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 5 structure: R2 O R3b Base OR3a N O OR¹ CO2R4 R6 Y X I Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I. 10 20 23 26 34 96 09 N ov 2 02 3 A B S T R A C T 0 9 N o v 2 0 2 3 0 B a s e O N P O 2 0 2 3 2 6 3 4 9 6 Y X 1 0

Description

2023263496   09 Nov 2023 This application was filed on March 25, 2008, as a PCT International Patent application in the name of Pharmasset, Inc., a U.S. national corporation, applicant for the 5 designation of all countries except the US, and Michael Joseph Sofia, a citizen of the U.S.; Jinfa Du, a citizen of the U.S.; Peiyuan Wang, a citizen of the People’s Republic of China; and Dhanapalan Nagarathnam, a citizen of the U.S.; applicants for the designation of the US only, this application is a divisional application of Australian Patent Application No. 2021202327, which in turn is a divisional application of Australian Patent Application No. 10   2017261454, which in turn is a divisional application of Australian Patent Application No. 2016213882, which in turn is a divisional application of Australian Patent Application No. 2014215983, which in turn is a divisional application of Australian Patent Application No. 2012241173, which in turn is a divisional application of Australian Patent Application No. 2008232827, and claims priority to U.S. Provisional Application Nos. 60 / 909,315, filed 15 March 30, 2007; 60 / 982,309, filed October 24, 2007; and U.S. Non-Provisional Application No. 12 / 053,015, filed March 21, 2008. The contents of each of the above-noted applications is hereby incorporated by reference in its entirety. Field of Invention 20 The present invention pertains to nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals. The invention provides novel chemical compounds, and the use of these compounds alone or in combination with 25 other antiviral agents for treating HCV infection. Background 2023263496   09 Nov 2023 Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals, estimated to be 2-15% of the world's population. There are an estimated 4.5 million infected people in the United States alone, according to the U.S. Center for Disease 5 Control. According to the World Health Organization, there are more than 200 million infected individuals worldwide, with at least 3 to 4 million people being infected each year. Once infected, about 20% of people clear the virus, but the rest can harbor HCV the rest of their lives. Ten to twenty percent of chronically infected individuals eventually develop liver-destroying cirrhosis or cancer. The viral disease is transmitted parenterally by 10 contaminated blood and blood products, contaminated needles, or sexually and vertically from infected mothers or carrier mothers to their offspring. Current treatments for HCV infection, which are restricted to immunotherapy with recombinant interferon-a alone or in combination with the nucleoside analog ribavirin, are of limited clinical benefit. Moreover, there is no established vaccine for HCV. Consequently, there is an urgent need for 15 improved therapeutic agents that effectively combat chronic HCV infection. The HCV virion is an enveloped positive-strand RNA virus with a single oligoribonucleotide genomic sequence of about 9600 bases which encodes a polyprotein of about 3,010 amino acids. The protein products of the HCV gene consist of the structural proteins C, El, and E2, and the non-structural proteins NS2, NS3, NS4A and NS4B, and 20 NS5A and NS5B. The nonstructural (NS) proteins are believed to provide the catalytic machinery for viral replication. The NS3 protease releases NS5B, the RNA-dependent RNA polymerase from the polyprotein chain. HCV NS5B polymerase is required for the synthesis of a double-stranded RNA from a single-stranded viral RNA that serves as a template in the replication cycle of HCV. Therefore, NS5B polymerase is considered to be 25 an essential component in the HCV replication complex (K. Ishi, et al, Heptalogy, 1999, 29: 1227-1235; V. Lohmann, et al., Virology, 1998, 249: 108-118). Inhibition of HCVNS5B 2023263496   09 Nov 2023 polymerase prevents formation of the double-stranded HCV RNA and therefore constitutes an attractive approach to the development of HCV-specific antiviral therapies. HCV belongs to a much larger family of viruses that share many common features. Flaviviridae Viruses The Flaviviridae family of viruses comprises at least three distinct genera: pestiviruses, which cause disease in cattle and pigs; flavivruses, which are the primary cause of diseases such as dengue fever and yellow fever; and hepaciviruses, whose sole member is HCV. The flavivirus genus includes more than 68 members separated into groups on the basis of serological relatedness (Calisher et al., J. Gen. Virol, 1993,70,37-43). Clinical symptoms vary and include fever, encephalitis and hemorrhagic fever {Fields Virology, Editors: Fields, B. N., Knipe, D. M., and Howley, P. M., Lippincott-Raven Publishers, Philadelphia, PA, 1996, Chapter 31, 931-959). Flaviviruses of global concern that are associated with human disease include the Dengue Hemorrhagic Fever viruses (DHF), yellow fever virus, shock syndrome and Japanese encephalitis virus (Halstead, S. B., Rev. Infect. Dis., 1984, 6, 251264; Halstead, S. B., Science, 239:476-481, 1988; Monath, T. P., New Eng. J. Med, 1988, 319, 64 1-643). The pestivirus genus includes bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV, also called hog cholera virus) and border disease virus (BDV) of sheep (Moennig, V. et al. Adv. Vir. Res. 1992, 41, 53-98). Pestivirus infections of domesticated livestock (cattle, pigs and sheep) cause significant economic losses worldwide. BVDV causes mucosal disease in cattle and is of significant economic importance to the livestock industry (Meyers, G. and Thiel, H.J., Advances in Virus Research, 1996, 47, 53-118; Moennig V., et al, Adv. Vir. Res. 1992, 41, 53-98). Human pestiviruses have not been as extensively characterized as the animal pestiviruses. However, serological surveys indicate considerable pestivirus exposure in humans. 2023263496   09 Nov 2023 Pestiviruses and hepaciviruses are closely related virus groups within the Flaviviridae family. Other closely related viruses in this family include the GB virus A, GB virus A-like agents, GB virus-B and GB virus-C (also called hepatitis G virus, HGV). The hepacivirus group (hepatitis C virus; HCV) consists of a number of closely related but genotypically 5 distinguishable viruses that infect humans. There are at least 6 HCV genotypes and more than 50 subtypes. Due to the similarities between pestiviruses and hepaciviruses, combined with the poor ability of hepaciviruses to grow efficiently in cell culture, bovine viral diarrhea virus (BVDV) is often used as a surrogate to study the HCV virus. The genetic organization of pestiviruses and hepaciviruses is very similar. These positive 10 stranded RNA viruses possess a single large open reading frame (ORF) encoding all the viral proteins necessary for virus replication. These proteins are expressed as a polyprotein that is co- and post-translationally processed by both cellular and virus-encoded proteinases to yield the mature viral proteins. The viral proteins responsible for the replication of the viral genome RNA are located within approximately the carboxy-terminal. Two-thirds of 15 the ORF are termed nonstructural (NS) proteins. The genetic organization and polyprotein processing of the nonstructural protein portion of the ORF for pestiviruses and hepaciviruses is very similar. For both the pestiviruses and hepaciviruses, the mature nonstructural (NS) proteins, in sequential order from the amino-terminus of the nonstructural protein coding region to the carboxy-terminus of the ORF, consist of p7, NS2, NS3, NS4A, NS4B, NS5A, 20 andNS5B. The NS proteins of pestiviruses and hepaciviruses share sequence domains that are characteristic of specific protein functions. For example, the NS3 proteins of viruses in both groups possess amino acid sequence motifs characteristic of serine proteinases and of helicases (Gorbalenya et al., Nature, 1988, 333, 22; Bazan and Fletterick Virology , 25   1989,171,637-639; Gorbalenya et al., Nucleic Acid Res.,1989, 17, 3889-3897). Similarly, the NS5B proteins of pestiviruses and hepaciviruses have the motifs characteristic of RNA- 2023263496   09 Nov 2023 directed RNA polymerases (Koonin, E.V. and Dolja, V.V., Crir. Rev. Biochem. Molec. Biol. 1993, 28, 375-430). The actual roles and functions of the NS proteins of pestiviruses and hepaciviruses in the lifecycle of the viruses are directly analogous. In both cases, the NS3 serine proteinase is responsible for all proteolytic processing of polyprotein precursors downstream of its position in the ORF (Wiskerchen and Collett, Virology, 1991, 184, 341-350; Bartenschlager et al., J. Virol. 1993, 67, 3835-3844; Eckart et al. Biochem. Biophys. Res. Comm. 1993,192, 399-406; Grakoui et al., J. Virol. 1993, 67, 2832-2843; Grakoui et al., Proc. Natl. Acad Sci. USA 1993, 90, 10583-10587; Hijikata et al., J. Virol. 1993, 67, 4665-4675; Tome et al., J. Virol., 1993, 67, 4017-4026). The NS4A protein, in both cases, acts as a cofactor with the NS3 serine protease (Bartenschlager et al., J. Virol. 1994, 68, 5045-5055; Failla et al., J. Virol. 1994, 68, 3753-3760; Xu et al., J. Virol., 1997, 71:53 12-5322). The NS3 protein of both viruses also functions as a helicase (Kim et al., Biochem. Biophys. Res. Comm., 1995, 215, 160-166; Jin and Peterson, Arch. Biochem. Biophys., 1995, 323, 47-53; Warrener and Collett, J. Virol. 1995, 69,1720-1726). Finally, the NS5B proteins of pestiviruses and hepaciviruses have the predicted RNA-directed RNA polymerases activity (Behrens et al., EMBO, 1996, 15, 12-22; Lechmann et al., J. Virol., 1997, 71, 8416-8428; Yuan et al., Biochem. Biophys. Res. Comm. 1997, 232, 231-235; Hagedorn, PCT WO 97 / 12033; Zhong etal,J. Virol., 1998,72, 9365-9369). Currently, there are limited treatment options for individuals infected with hepatitis C virus. The current approved therapeutic option is the use of immunotherapy with recombinant interferon-a alone or in combination with the nucleoside analog ribavirin. This therapy is limited in its clinical effectiveness and only 50% of treated patients respond to therapy. Therefore, there is significant need for more effective and novel therapies to address the unmet medical need posed by HCV infection. A number of potential molecular targets for drug development of direct acting antivirals as 2023263496   09 Nov 2023 anti -HCV therapeutics have now been identified including, but not limited to, the NS2-NS3 autoprotease, the N3 protease, the N3 helicase and the NS5B polymerase. The RNA-dependent RNA polymerase is absolutely essential for replication of the single-stranded, positive sense, RNA genome and this enzyme has elicited significant interest among 5 medicinal chemists. Inhibitors of HCV NS5B as potential therapies for HCV infection have been reviewed: Tan, S.-L., et al., Nature Rev. Drug Discov., 2002, 1, 867-881; Walker, M.P. et al., Exp. Opin. Investigational Drugs, 2003, 12, 1269-1280; Ni, Z-J., et al., Current Opinion in Drug Discovery and Development, 2004, 7, 446-459; Beaulieu, P. L., et al., Current Opinion in 10 Investigational Drugs, 2004, 5, 838-850; Wu, J., et al., Current Drug Targets-Infectious Disorders, 2003, 3, 207-219; Griffith, R.C., et al, Annual Reports in Medicinal Chemistry, 2004, 39, 223-237; Carrol, S., et al., Infectious Disorders-Drug Targets, 2006, 6, 17-29. The potential for the emergence of resistant HCV strains and the need to identify agents with broad genotype coverage supports the need for continuing efforts to identify novel and more 15 effective nucleosides as HCV NS5B inhibitors. Nucleoside inhibitors of NS5B polymerase can act either as a non-natural substrate that results in chain termination or as a competitive inhibitor which competes with nucleotide binding to the polymerase. To function as a chain terminator the nucleoside analog must be taken up by the cell and converted in vivo to a triphosphate to compete for the polymerase 20 nucleotide binding site. This conversion to the triphosphate is commonly mediated by cellular kinases which imparts additional structural requirements on a potential nucleoside polymerase inhibitor. Unfortunately, this limits the direct evaluation of nucleosides as inhibitors of HCV replication to cell-based assays capable of in situ phosphorylation. In some cases, the biological activity of a nucleoside is hampered by its poor substrate 25 characteristics for one or more of the kinases needed to convert it to the active triphosphate form. Formation of the monophosphate by a nucleoside kinase is generally viewed as the 2023263496   09 Nov 2023 rate limiting step of the three phosphorylation events. To circumvent the need for the initial phosphorylation step in the metabolism of a nucleoside to the active triphosphate analog, the preparation of stable phosphate prodrugs has been reported. Nucleoside phosphoramidate prodrugs have been shown to be precursors of the active nucleoside triphosphate and to 5 inhibit viral replication when administered to viral infected whole cells (McGuigan, C., et al., J. Med. Chem., 1996, 39, 1748-1753; Valette, G., et al., J. Med. Chem., 1996, 39, 19811990; Balzarini, J., et al., Proc. National Acad Sei USA, 1996, 93, 7295-7299; Siddiqui, A. Q., et al., J. Med. Chem., 1999, 42, 4122-4128; Eisenberg, E. J., et al., Nucleosides, Nucleotides and Nucleic Acids, 2001, 20, 1091-1098; Lee, W.A., et al., Antimicrobial 10 Agents and Chemotherapy, 2005, 49, 1898); US 2006 / 0241064; and WO 2007 / 095269. Also limiting the utility of nucleosides as viable therapeutic agents is their sometimes poor physicochemical and pharmacokinetic properties. These poor properties can limit the intestinal absorption of an agent and limit uptake into the target tissue or cell. To improve on their properties prodrugs of nucleosides have been employed. It has been demonstrated 15 that preparation of nucleoside phosphoramidates improves the systemic absorption of a nucleoside and furthermore, the phosphoramidate moiety of these "pronucleotides" is masked with neutral lipophilic groups to obtain a suitable partition coefficient to optimize uptake and transport into the cell dramatically enhancing the intracellular concentration of the nucleoside monophosphate analog relative to administering the parent nucleoside alone. 20 Enzyme-mediated hydrolysis of the phosphate ester moiety produces a nucleoside monophosphate wherein the rate limiting initial phosphorylation is unnecessary. SUMMARY OF THE INVENTION The present invention is directed toward novel phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its 25 stereoisomers, salts (acid or basic addition salts), hydrates, solvates, or crystalline forms thereof, represented by the following structure: 2023263496   09 Nov 2023 i wherein (a) R1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is 5 not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); 10   (b) R2 is hydrogen, C 1-10 alkyl, R3a or R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms, C(O)CR3aR3bNHR', where n is 2 to 4 and R1, R3a, and R3b; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, -(CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-15 indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is 20 hydrogen and R3a and R2 together are (CH2)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 R3’ is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, 25 CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), 2023263496   09 Nov 2023 CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, 5 alkoxy, di(lower alkyl)-amino, or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., -(CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, 10 CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OMe, halogen, NH2, or N3; 15    (h) Y is OH, H, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 20 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 25 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; the base is a naturally occurring or modified purine or pyrimidine base represented by the 30 following structures: 2023263496   09 Nov 2023 d wherein Z is N or CR12; R7, R8,R9, R10, and Rnare independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', 5   NR'2, lower alkyl of C1-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated (F, Cl, Br, I) lower alkenyl of C2-C6, lower alkynyl of C2-C6 such as C=CH, halogenated (F, Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower alkoxy of Ci-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', 10 wherein R' is an optionally substituted alkyl, which includes, but is not limited to, an optionally substituted C1-20 alkyl, an optionally substituted C1-10 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C2-C6, an optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(0)(Ci-2o alkyl), C(0)(Ci-io alkyl), or 15 C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2 lower alkyl of C1-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated (F, Cl, Br, I) lower alkenyl of C2-C6 , lower alkynyl of C2-C6, halogenated (F, 20 Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower alkoxy of Ci-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that when base is represented by the structure c with R11 being hydrogen, R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. 25 DEFINITIONS 2023263496   09 Nov 2023 The phrase "a" or "an" entity as used herein refers to one or more of that entity; for example, a compound refers to one or more compounds or at least one compound. As such, the terms "a" (or "an"), "one or more", and "at least one" can be used interchangeably herein. The phrase "as defined herein above" refers to the first definition provided in the Summary 5 of the Invention. The terms "optional" or "optionally" as used herein means that a subsequently described event or circumstance may but need not occur, and that the description includes instances where the event or circumstance occurs and instances in which it does not. For example, "optional bond" means that the bond may or may not be present, and that the description 10 includes single, double, or triple bonds. The term "independently" is used herein to indicate that a variable is applied in any one instance without regard to the presence or absence of a variable having that same or a different definition within the same compound. Thus, in a compound in which R appears twice and is defined as "independently carbon or nitrogen", both R's can be carbon, both R's 15 can be nitrogen, or one R' can be carbon and the other nitrogen. The term "alkenyl" refers to an unsubstituted hydrocarbon chain radical having from 2 to 10 carbon atoms having one or two olefinic double bonds, preferably one olefinic double bond. The term "C2-N alkenyl" refers to an alkenyl comprising 2 to N carbon atoms, where N is an integer having the following values: 3, 4, 5, 6, 7, 8, 9, or 10. The term "C2-10 alkenyl" refers 20 to an alkenyl comprising 2 to 10 carbon atoms. The term "C2-4 alkenyl" refers to an alkenyl comprising 2 to 4 carbon atoms. Examples include, but are not limited to, vinyl, 1-propenyl, 2-propenyl (allyl) or 2-butenyl (crotyl). The term "halogenated alkenyl" refers to an alkenyl comprising at least one of F, Cl, Br, and I. 25 The term "alkyl" refers to an unbranched or branched chain, saturated, monovalent hydrocarbon residue containing 1 to 30 carbon atoms. The term "Ci-m alkyl" refers to an alkyl comprising 1 to M carbon atoms, where M is an integer having the following values: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. The term "Ci-4 alkyl" refers to an alkyl containing 1 to 4 carbon atoms. The term 30 "lower alkyl" denotes a straight or branched chain hydrocarbon residue comprising 1 to 6 carbon atoms. "C1-20 alkyl" as used herein refers to an alkyl comprising 1 to 20 carbon atoms. "Ci-10 alkyl" as used herein refers to an alkyl comprising 1 to 10 carbons. Examples of alkyl groups include, but are not limited to, lower alkyl groups include methyl, ethyl, 2023263496   09 Nov 2023 propyl, z-propyl, zz-butyl, z-butyl, / -butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl. The term (ar)alkyl or (heteroaryl)alkyl indicate the alkyl group is optionally substituted by an aryl or a heteroaryl group respectively. The term "cycloalkyl" refers to an unsubstituted or substituted carbocycle, in which the 5 carbocycle contains 3 to 10 carbon atoms; preferably 3 to 8 carbon atoms; more preferably 3 to 6 carbon atoms (i.e., lower cycloalkyls). Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloalkyl alkyl" refers to an additionally unsubstituted or substituted alkyl substituted by a lower cycloalkyl. Examples of cycloalkyl alkyls include, but are not limited 10 to, any one of methyl, ethyl, propyl, i-propyl, n-butyl, i-butyl, t-butyl or pentyl, isopentyl, neopentyl, hexyl, heptyl, and octyl that is substituted with cyclopropyl, 2-methyl-cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "cycloheteroalkyl" refers to an unsubstituted or substituted heterocycle, in which the heterocycle contains 2 to 9 carbon atoms; preferably 2 to 7 carbon atoms; more 15 preferably 2 to 5 carbon atoms. Examples of cycloheteroalkyls include, but are not limited to, aziridin-2-yl, V-Ci-3-alkyl-aziridin-2-yl, azetidinyl, V-Ci-3-alkyl-azetidin-m'-yl, pyrrolidin-m'-yl, V-Ci-3-alkyl-pyrrolidin-m'-yl, piperidin-m'-yl, and V-Ci-3-alkyl-piperidin-m'-yl, where m' is 2, 3, or 4 depending on the cycloheteroalkyl. Specific examples of N-Ci-3-alkyl-cycloheteroalkyls include, but are not limited to, N-methyl-aziridin-2-yl, N-methyl-20 azetidin-3-yl, N-methyl-pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-2-yl, N-methyl-piperidin-3-yl, and N-methyl-piperidin-4-yl. In the instance of R4, the point of attachment between the cycloheteroalkyl ring carbon and the oxygen occurs at any one of m' The term "heterocycle" refers to an unsubstituted or substituted heterocycle containing carbon, hydrogen, and at least one of N, O, and S, where the C and N can be trivalent or 25 tetravalent, i.e., sp2- or sp3-hybridized. Examples of heterocycles include, but are not limited to, aziridine, azetidine, pyrrolidine, piperidine, imidazole, oxazole, piperazine, etc. In the instance of piperazine, as related to R10 for NR'2, the corresponding opposite nitrogen atom of the piperazinyl is substituted by a lower alkyl represented by the following structure: Preferably, the opposite nitrogen of the piperazinyl is substituted by a methyl group. 2023263496   09 Nov 2023 The term "halogenated alkyl" (or "haloalkyl") refers to an unbranched or branched chain alkyl comprising at least one of F, Cl, Br, and I. The term "Ci-m haloalkyl" refers to an alkyl comprising 1 to M carbon atoms that comprises at least one of F, Cl, Br, and I, where M is an integer having the following values: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 5    18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30. "C1-3 haloalkyl" refers to a haloalkyl comprising 1 to 3 carbons and at least one of F, Cl, Br, and I. The term "halogenated lower alkyl" (or "lower haloalkyl") refers to a haloalkyl comprising 1 to 6 carbon atoms and at least one of F, Cl, Br, and I. Examples include, but are not limited to, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, 10 diiodomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 1-iodoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-difluoroethyl, 2,2-dichloroethyl, 2,2-dibromomethyl, 2-2-diiodomethyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, 2,2,2-trifluoroethyl or 1,1,2,2,2-pentafluoroethyl. 15 The term "alkynyl" refers to an unbranched or branched hydrocarbon chain radical having from 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms, and having one triple bond. The term "C2-N alkynyl" refers to an alkynyl comprising 2 to N carbon atoms, where N is an integer having the following values: 3, 4, 5, 6, 7, 8, 9, or 10. The term "C C2-4 alkynyl" refers to an alkynyl comprising 2 to 4 carbon atoms. The term "C2-10 alkynyl" refers to an 20 alkynyl comprising 2 to 10 carbons. Examples include, but are limited to, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl or 3-butynyl. The term "halogenated alkynyl" refers to an unbranched or branched hydrocarbon chain radical having from 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms, and having one triple bond and at least one of F, Cl, Br, and I. 25 The term "cycloalkyl" refers to a saturated carbocyclic ring comprising 3 to 8 carbon atoms, i.e. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. The term "C3-7 cycloalkyl" as used herein refers to a cycloalkyl comprising 3 to 7 carbons in the carbocyclic ring. The term "alkoxy" refers to an -O-alkyl group or an -O-cycloalkyl group, wherein alkyl and 30 cycloalkyl are as defined above. Examples of-O-alkyl groups include, but are not limited to, methoxy, ethoxy, n-propyloxy, z-propyloxy, n-butyloxy, z-butyloxy, Lbutyloxy. "Lower alkoxy" as used herein denotes an alkoxy group with a "lower alkyl" group as previously defined. "C1-10 alkoxy" refers to an-O-alkyl wherein alkyl is C1-10. Examples of -O- 2023263496   09 Nov 2023 cycloalkyl groups include, but are not limited to, -O-c-propyl, -O-c-butyl, -O-c-pentyl, and -O-c-hexyl. The term "halogenated alkoxy" refers to an -O-alkyl group in which the alkyl group comprises at least one of F, Cl, Br, and I. 5 The term "halogenated lower alkoxy" refers to an -O-(lower alkyl) group in which the lower alkyl group comprises at least one of F, Cl, Br, and I. The term "amino acid" includes naturally occurring and synthetic a, P y or 5 amino acids, and includes but is not limited to, amino acids found in proteins, i.e. glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, proline, serine, threonine, 10 cysteine, tyrosine, asparagine, glutamine, aspartate, glutamate, lysine, arginine and histidine. In a preferred embodiment, the amino acid is in the L-configuration. Alternatively, the amino acid can be a derivative of alanyl, valinyl, leucinyl, isoleucinyl, prolinyl, phenylalaninyl, tryptophanyl, methioninyl, glycinyl, serinyl, threoninyl, cysteinyl, tyrosinyl, asparaginyl, glutaminyl, aspartoyl, glutaroyl, lysinyl, argininyl, histidinyl, P-alanyl, P 15 valinyl, P-leucinyl, P-isoleucinyl, P-prolinyl, P-phenylalaninyl, P-tryptophanyl, P-methioninyl, P-glycinyl, P-serinyl, P-threoninyl, P-cysteinyl, P-tyrosinyl, P-asparaginyl, P-glutaminyl, P-aspartoyl, P-glutaroyl, P-lysinyl, P-argininyl or P-histidinyl. When the term amino acid is used, it is considered to be a specific and independent disclosure of each of the esters of a, P y or 5 glycine, alanine, valine, leucine, isoleucine, methionine, phenylalanine, 20 tryptophan, proline, serine, threonine, cysteine, tyrosine, asparagine, glutamine, aspartate, glutamate, lysine, arginine and histidine in the D and L-configurations. The term "aminoacyl" includes N,N-unsubstituted, N,N-monosubstituted, and N,N-disubstituted derivatives of naturally occurring and synthetic a, P y or 5 amino acyls, where the amino acyls are derived from amino acids. The amino-nitrogen can be substituted or 25 unsubstituted. When the amino-nitrogen is substituted, the nitrogen is either mono- or disubstituted, where the substituent bound to the amino-nitrogen is a lower alkyl or an alkaryl. In the instance of its use for Y, the expression "O(aminoacyl)" is used. It is understood that the C3' carbon of the ribose is bound to the oxygen "O", which is then bound to the carbonyl carbon of the aminoacyl. 