Application Nos. 60/909,315, filed Mar. 30, 2007, and 60/982,309, filed Oct. 24, 2007, are hereby incorporated by reference in the present application so far as needed to supplement the present disclosure and/or rectify any errors. Moreover, the patent and non-patent references disclosed herein are incorporated by reference. In the event that the incorporated patent and non-patent reference contains a term that conflicts with a term disclosed in either one of the two Provisional Applications or the present application text, the meaning of the term contained in the present application text and the two Provisional Applications controls provided that the overall meaning of the incorporated subject matter is not lost.

TABLE-US-LTS-00001 LENGTHY TABLES The patent application contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).