30 The terms "alkylamino" or "arylamino" refer to an amino group that has one or two alkyl or aryl substituents, respectively. The term "protected," as used herein and unless otherwise defined, refers to a group that is added to an oxygen, nitrogen, or phosphorus atom to prevent its further reaction or for other 2023263496   09 Nov 2023 purposes. A wide variety of oxygen and nitrogen protecting groups are known to those skilled in the art of organic synthesis. Non-limiting examples include: C(O)-alkyl, C(O)Ph, C(O)aryl, CH3, CH2-alkyl, CH2-alkenyl, CH2PI1, CH2-aryl, CH2O-alkyl, CH2O-aryl, SO2-alkyl, SO2-aryl, tert-butyldimethylsilyl, ter / -butyldiphenylsilyl, and 1,3-(1,1,3,3 5 tetraisopropyldisiloxanylidene). The term "aryl," as used herein, and unless otherwise specified, refers to substituted or unsubstituted phenyl (Ph), biphenyl, or naphthyl, preferably the term aryl refers to substituted or unsubstituted phenyl. The aryl group can be substituted with one or more moieties selected from among hydroxyl, F, Cl, Br, I, amino, alkylamino, arylamino, alkoxy, 10 aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate, either unprotected, or protected as necessary, as known to those skilled in the art, for example, as taught in T.W. Greene and P.G. M. Wuts, "Protective Groups in Organic Synthesis," 3rd ed., John Wiley & Sons, 1999. The terms "alkaryl" or "alkylaryl" refer to an alkyl group with an aryl substituent, such as 15 benzyl. The terms "aralkyl" or "arylalkyl" refer to an aryl group with an alkyl substituent. The term "di(lower alkyl)amino-lower alkyl" refers to a lower alkyl substituted by an amino group that is itself substituted by two lower alkyl groups. Examples include, but are not limited to, (CH3)2NCH2, (CH3)2NCH2CH2, (CH3)2NCH2CH2CH2, etc. The examples above show lower alkyls substituted at the terminus carbon atom with an N,N-dimethyl-amino 20 substituent. These are intended as examples only and are not intended to limit the meaning of the term "di(lower alkyl)amino-lower alkyl" so as to require the same. It is contemplated that the lower alkyl chain can be substituted with an N,N-di(lower alkyl)-amino at any point along the chain, e.g., CH3CH(N-(lower alkyl)2)CH2CH2. The term "halo," as used herein, includes chloro, bromo, iodo and fluoro. 25 The term "acyl" refers to a substituent containing a carbonyl moiety and a non-carbonyl moiety. The carbonyl moiety contains a double-bond between the carbonyl carbon and a heteroatom, where the heteroatom is selected from among O, N and S. When the heteroatom is N, the N is substituted by a lower alkyl. The non-carbonyl moiety is selected from straight, branched, and cyclic alkyl, which includes, but is not limited to, a straight, 30 branched, or cyclic C1-20 alkyl, C1-10 alkyl, or lower alkyl; alkoxyalkyl, including methoxymethyl; aralkyl, including benzyl; aryloxyalkyl, such as phenoxymethyl; or aryl, including phenyl optionally substituted with halogen (F, Cl, Br, I), hydroxyl, Ci to C4 alkyl, or Ci to C4 alkoxy, sulfonate esters, such as alkyl or aralkyl sulphonyl, including 2023263496   09 Nov 2023 methanesulfonyl, the mono, di or triphosphate ester, trityl or monomethoxytrityl, substituted benzyl, trialkylsilyl (e.g. dimethyl-t-butylsilyl) or diphenylmethylsilyl. When at least one aryl group is present in the non-carbonyl moiety, it is preferred that the aryl group comprises a phenyl group. 5 The term "lower acyl" refers to an acyl group in which the non-carbonyl moiety is lower alkyl. The term "purine" or "pyrimidine" base includes, but is not limited to, adenine, N6-alkylpurines, N6-acylpurines (wherein acyl is C(O)(alkyl, aryl, alkylaryl, or arylalkyl), N6-benzylpurine, N6-halopurine, N6-vinylpurine, N6-acetylenic purine, N6-acyl purine, N6- 10 hydroxyalkyl purine, N6-allcylaminopurine, N6-thioallcyl purine, N2-alkylpurines, N2-alkyl-6-thiopurines, thymine, cytosine, 5-fluorocytosine, 5-methylcytosine, 6-azapyrimidine, including 6-azacytosine, 2- and / or 4-mercaptopyrmidine, uracil, 5-halouracil, including 5-fluorouracil, C5-alkylpyrimidines, C5-benzylpyrimidines, C5-halopyrimidines, C5-vinylpyrimidine, C5-acetylenic pyrimidine, C5-acyl pyrimidine, C5-hydroxyalkyl purine, C5- 15 amidopyrimidine, C5-cyanopyrimidine, ,C5-iodopyrimidine, C6-lodo-pyrimidine, C5-Br-vinyl pyrimidine, C6-Br-vinyl pyrimidine, C5-nitropyrimidine, C5-amino-pyrimidine, N2-alkylpurines, N2-alkyl-6-thiopurines, 5-azacytidinyl, 5-azauracilyl, triazolopyridinyl, imidazolopyridinyl, pyrrolopyrimidinyl, and pyrazolopyrimidinyl. Purine bases include, but are not limited to, guanine, adenine, hypoxanthine, 2,6-diaminopurine, and 6-chloropurine. 20 Functional oxygen and nitrogen groups on the base can be protected as necessary or desired. Suitable protecting groups are well known to those skilled in the art, and include trimethylsilyl, dimethylhexylsilyl, Z-butyldimethylsilyl, and / -butyl di phenyl s i lyl, trityl, alkyl groups, and acyl groups such as acetyl and propionyl, methanesulfonyl, and p-toluenesulfonyl. 25 The term "tautomerism" and "tautomers" have their accepted plain meanings. The term "P*" means that the phosphorous atom is chiral and that it has a corresponding Cahn-Ingold-Prelog designation of "R" or "S" which have their accepted plain meanings. It is contemplated that compounds of the formula I are racemic because the chirality at phosphorous. Applicants contemplate use of the racemate and / or the resolved enantiomers. 30 In some instances, an asterisk does not appear next to the phosphoroamidate phosphorous atom. In these instances, it is understood that the phosphorous atom is chiral and that one of ordinary skill understands this to be so unless the substituents bound to the phosphorous exclude the possibility of chirality at phosphorous, such as in P(O)Ch. DETAILED DESCRIPTION OF THE INVENTION 2023263496   09 Nov 2023 An aspect of the invention is directed to a compound, its salts, hydrates, solvates, crystalline forms, and the like represented by formula I: 5          wherein (a) R1 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 Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 10 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); (b) R2 is hydrogen, C 1-10 alkyl, R3a or R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms, C(O)CR3aR3bNHR', where n is 2 to 4 and R1, R3a, and R3b; 15   (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, - (CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b 20 together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3’ is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H 25 and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, 2023263496   09 Nov 2023 CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2PI1, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, 5 which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or - N(R3’)2); (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted 10 aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., -(CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot 15 be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OMe, halogen, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), 20 OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein 25 alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), 30   OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; the base is a naturally occurring or modified purine or pyrimidine base represented by the following structures: 2023263496   09 Nov 2023 d wherein Z is N or CR12; 5   R7, R8,R9, R10, and R1 'are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl of C1-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated (F, Cl, Br, I) lower alkenyl of C2-C6, lower alkynyl of C2-C6 such as C=CH, halogenated (F, Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower alkoxy of Ci-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, 10  CH=CHCO2H, or CH=CHCO2R', wherein R' is an optionally substituted alkyl, which includes, but is not limited to, an optionally substituted C1-20 alkyl, an optionally substituted C1-10 alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C2-C6, an optionally substituted lower alkenyl of C2-C6, or optionally substituted 15 acyl, which includes but is not limited to C(O) alkyl, C(0)(Ci-2o alkyl), C(0)(Ci-io alkyl), or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2 lower alkyl of C1-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, 20 halogenated (F, Cl, Br, I) lower alkenyl of C2-C6 , lower alkynyl of C2-C6, halogenated (F, Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower alkoxy of Ci-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that when base is represented by the structure c with R11 being hydrogen, R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. 25 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 2023263496   09 Nov 2023 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. 5 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. A first embodiment of the invention is directed to a compound represented by formula 1-1: 10 1-1 wherein (a) R1 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 15 at least one of Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); (b) R2 is hydrogen, C 1-10 alkyl, R3a or R3b and R2 together are (CH2)n so as to form a 20 cyclic ring that includes the adjoining N and C atoms, C(O)CR3aR3bNHR', where n is 2 to 4 and R1, R3a, and R3b; 2023263496   09 Nov 2023 (c) R3a and R3b are (i) independently selected from hydrogen, Ci-io alkyl, cycloalkyl, -(CH2)c(NR3’)2, Ci-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 5 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 10 where R3 is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, 15   CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or - 20   N(R3’)2); (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkylj-amino, or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkylj-amino, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; 25   (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., - (CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; 30   (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), 2023263496   09 Nov 2023 OCi-io haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), 5   NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), 10 SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; (i)    R7, R8,R9 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', 15 CONH2, CONHR', CONR'2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl. A first aspect of the first embodiment is directed to a compound represented by formula 1-1 wherein (a) R1 is hydrogen, n-alkyl or aryl, which includes, but is not limited to, phenyl or 20 naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C1-6 alkyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl; (b) R2 is hydrogen or CH3; (c) R3a and R3b are independently (i) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and 25 R3a and R2 together are (CH2)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 R3’ is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, - 30 CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, 2023263496   09 Nov 2023 CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), or CH2SH and R3b is H; (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy, di(lower alkyl)-amino, or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, 5 cycloheteroalkyl, aminoacyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, CN, CH3, vinyl, OCH3, OCH2CH3, CH2OH, CH2(halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH , base is cytosine and R6 is H, R5 cannot be N3; 10   (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)    X is H, OH, F, OMe, Cl, Br, I, NH2, or N3; (h)    Y is OH, H, C1-4 alkyl, vinyl, N3, CN, Cl, Br, F, I, O(Ci-6 acyl), O(Ci-4 alkyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to 15 three halogen (Cl, Br, F, I), NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OC1-4 haloalkyl, O(aminoacyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), 20 NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, or N(Ci-4 acyl)2; (i)    R7, R8,R9 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a 25   C2-C6 alkynyl. A second aspect of the first embodiment is directed to a compound represented by formula I-1 wherein (a) R1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the 30 substitutent of the substituted phenyl is at least one of a C1-3 alkyl, a C1-3 alkoxy, F, Cl, Br, I, nitro, cyano, and a C1-3 haloalkyl; 2023263496   09 Nov 2023 (b) R2 is hydrogen or CH3; (c) R3a and R3b are independently (i) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and 5 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 R3’ is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), 10 CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), or CH2SH and R3b is H; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 15 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 alkyljamino-lower alkyl, or aminoacyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2(halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the provisos 20 that when X is OH , base is cytosine and R6 is H, R5 cannot be N3; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)   X is H, OH, F, OCH3, NH2, or N3; (h)   Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2, or O(aminoacyl); 25   (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH5, CONH2, CONHCH3, or CON(CH3)2; and (j) R9 is selected from among OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, OC(O)(Cl-20 alkyl), which include but are not limited to OC(O)(CH2)sCH3, NHC(O)(Cl-20 30 alkyl), which include but are not limited to NHC(O)(CH2)sCH3, and N(C(O)(CH2)sCH3)2, 2023263496   09 Nov 2023 which include but is not limited to N(C(O)(CH2)sCH3)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. A third aspect of the first embodiment is directed to a compound represented by formula 1-1 wherein 5   (a) R1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH3, OCH3, F, Cl, Br, I, nitro, cyano, and a CHs-qXq, where X is F, Cl, Br, or I, and q is 1-3; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, 10 CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl or R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, - 15 CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 20 alkyl, or aminoacyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2(halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH , base is cytosine and R6 is H, R5 cannot be N3; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 25   (g)   X is H, OH, F, OCH3, NH2, or N3; (h)   Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2, or O(aminoacyl); (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CHs-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH3, 2023263496   09 Nov 2023 CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl'; and (j) R9 is selected from among OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, OC(O)(Cl-20 alkyl), which include but are not limited to OC(O)(CH2)sCH3, NHC(O)(Cl-20 5 alkyl), which include but are not limited to NHC(O)(CH2)sCH3, and N(C(O)(CH2)sCH3)2, which include but is not limited to N(C(O)(CH2)sCH3)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. A fourth aspect of the first embodiment is directed to a compound represented by formula I-2 R9 R3b R3a^7--- CO2R4 10 wherein 1-2 (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH3, OCH3, F, 15 Cl, Br, I, nitro, cyano, and a CHs-qXq, where X is F, Cl, Br, or I, and q is 1-3; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, 20 CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl or R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, 2023263496   09 Nov 2023 CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H; (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, 5 alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the provisos that when X 10 is OH , base is cytosine and R6 is H, R5 cannot be N3; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)    X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; (h)   Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2, or O(aminoacyl); 15   (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH5, CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl; and (j) R9 is selected from among OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, 20   OC(O)(Cl-20 alkyl), which include but are not limited to OC(O)(CH2)sCH3, NHC(O)(Cl-20 alkyl), which include but are not limited to NHC(O)(CH2)sCH3, and andN(C(O)(CH2)sCH3, which include but is not limited to N(C(O)(CH2)sCH3)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. A fifth aspect of the first embodiment is directed to a compound represented by formula 1-2 25 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; 2023263496   09 Nov 2023 (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; 5   (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I; 10   (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)   X is H, OH, F, OCH3, NH2, or N3; (h)    Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, or O(aminoacyl); (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH3, 15 CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl; and (j) R9 is selected from among OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, OC(0)(Ci-2o alkyl), which include but are not limited to OC(O)(CH2)SCH3, NHC(0)(Ci-2o alkyl), which include but are not limited to NHC(O)(CH2)SCH3, and N(C(O)(CH2)SCH3)2, 20 which include but is not limited to N(C(O)(CH2)SCH3)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. A sixth aspect of the first embodiment is directed to a compound represented by formula 1-2 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p25 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 2023263496   09 Nov 2023 (d) R4 is hydrogen, Ci-io alkyl, Ci-io alkyl optionally substituted with a lower alkyl, alkoxy or halogen, Ci-io haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; 5   (e)    R5 is H, OMe, CN, CH2F, F, Cl, Br, or I; (f)    R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, or N3; (h)    Y is H, OH, CH3, F, Cl, Br, I, or N3, OCH3, OC(O)CH3, or O(aminoacyl); (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3.qXq, where X is F, Cl, Br, or I 10 and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2; and (j) R9 is selected from among OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, OC(O)(Ci-20 alkyl), which include but are not limited to OC(O)(CH2)sCH3, NHC(0)(Ci-2o alkyl), which include but are not limited to NHC(O)(CH2)sCH3, and N(C(O)(CH2)sCH3)2, which include but is not limited to N(C(O)(CH2)sCH3)2, where s is an integer selected from 15    0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. A seventh aspect of the first embodiment is directed to a compound represented by formula 1-2 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p20 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 25 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; (e) R5 is H; 2023263496   09 Nov 2023 (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, or N3; (h) Y is OH, OCH3, OC(O)CH3, or O(aminoacyl); (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3.qXq, where X is F, Cl, Br, or I 5 and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2; and (j) R9 is selected from among OH, OCH3, NH2, NHCH3, N(CH3)2, OC(0)(Ci-2o alkyl), which include but are not limited to OC(O)(CH2)SCH3, NHC(0)(Ci-2o alkyl), which include but are not limited to NHC(O)(CH2)SCH3, and N(C(O)(CH2)SCH3)2, which include but is not limited to N(C(O)(CH2)SCH3)2, where s is an integer selected from among 0, 1,2, 3, 4, 5, 6, 10    7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. An eighth aspect of the first embodiment is directed to a compound represented by formula 1-2 wherein (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 15   (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 20 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, or N3; 25   (h) Y is OH, OCH3, OC(O)CH3, or O(aminoacyl); (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2; 2023263496   09 Nov 2023 (j) R9 is selected from among OH, OCH3, NH2, NHCH3, N(CH3)2, OC(O)(Ci-20 alkyl), which include but are not limited to OC(O)(CH2)sCH3, NHC(0)(Ci-2o alkyl), which include but are not limited to NHC(O)(CH2)sCH3, and N(C(O)(CH2)sCH3)2, which include but is not limited to N(C(O)(CH2)sCH3)2, where s is an integer selected from among 0, 1,2, 3, 4, 5, 6, 5    7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. 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 R1, R2, R3a, R3b, R4, R5, R6, X, Y, R7, and R8are defined in the Summary of the Invention section above. A first aspect of the second embodiment is directed to a compound represented by formula I-10   3 O 1-3 wherein (a) R1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is 15 not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1 ”, and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); 20   (b) R2 is hydrogen or CH3; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, -(CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said 2023263496   09 Nov 2023 aryl groups optionally substituted with a group selected from hydroxyl, Ci-io alkyl, Ci-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are Ci-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is 5 hydrogen and R3a and R2 together are (CH2)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 R3 is independently hydrogen or Ci-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, 10 CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), 15 CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, 20 aminoacyl, di(lower alkyljamino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., -(CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including 25 F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, 30 OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 2023263496   09 Nov 2023 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, or N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), 5    C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, or N(Ci-4 acyl)2; 10   (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, wherein R' is a Ci-2o alkyl; a Ci-2o cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl. The second aspect of the second embodiment is directed to a compound represented by 15 formula 1-3 wherein (a) R1 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 C1-6 alkyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, C1-6 haloalkyl; 20   (b) R2 is hydrogen or CH3; (c) R3a and R3b are independently (i) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3’ is 25 independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, CH(CH3)2, CH2CH(CH3)2, 30 CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), or CH2SH and R3b is H; 2023263496   09 Nov 2023 (d) R4 is hydrogen, Ci-io alkyl, Ci-io alkyl optionally substituted with a lower alkyl, alkoxy or halogen, Ci-io haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; 5   (e) R5 is H, CN, CH3, vinyl, OCH3, OCH2CH3, CH2OH, CH2(halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)    X is H, OH, F, OMe, halogen, NH2, or N3; (h)    Y is OH, H, C1-4 alkyl, vinyl, N3, CN, Cl, Br, F, I, O(Ci-6 acyl), O(Ci-4 alkyl), NH2, 10 NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OC1-10 haloalkyl, O(aminoacyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), 15 SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, 20 lower alkyl, halogenated (F, Cl, Br, I) lower alkyl, lower alkenyl of C2-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl. The third aspect of the second embodiment is directed to a compound represented by formula 1-3 25 wherein (a) R1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a C1-3 alkyl, a C1-3 alkoxy, F, Cl, Br, I, nitro, cyano, and a C1-3 haloalkyl; (b) R2 is hydrogen, CH3, R3a or R3b and R2 together are (CH2)3 so as to form a cyclic ring 30 that includes the adjoining N and C atoms, C(O)CR3aR3bNHR1, where n is 2 to 4 and R1, R3a, and R3b are as defined herein; 2023263496   09 Nov 2023 (c) R3a and R3b are independently (i) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3’ is 5 independently hydrogen or Ci-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, CH(CH3)2, CH2CH(CH3)2, 10 CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 15 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 alkyljamino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2(halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I; 20   (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)   X is H, OH, F, OCH3, halogen, NH2, or N3 (h)   Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2; (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, 25   N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH5, CONH2, CONHCH3, or CON(CH3)2. The fourth aspect of the second embodiment is directed to a compound represented by formula 1-3 wherein 2023263496   09 Nov 2023 (a) R1 is hydrogen, n-alkyl or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH3, OCH3, F, Cl, Br, I, nitro, cyano, and a CH3-qXq, where X is F, Cl, Br, or I, and q is 1-3; (b) R2 is hydrogen or CH3; 5   (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl or R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, 10 CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 15 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2(halo), such as CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 20   (g)   X is H, OH, F, OCH3, NH2, or N3; (h)   Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2; (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH3, 25 CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl. The fifth aspect of the second embodiment is directed to a compound represented by formula 1-4 2023263496   09 Nov 2023 1-4 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, or a substituted or unsubstituted 5 phenyl, where the substitutent of the substituted phenyl is at least one of a CH3, OCH3, F, Cl, Br, I, nitro, cyano, and a CH3-qXq, where X is F, Cl, Br, or I, and q is 1-3; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 10 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl or R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), 15 CH2SH, or lower cycloalkyl and R3b is H; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 20   (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; 2023263496   09 Nov 2023 (h) Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2; (i) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH3, 5 CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl, The sixth aspect of the second embodiment is directed to a compound represented by formula 1-4 wherein 10   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 15 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 20 di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OCH3, NH2, or N3; (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; 25   (i)    R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl. The seventh aspect of the second embodiment is directed to a compound represented by formula 1-4 2023263496   09 Nov 2023 wherein (a) R1 is hydrogen, methyl, ethyl, zz-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 5   (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 10 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e)    R5 is H, OMe, CN, CH2F, F, Cl, Br, or I; (f)    R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; 15   (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2; The eighth aspect of the second embodiment is directed to a compound represented by formula 1-4 20 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or 25 lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 2023263496   09 Nov 2023 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; 5   (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3.qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2. The ninth aspect of the second embodiment is directed to a compound represented by 10 formula 1-4 wherein (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or 15 lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 20   (e) R5 is H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, or N3; (h) Y is OH, OCH3, or OC(O)CH3; (i) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3-qXq, where X is F, Cl, Br, or I 25 and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2. A third embodiment of the invention is directed to a compound represented by formula I in 2023263496   09 Nov 2023 which the base is a structure represented by formula c above, wherein R1, R2, R3a, R3b, R4, R5, R6, X, Y, Z, R10, R11, and R12 are defined in the Summary of the Invention section above; with the proviso that R11 is not H. A first aspect of the third embodiment is directed to a compound represented by formula 1-5 1-5 wherein (a) R1 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 10 at least one of Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1 ”, and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); (b) R2 is hydrogen or CH3; 15   (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, - (CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b 20 together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3 is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H 25 and R3b is from H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, 2023263496   09 Nov 2023 CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, - 5 CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); 10   (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., - 15 (CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 20   (g) X is H, OH, F, OMe, halogen, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 25 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 30 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), 2023263496   09 Nov 2023 OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; (i)    R10 and R11 are independently H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl of C1-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, 5 halogenated (F, Cl, Br, I) lower alkenyl of C2-C6, lower alkynyl of C2-C6 such as C=CH, halogenated (F, Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower alkoxy of Ci-C6, CO2H, CO2R’, CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; wherein R' is an optionally substituted alkyl, which includes, but is not limited to, an 10 optionally substituted Ci-2o alkyl, an optionally substituted Ci-io alkyl, an optionally substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C2-C6, an optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(0)(Ci-2o alkyl), C(0)(Ci-io alkyl), or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C 15 atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2 lower alkyl of Ci-Ce, halogenated (F, Cl, Br, I) lower alkyl of Ci-Ce, lower alkenyl of C2-C6, halogenated (F, Cl, Br, I) lower alkenyl of C2-C6 , lower alkynyl of C2-C6, halogenated (F, 20 Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of Ci-Ce, halogenated (F, Cl, Br, I) lower alkoxy of Ci-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A second aspect of the third embodiment is directed to a compound represented by formula 1-5 25 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, 30 CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 2023263496   09 Nov 2023 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 5 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 10   (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; 15 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-20  C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A third aspect of the third embodiment is directed to a compound represented by formula 1-5 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p25 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 2023263496   09 Nov 2023 (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 5   (e) R5 is H, CN, CH2F, F, Cl, Br, or I; with the proviso that X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; 10   (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle 15 comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. 20 A fourth aspect of the third embodiment is directed to a compound represented by formula I-5 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 25   (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 2023263496   09 Nov 2023 (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 5   (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', 10   CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and 15   (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A fifth aspect of the third embodiment is directed to a compound represented by formula 1-5 20 wherein (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 25   (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 2023263496   09 Nov 2023 (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; 5   (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle 10 comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A sixth aspect of the third embodiment is directed to a compound represented by formula 1-5 15 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, 20 CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 25 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H. 2023263496   09 Nov 2023 (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)    X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, 5 CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 10   R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci- C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A seventh aspect of the third embodiment is directed to a compound represented by formula 1-5 wherein 15   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 20   (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; (e) R5 is H, CN, CH2F, F, Cl, Br, or I; with the proviso that X is OH, R6 is CH3 or CH2F, 25 R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; 2023263496   09 Nov 2023 (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 5   instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. 10 An eighth aspect of the third embodiment is directed to a compound represented by formula 1-5 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 15   (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 20 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; 25   (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; 2023263496   09 Nov 2023 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 5   R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci- C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A ninth aspect of the third embodiment is directed to a compound represented by formula I-5 wherein 10   (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 15 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; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; 20   (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 25 instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 2023263496   09 Nov 2023 R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A tenth aspect of the third embodiment is directed to a compound represented by formula I- 5   6 R10 1-6 wherein (a) R1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is 10 not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); 15   (b) R2 is hydrogen or CH3; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, -(CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 20 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 25 where R3 is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2- 2023263496   09 Nov 2023 indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, 5 CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); 10   (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., - 15 (CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 20   (g) X is H, OH, F, OMe, Cl, Br, I, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 25 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 30 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), 2023263496   09 Nov 2023 OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when 5   R10 is OH and R11 is not NH2; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 10   R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci- C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. An eleventh aspect of the third embodiment is directed to a compound represented by formula 1-6 wherein 15   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 20 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 25 di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; 2023263496   09 Nov 2023 (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; 5 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-10  C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A twelvth aspect of the third embodiment is directed to a compound represented by formula 1-6 wherein 15   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 20   (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; (e) R5 is H, CN, CH2F, F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or 25 CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; 2023263496   09 Nov 2023 (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 5   instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is a H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. 10 A thirteenth aspect of the third embodiment is directed to a compound represented by formula 1-6 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 15   (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 20 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; 25   (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; 2023263496   09 Nov 2023 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 5   R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci- C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A fourteenth aspect of the third embodiment is directed to a compound represented by formula 1-6 wherein 10   (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 15 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; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; 20   (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', with the proviso that when R10 is OH and R11 is not NH2; 25 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and 2023263496   09 Nov 2023 (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A fifteenth aspect of the third embodiment is directed to a compound represented by formula 5   1-6 wherein (a) R1 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 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-10   6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); (b) R2 is hydrogen or CH3; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, - 15   (CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H- indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together 20 are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3 is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2- 25 indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, - 30 CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); 2023263496   09 Nov 2023 (d) R4 is hydrogen, Ci-io alkyl, Ci-io alkyl optionally substituted with a lower alkyl, alkoxy or halogen, Ci-io haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; 5   (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., - (CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; 10   (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OMe, halogen, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), 15 S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen 20 (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 25 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle 30 comprising at least two carbon atoms; and (j) Z is N or CR12; and 2023263496   09 Nov 2023 R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. An sixteenth aspect of the third embodiment is directed to a compound represented by formula 1-6 5 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, 10 CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 15 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 20   (g)    X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 25 instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 2023263496   09 Nov 2023 R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A seventeenth aspect of the third embodiment is directed to a compound represented by formula 1-6 5 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or 10 lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 15   (e) R5 is H, CN, CH2F, F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; 20   (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and 25   (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. 2023263496   09 Nov 2023 An eighteenth aspect of the third embodiment is directed to a compound represented by formula 1-6 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p5 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 10 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; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; 15   (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 is NH2 and R11 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 20 instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. 25 A ninteenth aspect of the third embodiment is directed to a compound represented by formula 1-6 wherein 2023263496   09 Nov 2023 (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 5   (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; 10   (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 is NH2 and R11 are independently H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; 15 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-20  C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. 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 R11 is H and R2, R3a, R3b, R4, R5, R6, X, and Y are defined in the Summary of the Invention section above. 25 A first aspect of the fourth embodiment is directed to a compound represented by formula I-7 2023263496   09 Nov 2023 1-7 wherein (a) R1 is hydrogen, n-alkyl; branched alkyl; cycloalkyl; or aryl, which includes, but is 5 not limited to, phenyl or naphthyl, where phenyl or naphthyl are optionally substituted with at least one of Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); 10   (b) R2 is hydrogen or CH3; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, -(CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H-indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 15 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 20 where R3’ is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, 25   CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, - 2023263496   09 Nov 2023 CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); 5   (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyl)amino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., - 10 (CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 15   (g) X is H, OH, F, OMe, halogen, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 20 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 25 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; 30   (i)    R10 is H, F, Cl, Br, I, OH, OR', SH, SR', NH2, NHR', NR'2, lower alkyl of Ci-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated (F, Cl, Br, I) lower alkenyl of C2-C6, lower alkynyl of C2-C6 such as C=CH, halogenated (F, Cl, Br, 2023263496   09 Nov 2023 I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower alkoxy of C1-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', wherein R' is an optionally substituted alkyl, which includes, but is not limited to, an optionally substituted C1-20 alkyl, an optionally substituted C1-10 alkyl, an optionally 5 substituted lower alkyl; an optionally substituted cycloalkyl; an optionally substituted alkynyl of C2-C6, an optionally substituted lower alkenyl of C2-C6, or optionally substituted acyl, which includes but is not limited to C(O) alkyl, C(0)(Ci-2o alkyl), C(0)(Ci-io alkyl), or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and 10   (j) Z is N or CR12; and R12 is H, halogen (including F, Cl, Br, I), OH, OR', SH, SR', NH2, NHR', NR'2, NO2 lower alkyl of C1-C6, halogenated (F, Cl, Br, I) lower alkyl of C1-C6, lower alkenyl of C2-C6, halogenated (F, Cl, Br, I) lower alkenyl of C2-C6 , lower alkynyl of C2-C6, halogenated (F, Cl, Br, I) lower alkynyl of C2-C6, lower alkoxy of C1-C6, halogenated (F, Cl, Br, I) lower 15 alkoxy of Ci-C6, CO2H, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. A second aspect of the fourth embodiment is directed to a compound represented by formula 1-7 wherein 20   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 25 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 30 di(lower alkyl)amino-lower alkyl; 2023263496   09 Nov 2023 (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OCH3, halogen, NH2, or N3; 5   (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle 10 comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. 15   A third aspect of the third embodiment is directed to a compound represented by formula 1-7 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; 20   (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 25 di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH2F, F, Cl, Br, or I; with the proviso that X is OH, R6 is CH3 or CH2F, R5 cannot be H; 2023263496   09 Nov 2023 (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, 5 CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 10   R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. A fourth aspect of the fourth embodiment is directed to a compound represented by formula 1-7 15 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or 20 lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 25   (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; 2023263496   09 Nov 2023 (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 and R11 H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 5 instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso 10 that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. A fifth aspect of the fourth embodiment is directed to a compound represented by formula I-7 wherein (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 15   (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 20 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; 25   (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', 2023263496   09 Nov 2023 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 5   R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'. A sixth aspect of the fourth embodiment is directed to a compound represented by formula 1-8 wherein (a) R1 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 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-15   6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1", and -SO2C1-6 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); (b) R2 is hydrogen or CH3; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, -20   (CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H- indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together 2023263496   09 Nov 2023 are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3 is independently hydrogen or Ci-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H 5 and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, 10 CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); 15   (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyljamino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., - 20 (CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 25   (g) X is H, OH, F, OMe, halogen, NH2, or N3; (h) Y is OH, H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OC1-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 30 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen (Cl, Br, F, I), 2023263496   09 Nov 2023 NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), S0(Ci-4 acyl), S0(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), 5   OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 10 instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of C1-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that 15 when base is represented by the structure c with R11 being hydrogen, R12 is not a: (i) -C=C- H, (ii) -C=CH2, or (iii) -NO2. A seventh aspect of the fourth embodiment is directed to a compound represented by formula 1-8 wherein 20   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 25 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 30 di(lower alkyl)amino-lower alkyl; 2023263496   09 Nov 2023 (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OCH3, halogen, NH2, or N3; 5   (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle 10 comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. 15 An eighth aspect of the fourth embodiment is directed to a compound represented by formula 1-8 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 20   (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 25 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH2F, F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; 2023263496   09 Nov 2023 (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, 5 CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 10   R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci- C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. A ninth aspect of the fourth embodiment is directed to a compound represented by formula 1-8 15 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or 20 lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 25   (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; 2023263496   09 Nov 2023 (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the 5 instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci-C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso 10 that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. A tenth aspect of the fourth embodiment is directed to a compound represented by formula 1-8 wherein (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; 15   (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 20 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; 25   (h) Y is OH, NH2, OCH3, or OC(O)CH3; (i)    R10 is H, F, Br, I, OH, OR', NH2, NHR', NR'2, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R', 2023263496   09 Nov 2023 wherein R' is a lower alkyl, a lower cycloalkyl, or C(O)(lower alkyl) or alternatively, in the instance of NR'2, each R' comprise at least one C atom that are joined to form a heterocycle comprising at least two carbon atoms; and (j) Z is N or CR12; and 5   R12 is an H, halogen (including F, Cl, Br, I), OR', NH2, NHR', NR'2, NO2, lower alkyl of Ci- C6, CO2R', CONH2, CONHR', CONR'2, CH=CHCO2H, or CH=CHCO2R'; with the proviso that R12 is not a: (i) -C=C-H, (ii) -C=CH2, or (iii) -NO2. 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 R1, R2, R3a, R3b, R4, 10   R5, R6, X, and Y are defined in the Summary of the Invention section above. The first aspect of the fifth embodiment is directed to a compound represented by formula I-9 O 1-9 15 wherein (a) R1 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 C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, F, Cl, Br, I, nitro, cyano, Ci-6 haloalkyl, -N(R1T)2, C1-6 acylamino, -NHSO2C1-6 alkyl, -SO2N(R1T)2, COR1 ”, and -SO2C1-6 20 alkyl; (R1’ is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, Ci-10 alkyl, or C1-6 alkyl, R1" is -OR' or -N(R1T)2); (b) R2 is hydrogen or CH3; (c) R3a and R3b are (i) independently selected from hydrogen, C1-10 alkyl, cycloalkyl, -(CH2)c(NR3’)2, C1-6 hydroxyalkyl, -CH2SH, -(CH2)2S(O)dMe, -(CH2)3NHC(=NH)NH2, (1H- 2023263496   09 Nov 2023 indol-3-yl)methyl, (lH-imidazol-4-yl)methyl, -(CH2)eCOR3 , aryl and aryl C1-3 alkyl, said aryl groups optionally substituted with a group selected from hydroxyl, C1-10 alkyl, C1-6 alkoxy, halogen, nitro and cyano; (ii) R3a and R3b both are C1-6 alkyl; (iii) R3a and R3b together are(CH2)f so as to form a spiro ring; (iv) R3a is hydrogen and R3b and R2 together 5 are (CH2)n so as to form a cyclic ring that includes the adjoining N and C atoms (v) R3b is hydrogen and R3a and R2 together are (CH2)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 R3 is independently hydrogen or C1-6 alkyl and R3 is -OR' or -N(R3’)2); (vi) R3a is H and R3b is H, CH3, CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2- 10 indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; or (viii) R3a is CH3, -CH2CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, - 15 CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H, where R3 is independently hydrogen or alkyl, which includes, but is not limited to, C1-20 alkyl, C1-10 alkyl, or C1-6 alkyl, R3" is -OR' or -N(R3’)2); (d) R4 is hydrogen, C1-10 alkyl, C1-10 alkyl optionally substituted with a lower alkyl, 20 alkoxy or halogen, C1-10 haloalkyl, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aminoacyl, di(lower alkyljamino-lower alkyl, aryl, such as phenyl, heteroaryl, such as, pyridinyl, substituted aryl, or substituted heteroaryl; (e) R5 is H, a lower alkyl, CN, vinyl, O-(lower alkyl), hydroxyl lower alkyl, i.e., -(CH2)POH, where p is 1 -6, including hydroxyl methyl (CH2OH), CH2F, N3, CH2CN, 25 CH2NH2, CH2NHCH3, CH2N(CH3)2, alkyne (optionally substituted), or halogen, including F, Cl, Br, or I, with the provisos that when X is OH, base is cytosine and R6 is H, R5 cannot be N3 and when X is OH, R6 is CH3 or CH2F and B is a purine base, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OMe, halogen, NH2, or N3; 30   (h) Y is OH, H, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, vinyl, N3, CN, Cl, Br, F, I, NO2, OC(O)O(Ci-4 alkyl), OC(O)O(Ci-4 alkyl), OC(O)O(C2-4 alkynyl), OC(O)O(C2-4 alkenyl), OCi-10 haloalkyl, O(aminoacyl), 0(Ci-io acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 2023263496   09 Nov 2023 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-is acyl)2, wherein alkyl, alkynyl, alkenyl and vinyl are optionally substituted by N3, CN, one to three halogen 5 (Cl, Br, F, I), NO2, C(O)O(Ci-4 alkyl), C(O)O(Ci-4 alkyl), C(O)O(C2-4 alkynyl), C(O)O(C2-4 alkenyl), O(Ci-4 acyl), O(Ci-4 alkyl), O(C2-4 alkenyl), S(Ci-4 acyl), S(Ci-4 alkyl), S(C2-4 alkynyl), S(C2-4 alkenyl), SO(Ci-4 acyl), SO(Ci-4 alkyl), SO(C2-4 alkynyl), SO(C2-4 alkenyl), SO2(Ci-4 acyl), SO2(Ci-4 alkyl), SO2(C2-4 alkynyl), SO2(C2-4 alkenyl), OS(O)2(Ci-4 acyl), OS(O)2(Ci-4 alkyl), OS(O)2(C2-4 alkenyl), NH2, NH(Ci-4 alkyl), NH(C2-4 alkenyl), NH(C2-4 10 alkynyl), NH(Ci-4 acyl), N(Ci-4 alkyl)2, N(Ci-4 acyl)2. A second aspect of the fifth embodiment is directed to a compound represented by formula 1-9 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p15 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, 20 CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 25   (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H. (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g) X is H, OH, F, OCH3, halogen, NH2, or N3; (h) Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3; 30 A third aspect of the fifth embodiment is directed to a compound represented by formula 1-9 wherein 2023263496   09 Nov 2023 (a) R1 is hydrogen, methyl, ethyl, zz-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; 5   (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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 10 di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH2F, F, Cl, Br, or I; with the proviso that X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; 15   (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 N3, OCH3, or OC(O)CH3; A fourth aspect of the fifth embodiment is directed to a compound represented by formula I-9 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p20 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 25 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; 2023263496   09 Nov 2023 (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; 5 A fifth aspect of the fifth embodiment is directed to a compound represented by formula 1-9 wherein (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or 10 lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 15   (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; A sixth aspect of the fifth embodiment is directed to a compound represented by formula I- 20   10 O 2023263496   09 Nov 2023 1-10 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH3, OCH3, F, 5 Cl, Br, I, nitro, cyano, and a CH3-qXq, where X is F, Cl, Br, or I, and q is 1-3; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, 10 CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl or R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H; 15   (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, N3, CH2CN, CH2N3, CH2NH2, 20 CH2NHCH3, CH2N(CH3)2, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; (g)    X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; (h)   Y is OH, H, CH3, vinyl, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3, NH2, NHCH3, 25 NH(vinyl), NH(acetyl), NH(C(O)CH3), N(CH3)2, N(C(O)CH3)2; A seventh aspect of the fifth embodiment is directed to a compound represented by formula 1-10 wherein 2023263496   09 Nov 2023 (a) R1 is hydrogen, methyl, ethyl, zz-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, 5 CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 10 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, CN, CH3, OCH3, CH2OH, CH2F, halogen, including F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, F, or CN; 15   (g)    X is H, OH, F, OCH3, Cl, Br, I, NH2, or N3; and (h)    Y is OH, H, CH3, vinyl, NH2, N3, CN, Cl, Br, F, I, OC(O)CH3, OCH3. An eighth aspect of the fifth embodiment is directed to a compound represented by formula 1-10 wherein 20   (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p- chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen or CH3; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; 25   (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; 2023263496   09 Nov 2023 (e) R5 is H, CN, CH2F, F, Cl, Br, or I, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g)    X is H, OH, F, OCH3, F, Cl, Br, I, NH2 or N3; 5   (h)   Y is H, OH, CH3, F, Cl, Br, I, NH2 or N3, OCH3, or OC(O)CH3; A ninth aspect of the fifth embodiment is directed to a compound represented by formula I- 10 wherein (a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p10 chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, 15 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; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; 20   (g) X is H, OH, OCH3, F, NH2 or N3; (h) Y is OH, NH2, OCH3, or OC(O)CH3; A tenth aspect of the fifth embodiment is directed to a compound represented by formula I-10 wherein 25   (a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; (b) R2 is hydrogen; 2023263496   09 Nov 2023 (c) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; (d) R4 is hydrogen, CH3, Et, Tr, ”Pr, ”Bu, 2-butyl, 'Bu, benzyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl-aziridin-2-yl, N-methyl-azetidin-3-yl, N-methyl- 5 pyrrolidin-3-yl, N-methyl-pyrrolidin-4-yl, N-methyl-piperidin-4-yl, lower haloalkyl, or di(lower alkyl)amino-lower alkyl; (e) R5 is H, with the provisos that when X is OH, R6 is CH3 or CH2F, R5 cannot be H; (f) R6 is H, CH3, CH2F, CHF2, CF3, or F; (g) X is H, OH, OCH3, F, NH2 or N3; 10   (h) Y is OH, NH2, OCH3, or OC(O)CH3. 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 15 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 R1, R2, R3a, R3b, R4, R5, R6, X, and Y. In each of the presented tables, the phosphoramidate substituent containing the substituents R3a and R3b are depicted without reference to stereochemical structure (c / structures 1-1,1-3,1-5,1-7, and I- 20   9 above). It is contemplated that the compounds recited below embody compounds in which R3a projects toward the viewer while R3b projects away from the viewer (cf. structures 1-2,14,1-6,1-8, and 1-10). Moreover, it is contemplated that the compounds recited below also embody compounds in which R3a projects away from the viewer while R3b projects towards the viewer. Not meant to be limiting, however, it is contemplated that preferred compounds 25 are those in which R3a projects towards the viewer and R3b 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 30 that in a staggered (or zig-zag) line structure the oxo-substitutent projects towards the viewer while the OR1 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, 2023263496   09 Nov 2023 the structures below include all possible stereochemical configurations possible for phosphorus. II Table II-1. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-l-l ch3 H H H ch3 H ch3 OH OH H H nh2 II-1-2 ch3 H H ch3 ch3 H ch3 OH OH H H nh2 II-1-3 ch3 H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-1-4 ch3 H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-1-5 ch3 H H CH2Ph ch3 H ch3 OH OH H H nh2 II-1-6 ch3 H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-1-7 ch3 H H ch2ch2sch3 ch3 H ch3 OH OH H H nh2 II-1-8 ch3 * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-2. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-2-1 Et H H H ch3 H ch3 OH OH H H nh2 II-2-2 Et H H ch3 ch3 H ch3 OH OH H H nh2 II-2-3 Et H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-2-4 Et H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-2-5 Et H H CH2Ph ch3 H ch3 OH OH H H nh2 II-2-6 Et H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-2-7 Et H H ch2ch2sch3 ch3 H ch3 OH OH H H nh2 II-2-8 Et * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-3. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-3-1 !Pr H H H ch3 H ch3 OH OH H H nh2 II-3-2 !Pr H H ch3 ch3 H ch3 OH OH H H nh2 II-3-3 !Pr H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-3-4 !Pr H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-3-5 !Pr H H CH2Ph ch3 H ch3 OH OH H H nh2 II-3-6 !Pr H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-3-7 !Pr H H CH2CH2SCH3 ch3 H ch3 OH OH H H nh2 II-3-8 !Pr * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-4. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-4-1 'Bn H H H ch3 H ch3 OH OH H H nh2 II-4-2 'Bn H H ch3 ch3 H ch3 OH OH H H nh2 II-4-3 'Bn H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-4-4 'Bn H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-4-5 'Bn H H CH2Ph ch3 H ch3 OH OH H H nh2 II-4-6 'Bn H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-4-7 'Bn H H CH2CH2SCH3 ch3 H ch3 OH OH H H nh2 II-4-8 'Bn * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-5. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-5-1 Ph H H H ch3 H ch3 OH OH H H nh2 II-5-2 Ph H H ch3 ch3 H ch3 OH OH H H nh2 II-5-3 Ph H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-5-4 Ph H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-5-5 Ph H H CH2Ph ch3 H ch3 OH OH H H nh2 II-5-6 Ph H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-5-7 Ph H H CH2CH2SCH3 ch3 H ch3 OH OH H H nh2 II-5-8 Ph * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-6. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 ' R8 R9 II-6-1 p-Me-Ph H H H ch3 H ch3 OH OH H H NH2 II-6-2 p-Me-Ph H H CH3 ch3 H ch3 OH OH H H NH2 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-6-3 p-Me-Ph H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-6-4 p-Me-Ph H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-6-5 p-Me-Ph H H CH2Ph ch3 H ch3 OH OH H H nh2 II-6-6 p-Me-Ph H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-6-7 p-Me-Ph H H ch2ch2sch3 ch3 H ch3 OH OH H H nh2 II-6-8 p-Me-Ph * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-7. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-7-1 p-F-Ph H H H ch3 H ch3 OH OH H H nh2 II-7-2 p-F-Ph H H ch3 ch3 H ch3 OH OH H H nh2 II-7-3 p-F-Ph H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-7-4 p-F-Ph H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-7-6 p-F-Ph H H CH2Ph ch3 H ch3 OH OH H H nh2 II-7-7 p-F-Ph H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-7-8 p-F-Ph H H ch2ch2sch3 ch3 H ch3 OH OH H H nh2 II-7-20 p-F-Ph * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-8. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-8-1 p-Cl-Ph H H H ch3 H ch3 OH OH H H nh2 II-8-2 p-Cl-Ph H H ch3 ch3 H ch3 OH OH H H nh2 II-8-3 p-Cl-Ph H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-8-4 p-Cl-Ph H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-8-5 p-Cl-Ph H H CH2Ph ch3 H ch3 OH OH H H nh2 II-8-6 p-Cl-Ph H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-8-7 p-Cl-Ph H H ch2ch2sch3 ch3 H ch3 OH OH H H nh2 II-8-8 p-Cl-Ph * H * ch3 H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-9. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-9-1 p-Br-Ph H H H ch3 H ch3 OH OH H H nh2 II-9-2 p-Br-Ph H H ch3 ch3 H ch3 OH OH H H nh2 II-9-3 p-Br-Ph H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-9-4 p-Br-Ph H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-9-6 p-Br-Ph H H CH2Ph ch3 H ch3 OH OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-9-7 p-Br-Ph H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-9-8 p-Br-Ph H H CH2CH2SCH3 ch3 H ch3 OH OH H H nh2 II-9-20 p-Br-Ph * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-10. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-10-1 p-I-Ph H H H ch3 H ch3 OH OH H H nh2 II-10-2 p-I-Ph H H ch3 ch3 H ch3 OH OH H H nh2 II-10-3 p-I-Ph H H CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-10-4 p-I-Ph H H CH2CH(CH3)2 ch3 H ch3 OH OH H H nh2 II-10-5 p-I-Ph H H CH2Ph ch3 H ch3 OH OH H H nh2 II-10-6 p-I-Ph H H CH2-indol-3-yl ch3 H ch3 OH OH H H nh2 II-10-7 p-I-Ph H H ch2ch2sch3 ch3 H ch3 OH OH H H nh2 II-10-8 p-I-Ph * H * ch3 H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table II-11. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-ll-l ch3 H H H Et H ch3 OH OH H H nh2 II-11-2 ch3 H H ch3 Et H ch3 OH OH H H nh2 II-11-3 ch3 H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-11-4 ch3 H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-11-5 ch3 H H CH2Ph Et H ch3 OH OH H H nh2 II-11-6 ch3 H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-11-7 ch3 H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-11-8 ch3 * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-12. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-12-1 Et H H H Et H ch3 OH OH H H nh2 II-12-2 Et H H ch3 Et H ch3 OH OH H H nh2 II-12-3 Et H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-12-4 Et H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-12-5 Et H H CH2Ph Et H ch3 OH OH H H nh2 II-12-6 Et H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-12-7 Et H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-12-8 Et * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table 11-13. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-13-1 !Pr H H H Et H ch3 OH OH H H nh2 II-13-2 !Pr H H ch3 Et H ch3 OH OH H H nh2 II-13-3 !Pr H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-13-4 zpr H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-13-5 zpr H H CH2Ph Et H ch3 OH OH H H nh2 II-13-6 zpr H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-13-7 zpr H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-13-8 zpr * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-14. No R1 R2 R 3a R3b R4 R5 R6 X Y R7 R8 R9 II-14-1 'Bn H H H Et H ch3 OH OH H H nh2 II-14-2 'Bn H H ch3 Et H ch3 OH OH H H nh2 II-14-3 'Bn H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-14-4 'Bn H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-14-5 'Bn H H CH2Ph Et H ch3 OH OH H H nh2 II-14-6 'Bn H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-14-7 'Bn H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-14-8 'Bn * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-15. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-15-1 Ph H H H Et H ch3 OH OH H H nh2 II-15-2 Ph H H ch3 Et H ch3 OH OH H H nh2 II-15-3 Ph H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-15-4 Ph H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-15-5 Ph H H CH2Ph Et H ch3 OH OH H H nh2 II-15-6 Ph H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-15-7 Ph H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-15-8 Ph * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-16. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-16-1 p-Me-Ph H H H Et H ch3 OH OH H H nh2 II-16-2 p-Me-Ph H H ch3 Et H ch3 OH OH H H nh2 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-16-3 p-Me-Ph H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-16-4 p-Me-Ph H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-16-5 p-Me-Ph H H CH2Ph Et H ch3 OH OH H H nh2 II-16-6 p-Me-Ph H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-16-7 p-Me-Ph H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-16-8 p-Me-Ph * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-17. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-17-1 p-F-Ph H H H Et H ch3 OH OH H H nh2 II-17-2 p-F-Ph H H ch3 Et H ch3 OH OH H H nh2 II-17-3 p-F-Ph H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-17-4 p-F-Ph H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-17-5 p-F-Ph H H CH2Ph Et H ch3 OH OH H H nh2 II-17-6 p-F-Ph H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-17-7 p-F-Ph H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-17-8 p-F-Ph * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-18. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-18-1 p-Cl-Ph H H H Et H ch3 OH OH H H nh2 II-18-2 p-Cl-Ph H H ch3 Et H ch3 OH OH H H nh2 II-18-3 p-Cl-Ph H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-18-4 p-Cl-Ph H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-18-5 p-Cl-Ph H H CH2Ph Et H ch3 OH OH H H nh2 II-18-6 p-Cl-Ph H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-18-7 p-Cl-Ph H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-18-8 p-Cl-Ph * H * Et H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-19. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-19-1 p-Br-Ph H H H Et H ch3 OH OH H H nh2 II-19-2 p-Br-Ph H H ch3 Et H ch3 OH OH H H nh2 II-19-3 p-Br-Ph H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-19-4 p-Br-Ph H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-19-5 p-Br-Ph H H CH2Ph Et H ch3 OH OH H H nh2 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-19-6 p-Br-Ph H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-19-7 p-Br-Ph H H CH2CH2SCH3 Et H ch3 OH OH H H nh2 II-19-8 p-Br-Ph * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-20. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-20-1 p-I-Ph H H H Et H ch3 OH OH H H nh2 II-20-2 p-I-Ph H H ch3 Et H ch3 OH OH H H nh2 II-20-3 p-I-Ph H H CH(CH3)2 Et H ch3 OH OH H H nh2 II-20-4 p-I-Ph H H CH2CH(CH3)2 Et H ch3 OH OH H H nh2 II-20-5 p-I-Ph H H CH2Ph Et H ch3 OH OH H H nh2 II-20-6 p-I-Ph H H CH2-indol-3-yl Et H ch3 OH OH H H nh2 II-20-7 p-I-Ph H H ch2ch2sch3 Et H ch3 OH OH H H nh2 II-20-8 p-I-Ph * H * Et H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-21. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-21-1 ch3 H H H 'Pr H ch3 OH OH H H nh2 II-21-2 ch3 H H ch3 'Pr H ch3 OH OH H H nh2 II-21-3 ch3 H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-21-4 ch3 H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-21-5 ch3 H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-21-6 ch3 H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-21-7 ch3 H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-21-8 ch3 * H * 'Pr H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-22. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-22-1 Et H H H 'Pr H ch3 OH OH H H nh2 II-22-2 Et H H ch3 'Pr H ch3 OH OH H H nh2 II-22-3 Et H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-22-4 Et H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-22-5 Et H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-22-6 Et H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-22-7 Et H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-22-8 Et * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table 11-23. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-23-1 'Pr H H H 'Pr H ch3 OH OH H H nh2 II-23-2 'Pr H H ch3 'Pr H ch3 OH OH H H nh2 II-23-3 'Pr H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-23-4 'Pr H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-23-5 'Pr H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-23-6 'Pr H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-23-7 'Pr H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-23-8 'Pr * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-24. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-24-1 'Bn H H H 'Pr H ch3 OH OH H H nh2 II-24-2 'Bn H H ch3 'Pr H ch3 OH OH H H nh2 II-24-3 'Bn H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-24-4 'Bn H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-24-5 'Bn H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-24-6 'Bn H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-24-7 'Bn H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-24-8 'Bn * H * 'Pr H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-25. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-25-1 Ph H H H 'Pr H ch3 OH OH H H nh2 II-25-2 Ph H H ch3 'Pr H ch3 OH OH H H nh2 II-25-3 Ph H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-25-4 Ph H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-25-5 Ph H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-25-6 Ph H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-25-7 Ph H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-25-8 Ph * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 10 Table 11-26.________________________________________________________________________ N° R1 R2 R3a R3b           R4 R5 R6 X Y R7 R8 R9 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-26-1 p-Me-Ph H H H 'Pr H ch3 OH OH H H nh2 II-26-2 p-Me-Ph H H ch3 'Pr H ch3 OH OH H H nh2 II-26-3 p-Me-Ph H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-26-4 p-Me-Ph H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-26-5 p-Me-Ph H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-26-6 p-Me-Ph H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-26-7 p-Me-Ph H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-26-8 p-Me-Ph * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-27. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-27-1 p-F-Ph H H H 'Pr H ch3 OH OH H H nh2 II-27-2 p-F-Ph H H ch3 'Pr H ch3 OH OH H H nh2 II-27-3 p-F-Ph H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-27-4 p-F-Ph H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-27-5 p-F-Ph H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-27-6 p-F-Ph H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-27-7 p-F-Ph H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-27-8 p-F-Ph * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-28. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-28-1 p-Cl-Ph H H H 'Pr H ch3 OH OH H H nh2 II-28-2 p-Cl-Ph H H ch3 'Pr H ch3 OH OH H H nh2 II-28-3 p-Cl-Ph H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-28-4 p-Cl-Ph H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-28-5 p-Cl-Ph H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-28-6 p-Cl-Ph H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-28-7 p-Cl-Ph H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-28-8 p-Cl-Ph * H * 'Pr H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-29. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-29-1 p-Br-Ph H H H 'Pr H ch3 OH OH H H nh2 II-29-2 p-Br-Ph H H ch3 'Pr H ch3 OH OH H H nh2 II-29-3 p-Br-Ph H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-29-4 p-Br-Ph H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-29-5 p-Br-Ph H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-29-6 p-Br-Ph H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-29-7 p-Br-Ph H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-29-8 p-Br-Ph * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-30. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-30-1 p-I-Ph H H H 'Pr H ch3 OH OH H H nh2 II-30-2 p-I-Ph H H ch3 'Pr H ch3 OH OH H H nh2 II-30-3 p-I-Ph H H CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-30-4 p-I-Ph H H CH2CH(CH3)2 'Pr H ch3 OH OH H H nh2 II-30-5 p-I-Ph H H CH2Ph 'Pr H ch3 OH OH H H nh2 II-30-6 p-I-Ph H H CH2-indol-3-yl 'Pr H ch3 OH OH H H nh2 II-30-7 p-I-Ph H H ch2ch2sch3 'Pr H ch3 OH OH H H nh2 II-30-8 p-I-Ph * H * 'Pr H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-31. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-31-1 ch3 H H H "Bu H ch3 OH OH H H nh2 II-31-2 ch3 H H ch3 "Bu H ch3 OH OH H H nh2 II-31-3 ch3 H H CH(CH3)2 "Bu H ch3 OH OH H H nh2 II-31-4 ch3 H H CH2CH(CH3)2 "Bu H ch3 OH OH H H nh2 II-31-5 ch3 H H CH2Ph "Bu H ch3 OH OH H H nh2 II-31-6 ch3 H H CH2-indol-3-yl "Bu H ch3 OH OH H H nh2 II-31-7 ch3 H H ch2ch2sch3 "Bu H ch3 OH OH H H nh2 II-31-8 ch3 * H * "Bu H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-32. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-32-1 Et H H H "Bu H ch3 OH OH H H nh2 II-32-2 Et H H ch3 "Bu H ch3 OH OH H H nh2 II-32-3 Et H H CH(CH3)2 "Bu H ch3 OH OH H H nh2 II-32-4 Et H H CH2CH(CH3)2 "Bu H ch3 OH OH H H nh2 II-32-5 Et H H CH2Ph "Bu H ch3 OH OH H H nh2 II-32-6 Et H H CH2-indol-3-yl "Bu H ch3 OH OH H H nh2 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-32-7 Et H H CH2CH2SCH3 ”Bu H ch3 OH OH H H nh2 II-32-8 Et * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-33. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-33-1 !Pr H H H ”Bu H ch3 OH OH H H nh2 II-33-2 !Pr H H ch3 ”Bu H ch3 OH OH H H nh2 II-33-3 !Pr H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-33-4 !Pr H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-33-5 !Pr H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-33-6 !Pr H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-33-7 !Pr H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-33-8 !Pr * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table 11-34. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-34-1 'Bn H H H ”Bu H ch3 OH OH H H nh2 II-34-2 'Bn H H ch3 ”Bu H ch3 OH OH H H nh2 II-34-3 'Bn H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-34-4 'Bn H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-34-5 'Bn H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-34-6 'Bn H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-34-7 'Bn H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-34-8 'Bn * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-35. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-35-1 Ph H H H ”Bu H ch3 OH OH H H nh2 II-35-2 Ph H H ch3 ”Bu H ch3 OH OH H H nh2 II-35-3 Ph H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-35-4 Ph H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-35-5 Ph H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-35-6 Ph H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-35-7 Ph H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-35-8 Ph * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table 11-36. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-36-1 p-Me-Ph H H H ”Bu H ch3 OH OH H H nh2 II-36-2 p-Me-Ph H H ch3 ”Bu H ch3 OH OH H H nh2 II-36-3 p-Me-Ph H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-36-4 p-Me-Ph H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-36-5 p-Me-Ph H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-36-6 p-Me-Ph H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-36-7 p-Me-Ph H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-36-8 p-Me-Ph * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-37. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-37-1 p-F-Ph H H H ”Bu H ch3 OH OH H H nh2 II-37-2 p-F-Ph H H ch3 ”Bu H ch3 OH OH H H nh2 II-37-3 p-F-Ph H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-37-4 p-F-Ph H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-37-5 p-F-Ph H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-37-6 p-F-Ph H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-37-7 p-F-Ph H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-37-8 p-F-Ph * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-38. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-38-1 p-Cl-Ph H H H ”Bu H ch3 OH OH H H nh2 II-38-2 p-Cl-Ph H H ch3 ”Bu H ch3 OH OH H H nh2 II-38-3 p-Cl-Ph H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-38-4 p-Cl-Ph H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-38-5 p-Cl-Ph H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-38-6 p-Cl-Ph H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-38-7 p-Cl-Ph H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-38-8 p-Cl-Ph * H * ”Bu H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-39. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-39-1 p-Br-Ph H H H ”Bu H ch3 OH OH H H nh2 II-39-2 p-Br-Ph H H ch3 ”Bu H ch3 OH OH H H nh2 II-39-3 p-Br-Ph H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-39-4 p-Br-Ph H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-39-5 p-Br-Ph H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-39-6 p-Br-Ph H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 II-39-7 p-Br-Ph H H ch2ch2sch3 ”Bu H ch3 OH OH H H nh2 II-39-8 p-Br-Ph * H * ”Bu H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-40. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-40-1 p-I-Ph H H H ”Bu H ch3 OH OH H H nh2 II-40-2 p-I-Ph H H ch3 ”Bu H ch3 OH OH H H nh2 II-40-3 p-I-Ph H H CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-40-4 p-I-Ph H H CH2CH(CH3)2 ”Bu H ch3 OH OH H H nh2 II-40-5 p-I-Ph H H CH2Ph ”Bu H ch3 OH OH H H nh2 II-40-6 p-I-Ph H H CH2-indol-3-yl ”Bu H ch3 OH OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-40-7 p-I-Ph H H CH2CH2SCH3 "Bn H CH3 OH OH H H NH2 II-40-8 p-I-Ph * H * ”Bu H CH3 OH OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-41. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-41-1 ch3 h H H Bz H ch3 oh OH H H nh2 II-41-2 ch3 h H ch3 Bz H ch3 oh OH H H nh2 II-41-3 ch3 h H CH(CH3)2 Bz H ch3 oh OH H H nh2 II-41-4 ch3 h H CH2CH(CH3)2 Bz H ch3 oh OH H H nh2 II-41-5 ch3 h H CH2Ph Bz H ch3 oh OH H H nh2 II-41-6 ch3 h H CH2-indol-3-yl Bz H ch3 oh OH H H nh2 II-41-7 ch3 h H CH2CH2SCH3 Bz H ch3 oh OH H H nh2 II-41-8 ch3 * H * Bz H ch3 oh OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-42. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-42-1 Et H H H Bz H ch3 oh OH H H nh2 II-42-2 Et H H ch3 Bz H ch3 oh OH H H nh2 II-42-3 Et H H CH(CH3)2 Bz H ch3 oh OH H H nh2 II-42-4 Et H H CH2CH(CH3)2 Bz H ch3 oh OH H H nh2 II-42-5 Et H H CH2Ph Bz H ch3 oh OH H H nh2 II-42-6 Et H H CH2-indol-3-yl Bz H ch3 oh OH H H nh2 II-42-7 Et H H CH2CH2SCH3 Bz H ch3 oh OH H H nh2 II-42-8 Et * H * Bz H ch3 oh OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-43. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 *R2 and II-43-1 !Pr H H H Bz H ch3 oh OH H H NH2 R3b joined II-43-2 !Pr H H ch3 Bz H ch3 oh OH H H NH2 together II-43-3 !Pr H H CH(CH3)2 Bz H ch3 oh OH H H ^2 by (CH2)3 II-43-4 !Pr H H CH2CH(CH3)2 Bz H ch3 oh OH H H nh2 , p to torm II-43-5 !Pr H H CH2Ph Bz H ch3 oh OH H H nh2 ,, five- II-43-6 !Pr H H CH2-indol-3-yl Bz H ch3 oh OH H H nh2 membere II-43-7 'Pr H H CH2CH2SCH3 Bz H ch3 oh OH H H nh2 II-43-8 rpr * H * Bz H ch3 oh OH H H nh; dni18' 15 Table 11-44. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-44-1 'Bn H H H Bz H ch3 OH OH H H nh2 II-44-2 'Bn H H ch3 Bz H ch3 OH OH H H nh2 II-44-3 'Bn H H CH(CH3)2 Bz H ch3 OH OH H H nh2 11-44-4 'Bn H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-44-5 'Bn H H CH2Ph Bz H ch3 OH OH H H nh2 II-44-6 'Bn H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 II-44-7 'Bn H H ch2ch2sch3 Bz H ch3 OH OH H H nh2 II-44-8 'Bn * H * Bz H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-45. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-45-1 Ph H H H Bz H ch3 OH OH H H nh2 II-45-2 Ph H H ch3 Bz H ch3 OH OH H H nh2 II-45-3 Ph H H CH(CH3)2 Bz H ch3 OH OH H H nh2 II-45-4 Ph H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-45-5 Ph H H CH2Ph Bz H ch3 OH OH H H nh2 II-45-6 Ph H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 II-45-7 Ph H H ch2ch2sch3 Bz H ch3 OH OH H H nh2 II-45-8 Ph * H * Bz H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-46. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-46-1 p-Me-Ph H H H Bz H ch3 OH OH H H nh2 II-46-2 p-Me-Ph H H ch3 Bz H ch3 OH OH H H nh2 II-46-3 p-Me-Ph H H CH(CH3)2 Bz H ch3 OH OH H H nh2 II-46-4 p-Me-Ph H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-46-5 p-Me-Ph H H CH2Ph Bz H ch3 OH OH H H nh2 II-46-6 p-Me-Ph H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 II-46-7 p-Me-Ph H H ch2ch2sch3 Bz H ch3 OH OH H H nh2 II-46-8 p-Me-Ph * H * Bz H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-47. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-47-1 p-F-Ph H H H Bz H ch3 OH OH H H nh2 II-47-2 p-F-Ph H H ch3 Bz H ch3 OH OH H H nh2 II-47-3 p-F-Ph H H CH(CH3)2 Bz H ch3 OH OH H H nh2 2023263496   09 Nov 2023 No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-47-4 p-F-Ph H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-47-5 p-F-Ph H H CH2Ph Bz H ch3 OH OH H H nh2 II-47-6 p-F-Ph H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 II-47-7 p-F-Ph H H ch2ch2sch3 Bz H ch3 OH OH H H nh2 II-47-8 p-F-Ph * H * Bz H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-48. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-48-1 p-Cl-Ph H H H Bz H ch3 OH OH H H nh2 II-48-2 p-Cl-Ph H H ch3 Bz H ch3 OH OH H H nh2 II-48-3 p-Cl-Ph H H CH(CH3)2 Bz H ch3 OH OH H H nh2 II-48-4 p-Cl-Ph H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-48-5 p-Cl-Ph H H CH2Ph Bz H ch3 OH OH H H nh2 II-48-6 p-Cl-Ph H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 II-48-7 p-Cl-Ph H H ch2ch2sch3 Bz H ch3 OH OH H H nh2 II-48-8 p-Cl-Ph * H * Bz H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-49. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-49-1 p-Br-Ph H H H Bz H ch3 OH OH H H nh2 II-49-2 p-Br-Ph H H ch3 Bz H ch3 OH OH H H nh2 II-49-3 p-Br-Ph H H CH(CH3)2 Bz H ch3 OH OH H H nh2 II-49-4 p-Br-Ph H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-49-5 p-Br-Ph H H CH2Ph Bz H ch3 OH OH H H nh2 II-49-6 p-Br-Ph H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 II-49-7 p-Br-Ph H H ch2ch2sch3 Bz H ch3 OH OH H H nh2 II-49-8 p-Br-Ph * H * Bz H ch3 OH OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table 11-50. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-50-1 p-I-Ph H H H Bz H ch3 OH OH H H nh2 II-50-2 p-I-Ph H H ch3 Bz H ch3 OH OH H H nh2 II-50-3 p-I-Ph H H CH(CH3)2 Bz H ch3 OH OH H H nh2 II-50-4 p-I-Ph H H CH2CH(CH3)2 Bz H ch3 OH OH H H nh2 II-50-5 p-I-Ph H H CH2Ph Bz H ch3 OH OH H H nh2 II-50-6 p-I-Ph H H CH2-indol-3-yl Bz H ch3 OH OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 II-50-7 p-I-Ph H H CH2CH2SCH3 Bz H ch3 OH OH H H nh2 II-50-8 p-I-Ph * H * Bz H ch3 OH OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-l. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-l-l ch3 H H H ch3 H ch3 F OH H H nh2 III-1-2 ch3 H H ch3 ch3 H ch3 F OH H H nh2 III-1-3 ch3 H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-1-4 ch3 H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-1-5 ch3 H H CH2Ph ch3 H ch3 F OH H H nh2 III-1-6 ch3 H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-1-7 ch3 H H CH2CH2SCH3 ch3 H ch3 F OH H H nh2 III-1-8 ch3 * H * ch3 H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-2. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-2-1 Et H H H ch3 H ch3 F OH H H nh2 III-2-2 Et H H ch3 ch3 H ch3 F OH H H nh2 III-2-3 Et H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-2-4 Et H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-2-5 Et H H CH2Ph ch3 H ch3 F OH H H nh2 III-2-6 Et H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-2-7 Et H H ch2ch2sch3 ch3 H ch3 F OH H H nh2 III-2-8 Et * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table III-3. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-3-1 !Pr H H H CH3 H ch3 F OH H H nh2 III-3-2 !Pr H H ch3 CH3 H ch3 F OH H H nh2 III-3-3 !Pr H H CH(CH3)2 CH3 H ch3 F OH H H nh2 III-3-4 zpr H H CH2CH(CH3)2 CH3 H ch3 F OH H H nh2 III-3-5 zpr H H CH2Ph CH3 H ch3 F OH H H nh2 III-3-6 zpr H H CH2-indol-3-yl CH3 H ch3 F OH H H nh2 III-3-7 zpr H H CH2CH2SCH3 CH3 H ch3 F OH H H nh2 III-3-8 zpr * H * CH3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-4. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-4-1 'Bn H H H ch3 H ch3 F OH H H nh2 III-4-2 'Bn H H ch3 ch3 H ch3 F OH H H nh2 III-4-3 'Bn H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-4-4 'Bn H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-4-5 'Bn H H CH2Ph ch3 H ch3 F OH H H nh2 III-4-6 'Bn H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-4-7 'Bn H H CH2CH2SCH3 ch3 H ch3 F OH H H nh2 III-4-8 'Bn * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-5. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-5-1 Ph H H H ch3 H ch3 F OH H H nh2 III-5-2 Ph H H ch3 ch3 H ch3 F OH H H nh2 III-5-3 Ph H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-5-4 Ph H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-5-5 Ph H H CH2Ph ch3 H ch3 F OH H H nh2 III-5-6 Ph H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-5-7 Ph H H CH2CH2SCH3 ch3 H ch3 F OH H H nh2 III-5-8 Ph * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table III-6. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-6-1 p-Me-Ph H H H ch3 H ch3 F OH H H nh2 III-6-2 p-Me-Ph H H ch3 ch3 H ch3 F OH H H nh2 III-6-3 p-Me-Ph H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-6-4 p-Me-Ph H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-6-5 p-Me-Ph H H CH2Ph ch3 H ch3 F OH H H nh2 III-6-6 p-Me-Ph H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-6-7 p-Me-Ph H H ch2ch2sch3 ch3 H ch3 F OH H H nh2 III-6-8 p-Me-Ph * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-7. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-7-1 p-F-Ph H H H ch3 H ch3 F OH H H nh2 III-7-2 p-F-Ph H H ch3 ch3 H ch3 F OH H H nh2 III-7-3 p-F-Ph H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-7-4 p-F-Ph H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-7-6 p-F-Ph H H CH2Ph ch3 H ch3 F OH H H nh2 III-7-7 p-F-Ph H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-7-8 p-F-Ph H H ch2ch2sch3 ch3 H ch3 F OH H H nh2 III-7-20 p-F-Ph * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table III-8. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-8-1 p-Cl-Ph H H H ch3 H ch3 F OH H H nh2 III-8-2 p-Cl-Ph H H ch3 ch3 H ch3 F OH H H nh2 III-8-3 p-Cl-Ph H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-8-4 p-Cl-Ph H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-8-5 p-Cl-Ph H H CH2Ph ch3 H ch3 F OH H H nh2 III-8-6 p-Cl-Ph H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-8-7 p-Cl-Ph H H ch2ch2sch3 ch3 H ch3 F OH H H nh2 III-8-8 p-Cl-Ph * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-9. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-9-1 p-Br-Ph H H H ch3 H ch3 F OH H H nh2 III-9-2 p-Br-Ph H H ch3 ch3 H ch3 F OH H H nh2 III-9-3 p-Br-Ph H H CH(CH3)2 ch3 H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 r3e ' R3b R4 R5 R6 X Y R7 R8 R9 III-9-4 p-Br-Ph H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-9-6 p-Br-Ph H H CH2Ph ch3 H ch3 F OH H H nh2 III-9-7 p-Br-Ph H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-9-8 p-Br-Ph H H ch2ch2sch3 ch3 H ch3 F OH H H nh2 III-9-20 p-Br-Ph * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-10. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-10-1 p-I-Ph H H H ch3 H ch3 F OH H H nh2 III-10-2 p-I-Ph H H ch3 ch3 H ch3 F OH H H nh2 III-10-3 p-I-Ph H H CH(CH3)2 ch3 H ch3 F OH H H nh2 III-10-4 p-I-Ph H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 III-10-5 p-I-Ph H H CH2Ph ch3 H ch3 F OH H H nh2 III-10-6 p-I-Ph H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 III-10-7 p-I-Ph H H ch2ch2sch3 ch3 H ch3 F OH H H nh2 III-10-8 p-I-Ph * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-ll. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-ll-l ch3 H H H Et H ch3 F OH H H nh2 III-11-2 ch3 H H ch3 Et H ch3 F OH H H nh2 III-11-3 ch3 H H CH(CH3)2 Et H ch3 F OH H H nh2 III-11-4 ch3 H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-11-5 ch3 H H CH2Ph Et H ch3 F OH H H nh2 III-11-6 ch3 H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-11-7 ch3 H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-11-8 ch3 * H * Et H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-12. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-12-1 Et H H H Et H ch3 F OH H H nh2 III-12-2 Et H H ch3 Et H ch3 F OH H H nh2 III-12-3 Et H H CH(CH3)2 Et H ch3 F OH H H nh2 III-12-4 Et H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-12-5 Et H H CH2Ph Et H ch3 F OH H H nh2 III-12-6 Et H H CH2-indol-3-yl Et H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-12-7 Et H H CH2CH2SCH3 Et H ch3 F OH H H nh2 III-12-8 Et * H * Et H ch3 F OH H H nh2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table III-13. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-13-1 Tr H H H Et H ch3 F OH H H nh2 III-13-2 Tr H H ch3 Et H ch3 F OH H H nh2 III-13-3 Tr H H CH(CH3)2 Et H ch3 F OH H H nh2 III-13-4 Tr H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-13-5 Tr H H CH2Ph Et H ch3 F OH H H nh2 III-13-6 Tr H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-13-7 Tr H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-13-8 Tr * H * Et H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-14. Ns R1 R2 R R3b R4 R5 R6 X Y R7 R8 R9 3a III-14- Tu H H H Et H ch3 F OH H H nh2 1 III-14- Tu H H ch3 Et H ch3 F OH H H nh2 2 III-14- 'Bn H H CH(CH3)2 Et H ch3 F OH H H nh2 3 III-14- 'Bn H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 4 III-14- 'Bn H H CH2Ph Et H ch3 F OH H H nh2 5 III-14- 'Bn H H CH2-indol-3-yl Et H ch3 F OH H H nh2 6 III-14- 'Bn H H ch2ch2sch3 Et H ch3 F OH H H nh2 7 III-14- 'Bn * H * Et H ch3 F OH H H nh2 8 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-15. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-15-1 Ph H H H Et H ch3 F OH H H nh2 III-15-2 Ph H H ch3 Et H ch3 F OH H H nh2 III-15-3 Ph H H CH(CH3)2 Et H ch3 F OH H H nh2 III-15-4 Ph H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-15-5 Ph H H CH2Ph Et H ch3 F OH H H nh2 III-15-6 Ph H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-15-7 Ph H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-15-8 Ph * H * Et H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-16. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-16-1 p-Me-Ph H H H Et H ch3 F OH H H nh2 III-16-2 p-Me-Ph H H ch3 Et H ch3 F OH H H nh2 III-16-3 p-Me-Ph H H CH(CH3)2 Et H ch3 F OH H H nh2 III-16-4 p-Me-Ph H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-16-5 p-Me-Ph H H CH2Ph Et H ch3 F OH H H nh2 III-16-6 p-Me-Ph H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-16-7 p-Me-Ph H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-16-8 p-Me-Ph * H * Et H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-17. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-17-1 p-F-Ph H H H Et H ch3 F OH H H nh2 III-17-2 p-F-Ph H H ch3 Et H ch3 F OH H H nh2 III-17-3 p-F-Ph H H CH(CH3)2 Et H ch3 F OH H H nh2 III-17-4 p-F-Ph H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-17-5 p-F-Ph H H CH2Ph Et H ch3 F OH H H nh2 III-17-6 p-F-Ph H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-17-7 p-F-Ph H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-17-8 p-F-Ph * H * Et H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-18. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-18-1 p-Cl-Ph H H H Et H ch3 F OH H H nh2 III-18-2 p-Cl-Ph H H ch3 Et H ch3 F OH H H nh2 III-18-3 p-Cl-Ph H H CH(CH3)2 Et H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-18-4 p-Cl-Ph H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-18-5 p-Cl-Ph H H CH2Ph Et H ch3 F OH H H nh2 III-18-6 p-Cl-Ph H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-18-7 p-Cl-Ph H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-18-8 p-Cl-Ph * H * Et H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-19. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-19-1 p-Br-Ph H H H Et H ch3 F OH H H nh2 III-19-2 p-Br-Ph H H ch3 Et H ch3 F OH H H nh2 III-19-3 p-Br-Ph H H CH(CH3)2 Et H ch3 F OH H H nh2 III-19-4 p-Br-Ph H H CH2CH(CH3)2 Et H ch3 F OH H H nh2 III-19-5 p-Br-Ph H H CH2Ph Et H ch3 F OH H H nh2 III-19-6 p-Br-Ph H H CH2-indol-3-yl Et H ch3 F OH H H nh2 III-19-7 p-Br-Ph H H ch2ch2sch3 Et H ch3 F OH H H nh2 III-19-8 p-Br-Ph * H * Et H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-20. Ns R1 R2 R3 a R3b R4 R5 R6 X Y R7 R8 R9 III-20-1 p-I-Ph H H H Et H CH3 F OH H H NH2 III-20-2 p-I-Ph H H ch3 Et H CH3 F OH H H NH2 III-20-3 p-I-Ph H H CH(CH3)2 Et H CH3 F OH H H NH2 III-20-4 p-I-Ph H H CH2CH(CH3)2 Et H CH3 F OH H H NH2 III-20-5 p-I-Ph H H CH2Ph Et H CH3 F OH H H NH2 III-20-6 p-I-Ph H H CH2-indol-3-yl Et H CH3 F OH H H NH2 III-20-7 p-I-Ph H H ch2ch2sch3 Et H CH3 F OH H H NH2 III-20-8 p-I-Ph * H * Et H CH3 F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-21. Ns R1 R2 : R3a R3b R4 R5 R6 X Y R7 R8 R9 III-21-1 ch3 h H H 'Pr H CH3 F OH H H NH2 III-21-2 ch3 h H ch3 'Pr H CH3 F OH H H NH2 III-21-3 ch3 h H CH(CH3)2 'Pr H CH3 F OH H H NH2 III-21-4 ch3 h H CH2CH(CH3)2 'Pr H CH3 F OH H H NH2 III-21-5 ch3 h H CH2Ph 'Pr H CH3 F OH H H NH2 III-21-6 ch3 h H CH2-indol-3-yl 'Pr H CH3 F OH H H NH2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-21-7 ch3 H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-21-8 ch3 * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-22. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-22-1 Et H H H 'Pr H ch3 F OH H H nh2 III-22-2 Et H H ch3 'Pr H ch3 F OH H H nh2 III-22-3 Et H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-22-4 Et H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-22-5 Et H H CH2Ph 'Pr H ch3 F OH H H nh2 III-22-6 Et H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-22-7 Et H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-22-8 Et * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-23. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-23-1 'Pr H H H 'Pr H ch3 F OH H H nh2 III-23-2 'Pr H H ch3 'Pr H ch3 F OH H H nh2 III-23-3 'Pr H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-23-4 'Pr H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-23-5 'Pr H H CH2Ph 'Pr H ch3 F OH H H nh2 III-23-6 'Pr H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-23-7 'Pr H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-23-8 'Pr * H * 'Pr H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-24. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-24-1 'Bn H H H 'Pr H ch3 F OH H H nh2 III-24-2 'Bn H H ch3 'Pr H ch3 F OH H H nh2 III-24-3 'Bn H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-24-4 'Bn H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-24-5 'Bn H H CH2Ph 'Pr H ch3 F OH H H nh2 III-24-6 'Bn H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-24-7 'Bn H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-24-8 'Bn * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-25-1 Ph H H H 'Pr H ch3 F OH H H nh2 III-25-2 Ph H H ch3 'Pr H ch3 F OH H H nh2 III-25-3 Ph H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-25-4 Ph H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-25-5 Ph H H CH2Ph 'Pr H ch3 F OH H H nh2 III-25-6 Ph H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-25-7 Ph H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-25-8 Ph * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-26. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-26-1 p-Me-Ph H H H 'Pr H ch3 F OH H H nh2 III-26-2 p-Me-Ph H H ch3 'Pr H ch3 F OH H H nh2 III-26-3 p-Me-Ph H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-26-4 p-Me-Ph H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-26-5 p-Me-Ph H H CH2Ph 'Pr H ch3 F OH H H nh2 III-26-6 p-Me-Ph H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-26-7 p-Me-Ph H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-26-8 p-Me-Ph * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table III-27. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-27-1 p-F-Ph H H H 'Pr H ch3 F OH H H nh2 III-27-2 p-F-Ph H H ch3 'Pr H ch3 F OH H H nh2 III-27-3 p-F-Ph H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-27-4 p-F-Ph H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-27-5 p-F-Ph H H CH2Ph 'Pr H ch3 F OH H H nh2 III-27-6 p-F-Ph H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-27-7 p-F-Ph H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-27-8 p-F-Ph * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-28. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-28-1 p-Cl-Ph H H H 'Pr H ch3 F OH H H nh2 III-28-2 p-Cl-Ph H H ch3 'Pr H ch3 F OH H H nh2 III-28-3 p-Cl-Ph H H CH(CH3)2 'Pr H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-28-4 p-Cl-Ph H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-28-5 p-Cl-Ph H H CH2Ph 'Pr H ch3 F OH H H nh2 III-28-6 p-Cl-Ph H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-28-7 p-Cl-Ph H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-28-8 p-Cl-Ph * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-29. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-29-1 p-Br-Ph H H H 'Pr H ch3 F OH H H nh2 III-29-2 p-Br-Ph H H ch3 'Pr H ch3 F OH H H nh2 III-29-3 p-Br-Ph H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-29-4 p-Br-Ph H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-29-5 p-Br-Ph H H CH2Ph 'Pr H ch3 F OH H H nh2 III-29-6 p-Br-Ph H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-29-7 p-Br-Ph H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-29-8 p-Br-Ph * H * 'Pr H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-30. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-30-1 p-I-Ph H H H 'Pr H ch3 F OH H H nh2 III-30-2 p-I-Ph H H ch3 'Pr H ch3 F OH H H nh2 III-30-3 p-I-Ph H H CH(CH3)2 'Pr H ch3 F OH H H nh2 III-30-4 p-I-Ph H H CH2CH(CH3)2 'Pr H ch3 F OH H H nh2 III-30-5 p-I-Ph H H CH2Ph 'Pr H ch3 F OH H H nh2 III-30-6 p-I-Ph H H CH2-indol-3-yl 'Pr H ch3 F OH H H nh2 III-30-7 p-I-Ph H H ch2ch2sch3 'Pr H ch3 F OH H H nh2 III-30-8 p-I-Ph * H * 'Pr H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-31. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-31-1 ch3 H H H "Bu H ch3 F OH H H nh2 III-31-2 ch3 H H ch3 "Bu H ch3 F OH H H nh2 III-31-3 ch3 H H CH(CH3)2 "Bu H ch3 F OH H H nh2 III-31-4 ch3 H H CH2CH(CH3)2 "Bu H ch3 F OH H H nh2 III-31-5 ch3 H H CH2Ph "Bu H ch3 F OH H H nh2 III-31-6 ch3 H H CH2-indol-3-yl "Bu H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-31-7 ch3 H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-31-8 ch3 * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-32. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-32-1 Et H H H ”Bu H ch3 F OH H H nh2 III-32-2 Et H H ch3 ”Bu H ch3 F OH H H nh2 III-32-3 Et H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-32-4 Et H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-32-5 Et H H CH2Ph ”Bu H ch3 F OH H H nh2 III-32-6 Et H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-32-7 Et H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-32-8 Et * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-33. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-33-1 Tr H H H ”Bu H ch3 F OH H H nh2 III-33-2 Tr H H ch3 ”Bu H ch3 F OH H H nh2 III-33-3 !Pr H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-33-4 Tr H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-33-5 Tr H H CH2Ph ”Bu H ch3 F OH H H nh2 III-33-6 Tr H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-33-7 Tr H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-33-8 Tr * H * ”Bu H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-34-1 'Bn H H H ”Bu H ch3 F OH H H nh2 III-34-2 'Bn H H ch3 ”Bu H ch3 F OH H H nh2 III-34-3 'Bn H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-34-4 'Bn H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-34-5 'Bn H H CH2Ph ”Bu H ch3 F OH H H nh2 III-34-6 'Bn H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-34-7 'Bn H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-34-8 'Bn * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-35. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-35-1 Ph H H H ”Bu H ch3 F OH H H nh2 III-35-2 Ph H H ch3 ”Bu H ch3 F OH H H nh2 III-35-3 Ph H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-35-4 Ph H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-35-5 Ph H H CH2Ph ”Bu H ch3 F OH H H nh2 III-35-6 Ph H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-35-7 Ph H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-35-8 Ph * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table III-36. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-36-1 p-Me-Ph H H H ”Bu H ch3 F OH H H nh2 III-36-2 p-Me-Ph H H ch3 ”Bu H ch3 F OH H H nh2 III-36-3 p-Me-Ph H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-36-4 p-Me-Ph H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-36-5 p-Me-Ph H H CH2Ph ”Bu H ch3 F OH H H nh2 III-36-6 p-Me-Ph H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-36-7 p-Me-Ph H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-36-8 p-Me-Ph * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-37. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-37-1 p-F-Ph H H H ”Bu H ch3 F OH H H nh2 III-37-2 p-F-Ph H H ch3 ”Bu H ch3 F OH H H nh2 III-37-3 p-F-Ph H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 - Ill - 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-37-4 p-F-Ph H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-37-5 p-F-Ph H H CH2Ph ”Bu H ch3 F OH H H nh2 III-37-6 p-F-Ph H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-37-7 p-F-Ph H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-37-8 p-F-Ph * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-38. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-38-1 p-Cl-Ph H H H ”Bu H ch3 F OH H H nh2 III-38-2 p-Cl-Ph H H ch3 ”Bu H ch3 F OH H H nh2 III-38-3 p-Cl-Ph H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-38-4 p-Cl-Ph H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-38-5 p-Cl-Ph H H CH2Ph ”Bu H ch3 F OH H H nh2 III-38-6 p-Cl-Ph H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-38-7 p-Cl-Ph H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-38-8 p-Cl-Ph * H * ”Bu H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-39. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-39-1 p-Br-Ph H H H ”Bu H ch3 F OH H H nh2 III-39-2 p-Br-Ph H H ch3 ”Bu H ch3 F OH H H nh2 III-39-3 p-Br-Ph H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-39-4 p-Br-Ph H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-39-5 p-Br-Ph H H CH2Ph ”Bu H ch3 F OH H H nh2 III-39-6 p-Br-Ph H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 III-39-7 p-Br-Ph H H ch2ch2sch3 ”Bu H ch3 F OH H H nh2 III-39-8 p-Br-Ph * H * ”Bu H ch3 F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-40. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-40-1 p-I-Ph H H H ”Bu H ch3 F OH H H nh2 III-40-2 p-I-Ph H H ch3 ”Bu H ch3 F OH H H nh2 III-40-3 p-I-Ph H H CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-40-4 p-I-Ph H H CH2CH(CH3)2 ”Bu H ch3 F OH H H nh2 III-40-5 p-I-Ph H H CH2Ph ”Bu H ch3 F OH H H nh2 III-40-6 p-I-Ph H H CH2-indol-3-yl ”Bu H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-40-7 p-I-Ph H H CH2CH2SCH3 "Bu H CH3 F OH H H NH2 III-40-8 p-I-Ph * H * ”Bu H CH3 F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-41. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-41-1 ch3 H H H Bz H ch3 f OH H H nh2 III-41-2 ch3 H H ch3 Bz H ch3 f OH H H nh2 III-41-3 ch3 H H CH(CH3)2 Bz H ch3 f OH H H nh2 III-41-4 ch3 H H CH2CH(CH3)2 Bz H ch3 f OH H H nh2 III-41-5 ch3 H H CH2Ph Bz H ch3 f OH H H nh2 III-41-6 ch3 H H CH2-indol-3-yl Bz H ch3 f OH H H nh2 III-41-7 ch3 H H ch2ch2sch3 Bz H ch3 f OH H H nh2 III-41-8 ch3 * H * Bz H ch3 f OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-42. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-42-1 Et H H H Bz H ch3 f OH H H nh2 III-42-2 Et H H ch3 Bz H ch3 f OH H H nh2 III-42-3 Et H H CH(CH3)2 Bz H ch3 f OH H H nh2 III-42-4 Et H H CH2CH(CH3)2 Bz H ch3 f OH H H nh2 III-42-5 Et H H CH2Ph Bz H ch3 f OH H H nh2 III-42-6 Et H H CH2-indol-3-yl Bz H ch3 f OH H H nh2 III-42-7 Et H H ch2ch2sch3 Bz H ch3 f OH H H nh2 III-42-8 Et * H * Bz H ch3 f OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-43. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 *R2 and III-43-1 Tr H H H Bz H ch3 f OH H H NH2 R3b joined III-43-2 Tr H H ch3 Bz H ch3 f OH H H NH2 together III-43-3 Tr H H CH(CH3)2 Bz H ch3 f OH H H by (CH2)3 III-43-4 Tr H H CH2CH(CH3)2 Bz H ch3 f OH H H nh2 . p to torm III-43-5 Tr H H CH2Ph Bz H ch3 f OH H H nh2 ,, five- III-43-6 Tr H H CH2-indol-3-yl Bz H ch3 f OH H H nh2 membered III-43-7 Tr H H ch2ch2sch3 Bz H ch3 f OH H H nh2 III-43-8 Tr * H * Bz H ch3 f OH H H nh2 rmg’ 15 Table III-44. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-44-1 'Bn H H H Bz H ch3 F OH H H nh2 III-44-2 'Bn H H ch3 Bz H ch3 F OH H H nh2 III-44-3 'Bn H H CH(CH3)2 Bz H ch3 F OH H H nh2 III-44-4 'Bn H H CH2CH(CH3)2 Bz H ch3 F OH H H nh2 III-44-5 'Bn H H CH2Ph Bz H ch3 F OH H H nh2 III-44-6 'Bn H H CH2-indol-3-yl Bz H ch3 F OH H H nh2 III-44-7 'Bn H H ch2ch2sch3 Bz H ch3 F OH H H nh2 III-44-8 'Bn * H * Bz H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-45-1 Ph H H H Bz H ch3 F OH H H nh2 III-45-2 Ph H H ch3 Bz H ch3 F OH H H nh2 III-45-3 Ph H H CH(CH3)2 Bz H ch3 F OH H H nh2 III-45-4 Ph H H CH2CH(CH3)2 Bz H ch3 F OH H H nh2 III-45-5 Ph H H CH2Ph Bz H ch3 F OH H H nh2 III-45-6 Ph H H CH2-indol-3-yl Bz H ch3 F OH H H nh2 III-45-7 Ph H H ch2ch2sch3 Bz H ch3 F OH H H nh2 III-45-8 Ph * H * Bz H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-46. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-46-1 p-Me-Ph H H H Bz H ch3 F OH H H nh2 III-46-2 p-Me-Ph H H ch3 Bz H ch3 F OH H H nh2 III-46-3 p-Me-Ph H H CH(CH3)2 Bz H ch3 F OH H H nh2 III-46-4 p-Me-Ph H H CH2CH(CH3)2 Bz H ch3 F OH H H nh2 III-46-5 p-Me-Ph H H CH2Ph Bz H ch3 F OH H H nh2 III-46-6 p-Me-Ph H H CH2-indol-3-yl Bz H ch3 F OH H H nh2 III-46-7 p-Me-Ph H H ch2ch2sch3 Bz H ch3 F OH H H nh2 III-46-8 p-Me-Ph * H * Bz H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table III-47. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-47-1 p-F-Ph H H H Bz H ch3 F OH H H nh2 III-47-2 p-F-Ph H H ch3 Bz H ch3 F OH H H nh2 III-47-3 p-F-Ph H H CH(CH3)2 Bz H ch3 F OH H H nh2 III-47-4 p-F-Ph H H CH2CH(CH3)2 Bz H ch3 F OH H H nh2 III-47-5 p-F-Ph H H CH2Ph Bz H ch3 F OH H H nh2 III-47-6 p-F-Ph H H CH2-indol-3-yl Bz H ch3 F OH H H nh2 III-47-7 p-F-Ph H H ch2ch2sch3 Bz H ch3 F OH H H nh2 III-47-8 p-F-Ph * H * Bz H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-48. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-48-1 p-Cl-Ph H H H Bz H ch3 F OH H H nh2 III-48-2 p-Cl-Ph H H ch3 Bz H ch3 F OH H H nh2 III-48-3 p-Cl-Ph H H CH(CH3)2 Bz H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-48-4 p-Cl-Ph H H CH2CH(CH3)2 Bz H ch3 F OH H H nh2 III-48-5 p-Cl-Ph H H CH2Ph Bz H ch3 F OH H H nh2 III-48-6 p-Cl-Ph H H CH2-indol-3-yl Bz H ch3 F OH H H nh2 III-48-7 p-Cl-Ph H H ch2ch2sch3 Bz H ch3 F OH H H nh2 III-48-8 p-Cl-Ph * H * Bz H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1        R2 R3a ' R3b R4 R5 R6 X Y R7 R8 R9 III-49-1 p-Br-Ph H H H Bz H CH3 F OH H H nh2 III-49-2 p-Br-Ph H H ch3 Bz H CH3 F OH H H nh2 III-49-3 p-Br-Ph H H CH(CH3)2 Bz H CH3 F OH H H nh2 III-49-4 p-Br-Ph H H CH2CH(CH3)2 Bz H CH3 F OH H H nh2 III-49-5 p-Br-Ph H H CH2Ph Bz H CH3 F OH H H nh2 III-49-6 p-Br-Ph H H CH2-indol-3-yl Bz H CH3 F OH H H nh2 III-49-7 p-Br-Ph H H ch2ch2sch3 Bz H CH3 F OH H H nh2 III-49-8 p-Br-Ph * H * Bz H CH3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table III-50. Ns R1      R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 III-50-1 p-I-Ph H H H Bz H CH3 F OH H H nh2 III-50-2 p-I-Ph H H ch3 Bz H CH3 F OH H H nh2 III-50-3 p-I-Ph H H CH(CH3)2 Bz H CH3 F OH H H nh2 III-50-4 p-I-Ph H H CH2CH(CH3)2 Bz H CH3 F OH H H nh2 III-50-5 p-I-Ph H H CH2Ph Bz H CH3 F OH H H nh2 III-50-6 p-I-Ph H H CH2-indol-3-yl Bz H CH3 F OH H H nh2 III-50-7 p-I-Ph H H ch2ch2sch3 Bz H CH3 F OH H H nh2 III-50-8 p-I-Ph * H * Bz H CH3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-1. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-1-1 ch3 H H H ch3 H F F OH H H nh2 IV-1-2 ch3 H H ch3 ch3 H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-1-3 ch3 H H CH(CH3)2 ch3 H F F OH H H nh2 IV-1-4 ch3 H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-1-5 ch3 H H CH2Ph ch3 H F F OH H H nh2 IV-1-6 ch3 H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-1-7 ch3 H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-1-8 ch3 * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-2. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-2-1 Et H H H ch3 H F F OH H H nh2 IV-2-2 Et H H ch3 ch3 H F F OH H H nh2 IV-2-3 Et H H CH(CH3)2 ch3 H F F OH H H nh2 IV-2-4 Et H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-2-5 Et H H CH2Ph ch3 H F F OH H H nh2 IV-2-6 Et H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-2-7 Et H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-2-8 Et * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-3. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-3-1 zpr H H H ch3 H F F OH H H nh2 IV-3-2 !Pr H H ch3 ch3 H F F OH H H nh2 IV-3-3 !Pr H H CH(CH3)2 ch3 H F F OH H H nh2 IV-3-4 !Pr H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-3-5 !Pr H H CH2Ph ch3 H F F OH H H nh2 IV-3-6 !Pr H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-3-7 !Pr H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-3-8 !Pr * H * ch3 H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-4. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-4-1 'Bn H H H ch3 H ch3 F OH H H nh2 IV-4-2 'Bn H H ch3 ch3 H ch3 F OH H H nh2 IV-4-3 'Bn H H CH(CH3)2 ch3 H ch3 F OH H H nh2 IV-4-4 'Bn H H CH2CH(CH3)2 ch3 H ch3 F OH H H nh2 IV-4-5 'Bn H H CH2Ph ch3 H ch3 F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-4-6 'Bn H H CH2-indol-3-yl ch3 H ch3 F OH H H nh2 IV-4-7 'Bn H H CH2CH2SCH3 ch3 H ch3 F OH H H nh2 IV-4-8 'Bn * H * ch3 H ch3 F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-5-1 Ph H H H ch3 H F F OH H H nh2 IV-5-2 Ph H H ch3 ch3 H F F OH H H nh2 IV-5-3 Ph H H CH(CH3)2 ch3 H F F OH H H nh2 IV-5-4 Ph H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-5-5 Ph H H CH2Ph ch3 H F F OH H H nh2 IV-5-6 Ph H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-5-7 Ph H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-5-8 Ph * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-6. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-6-1 p-Me-Ph H H H ch3 H F F OH H H nh2 IV-6-2 p-Me-Ph H H ch3 ch3 H F F OH H H nh2 IV-6-3 p-Me-Ph H H CH(CH3)2 ch3 H F F OH H H nh2 IV-6-4 p-Me-Ph H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-6-5 p-Me-Ph H H CH2Ph ch3 H F F OH H H nh2 IV-6-6 p-Me-Ph H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-6-7 p-Me-Ph H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-6-8 p-Me-Ph * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table IV-7. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-7-1 p-F-Ph H H H ch3 H F F OH H H nh2 IV-7-2 p-F-Ph H H ch3 ch3 H F F OH H H nh2 IV-7-3 p-F-Ph H H CH(CH3)2 ch3 H F F OH H H nh2 IV-7-4 p-F-Ph H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-7-6 p-F-Ph H H CH2Ph ch3 H F F OH H H nh2 IV-7-7 p-F-Ph H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-7-8 p-F-Ph H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-7-20 p-F-Ph * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-8. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-8-1 p-Cl-Ph H H H ch3 H F F OH H H nh2 IV-8-2 p-Cl-Ph H H ch3 ch3 H F F OH H H nh2 IV-8-3 p-Cl-Ph H H CH(CH3)2 ch3 H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-8-4 p-Cl-Ph H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-8-5 p-Cl-Ph H H CH2Ph ch3 H F F OH H H nh2 IV-8-6 p-Cl-Ph H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-8-7 p-Cl-Ph H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-8-8 p-Cl-Ph * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-9. Ns R1 R2 R3e ' R3b R4 R5 R6 X Y R7 R8 R9 IV-9-1 p-Br-Ph H H H ch3 H F F OH H H nh2 IV-9-2 p-Br-Ph H H ch3 ch3 H F F OH H H nh2 IV-9-3 p-Br-Ph H H CH(CH3)2 ch3 H F F OH H H nh2 IV-9-4 p-Br-Ph H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-9-6 p-Br-Ph H H CH2Ph ch3 H F F OH H H nh2 IV-9-7 p-Br-Ph H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-9-8 p-Br-Ph H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-9-20 p-Br-Ph * H * ch3 H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-10. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-10-1 p-I-Ph H H H ch3 H F F OH H H nh2 IV-10-2 p-I-Ph H H ch3 ch3 H F F OH H H nh2 IV-10-3 p-I-Ph H H CH(CH3)2 ch3 H F F OH H H nh2 IV-10-4 p-I-Ph H H CH2CH(CH3)2 ch3 H F F OH H H nh2 IV-10-5 p-I-Ph H H CH2Ph ch3 H F F OH H H nh2 IV-10-6 p-I-Ph H H CH2-indol-3-yl ch3 H F F OH H H nh2 IV-10-7 p-I-Ph H H ch2ch2sch3 ch3 H F F OH H H nh2 IV-10-8 p-I-Ph * H * ch3 H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-11. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-11-1 ch3 H H H Et H F F OH H H nh2 IV-11-2 ch3 H H ch3 Et H F F OH H H nh2 IV-11-3 ch3 H H CH(CH3)2 Et H F F OH H H nh2 IV-11-4 ch3 H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-11-5 ch3 H H CH2Ph Et H F F OH H H nh2 IV-11-6 ch3 H H CH2-indol-3-yl Et H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-11-7 ch3 H H ch2ch2sch3 Et H F F OH H H nh2 IV-11-8 ch3 * H * Et H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-12. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-12-1 Et H H H Et H F F OH H H nh2 IV-12-2 Et H H ch3 Et H F F OH H H nh2 IV-12-3 Et H H CH(CH3)2 Et H F F OH H H nh2 IV-12-4 Et H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-12-5 Et H H CH2Ph Et H F F OH H H nh2 IV-12-6 Et H H CH2-indol-3-yl Et H F F OH H H nh2 IV-12-7 Et H H ch2ch2sch3 Et H F F OH H H nh2 IV-12-8 Et * H * Et H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-13. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-13-1 !Pr H H H Et H F F OH H H nh2 IV-13-2 zpr H H ch3 Et H F F OH H H nh2 IV-13-3 zpr H H CH(CH3)2 Et H F F OH H H nh2 IV-13-4 zpr H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-13-5 zpr H H CH2Ph Et H F F OH H H nh2 IV-13-6 !Pr H H CH2-indol-3-yl Et H F F OH H H nh2 IV-13-7 !Pr H H ch2ch2sch3 Et H F F OH H H nh2 IV-13-8 !Pr * H * Et H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-14. Ns R1 R2 R 3a R3b R4 R5 R6 X Y R7 R8 R9 IV-14- 1 'Bn H H H Et H F F OH H H NH2 IV-14- 2 'Bn H H ch3 Et H F F OH H H NH2 IV-14- 3 'Bn H H CH(CH3)2 Et H F F OH H H NH2 IV-14- 'Bn H H CH2CH(CH3)2 Et H F F OH H H NH2 2023263496   09 Nov 2023 Ns R1 R2 R 3a R3b             R4 R5 R6 X Y R7 R8 R9 IV-14- 5 'Bn H H CH2Ph        Et H F F OH H H NH2 IV-14- 6 'Bn H H CH2-indol-3-yl Et H F F OH H H NH2 IV-14- 7 'Bn H H CH2CH2SCH3 Et H F F OH H H NH2 IV-14- 8 'Bn * H *              Et H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-15. Ns R1 R2 R3a R3b            R4 R5 R6 X Y R7 R8 R9 IV-15-1 Ph H H H           Et H F F OH H H NH2 IV-15-2 Ph H H CH3          Et H F F OH H H NH2 IV-15-3 Ph H H CH(CH3)2     Et H F F OH H H NH2 IV-15-4 Ph H H CH2CH(CH3)2 Et H F F OH H H NH2 IV-15-5 Ph H H CH2Ph       Et H F F OH H H NH2 IV-15-6 Ph H H CH2-indol-3-yl Et H F F OH H H NH2 IV-15-7 Ph H H CH2CH2SCH3 Et H F F OH H H NH2 IV-15-8 Ph * H *             Et H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-16. Ns R1 R2 R3a R3b             R4 R5 R6 X Y R7 R8 R9 IV-16-1 p-Me-Ph H H H           Et H F F OH H H NH2 IV-16-2 p-Me-Ph H H CH3          Et H F F OH H H NH2 IV-16-3 p-Me-Ph H H CH(CH3)2     Et H F F OH H H NH2 IV-16-4 p-Me-Ph H H CH2CH(CH3)2 Et H F F OH H H NH2 IV-16-5 p-Me-Ph H H CH2Ph       Et H F F OH H H NH2 IV-16-6 p-Me-Ph H H CH2-indol-3-yl Et H F F OH H H NH2 IV-16-7 p-Me-Ph H H CH2CH2SCH3 Et H F F OH H H NH2 IV-16-8 p-Me-Ph * H *             Et H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-17. Ns R1 R2 R3a R3b             R4 R5 R6 X Y R7 R8 R9 IV-17-1 p-F-Ph H H H           Et H F F OH H H NH2 IV-17-2 p-F-Ph H H CH3          Et H F F OH H H NH2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-17-3 p-F-Ph H H CH(CH3)2 Et H F F OH H H nh2 IV-17-4 p-F-Ph H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-17-5 p-F-Ph H H CH2Ph Et H F F OH H H nh2 IV-17-6 p-F-Ph H H CH2-indol-3-yl Et H F F OH H H nh2 IV-17-7 p-F-Ph H H ch2ch2sch3 Et H F F OH H H nh2 IV-17-8 p-F-Ph * H * Et H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-18. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-18-1 p-Cl-Ph H H H Et H F F OH H H nh2 IV-18-2 p-Cl-Ph H H ch3 Et H F F OH H H nh2 IV-18-3 p-Cl-Ph H H CH(CH3)2 Et H F F OH H H nh2 IV-18-4 p-Cl-Ph H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-18-5 p-Cl-Ph H H CH2Ph Et H F F OH H H nh2 IV-18-6 p-Cl-Ph H H CH2-indol-3-yl Et H F F OH H H nh2 IV-18-7 p-Cl-Ph H H CH2CH2SCH3 Et H F F OH H H nh2 IV-18-8 p-Cl-Ph * H * Et H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-19. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-19-1 p-Br-Ph H H H Et H F F OH H H nh2 IV-19-2 p-Br-Ph H H ch3 Et H F F OH H H nh2 IV-19-3 p-Br-Ph H H CH(CH3)2 Et H F F OH H H nh2 IV-19-4 p-Br-Ph H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-19-5 p-Br-Ph H H CH2Ph Et H F F OH H H nh2 IV-19-6 p-Br-Ph H H CH2-indol-3-yl Et H F F OH H H nh2 IV-19-7 p-Br-Ph H H ch2ch2sch3 Et H F F OH H H nh2 IV-19-8 p-Br-Ph * H * Et H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-20. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-20-1 p-I-Ph H H H Et H F F OH H H nh2 IV-20-2 p-I-Ph H H ch3 Et H F F OH H H nh2 IV-20-3 p-I-Ph H H CH(CH3)2 Et H F F OH H H nh2 IV-20-4 p-I-Ph H H CH2CH(CH3)2 Et H F F OH H H nh2 IV-20-5 p-I-Ph H H CH2Ph Et H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-20-6 p-I-Ph H H CH2-indol-3-yl Et H F F OH H H NH2 IV-20-7 p-I-Ph H H CH2CH2SCH3 Et H F F OH H H NH2 IV-20-8 p-I-Ph * H * Et H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-21. Ns R1 R2 R3 a R3b R4 R ! R( ’ X Y R7 R8 1 R9 IV-21-1 ch3 H H H 'Pr H F F OH H H nh2 IV-21-2 ch3 H H ch3 'Pr H F F OH H H nh2 IV-21-3 ch3 H H CH(CH3)2 'Pr H F F OH H H nh2 IV-21-4 ch3 H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-21-5 ch3 H H CH2Ph 'Pr H F F OH H H nh2 IV-21-6 ch3 H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-21-7 ch3 H H ch2ch2sch3 'Pr H F F OH H H nh2 IV-21-8 ch3 * H * 'Pr H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-22. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-22-1 Et H H H 'Pr H F F OH H H nh2 IV-22-2 Et H H ch3 'Pr H F F OH H H nh2 IV-22-3 Et H H CH(CH3)2 'Pr H F F OH H H nh2 IV-22-4 Et H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-22-5 Et H H CH2Ph 'Pr H F F OH H H nh2 IV-22-6 Et H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-22-7 Et H H ch2ch2sch3 'Pr H F F OH H H nh2 IV-22-8 Et * H * 'Pr H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-23. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-23-1 'Pr H H H 'Pr H F F OH H H nh2 IV-23-2 'Pr H H ch3 'Pr H F F OH H H nh2 IV-23-3 'Pr H H CH(CH3)2 'Pr H F F OH H H nh2 IV-23-4 'Pr H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-23-5 'Pr H H CH2Ph 'Pr H F F OH H H nh2 IV-23-6 'Pr H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-23-7 'Pr H H ch2ch2sch3 'Pr H F F OH H H nh2 IV-23-8 'Pr * H * 'Pr H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-24. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-24-1 'Bu H H H 'Pr H F F OH H H nh2 IV-24-2 'Bu H H ch3 'Pr H F F OH H H nh2 IV-24-3 'Bu H H CH(CH3)2 'Pr H F F OH H H nh2 IV-24-4 'Bu H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-24-5 'Bu H H CH2Ph 'Pr H F F OH H H nh2 IV-24-6 'Bu H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-24-7 'Bu H H ch2ch2sch3 'Pr H F F OH H H nh2 IV-24-8 'Bu * H * 'Pr H F F OH H H nh2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table IV-25. Ns      R1 R2 R3a R3b           R4 R5 R6 X Y R7 R8 R9 IV-25-1 Ph H H H           'Pr H F F OH H H NH2 IV-25-2 Ph H H CH3         'Pr HF F OH H H NH2 IV-25-3 Ph H H CH(CH3)2     'Pr HF F OH H H NH2 IV-25-4 Ph H H CH2CH(CH3)2 'Pr HF F OH H H NH2 IV-25-5 Ph H H CH2Ph       'Pr HF F OH H H NH2 IV-25-6 Ph H H CH2-indol-3-yl 'Pr HF F OH H H NH2 IV-25-7 Ph H H CH2CH2SCH3 'Pr HF F OH H H NH2 IV-25-8 Ph * H *            'Pr H F F OH H H NH2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table IV-26. Ns      R1        R2 R3a R3b           R4 R5 R6 X Y R7 R8 R9 IV-26-1 p-Me-Ph H H H           'Pr H F F OH H H NH2 IV-26-2 p-Me-Ph H H CH3         'Pr HF F OH H H NH2 IV-26-3 p-Me-Ph H H CH(CH3)2     'Pr HF F OH H H NH2 IV-26-4 p-Me-Ph H H CH2CH(CH3)2 'Pr HF F OH H H NH2 IV-26-5 p-Me-Ph H H CH2Ph       'Pr HF F OH H H NH2 IV-26-6 p-Me-Ph H H CH2-indol-3-yl 'Pr HF F OH H H NH2 IV-26-7 p-Me-Ph H H CH2CH2SCH3 'Pr HF F OH H H NH2 IV-26-8 p-Me-Ph * H *            'Pr H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-27. Ns      R1      R2 R3a R3b           R4 R5 R6 X Y R7 R8 R9 IV-27-1 p-F-Ph H H H            'Pr H F F OH H H NH2 IV-27-2 p-F-Ph H H CH3         'Pr HF F OH H H NH2 IV-27-3 p-F-Ph H H CH(CH3)2     'Pr HF F OH H H NH2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-27-4 p-F-Ph H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-27-5 p-F-Ph H H CH2Ph 'Pr H F F OH H H nh2 IV-27-6 p-F-Ph H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-27-7 p-F-Ph H H ch2ch2sch3 'Pr H F F OH H H nh2 IV-27-8 p-F-Ph * H * 'Pr H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-28. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-28-1 p-Cl-Ph H H H 'Pr H F F OH H H nh2 IV-28-2 p-Cl-Ph H H ch3 'Pr H F F OH H H nh2 IV-28-3 p-Cl-Ph H H CH(CH3)2 'Pr H F F OH H H nh2 IV-28-4 p-Cl-Ph H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-28-5 p-Cl-Ph H H CH2Ph 'Pr H F F OH H H nh2 IV-28-6 p-Cl-Ph H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-28-7 p-Cl-Ph H H CH2CH2SCH3 'Pr H F F OH H H nh2 IV-28-8 p-Cl-Ph * H * 'Pr H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-29. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-29-1 p-Br-Ph H H H 'Pr H F F OH H H nh2 IV-29-2 p-Br-Ph H H ch3 'Pr H F F OH H H nh2 IV-29-3 p-Br-Ph H H CH(CH3)2 'Pr H F F OH H H nh2 IV-29-4 p-Br-Ph H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-29-5 p-Br-Ph H H CH2Ph 'Pr H F F OH H H nh2 IV-29-6 p-Br-Ph H H CH2-indol-3-yl 'Pr H F F OH H H nh2 IV-29-7 p-Br-Ph H H ch2ch2sch3 'Pr H F F OH H H nh2 IV-29-8 p-Br-Ph * H * 'Pr H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-30. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-30-1 p-I-Ph H H H 'Pr H F F OH H H nh2 IV-30-2 p-I-Ph H H ch3 'Pr H F F OH H H nh2 IV-30-3 p-I-Ph H H CH(CH3)2 'Pr H F F OH H H nh2 IV-30-4 p-I-Ph H H CH2CH(CH3)2 'Pr H F F OH H H nh2 IV-30-5 p-I-Ph H H CH2Ph 'Pr H F F OH H H nh2 IV-30-6 p-I-Ph H H CH2-indol-3-yl 'Pr H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-30-7 p-I-Ph H H CH2CH2SCH3 'Pr HF F OH H H NH2 IV-30-8 p-I-Ph * H * 'Pr HF F OH H H NH2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table IV-31. Ns R1 R2 R3 a R3b R4 R5 R6 X Y R7 R8 R9 IV-31-1 ch3 h H H "Bu H F F OH H H NH2 IV-31-2 ch3 h H ch3 "Bu H F F OH H H NH2 IV-31-3 ch3 h H CH(CH3)2 "Bu H F F OH H H NH2 IV-31-4 ch3 h H CH2CH(CH3)2 "Bu H F F OH H H NH2 IV-31-5 ch3 h H CH2Ph "Bu H F F OH H H NH2 IV-31-6 ch3 h H CH2-indol-3-yl "Bu H F F OH H H NH2 IV-31-7 ch3 h H ch2ch2sch3 "Bu H F F OH H H NH2 IV-31-8 ch3 * H * "Bu H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-32. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-32-1 Et H H H "Bu H F F OH H H NH2 IV-32-2 Et H H ch3 "Bu H F F OH H H NH2 IV-32-3 Et H H CH(CH3)2 "Bu H F F OH H H NH2 IV-32-4 Et H H CH2CH(CH3)2 "Bu H F F OH H H NH2 IV-32-5 Et H H CH2Ph "Bu H F F OH H H NH2 IV-32-6 Et H H CH2-indol-3-yl "Bu H F F OH H H NH2 IV-32-7 Et H H ch2ch2sch3 "Bu H F F OH H H NH2 IV-32-8 Et * H * "Bu H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-33. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-33-1 'Pr H H H "Bu H F F OH H H NH2 IV-33-2 'Pr H H ch3 "Bu H F F OH H H NH2 IV-33-3 'Pr H H CH(CH3)2 "Bu H F F OH H H NH2 IV-33-4 'Pr H H CH2CH(CH3)2 "Bu H F F OH H H NH2 IV-33-5 'Pr H H CH2Ph "Bu H F F OH H H NH2 IV-33-6 'Pr H H CH2-indol-3-yl "Bu H F F OH H H NH2 IV-33-7 'Pr H H ch2ch2sch3 "Bu H F F OH H H NH2 IV-33-8 zPj- * H * "Bu H F F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table IV-34. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-34-1 'Bu H H H "Bu H F F OH H H nh2 IV-34-2 'Bu H H ch3 "Bu H F F OH H H nh2 IV-34-3 'Bu H H CH(CH3)2 "Bu H F F OH H H nh2 IV-34-4 'Bu H H CH2CH(CH3)2 "Bu H F F OH H H nh2 IV-34-5 'Bu H H CH2Ph "Bu H F F OH H H nh2 IV-34-6 'Bu H H CH2-indol-3-yl "Bu H F F OH H H nh2 IV-34-7 'Bu H H ch2ch2sch3 "Bu H F F OH H H nh2 IV-34-8 'Bu * H * "Bu H F F OH H H nh2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table IV-35. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-35-1 Ph H H H "Bu H F F OH H H nh2 IV-35-2 Ph H H ch3 "Bu H F F OH H H nh2 IV-35-3 Ph H H CH(CH3)2 "Bu H F F OH H H nh2 IV-35-4 Ph H H CH2CH(CH3)2 "Bu H F F OH H H nh2 IV-35-5 Ph H H CH2Ph "Bu H F F OH H H nh2 IV-35-6 Ph H H CH2-indol-3-yl "Bu H F F OH H H nh2 IV-35-7 Ph H H ch2ch2sch3 "Bu H F F OH H H nh2 IV-35-8 Ph * H * "Bu H F F OH H H nh2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table IV-36. Ns R1        R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-36-1 p-Me-Ph H H H "Bu H F F OH H H nh2 IV-36-2 p-Me-Ph H H CH3 "Bu H F F OH H H nh2 IV-36-3 p-Me-Ph H H CH(CH3)2 "Bu H F F OH H H nh2 IV-36-4 p-Me-Ph H H CH2CH(CH3)2 "Bu H F F OH H H nh2 IV-36-5 p-Me-Ph H H CH2Ph "Bu H F F OH H H nh2 IV-36-6 p-Me-Ph H H CH2-indol-3-yl "Bu H F F OH H H nh2 IV-36-7 p-Me-Ph H H CH2CH2SCH3 "Bu H F F OH H H nh2 IV-36-8 p-Me-Ph * H * "Bu H F F OH H H nh2 *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table IV-37. Ns R1      R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-37-1 p-F-Ph H H H "Bu H F F OH H H nh2 IV-37-2 p-F-Ph H H CH3 "Bu H F F OH H H nh2 IV-37-3 p-F-Ph H H CH(CH3)2 "Bu H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-37-4 p-F-Ph H H CH2CH(CH3)2 ”Bu H F F OH H H nh2 IV-37-5 p-F-Ph H H CH2Ph ”Bu H F F OH H H nh2 IV-37-6 p-F-Ph H H CH2-indol-3-yl ”Bu H F F OH H H nh2 IV-37-7 p-F-Ph H H ch2ch2sch3 ”Bu H F F OH H H nh2 IV-37-8 p-F-Ph * H * ”Bu H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-38. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-38-1 p-Cl-Ph H H H ”Bu H F F OH H H nh2 IV-38-2 p-Cl-Ph H H ch3 ”Bu H F F OH H H nh2 IV-38-3 p-Cl-Ph H H CH(CH3)2 ”Bu H F F OH H H nh2 IV-38-4 p-Cl-Ph H H CH2CH(CH3)2 ”Bu H F F OH H H nh2 IV-38-5 p-Cl-Ph H H CH2Ph ”Bu H F F OH H H nh2 IV-38-6 p-Cl-Ph H H CH2-indol-3-yl ”Bu H F F OH H H nh2 IV-38-7 p-Cl-Ph H H CH2CH2SCH3 ”Bu H F F OH H H nh2 IV-38-8 p-Cl-Ph * H * ”Bu H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-39. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-39-1 p-Br-Ph H H H ”Bu H F F OH H H nh2 IV-39-2 p-Br-Ph H H ch3 ”Bu H F F OH H H nh2 IV-39-3 p-Br-Ph H H CH(CH3)2 ”Bu H F F OH H H nh2 IV-39-4 p-Br-Ph H H CH2CH(CH3)2 ”Bu H F F OH H H nh2 IV-39-5 p-Br-Ph H H CH2Ph ”Bu H F F OH H H nh2 IV-39-6 p-Br-Ph H H CH2-indol-3-yl ”Bu H F F OH H H nh2 IV-39-7 p-Br-Ph H H ch2ch2sch3 ”Bu H F F OH H H nh2 IV-39-8 p-Br-Ph * H * ”Bu H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-40. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-40-1 p-I-Ph H H H ”Bu H F F OH H H nh2 IV-40-2 p-I-Ph H H ch3 ”Bu H F F OH H H nh2 IV-40-3 p-I-Ph H H CH(CH3)2 ”Bu H F F OH H H nh2 IV-40-4 p-I-Ph H H CH2CH(CH3)2 ”Bu H F F OH H H nh2 IV-40-5 p-I-Ph H H CH2Ph ”Bu H F F OH H H nh2 IV-40-6 p-I-Ph H H CH2-indol-3-yl ”Bu H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-40-7 p-I-Ph H H CH2CH2SCH3 ”Bu H F F OH H H nh2 IV-40-8 p-I-Ph * H * ”Bu H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-41. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-41-1 ch3 H H H Bz H F F OH H H nh2 IV-41-2 ch3 H H ch3 Bz H F F OH H H nh2 IV-41-3 ch3 H H CH(CH3)2 Bz H F F OH H H nh2 IV-41-4 ch3 H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-41-5 ch3 H H CH2Ph Bz H F F OH H H nh2 IV-41-6 ch3 H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-41-7 ch3 H H ch2ch2sch3 Bz H F F OH H H nh2 IV-41-8 ch3 * H * Bz H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-42. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-42-1 Et H H H Bz H F F OH H H nh2 IV-42-2 Et H H ch3 Bz H F F OH H H nh2 IV-42-3 Et H H CH(CH3)2 Bz H F F OH H H nh2 IV-42-4 Et H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-42-5 Et H H CH2Ph Bz H F F OH H H nh2 IV-42-6 Et H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-42-7 Et H H ch2ch2sch3 Bz H F F OH H H nh2 IV-42-8 Et * H * Bz H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-43. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 *R2 and R3b IV-43-1 !Pr H H H Bz H F F OH H H nh2 joined IV-43-2 !Pr H H ch3 Bz H F F OH H H nh2 together by IV-43-3 !Pr H H CH(CH3)2 Bz H F F OH H H W (CH2)3 to IV-43-4 !Pr H H CH2CH(CH3)2 Bz H F F OH H H nh2 form five- IV-43-5 !Pr H H CH2Ph Bz H F F OH H H nh2 membered IV-43-6 zpr H H CH2-indol-3-yl Bz H F F OH H H nh2 ring. IV-43-7 zpr H H ch2ch2sch3 Bz H F F OH H H nh2 IV-43-8 zpr * H * Bz H F F OH H H nh2 Table IV- 15 44. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-44-1 'Bn H H H Bz H F F OH H H nh2 IV-44-2 'Bn H H ch3 Bz H F F OH H H nh2 IV-44-3 'Bn H H CH(CH3)2 Bz H F F OH H H nh2 IV-44-4 'Bn H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-44-5 'Bn H H CH2Ph Bz H F F OH H H nh2 IV-44-6 'Bn H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-44-7 'Bn H H ch2ch2sch3 Bz H F F OH H H nh2 IV-44-8 'Bn * H * Bz H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-45. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-45-1 Ph H H H Bz H F F OH H H nh2 IV-45-2 Ph H H ch3 Bz H F F OH H H nh2 IV-45-3 Ph H H CH(CH3)2 Bz H F F OH H H nh2 IV-45-4 Ph H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-45-5 Ph H H CH2Ph Bz H F F OH H H nh2 IV-45-6 Ph H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-45-7 Ph H H ch2ch2sch3 Bz H F F OH H H nh2 IV-45-8 Ph * H * Bz H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-46. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-46-1 p-Me-Ph H H H Bz H F F OH H H nh2 IV-46-2 p-Me-Ph H H ch3 Bz H F F OH H H nh2 IV-46-3 p-Me-Ph H H CH(CH3)2 Bz H F F OH H H nh2 IV-46-4 p-Me-Ph H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-46-5 p-Me-Ph H H CH2Ph Bz H F F OH H H nh2 IV-46-6 p-Me-Ph H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-46-7 p-Me-Ph H H ch2ch2sch3 Bz H F F OH H H nh2 IV-46-8 p-Me-Ph * H * Bz H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-47. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-47-1 p-F-Ph H H H Bz H F F OH H H nh2 IV-47-2 p-F-Ph H H ch3 Bz H F F OH H H nh2 IV-47-3 p-F-Ph H H CH(CH3)2 Bz H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-47-4 p-F-Ph H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-47-5 p-F-Ph H H CH2Ph Bz H F F OH H H nh2 IV-47-6 p-F-Ph H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-47-7 p-F-Ph H H ch2ch2sch3 Bz H F F OH H H nh2 IV-47-8 p-F-Ph * H * Bz H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-48. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-48-1 p-Cl-Ph H H H Bz H F F OH H H nh2 IV-48-2 p-Cl-Ph H H ch3 Bz H F F OH H H nh2 IV-48-3 p-Cl-Ph H H CH(CH3)2 Bz H F F OH H H nh2 IV-48-4 p-Cl-Ph H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-48-5 p-Cl-Ph H H CH2Ph Bz H F F OH H H nh2 IV-48-6 p-Cl-Ph H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-48-7 p-Cl-Ph H H CH2CH2SCH3 Bz H F F OH H H nh2 IV-48-8 p-Cl-Ph * H * Bz H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-49. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-49-1 p-Br-Ph H H H Bz H F F OH H H nh2 IV-49-2 p-Br-Ph H H ch3 Bz H F F OH H H nh2 IV-49-3 p-Br-Ph H H CH(CH3)2 Bz H F F OH H H nh2 IV-49-4 p-Br-Ph H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-49-5 p-Br-Ph H H CH2Ph Bz H F F OH H H nh2 IV-49-6 p-Br-Ph H H CH2-indol-3-yl Bz H F F OH H H nh2 IV-49-7 p-Br-Ph H H ch2ch2sch3 Bz H F F OH H H nh2 IV-49-8 p-Br-Ph * H * Bz H F F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table IV-50. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-50-1 p-I-Ph H H H Bz H F F OH H H nh2 IV-50-2 p-I-Ph H H ch3 Bz H F F OH H H nh2 IV-50-3 p-I-Ph H H CH(CH3)2 Bz H F F OH H H nh2 IV-50-4 p-I-Ph H H CH2CH(CH3)2 Bz H F F OH H H nh2 IV-50-5 p-I-Ph H H CH2Ph Bz H F F OH H H nh2 IV-50-6 p-I-Ph H H CH2-indol-3-yl Bz H F F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 IV-50-7 p-I-Ph H H CH2CH2SCH3 Bz H F F OH H H nh2 IV-50-8 p-I-Ph * H * Bz H F F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3iJ ' R3b R4 R5 R6 X Y R7 R8 R9 V-l-1 ch3 H H H ch3 H H F OH H H nh2 V-l-2 ch3 H H ch3 ch3 H H F OH H H nh2 V-l-3 ch3 H H CH(CH3)2 ch3 H H F OH H H nh2 V-l-4 ch3 H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-l-5 ch3 H H CH2Ph ch3 H H F OH H H nh2 V-l-6 ch3 H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-l-7 ch3 H H ch2ch2sch3 ch3 H H F OH H H nh2 V-l-8 ch3 * H * ch3 H H F OH H H nh2 *R2 and R3b Table V-2. joined together by (CH2)3 to form five-membered ring. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-2-1 Et H H H ch3 H H F OH H H nh2 V-2-2 Et H H ch3 ch3 H H F OH H H nh2 V-2-3 Et H H CH(CH3)2 ch3 H H F OH H H nh2 V-2-4 Et H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-2-5 Et H H CH2Ph ch3 H H F OH H H nh2 V-2-6 Et H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-2-7 Et H H ch2ch2sch3 ch3 H H F OH H H nh2 V-2-8 Et * H * ch3 H H F OH H H nh2 *R2 and R3b Table V-3. joined together by (CH2)3 to form five-membered ring. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-3-1 !Pr H H H ch3 H H F OH H H nh2 V-3-2 !Pr H H ch3 ch3 H H F OH H H nh2 V-3-3 !Pr H H CH(CH3)2 ch3 H H F OH H H nh2 V-3-4 !Pr H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-3-5 zpr H H CH2Ph ch3 H H F OH H H nh2 V-3-6 zpr H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-3-7 zpr H H ch2ch2sch3 ch3 H H F OH H H nh2 V-3-8 zpr * H * ch3 H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-4-1 T3u H H H ch3 H H F OH H H nh2 V-4-2 T3u H H ch3 ch3 H H F OH H H nh2 V-4-3 T3u H H CH(CH3)2 ch3 H H F OH H H nh2 V-4-4 'Bn H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-4-5 'Bn H H CH2Ph ch3 H H F OH H H nh2 V-4-6 'Bn H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-4-7 'Bn H H CH2CH2SCH3 ch3 H H F OH H H nh2 V-4-8 'Bn * H * ch3 H H F OH H H nh2 *R2 and R3b Table V-5. joined together by (CH2)3 to form five-membered ring. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-5-1 Ph H H H ch3 H H F OH H H nh2 V-5-2 Ph H H ch3 ch3 H H F OH H H nh2 V-5-3 Ph H H CH(CH3)2 ch3 H H F OH H H nh2 V-5-4 Ph H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-5-5 Ph H H CH2Ph ch3 H H F OH H H nh2 V-5-6 Ph H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-5-7 Ph H H CH2CH2SCH3 ch3 H H F OH H H nh2 V-5-8 Ph * H * ch3 H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table V-6. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-6-1 p-Me-Ph H H H ch3 H H F OH H H nh2 V-6-2 p-Me-Ph H H ch3 ch3 H H F OH H H nh2 V-6-3 p-Me-Ph H H CH(CH3)2 ch3 H H F OH H H nh2 V-6-4 p-Me-Ph H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-6-5 p-Me-Ph H H CH2Ph ch3 H H F OH H H nh2 V-6-6 p-Me-Ph H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-6-7 p-Me-Ph H H ch2ch2sch3 ch3 H H F OH H H nh2 V-6-8 p-Me-Ph * H * ch3 H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-7. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-7-1 p-F-Ph H H H ch3 H H F OH H H nh2 V-7-2 p-F-Ph H H ch3 ch3 H H F OH H H nh2 V-7-3 p-F-Ph H H CH(CH3)2 ch3 H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-7-4 p-F-Ph H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-7-6 p-F-Ph H H CH2Ph ch3 H H F OH H H nh2 V-7-7 p-F-Ph H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-7-8 p-F-Ph H H ch2ch2sch3 ch3 H H F OH H H nh2 V-7-20 p-F-Ph * H * ch3 H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-8. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-8-1 p-Cl-Ph H H H ch3 H H F OH H H nh2 V-8-2 p-Cl-Ph H H ch3 ch3 H H F OH H H nh2 V-8-3 p-Cl-Ph H H CH(CH3)2 ch3 H H F OH H H nh2 V-8-4 p-Cl-Ph H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-8-5 p-Cl-Ph H H CH2Ph ch3 H H F OH H H nh2 V-8-6 p-Cl-Ph H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-8-7 p-Cl-Ph H H ch2ch2sch3 ch3 H H F OH H H nh2 V-8-8 p-Cl-Ph * H * ch3 H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-9. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-9-1 p-Br-Ph H H H ch3 H H F OH H H nh2 V-9-2 p-Br-Ph H H ch3 ch3 H H F OH H H nh2 V-9-3 p-Br-Ph H H CH(CH3)2 ch3 H H F OH H H nh2 V-9-4 p-Br-Ph H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-9-6 p-Br-Ph H H CH2Ph ch3 H H F OH H H nh2 V-9-7 p-Br-Ph H H CH2-indol-3-yl ch3 H H F OH H H nh2 V-9-8 p-Br-Ph H H ch2ch2sch3 ch3 H H F OH H H nh2 V-9-20 p-Br-Ph * H * ch3 H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-10. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-10-1 p-I-Ph H H H ch3 H H F OH H H nh2 V-10-2 p-I-Ph H H ch3 ch3 H H F OH H H nh2 V-10-3 p-I-Ph H H CH(CH3)2 ch3 H H F OH H H nh2 V-10-4 p-I-Ph H H CH2CH(CH3)2 ch3 H H F OH H H nh2 V-10-5 p-I-Ph H H CH2Ph ch3 H H F OH H H nh2 V-10-6 p-I-Ph H H CH2-indol-3-yl ch3 H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-10-7 p-I-Ph H H CH2CH2SCH3 ch3 H H F OH H H nh2 V-10-8 p-I-Ph * H * ch3 H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-ll. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-ll-1 ch3 H H H Et H H F OH H H nh2 V-ll-2 ch3 H H ch3 Et H H F OH H H nh2 V-ll-3 ch3 H H CH(CH3)2 Et H H F OH H H nh2 V-ll-4 ch3 H H CH2CH(CH3)2 Et H H F OH H H nh2 V-ll-5 ch3 H H CH2Ph Et H H F OH H H nh2 V-ll-6 ch3 H H CH2-indol-3-yl Et H H F OH H H nh2 V-ll-7 ch3 H H ch2ch2sch3 Et H H F OH H H nh2 V-ll-8 ch3 * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-12. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-12-1 Et H H H Et H H F OH H H nh2 V-12-2 Et H H ch3 Et H H F OH H H nh2 V-12-3 Et H H CH(CH3)2 Et H H F OH H H nh2 V-12-4 Et H H CH2CH(CH3)2 Et H H F OH H H nh2 V-12-5 Et H H CH2Ph Et H H F OH H H nh2 V-12-6 Et H H CH2-indol-3-yl Et H H F OH H H nh2 V-12-7 Et H H ch2ch2sch3 Et H H F OH H H nh2 V-12-8 Et * H * Et H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-13. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-13-1 !Pr H H H Et H H F OH H H nh2 V-13-2 !Pr H H ch3 Et H H F OH H H nh2 V-13-3 !Pr H H CH(CH3)2 Et H H F OH H H nh2 V-13-4 !Pr H H CH2CH(CH3)2 Et H H F OH H H nh2 V-13-5 !Pr H H CH2Ph Et H H F OH H H nh2 V-13-6 !Pr H H CH2-indol-3-yl Et H H F OH H H nh2 V-13-7 !Pr H H ch2ch2sch3 Et H H F OH H H nh2 V-13-8 !Pr * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R 3a R3b R4 R5 R6 X Y R7 R8 R9 V-14-1 'Bn H H H Et H H F OH H H nh2 V-14-2 'Bn H H ch3 Et H H F OH H H nh2 V-14-3 'Bn H H CH(CH3)2 Et H H F OH H H nh2 V-14-4 'Bn H H CH2CH(CH3)2 Et H H F OH H H nh2 V-14-5 'Bn H H CH2Ph Et H H F OH H H nh2 V-14-6 'Bn H H CH2-indol-3-yl Et H H F OH H H nh2 V-14-7 'Bn H H ch2ch2sch3 Et H H F OH H H nh2 V-14-8 'Bn * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-15. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-15-1 Ph H H H Et H H F OH H H nh2 V-15-2 Ph H H ch3 Et H H F OH H H nh2 V-15-3 Ph H H CH(CH3)2 Et H H F OH H H nh2 V-15-4 Ph H H CH2CH(CH3)2 Et H H F OH H H nh2 V-15-5 Ph H H CH2Ph Et H H F OH H H nh2 V-15-6 Ph H H CH2-indol-3-yl Et H H F OH H H nh2 V-15-7 Ph H H ch2ch2sch3 Et H H F OH H H nh2 V-15-8 Ph * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table V-16.________________________________________________________________ No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-16-1 p-Me-Ph H H H Et H H F OH H H nh2 V-16-2 p-Me-Ph H H ch3 Et H H F OH H H nh2 V-16-3 p-Me-Ph H H CH(CH3)2 Et H H F OH H H nh2 V-16-4 p-Me-Ph H H CH2CH(CH3)2 Et H H F OH H H nh2 V-16-5 p-Me-Ph H H CH2Ph Et H H F OH H H nh2 V-16-6 p-Me-Ph H H CH2-indol-3-yl Et H H F OH H H nh2 V-16-7 p-Me-Ph H H CH2CH2SCH3 Et H H F OH H H nh2 V-16-8 p-Me-Ph * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-17. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-17-1 p-F-Ph H H H Et H H F OH H H nh2 V-17-2 p-F-Ph H H ch3 Et H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-17-3 p-F-Ph H H CH(CH3)2 Et H H F OH H H nh2 V-17-4 p-F-Ph H H CH2CH(CH3)2 Et H H F OH H H nh2 V-17-5 p-F-Ph H H CH2Ph Et H H F OH H H nh2 V-17-6 p-F-Ph H H CH2-indol-3-yl Et H H F OH H H nh2 V-17-7 p-F-Ph H H ch2ch2sch3 Et H H F OH H H nh2 V-17-8 p-F-Ph * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-18. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-18-1 p-Cl-Ph H H H Et H H F OH H H nh2 V-18-2 p-Cl-Ph H H ch3 Et H H F OH H H nh2 V-18-3 p-Cl-Ph H H CH(CH3)2 Et H H F OH H H nh2 V-18-4 p-Cl-Ph H H CH2CH(CH3)2 Et H H F OH H H nh2 V-18-5 p-Cl-Ph H H CH2Ph Et H H F OH H H nh2 V-18-6 p-Cl-Ph H H CH2-indol-3-yl Et H H F OH H H nh2 V-18-7 p-Cl-Ph H H ch2ch2sch3 Et H H F OH H H nh2 V-18-8 p-Cl-Ph * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-19. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-19-1 p-Br-Ph H H H Et H H F OH H H nh2 V-19-2 p-Br-Ph H H ch3 Et H H F OH H H nh2 V-19-3 p-Br-Ph H H CH(CH3)2 Et H H F OH H H nh2 V-19-4 p-Br-Ph H H CH2CH(CH3)2 Et H H F OH H H nh2 V-19-5 p-Br-Ph H H CH2Ph Et H H F OH H H nh2 V-19-6 p-Br-Ph H H CH2-indol-3-yl Et H H F OH H H nh2 V-19-7 p-Br-Ph H H ch2ch2sch3 Et H H F OH H H nh2 V-19-8 p-Br-Ph * H * Et H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-20. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-20-1 p-I-Ph H H H Et H H F OH H H nh2 V-20-2 p-I-Ph H H ch3 Et H H F OH H H nh2 V-20-3 p-I-Ph H H CH(CH3)2 Et H H F OH H H nh2 V-20-4 p-I-Ph H H CH2CH(CH3)2 Et H H F OH H H nh2 V-20-5 p-I-Ph H H CH2Ph Et H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-20-6 p-I-Ph H H CH2-indol-3-yl Et H H F OH H H nh2 V-20-7 p-I-Ph H H CH2CH2SCH3 Et H H F OH H H nh2 V-20-8 p-I-Ph * H * Et H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-21. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-21-1 ch3 H H H 'Pr H H F OH H H nh2 V-21-2 ch3 H H ch3 'Pr H H F OH H H nh2 V-21-3 ch3 H H CH(CH3)2 'Pr H H F OH H H nh2 V-21-4 ch3 H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-21-5 ch3 H H CH2Ph 'Pr H H F OH H H nh2 V-21-6 ch3 H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-21-7 ch3 H H ch2ch2sch3 'Pr H H F OH H H nh2 V-21-8 ch3 * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-22. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-22-1 Et H H H 'Pr H H F OH H H nh2 V-22-2 Et H H ch3 'Pr H H F OH H H nh2 V-22-3 Et H H CH(CH3)2 'Pr H H F OH H H nh2 V-22-4 Et H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-22-5 Et H H CH2Ph 'Pr H H F OH H H nh2 V-22-6 Et H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-22-7 Et H H ch2ch2sch3 'Pr H H F OH H H nh2 V-22-8 Et * H * 'Pr H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-23. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-23-1 'Pr H H H 'Pr H H F OH H H nh2 V-23-2 'Pr H H ch3 'Pr H H F OH H H nh2 V-23-3 'Pr H H CH(CH3)2 'Pr H H F OH H H nh2 V-23-4 'Pr H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-23-5 'Pr H H CH2Ph 'Pr H H F OH H H nh2 V-23-6 'Pr H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-23-7 'Pr H H ch2ch2sch3 'Pr H H F OH H H nh2 V-23-8 'Pr * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-24-1 'Bn H H H 'Pr H H F OH H H nh2 V-24-2 'Bn H H ch3 'Pr H H F OH H H nh2 V-24-3 'Bn H H CH(CH3)2 'Pr H H F OH H H nh2 V-24-4 'Bn H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-24-5 'Bn H H CH2Ph 'Pr H H F OH H H nh2 V-24-6 'Bn H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-24-7 'Bn H H ch2ch2sch3 'Pr H H F OH H H nh2 V-24-8 'Bn * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-25. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-25-1 Ph H H H 'Pr H H F OH H H nh2 V-25-2 Ph H H ch3 'Pr H H F OH H H nh2 V-25-3 Ph H H CH(CH3)2 'Pr H H F OH H H nh2 V-25-4 Ph H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-25-5 Ph H H CH2Ph 'Pr H H F OH H H nh2 V-25-6 Ph H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-25-7 Ph H H ch2ch2sch3 'Pr H H F OH H H nh2 V-25-8 Ph * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table V-26. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-26-1 p-Me-Ph H H H 'Pr H H F OH H H nh2 V-26-2 p-Me-Ph H H ch3 'Pr H H F OH H H nh2 V-26-3 p-Me-Ph H H CH(CH3)2 'Pr H H F OH H H nh2 V-26-4 p-Me-Ph H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-26-5 p-Me-Ph H H CH2Ph 'Pr H H F OH H H nh2 V-26-6 p-Me-Ph H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-26-7 p-Me-Ph H H CH2CH2SCH3 'Pr H H F OH H H nh2 V-26-8 p-Me-Ph * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-27. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-27-1 p-F-Ph H H H 'Pr H H F OH H H nh2 V-27-2 p-F-Ph H H ch3 'Pr H H F OH H H nh2 V-27-3 p-F-Ph H H CH(CH3)2 'Pr H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-27-4 p-F-Ph H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-27-5 p-F-Ph H H CH2Ph 'Pr H H F OH H H nh2 V-27-6 p-F-Ph H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-27-7 p-F-Ph H H ch2ch2sch3 'Pr H H F OH H H nh2 V-27-8 p-F-Ph * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-28. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-28-1 p-Cl-Ph H H H 'Pr H H F OH H H nh2 V-28-2 p-Cl-Ph H H ch3 'Pr H H F OH H H nh2 V-28-3 p-Cl-Ph H H CH(CH3)2 'Pr H H F OH H H nh2 V-28-4 p-Cl-Ph H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-28-5 p-Cl-Ph H H CH2Ph 'Pr H H F OH H H nh2 V-28-6 p-Cl-Ph H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-28-7 p-Cl-Ph H H ch2ch2sch3 'Pr H H F OH H H nh2 V-28-8 p-Cl-Ph * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-29. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-29-1 p-Br-Ph H H H 'Pr H H F OH H H nh2 V-29-2 p-Br-Ph H H ch3 'Pr H H F OH H H nh2 V-29-3 p-Br-Ph H H CH(CH3)2 'Pr H H F OH H H nh2 V-29-4 p-Br-Ph H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-29-5 p-Br-Ph H H CH2Ph 'Pr H H F OH H H nh2 V-29-6 p-Br-Ph H H CH2-indol-3-yl 'Pr H H F OH H H nh2 V-29-7 p-Br-Ph H H ch2ch2sch3 'Pr H H F OH H H nh2 V-29-8 p-Br-Ph * H * 'Pr H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-30. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-30-1 p-I-Ph H H H 'Pr H H F OH H H nh2 V-30-2 p-I-Ph H H ch3 'Pr H H F OH H H nh2 V-30-3 p-I-Ph H H CH(CH3)2 'Pr H H F OH H H nh2 V-30-4 p-I-Ph H H CH2CH(CH3)2 'Pr H H F OH H H nh2 V-30-5 p-I-Ph H H CH2Ph 'Pr H H F OH H H nh2 V-30-6 p-I-Ph H H CH2-indol-3-yl 'Pr H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-30-7 p-I-Ph H H CH2CH2SCH3 'Pr H H F OH H H nh2 V-30-8 p-I-Ph * H * 'Pr H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-31-1 ch3 H H H ”Bu H H F OH H H nh2 V-31-2 ch3 H H ch3 ”Bu H H F OH H H nh2 V-31-3 ch3 H H CH(CH3)2 ”Bu H H F OH H H nh2 V-31-4 ch3 H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-31-5 ch3 H H CH2Ph ”Bu H H F OH H H nh2 V-31-6 ch3 H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-31-7 ch3 H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-31-8 ch3 * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-32. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-32-1 Et H H H ”Bu H H F OH H H nh2 V-32-2 Et H H ch3 ”Bu H H F OH H H nh2 V-32-3 Et H H CH(CH3)2 ”Bu H H F OH H H nh2 V-32-4 Et H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-32-5 Et H H CH2Ph ”Bu H H F OH H H nh2 V-32-6 Et H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-32-7 Et H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-32-8 Et * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table V-33. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-33-1 !Pr H H H ”Bu H H F OH H H nh2 V-33-2 !Pr H H ch3 ”Bu H H F OH H H nh2 V-33-3 !Pr H H CH(CH3)2 ”Bu H H F OH H H nh2 V-33-4 !Pr H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-33-5 zpr H H CH2Ph ”Bu H H F OH H H nh2 V-33-6 zpr H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-33-7 zpr H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-33-8 zpr * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-34-1 T3u H H H ”Bu H H F OH H H nh2 V-34-2 T3u H H ch3 ”Bu H H F OH H H nh2 V-34-3 T3u H H CH(CH3)2 ”Bu H H F OH H H nh2 V-34-4 'Bn H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-34-5 'Bn H H CH2Ph ”Bu H H F OH H H nh2 V-34-6 'Bn H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-34-7 'Bn H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-34-8 'Bn * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-35. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-35-1 Ph H H H ”Bu H H F OH H H nh2 V-35-2 Ph H H ch3 ”Bu H H F OH H H nh2 V-35-3 Ph H H CH(CH3)2 ”Bu H H F OH H H nh2 V-35-4 Ph H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-35-5 Ph H H CH2Ph ”Bu H H F OH H H nh2 V-35-6 Ph H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-35-7 Ph H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-35-8 Ph * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table V-36. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-36-1 p-Me-Ph H H H ”Bu H H F OH H H nh2 V-36-2 p-Me-Ph H H ch3 ”Bu H H F OH H H nh2 V-36-3 p-Me-Ph H H CH(CH3)2 ”Bu H H F OH H H nh2 V-36-4 p-Me-Ph H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-36-5 p-Me-Ph H H CH2Ph ”Bu H H F OH H H nh2 V-36-6 p-Me-Ph H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-36-7 p-Me-Ph H H CH2CH2SCH3 ”Bu H H F OH H H nh2 V-36-8 p-Me-Ph * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-37. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-37-1 p-F-Ph H H H ”Bu H H F OH H H nh2 V-37-2 p-F-Ph H H ch3 ”Bu H H F OH H H nh2 V-37-3 p-F-Ph H H CH(CH3)2 ”Bu H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-37-4 p-F-Ph H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-37-5 p-F-Ph H H CH2Ph ”Bu H H F OH H H nh2 V-37-6 p-F-Ph H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-37-7 p-F-Ph H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-37-8 p-F-Ph * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-38. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-38-1 p-Cl-Ph H H H ”Bu H H F OH H H nh2 V-38-2 p-Cl-Ph H H ch3 ”Bu H H F OH H H nh2 V-38-3 p-Cl-Ph H H CH(CH3)2 ”Bu H H F OH H H nh2 V-38-4 p-Cl-Ph H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-38-5 p-Cl-Ph H H CH2Ph ”Bu H H F OH H H nh2 V-38-6 p-Cl-Ph H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-38-7 p-Cl-Ph H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-38-8 p-Cl-Ph * H * ”Bu H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-39. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-39-1 p-Br-Ph H H H ”Bu H H F OH H H nh2 V-39-2 p-Br-Ph H H ch3 ”Bu H H F OH H H nh2 V-39-3 p-Br-Ph H H CH(CH3)2 ”Bu H H F OH H H nh2 V-39-4 p-Br-Ph H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-39-5 p-Br-Ph H H CH2Ph ”Bu H H F OH H H nh2 V-39-6 p-Br-Ph H H CH2-indol-3-yl ”Bu H H F OH H H nh2 V-39-7 p-Br-Ph H H ch2ch2sch3 ”Bu H H F OH H H nh2 V-39-8 p-Br-Ph * H * ”Bu H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-40. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-40-1 p-I-Ph H H H ”Bu H H F OH H H nh2 V-40-2 p-I-Ph H H ch3 ”Bu H H F OH H H nh2 V-40-3 p-I-Ph H H CH(CH3)2 ”Bu H H F OH H H nh2 V-40-4 p-I-Ph H H CH2CH(CH3)2 ”Bu H H F OH H H nh2 V-40-5 p-I-Ph H H CH2Ph ”Bu H H F OH H H nh2 V-40-6 p-I-Ph H H CH2-indol-3-yl ”Bu H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-40-7 p-I-Ph H H CH2CH2SCH3 ”Bu H H F OH H H NH2 V-40-8 p-I-Ph * H * ”Bu H H F OH H H NH2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-41. Ns R1 R2 R3 a R3b R4 R5 R6 X Y R7 R8 R9 V-41-1 ch3 H H H Bz H H F OH H H nh2 V-41-2 ch3 H H ch3 Bz H H F OH H H nh2 V-41-3 ch3 H H CH(CH3)2 Bz H H F OH H H nh2 V-41-4 ch3 H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-41-5 ch3 H H CH2Ph Bz H H F OH H H nh2 V-41-6 ch3 H H CH2-indol-3-yl Bz H H F OH H H nh2 V-41-7 ch3 H H ch2ch2sch3 Bz H H F OH H H nh2 V-41-8 ch3 * H * Bz H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-42. Ns R1 R2 R3a R3b             R L4 R5 R6 X Y R7 ] R8 R9 V-42-1 Et H H H Bz H H F OH H H nh2 V-42-2 Et H H ch3 Bz H H F OH H H nh2 V-42-3 Et H H CH(CH3)2 Bz H H F OH H H nh2 V-42-4 Et H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-42-5 Et H H CH2Ph Bz H H F OH H H nh2 V-42-6 Et H H CH2-indol-3-yl Bz H H F OH H H nh2 V-42-7 Et H H ch2ch2sch3 Bz H H F OH H H nh2 V-42-8 Et * H * Bz H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-43. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 *R2 and R3b V-43-1 !Pr H H H Bz H H F OH H H nh2 joined V-43-2 !Pr H H ch3 Bz H H F OH H H nh2 together by V-43-3 !Pr H H CH(CH3)2 Bz H H F OH H H Njljj2 (CH2)3 to V-43-4 !Pr H H CH2CH(CH3)2 Bz H H F OH H H nh2 form five- V-43-5 !Pr H H CH2Ph Bz H H F OH H H nh2 membered V-43-6 zpr H H CH2-indol-3-yl Bz H H F OH H H nh2 ring. V-43-7 zpr H H ch2ch2sch3 Bz H H F OH H H nh2 V-43-8 zpr * H * Bz H H F OH H H nh2 Table V-44. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-44-1 'Bn H H H Bz H H F OH H H nh2 V-44-2 'Bn H H ch3 Bz H H F OH H H nh2 V-44-3 'Bn H H CH(CH3)2 Bz H H F OH H H nh2 V-44-4 'Bn H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-44-5 'Bn H H CH2Ph Bz H H F OH H H nh2 V-44-6 'Bn H H CH2-indol-3-yl Bz H H F OH H H nh2 V-44-7 'Bn H H ch2ch2sch3 Bz H H F OH H H nh2 V-44-8 'Bn * H * Bz H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-45. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-45-1 Ph H H H Bz H H F OH H H nh2 V-45-2 Ph H H ch3 Bz H H F OH H H nh2 V-45-3 Ph H H CH(CH3)2 Bz H H F OH H H nh2 V-45-4 Ph H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-45-5 Ph H H CH2Ph Bz H H F OH H H nh2 V-45-6 Ph H H CH2-indol-3-yl Bz H H F OH H H nh2 V-45-7 Ph H H ch2ch2sch3 Bz H H F OH H H nh2 V-45-8 Ph * H * Bz H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-46. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-46-1 p-Me-Ph H H H Bz H H F OH H H nh2 V-46-2 p-Me-Ph H H ch3 Bz H H F OH H H nh2 V-46-3 p-Me-Ph H H CH(CH3)2 Bz H H F OH H H nh2 V-46-4 p-Me-Ph H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-46-5 p-Me-Ph H H CH2Ph Bz H H F OH H H nh2 V-46-6 p-Me-Ph H H CH2-indol-3-yl Bz H H F OH H H nh2 V-46-7 p-Me-Ph H H CH2CH2SCH3 Bz H H F OH H H nh2 V-46-8 p-Me-Ph * H * Bz H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-47. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-47-1 p-F-Ph H H H Bz H H F OH H H nh2 V-47-2 p-F-Ph H H ch3 Bz H H F OH H H nh2 V-47-3 p-F-Ph H H CH(CH3)2 Bz H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-47-4 p-F-Ph H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-47-5 p-F-Ph H H CH2Ph Bz H H F OH H H nh2 V-47-6 p-F-Ph H H CH2-indol-3-yl Bz H H F OH H H nh2 V-47-7 p-F-Ph H H ch2ch2sch3 Bz H H F OH H H nh2 V-47-8 p-F-Ph * H * Bz H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-48. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-48-1 p-Cl-Ph H H H Bz H H F OH H H nh2 V-48-2 p-Cl-Ph H H ch3 Bz H H F OH H H nh2 V-48-3 p-Cl-Ph H H CH(CH3)2 Bz H H F OH H H nh2 V-48-4 p-Cl-Ph H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-48-5 p-Cl-Ph H H CH2Ph Bz H H F OH H H nh2 V-48-6 p-Cl-Ph H H CH2-indol-3-yl Bz H H F OH H H nh2 V-48-7 p-Cl-Ph H H ch2ch2sch3 Bz H H F OH H H nh2 V-48-8 p-Cl-Ph * H * Bz H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-49. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-49-1 p-Br-Ph H H H Bz H H F OH H H nh2 V-49-2 p-Br-Ph H H ch3 Bz H H F OH H H nh2 V-49-3 p-Br-Ph H H CH(CH3)2 Bz H H F OH H H nh2 V-49-4 p-Br-Ph H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-49-5 p-Br-Ph H H CH2Ph Bz H H F OH H H nh2 V-49-6 p-Br-Ph H H CH2-indol-3-yl Bz H H F OH H H nh2 V-49-7 p-Br-Ph H H ch2ch2sch3 Bz H H F OH H H nh2 V-49-8 p-Br-Ph * H * Bz H H F OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table V-50. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-50-1 p-I-Ph H H H Bz H H F OH H H nh2 V-50-2 p-I-Ph H H ch3 Bz H H F OH H H nh2 V-50-3 p-I-Ph H H CH(CH3)2 Bz H H F OH H H nh2 V-50-4 p-I-Ph H H CH2CH(CH3)2 Bz H H F OH H H nh2 V-50-5 p-I-Ph H H CH2Ph Bz H H F OH H H nh2 V-50-6 p-I-Ph H H CH2-indol-3-yl Bz H H F OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 V-50-7 p-I-Ph H H CH2CH2SCH3 Bz H H F OH H H nh2 V-50-8 p-I-Ph * H * Bz H H F OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. VI Table VI-1. Ns R1 R2 R3a ' R3b R4 R5 R6 X Y R7 R8 VI-1-1 ch3 H H H ch3 H F H OH H H VI-1-2 ch3 H H ch3 ch3 H F H OH H H VI-1-3 ch3 H H CH(CH3)2 ch3 H F H OH H H VI-1-4 ch3 H H CH2CH(CH3)2 ch3 H F H OH H H VI-1-5 ch3 H H CH2Ph ch3 H F H OH H H VI-1-6 ch3 H H CH2-indol-3-yl ch3 H F H OH H H VI-1-7 ch3 H H ch2ch2sch3 ch3 H F H OH H H VI-1-8 ch3 * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-2. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-2-1 Et H H H ch3 H F H OH H H VI-2-2 Et H H ch3 ch3 H F H OH H H VI-2-3 Et H H CH(CH3)2 ch3 H F H OH H H VI-2-4 Et H H CH2CH(CH3)2 ch3 H F H OH H H VI-2-5 Et H H CH2Ph ch3 H F H OH H H VI-2-6 Et H H CH2-indol-3-yl ch3 H F H OH H H VI-2-7 Et H H ch2ch2sch3 ch3 H F H OH H H VI-2-8 Et * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Table VI-3. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-3-1 !Pr H H H ch3 H F H OH H H VI-3-2 !Pr H H ch3 ch3 H F H OH H H VI-3-3 !Pr H H CH(CH3)2 ch3 H F H OH H H VI-3-4 zpr H H CH2CH(CH3)2 ch3 H F H OH H H VI-3-5 zpr H H CH2Ph ch3 H F H OH H H VI-3-6 zpr H H CH2-indol-3-yl ch3 H F H OH H H VI-3-7 zpr H H CH2CH2SCH3 ch3 H F H OH H H VI-3-8 zpr * H * ch3 H F H OH H H *R2 and R3b Table VI-4. joined together by (CH2)3 to form five-membered ring. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-4-1 'Bn H H H ch3 H F H OH H H VI-4-2 'Bn H H ch3 ch3 H F H OH H H VI-4-3 'Bn H H CH(CH3)2 ch3 H F H OH H H VI-4-4 'Bn H H CH2CH(CH3)2 ch3 H F H OH H H VI-4-5 'Bn H H CH2Ph ch3 H F H OH H H VI-4-6 'Bn H H CH2-indol-3-yl ch3 H F H OH H H VI-4-7 'Bn H H CH2CH2SCH3 ch3 H F H OH H H VI-4-8 'Bn * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-5-1 Ph H H H ch3 H F H OH H H VI-5-2 Ph H H ch3 ch3 H F H OH H H VI-5-3 Ph H H CH(CH3)2 ch3 H F H OH H H VI-5-4 Ph H H CH2CH(CH3)2 ch3 H F H OH H H VI-5-5 Ph H H CH2Ph ch3 H F H OH H H VI-5-6 Ph H H CH2-indol-3-yl ch3 H F H OH H H VI-5-7 Ph H H ch2ch2sch3 ch3 H F H OH H H VI-5-8 Ph * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-6. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-6-1 p-Me-Ph H H H ch3 H F H OH H H VI-6-2 p-Me-Ph H H ch3 ch3 H F H OH H H VI-6-3 p-Me-Ph H H CH(CH3)2 ch3 H F H OH H H VI-6-4 p-Me-Ph H H CH2CH(CH3)2 ch3 H F H OH H H VI-6-5 p-Me-Ph H H CH2Ph ch3 H F H OH H H VI-6-6 p-Me-Ph H H CH2-indol-3-yl ch3 H F H OH H H VI-6-7 p-Me-Ph H H ch2ch2sch3 ch3 H F H OH H H VI-6-8 p-Me-Ph * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table VI-7. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-7-1 p-F-Ph H H H ch3 H F H OH H H VI-7-2 p-F-Ph H H ch3 ch3 H F H OH H H VI-7-3 p-F-Ph H H CH(CH3)2 ch3 H F H OH H H VI-7-4 p-F-Ph H H CH2CH(CH3)2 ch3 H F H OH H H VI-7-6 p-F-Ph H H CH2Ph ch3 H F H OH H H VI-7-7 p-F-Ph H H CH2-indol-3-yl ch3 H F H OH H H VI-7-8 p-F-Ph H H ch2ch2sch3 ch3 H F H OH H H VI-7-20 p-F-Ph * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-8-1 p-Cl-Ph H H H ch3 H F H OH H H VI-8-2 p-Cl-Ph H H ch3 ch3 H F H OH H H VI-8-3 p-Cl-Ph H H CH(CH3)2 ch3 H F H OH H H VI-8-4 p-Cl-Ph H H CH2CH(CH3)2 ch3 H F H OH H H VI-8-5 p-Cl-Ph H H CH2Ph ch3 H F H OH H H VI-8-6 p-Cl-Ph H H CH2-indol-3-yl ch3 H F H OH H H VI-8-7 p-Cl-Ph H H CH2CH2SCH3 ch3 H F H OH H H VI-8-8 p-Cl-Ph * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-9. Ns R1 R2 R3e ' R3b R4 R5 R6 X Y R7 R8 VI-9-1 p-Br-Ph H H H ch3 H F H OH H H VI-9-2 p-Br-Ph H H ch3 ch3 H F H OH H H VI-9-3 p-Br-Ph H H CH(CH3)2 ch3 H F H OH H H VI-9-4 p-Br-Ph H H CH2CH(CH3)2 ch3 H F H OH H H VI-9-6 p-Br-Ph H H CH2Ph ch3 H F H OH H H VI-9-7 p-Br-Ph H H CH2-indol-3-yl ch3 H F H OH H H VI-9-8 p-Br-Ph H H CH2CH2SCH3 ch3 H F H OH H H VI-9-20 p-Br-Ph * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-10. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-10-1 p-I-Ph H H H ch3 H F H OH H H VI-10-2 p-I-Ph H H ch3 ch3 H F H OH H H VI-10-3 p-I-Ph H H CH(CH3)2 ch3 H F H OH H H VI-10-4 p-I-Ph H H CH2CH(CH3)2 ch3 H F H OH H H VI-10-5 p-I-Ph H H CH2Ph ch3 H F H OH H H VI-10-6 p-I-Ph H H CH2-indol-3-yl ch3 H F H OH H H VI-10-7 p-I-Ph H H CH2CH2SCH3 ch3 H F H OH H H VI-10-8 p-I-Ph * H * ch3 H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3iJ ' R3b R4 R5 R6 X Y R7 R8 VI-11-1 ch3 H H H Et H F H OH H H VI-11-2 ch3 H H ch3 Et H F H OH H H VI-11-3 ch3 H H CH(CH3)2 Et H F H OH H H VI-11-4 ch3 H H CH2CH(CH3)2 Et H F H OH H H VI-11-5 ch3 H H CH2Ph Et H F H OH H H VI-11-6 ch3 H H CH2-indol-3-yl Et H F H OH H H VI-11-7 ch3 H H ch2ch2sch3 Et H F H OH H H VI-11-8 ch3 * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-12. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-12-1 Et H H H Et H F H OH H H VI-12-2 Et H H ch3 Et H F H OH H H VI-12-3 Et H H CH(CH3)2 Et H F H OH H H VI-12-4 Et H H CH2CH(CH3)2 Et H F H OH H H VI-12-5 Et H H CH2Ph Et H F H OH H H VI-12-6 Et H H CH2-indol-3-yl Et H F H OH H H VI-12-7 Et H H ch2ch2sch3 Et H F H OH H H VI-12-8 Et * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-13. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-13-1 !Pr H H H Et H F H OH H H VI-13-2 !Pr H H ch3 Et H F H OH H H VI-13-3 !Pr H H CH(CH3)2 Et H F H OH H H VI-13-4 !Pr H H CH2CH(CH3)2 Et H F H OH H H VI-13-5 zpr H H CH2Ph Et H F H OH H H VI-13-6 zpr H H CH2-indol-3-yl Et H F H OH H H VI-13-7 zpr H H ch2ch2sch3 Et H F H OH H H VI-13-8 zpr * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-14-1 'Bn H H H Et H F H OH H H VI-14-2 'Bn H H CH3 Et H F H OH H H VI-14-3 'Bn H H CH(CH3)2 Et H F H OH H H VI-14-4 'Bn H H CH2CH(CH3)2 Et H F H OH H H VI-14-5 'Bn H H CH2Ph Et H F H OH H H VI-14-6 'Bn H H CH2-indol-3-yl Et H F H OH H H VI-14-7 'Bn H H CH2CH2SCH3 Et H F H OH H H VI-14-8 'Bn * H * Et H F H OH H H *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table VI-15. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-15-1 Ph H H H Et H F H OH H H VI-15-2 Ph H H ch3 Et H F H OH H H VI-15-3 Ph H H CH(CH3)2     Et H F H OH H H VI-15-4 Ph H H CH2CH(CH3)2 Et H F H OH H H VI-15-5 Ph H H CH2Ph       Et H F H OH H H VI-15-6 Ph H H ch2 -indol-3-yl Et H F H OH H H VI-15-7 Ph H H CH2CH2SCH3 Et H F H OH H H VI-15-8 Ph * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-16. Ns R1         R2 R3a R3b             R4 R5 R 6 X Y R7 R8 VI-16-1 p-Me-Ph H H H            Et H F H OH H H VI-16-2 p-Me-Ph H H CH3          Et H F H OH H H VI-16-3 p-Me-Ph H H CH(CH3)2      Et H F H OH H H VI-16-4 p-Me-Ph H H CH2CH(CH3)2 Et H F H OH H H VI-16-5 p-Me-Ph H H CH2Ph        Et H F H OH H H VI-16-6 p-Me-Ph H H CH2-indol-3-yl Et H F H OH H H VI-16-7 p-Me-Ph H H CH2CH2SCH3 Et H F H OH H H VI-16-8 p-Me-Ph * H *               Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-17. Ns R1      R2 R3a R3b            R4 R5 R6 X Y R7 R8 VI-17-1 p-F-Ph H H H            Et H F H OH H H VI-17-2 p-F-Ph H H CH3          Et H F H OH H H VI-17-3 p-F-Ph H H CH(CH3)2      Et H F H OH H H 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-17-4 p-F-Ph H H CH2CH(CH3)2 Et H F H OH H H VI-17-5 p-F-Ph H H CH2Ph Et H F H OH H H VI-17-6 p-F-Ph H H CH2-indol-3-yl Et H F H OH H H VI-17-7 p-F-Ph H H ch2ch2sch3 Et H F H OH H H VI-17-8 p-F-Ph * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-18. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-18-1 p-Cl-Ph H H H Et H F H OH H H VI-18-2 p-Cl-Ph H H ch3 Et H F H OH H H VI-18-3 p-Cl-Ph H H CH(CH3)2 Et H F H OH H H VI-18-4 p-Cl-Ph H H CH2CH(CH3)2 Et H F H OH H H VI-18-5 p-Cl-Ph H H CH2Ph Et H F H OH H H VI-18-6 p-Cl-Ph H H CH2-indol-3-yl Et H F H OH H H VI-18-7 p-Cl-Ph H H CH2CH2SCH3 Et H F H OH H H VI-18-8 p-Cl-Ph * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-19. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-19-1 p-Br-Ph H H H Et H F H OH H H VI-19-2 p-Br-Ph H H ch3 Et H F H OH H H VI-19-3 p-Br-Ph H H CH(CH3)2 Et H F H OH H H VI-19-4 p-Br-Ph H H CH2CH(CH3)2 Et H F H OH H H VI-19-5 p-Br-Ph H H CH2Ph Et H F H OH H H VI-19-6 p-Br-Ph H H CH2-indol-3-yl Et H F H OH H H VI-19-7 p-Br-Ph H H ch2ch2sch3 Et H F H OH H H VI-19-8 p-Br-Ph * H * Et H F H OH H H 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-20. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 r! VI-20-1 p-I-Ph H H H Et H F H OH H H VI-20-2 p-I-Ph H H ch3 Et H F H OH H H VI-20-3 p-I-Ph H H CH(CH3)2 Et H F H OH H H VI-20-4 p-I-Ph H H CH2CH(CH3)2 Et H F H OH H H VI-20-5 p-I-Ph H H CH2Ph Et H F H OH H H VI-20-6 p-I-Ph H H CH2-indol-3-yl Et H F H OH H H 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-20-7 p-I-Ph H H CH2CH2SCH3 Et H F H OH H H VI-20-8 p-I-Ph * H * Et H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-21. Ns R1 R2 R3 a R3b R4 R5 R( ’ X Y R7 R8 VI-21-1 ch3 h H H 'Pr H F H OH H H VI-21-2 ch3 h H ch3 'Pr H F H OH H H VI-21-3 ch3 h H CH(CH3)2 'Pr H F H OH H H VI-21-4 ch3 h H CH2CH(CH3)2 'Pr H F H OH H H VI-21-5 ch3 h H CH2Ph 'Pr H F H OH H H VI-21-6 ch3 h H CH2-indol-3-yl 'Pr H F H OH H H VI-21-7 ch3 h H ch2ch2sch3 'Pr H F H OH H H VI-21-8 ch3 * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-22. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-22-1 Et H H H 'Pr H F H OH H H VI-22-2 Et H H ch3 'Pr H F H OH H H VI-22-3 Et H H CH(CH3)2 'Pr H F H OH H H VI-22-4 Et H H CH2CH(CH3)2 'Pr H F H OH H H VI-22-5 Et H H CH2Ph 'Pr H F H OH H H VI-22-6 Et H H CH2-indol-3-yl 'Pr H F H OH H H VI-22-7 Et H H ch2ch2sch3 'Pr H F H OH H H VI-22-8 Et * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-23. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-23-1 'Pr H H H 'Pr H F H OH H H VI-23-2 'Pr H H ch3 'Pr H F H OH H H VI-23-3 'Pr H H CH(CH3)2 'Pr H F H OH H H VI-23-4 'Pr H H CH2CH(CH3)2 'Pr H F H OH H H VI-23-5 'Pr H H CH2Ph 'Pr H F H OH H H VI-23-6 'Pr H H CH2-indol-3-yl 'Pr H F H OH H H VI-23-7 'Pr H H ch2ch2sch3 'Pr H F H OH H H VI-23-8 zPj- * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-24-1 'Bn H H H 'Pr H F H OH H H VI-24-2 'Bn H H ch3 'Pr H F H OH H H VI-24-3 'Bn H H CH(CH3)2 'Pr H F H OH H H VI-24-4 'Bn H H CH2CH(CH3)2 'Pr H F H OH H H VI-24-5 'Bn H H CH2Ph 'Pr H F H OH H H VI-24-6 'Bn H H CH2-indol-3-yl 'Pr H F H OH H H VI-24-7 'Bn H H ch2ch2sch3 'Pr H F H OH H H VI-24-8 'Bn * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-25. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-25-1 Ph H H H 'Pr H F H OH H H VI-25-2 Ph H H ch3 'Pr H F H OH H H VI-25-3 Ph H H CH(CH3)2 'Pr H F H OH H H VI-25-4 Ph H H CH2CH(CH3)2 'Pr H F H OH H H VI-25-5 Ph H H CH2Ph 'Pr H F H OH H H VI-25-6 Ph H H CH2-indol-3-yl 'Pr H F H OH H H VI-25-7 Ph H H ch2ch2sch3 'Pr H F H OH H H VI-25-8 Ph * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table VI-26. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-26-1 p-Me-Ph H H H 'Pr H F H OH H H VI-26-2 p-Me-Ph H H ch3 'Pr H F H OH H H VI-26-3 p-Me-Ph H H CH(CH3)2 'Pr H F H OH H H VI-26-4 p-Me-Ph H H CH2CH(CH3)2 'Pr H F H OH H H VI-26-5 p-Me-Ph H H CH2Ph 'Pr H F H OH H H VI-26-6 p-Me-Ph H H CH2-indol-3-yl 'Pr H F H OH H H VI-26-7 p-Me-Ph H H ch2ch2sch3 'Pr H F H OH H H VI-26-8 p-Me-Ph * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-27. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-27-1 p-F-Ph H H H 'Pr H F H OH H H VI-27-2 p-F-Ph H H ch3 'Pr H F H OH H H VI-27-3 p-F-Ph H H CH(CH3)2 'Pr H F H OH H H 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-27-4 p-F-Ph H H CH2CH(CH3)2 'Pr H F H OH H H VI-27-5 p-F-Ph H H CH2Ph 'Pr H F H OH H H VI-27-6 p-F-Ph H H CH2-indol-3-yl 'Pr H F H OH H H VI-27-7 p-F-Ph H H ch2ch2sch3 'Pr H F H OH H H VI-27-8 p-F-Ph * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-28. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-28-1 p-Cl-Ph H H H 'Pr H F H OH H H VI-28-2 p-Cl-Ph H H ch3 'Pr H F H OH H H VI-28-3 p-Cl-Ph H H CH(CH3)2 'Pr H F H OH H H VI-28-4 p-Cl-Ph H H CH2CH(CH3)2 'Pr H F H OH H H VI-28-5 p-Cl-Ph H H CH2Ph 'Pr H F H OH H H VI-28-6 p-Cl-Ph H H CH2-indol-3-yl 'Pr H F H OH H H VI-28-7 p-Cl-Ph H H CH2CH2SCH3 'Pr H F H OH H H VI-28-8 p-Cl-Ph * H * 'Pr H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-29. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-29-1 p-Br-Ph H H H 'Pr H F H OH H H VI-29-2 p-Br-Ph H H ch3 'Pr H F H OH H H VI-29-3 p-Br-Ph H H CH(CH3)2 'Pr H F H OH H H VI-29-4 p-Br-Ph H H CH2CH(CH3)2 'Pr H F H OH H H VI-29-5 p-Br-Ph H H CH2Ph 'Pr H F H OH H H VI-29-6 p-Br-Ph H H CH2-indol-3-yl 'Pr H F H OH H H VI-29-7 p-Br-Ph H H ch2ch2sch3 'Pr H F H OH H H VI-29-8 p-Br-Ph * H * 'Pr H F H OH H H 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-30. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 r! VI-30-1 p-I-Ph H H H 'Pr H F H OH H H VI-30-2 p-I-Ph H H ch3 'Pr H F H OH H H VI-30-3 p-I-Ph H H CH(CH3)2 'Pr H F H OH H H VI-30-4 p-I-Ph H H CH2CH(CH3)2 'Pr H F H OH H H VI-30-5 p-I-Ph H H CH2Ph 'Pr H F H OH H H VI-30-6 p-I-Ph H H CH2-indol-3-yl 'Pr H F H OH H H 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-30-7 p-I-Ph H H CH2CH2SCH3 'Pr HF H OH H H VI-30-8 p-I-Ph * H * 'Pr HF H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-31. Ns R1 R2 R3 a R3b R4 R5 R6 X Y R7 R8 VI-31-1 ch3 h H H "Bu H F H OH H H VI-31-2 ch3 h H ch3 "Bu H F H OH H H VI-31-3 ch3 h H CH(CH3)2 "Bu H F H OH H H VI-31-4 ch3 h H CH2CH(CH3)2 "Bu H F H OH H H VI-31-5 ch3 h H CH2Ph "Bu H F H OH H H VI-31-6 ch3 h H CH2-indol-3-yl "Bu H F H OH H H VI-31-7 ch3 h H ch2ch2sch3 "Bu H F H OH H H VI-31-8 ch3 * H * "Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-32. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-32-1 Et H H H "Bu H F H OH H H VI-32-2 Et H H ch3 "Bu H F H OH H H VI-32-3 Et H H CH(CH3)2 "Bu H F H OH H H VI-32-4 Et H H CH2CH(CH3)2 "Bu H F H OH H H VI-32-5 Et H H CH2Ph "Bu H F H OH H H VI-32-6 Et H H CH2-indol-3-yl "Bu H F H OH H H VI-32-7 Et H H ch2ch2sch3 "Bu H F H OH H H VI-32-8 Et * H * "Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-33. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-33-1 'Pr H H H ”Bu H F H OH H H VI-33-2 'Pr H H ch3 ”Bu H F H OH H H VI-33-3 'Pr H H CH(CH3)2 ”Bu H F H OH H H VI-33-4 'Pr H H CH2CH(CH3)2 ”Bu H F H OH H H VI-33-5 'Pr H H CH2Ph ”Bu H F H OH H H VI-33-6 'Pr H H CH2-indol-3-yl ”Bu H F H OH H H VI-33-7 'Pr H H ch2ch2sch3 ”Bu H F H OH H H VI-33-8 zPj- * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-34-1 'Bn H H H ”Bu H F H OH H H VI-34-2 'Bn H H ch3 ”Bu H F H OH H H VI-34-3 'Bn H H CH(CH3)2 ”Bu H F H OH H H VI-34-4 'Bn H H CH2CH(CH3)2 ”Bu H F H OH H H VI-34-5 'Bn H H CH2Ph ”Bu H F H OH H H VI-34-6 'Bn H H CH2-indol-3-yl ”Bu H F H OH H H VI-34-7 'Bn H H ch2ch2sch3 ”Bu H F H OH H H VI-34-8 'Bn * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-35. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-35-1 Ph H H H ”Bu H F H OH H H VI-35-2 Ph H H ch3 ”Bu H F H OH H H VI-35-3 Ph H H CH(CH3)2 ”Bu H F H OH H H VI-35-4 Ph H H CH2CH(CH3)2 ”Bu H F H OH H H VI-35-5 Ph H H CH2Ph ”Bu H F H OH H H VI-35-6 Ph H H CH2-indol-3-yl ”Bu H F H OH H H VI-35-7 Ph H H ch2ch2sch3 ”Bu H F H OH H H VI-35-8 Ph * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table VI-36. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-36-1 p-Me-Ph H H H ”Bu H F H OH H H VI-36-2 p-Me-Ph H H ch3 ”Bu H F H OH H H VI-36-3 p-Me-Ph H H CH(CH3)2 ”Bu H F H OH H H VI-36-4 p-Me-Ph H H CH2CH(CH3)2 ”Bu H F H OH H H VI-36-5 p-Me-Ph H H CH2Ph ”Bu H F H OH H H VI-36-6 p-Me-Ph H H CH2-indol-3-yl ”Bu H F H OH H H VI-36-7 p-Me-Ph H H ch2ch2sch3 ”Bu H F H OH H H VI-36-8 p-Me-Ph * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-37. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-37-1 p-F-Ph H H H ”Bu H F H OH H H VI-37-2 p-F-Ph H H ch3 ”Bu H F H OH H H VI-37-3 p-F-Ph H H CH(CH3)2 ”Bu H F H OH H H 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-37-4 p-F-Ph H H CH2CH(CH3)2 ”Bu H F H OH H H VI-37-5 p-F-Ph H H CH2Ph ”Bu H F H OH H H VI-37-6 p-F-Ph H H CH2-indol-3-yl ”Bu H F H OH H H VI-37-7 p-F-Ph H H ch2ch2sch3 ”Bu H F H OH H H VI-37-8 p-F-Ph * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-38-1 p-Cl-Ph H H H ”Bu H F H OH H H VI-38-2 p-Cl-Ph H H ch3 ”Bu H F H OH H H VI-38-3 p-Cl-Ph H H CH(CH3)2 ”Bu H F H OH H H VI-38-4 p-Cl-Ph H H CH2CH(CH3)2 ”Bu H F H OH H H VI-38-5 p-Cl-Ph H H CH2Ph ”Bu H F H OH H H VI-38-6 p-Cl-Ph H H CH2-indol-3-yl ”Bu H F H OH H H VI-38-7 p-Cl-Ph H H CH2CH2SCH3 ”Bu H F H OH H H VI-38-8 p-Cl-Ph * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-39. Ns R1 R2 FT ' R3b R4 R5 R6 X Y R7 R8 VI-39-1 p-Br-Ph H H H ”Bu H F H OH H H VI-39-2 p-Br-Ph H H ch3 ”Bu H F H OH H H VI-39-3 p-Br-Ph H H CH(CH3)2 ”Bu H F H OH H H VI-39-4 p-Br-Ph H H CH2CH(CH3)2 ”Bu H F H OH H H VI-39-5 p-Br-Ph H H CH2Ph ”Bu H F H OH H H VI-39-6 p-Br-Ph H H CH2-indol-3-yl ”Bu H F H OH H H VI-39-7 p-Br-Ph H H ch2ch2sch3 ”Bu H F H OH H H VI-39-8 p-Br-Ph * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-40. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-40-1 p-I-Ph H H H ”Bu H F H OH H H VI-40-2 p-I-Ph H H ch3 ”Bu H F H OH H H VI-40-3 p-I-Ph H H CH(CH3)2 ”Bu H F H OH H H VI-40-4 p-I-Ph H H CH2CH(CH3)2 ”Bu H F H OH H H VI-40-5 p-I-Ph H H CH2Ph ”Bu H F H OH H H VI-40-6 p-I-Ph H H CH2-indol-3-yl ”Bu H F H OH H H VI-40-7 p-I-Ph H H ch2ch2sch3 ”Bu H F H OH H H VI-40-8 p-I-Ph * H * ”Bu H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3iJ ' R3b R4 R5 R6 X Y R7 R8 VI-41-1 ch3 H H H Bz H F H OH H H VI-41-2 ch3 H H ch3 Bz H F H OH H H VI-41-3 ch3 H H CH(CH3)2 Bz H F H OH H H VI-41-4 ch3 H H CH2CH(CH3)2 Bz H F H OH H H VI-41-5 ch3 H H CH2Ph Bz H F H OH H H VI-41-6 ch3 H H CH2-indol-3-yl Bz H F H OH H H VI-41-7 ch3 H H ch2ch2sch3 Bz H F H OH H H VI-41-8 ch3 * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VL42. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-42-1 Et H H H Bz H F H OH H H VI-42-2 Et H H ch3 Bz H F H OH H H VI-42-3 Et H H CH(CH3)2 Bz H F H OH H H VI-42-4 Et H H CH2CH(CH3)2 Bz H F H OH H H VI-42-5 Et H H CH2Ph Bz H F H OH H H VI-42-6 Et H H CH2-indol-3-yl Bz H F H OH H H VI-42-7 Et H H ch2ch2sch3 Bz H F H OH H H VI-42-8 Et * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-43. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-43-1 !Pr H H H Bz H F H OH H H VI-43-2 zpr H H ch3 Bz H F H OH H H VI-43-3 zpr H H CH(CH3)2 Bz H F H OH H H VI-43-4 zpr H H CH2CH(CH3)2 Bz H F H OH H H VI-43-5 zpr H H CH2Ph Bz H F H OH H H VI-43-6 !Pr H H CH2-indol-3-yl Bz H F H OH H H VI-43-7 !Pr H H ch2ch2sch3 Bz H F H OH H 1j9 VI-43-8 !Pr * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-44-1 'Bn H H H Bz H F H OH H H VI-44-2 'Bn H H ch3 Bz H F H OH H H VI-44-3 'Bn H H CH(CH3)2 Bz H F H OH H H VI-44-4 'Bn H H CH2CH(CH3)2 Bz H F H OH H H VI-44-5 'Bn H H CH2Ph Bz H F H OH H H VI-44-6 'Bn H H CH2-indol-3-yl Bz H F H OH H H VI-44-7 'Bn H H CH2CH2SCH3 Bz H F H OH H H VI-44-8 'Bn * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VI-45. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-45-1 Ph H H H Bz H F H OH H H VI-45-2 Ph H H ch3 Bz H F H OH H H VI-45-3 Ph H H CH(CH3)2 Bz H F H OH H H VI-45-4 Ph H H CH2CH(CH3)2 Bz H F H OH H H VI-45-5 Ph H H CH2Ph Bz H F H OH H H VI-45-6 Ph H H CH2-indol-3-yl Bz H F H OH H H VI-45-7 Ph H H CH2CH2SCH3 Bz H F H OH H H VI-45-8 Ph * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table VI-46. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-46-1 p-Me-Ph H H H Bz H F H OH H H VI-46-2 p-Me-Ph H H ch3 Bz H F H OH H H VI-46-3 p-Me-Ph H H CH(CH3)2 Bz H F H OH H H VI-46-4 p-Me-Ph H H CH2CH(CH3)2 Bz H F H OH H H VI-46-5 p-Me-Ph H H CH2Ph Bz H F H OH H H VI-46-6 p-Me-Ph H H CH2-indol-3-yl Bz H F H OH H H VI-46-7 p-Me-Ph H H CH2CH2SCH3 Bz H F H OH H H VI-46-8 p-Me-Ph * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-47-1 p-F-Ph H H H Bz H F H OH H H VI-47-2 p-F-Ph H H ch3 Bz H F H OH H H VI-47-3 p-F-Ph H H CH(CH3)2 Bz H F H OH H H VI-47-4 p-F-Ph H H CH2CH(CH3)2 Bz H F H OH H H VI-47-5 p-F-Ph H H CH2Ph Bz H F H OH H H VI-47-6 p-F-Ph H H CH2-indol-3-yl Bz H F H OH H H VI-47-7 p-F-Ph H H CH2CH2SCH3 Bz H F H OH H H VI-47-8 p-F-Ph * H * Bz H F H OH H H *R2 and R3bjoined together by (CH2)3 to form five-membered ring. Table VL48. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-48-1 p-Cl-Ph H H H Bz H F H OH H H VI-48-2 p-Cl-Ph H H ch3 Bz H F H OH H H VI-48-3 p-Cl-Ph H H CH(CH3)2 Bz H F H OH H H VI-48-4 p-Cl-Ph H H CH2CH(CH3)2 Bz H F H OH H H VI-48-5 p-Cl-Ph H H CH2Ph Bz H F H OH H H VI-48-6 p-Cl-Ph H H CH2-indol-3-yl Bz H F H OH H H VI-48-7 p-Cl-Ph H H CH2CH2SCH3 Bz H F H OH H H VI-48-8 p-Cl-Ph * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VL49. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-49-1 p-Br-Ph H H H Bz H F H OH H H VI-49-2 p-Br-Ph H H ch3 Bz H F H OH H H VI-49-3 p-Br-Ph H H CH(CH3)2 Bz H F H OH H H VI-49-4 p-Br-Ph H H CH2CH(CH3)2 Bz H F H OH H H VI-49-5 p-Br-Ph H H CH2Ph Bz H F H OH H H VI-49-6 p-Br-Ph H H CH2-indol-3-yl Bz H F H OH H H VI-49-7 p-Br-Ph H H CH2CH2SCH3 Bz H F H OH H H VI-49-8 p-Br-Ph * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 VI-50-1 p-I-Ph H H H Bz H F H OH H H VI-50-2 p-I-Ph H H ch3 Bz H F H OH H H VI-50-3 p-I-Ph H H CH(CH3)2 Bz H F H OH H H VI-50-4 p-I-Ph H H CH2CH(CH3)2 Bz H F H OH H H VI-50-5 p-I-Ph H H CH2Ph Bz H F H OH H H VI-50-6 p-I-Ph H H CH2-indol-3-yl Bz H F H OH H H VI-50-7 p-I-Ph H H ch2ch2sch3 Bz H F H OH H H VI-50-8 p-I-Ph * H * Bz H F H OH H H *R2 and R3b joined together by (CH2)3 to form five-membered ring. VII Table VII-1. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-1-1 ch3 H H H ch3 H F H OH H H nh2 VII-1-2 ch3 H H ch3 ch3 H F H OH H H nh2 VII-1-3 ch3 H H CH(CH3)2 ch3 H F H OH H H nh2 VII-1-4 ch3 H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-1-5 ch3 H H CH2Ph ch3 H F H OH H H nh2 VII-1-6 ch3 H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-1-7 ch3 H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-1-8 ch3 * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-2. Ns       R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-2-1 Et H H H ch3 H F H OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-2-2 Et H H ch3 CH3 H F H OH H H nh2 VII-2-3 Et H H CH(CH3)2 CH3 H F H OH H H nh2 VII-2-4 Et H H CH2CH(CH3)2 CH3 H F H OH H H nh2 VII-2-5 Et H H CH2Ph CH3 H F H OH H H nh2 VII-2-6 Et H H CH2-indol-3-yl CH3 H F H OH H H nh2 VII-2-7 Et H H CH2CH2SCH3 CH3 H F H OH H H nh2 VII-2-8 Et * H * CH3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-3. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-3-1 !Pr H H H ch3 H F H OH H H nh2 VII-3-2 !Pr H H ch3 ch3 H F H OH H H nh2 VII-3-3 !Pr H H CH(CH3)2 ch3 H F H OH H H nh2 VII-3-4 !Pr H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-3-5 zpr H H CH2Ph ch3 H F H OH H H nh2 VII-3-6 zpr H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-3-7 zpr H H CH2CH2SCH3 ch3 H F H OH H H nh2 VII-3-8 zpr * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-4. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-4-1 'Bn H H H CEE H F H OH H H nh2 VII-4-2 'Bn H H ch3 ch3 H F H OH H H nh2 VII-4-3 'Bn H H CH(CH3)2 ch3 H F H OH H H nh2 VII-4-4 'Bn H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-4-5 'Bn H H CH2Ph ch3 H F H OH H H nh2 VII-4-6 'Bn H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-4-7 'Bn H H CH2CH2SCH3 ch3 H F H OH H H nh2 VII-4-8 'Bn * H * ch3 H F H OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-5-1 Ph H H H ch3 H F H OH H H nh2 VII-5-2 Ph H H ch3 ch3 H F H OH H H nh2 VII-5-3 Ph H H CH(CH3)2 ch3 H F H OH H H nh2 VII-5-4 Ph H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-5-5 Ph H H CH2Ph ch3 H F H OH H H nh2 VII-5-6 Ph H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-5-7 Ph H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-5-8 Ph * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-6. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-6-1 p-Me-Ph H H H ch3 H F H OH H H nh2 VII-6-2 p-Me-Ph H H ch3 ch3 H F H OH H H nh2 VII-6-3 p-Me-Ph H H CH(CH3)2 ch3 H F H OH H H nh2 VII-6-4 p-Me-Ph H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-6-5 p-Me-Ph H H CH2Ph ch3 H F H OH H H nh2 VII-6-6 p-Me-Ph H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-6-7 p-Me-Ph H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-6-8 p-Me-Ph * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table VII-7. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-7-1 p-F-Ph H H H ch3 H F H OH H H nh2 VII-7-2 p-F-Ph H H ch3 ch3 H F H OH H H nh2 VII-7-3 p-F-Ph H H CH(CH3)2 ch3 H F H OH H H nh2 VII-7-4 p-F-Ph H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-7-6 p-F-Ph H H CH2Ph ch3 H F H OH H H nh2 VII-7-7 p-F-Ph H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-7-8 p-F-Ph H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-7-20 p-F-Ph * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-8. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-8-1 p-Cl-Ph H H H ch3 H F H OH H H nh2 VII-8-2 p-Cl-Ph H H ch3 ch3 H F H OH H H nh2 VII-8-3 p-Cl-Ph H H CH(CH3)2 ch3 H F H OH H H nh2 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-8-4 p-Cl-Ph H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-8-5 p-Cl-Ph H H CH2Ph ch3 H F H OH H H nh2 VII-8-6 p-Cl-Ph H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-8-7 p-Cl-Ph H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-8-8 p-Cl-Ph * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-9. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-9-1 p-Br-Ph H H H ch3 H F H OH H H nh2 VII-9-2 p-Br-Ph H H ch3 ch3 H F H OH H H nh2 VII-9-3 p-Br-Ph H H CH(CH3)2 ch3 H F H OH H H nh2 VII-9-4 p-Br-Ph H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-9-6 p-Br-Ph H H CH2Ph ch3 H F H OH H H nh2 VII-9-7 p-Br-Ph H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-9-8 p-Br-Ph H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-9-20 p-Br-Ph * H * ch3 H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-10. Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-10-1 p-I-Ph H H H ch3 H F H OH H H nh2 VII-10-2 p-I-Ph H H ch3 ch3 H F H OH H H nh2 VII-10-3 p-I-Ph H H CH(CH3)2 ch3 H F H OH H H nh2 VII-10-4 p-I-Ph H H CH2CH(CH3)2 ch3 H F H OH H H nh2 VII-10-5 p-I-Ph H H CH2Ph ch3 H F H OH H H nh2 VII-10-6 p-I-Ph H H CH2-indol-3-yl ch3 H F H OH H H nh2 VII-10-7 p-I-Ph H H ch2ch2sch3 ch3 H F H OH H H nh2 VII-10-8 p-I-Ph * H * ch3 H F H OH H H nh2 5   *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-11-1 ch3 H H H Et H F H OH H H nh2 VII-11-2 ch3 H H ch3 Et H F H OH H H nh2 VII-11-3 ch3 H H CH(CH3)2 Et H F H OH H H nh2 VII-11-4 ch3 H H CH2CH(CH3)2 Et H F H OH H H nh2 VII-11-5 ch3 H H CH2Ph Et H F H OH H H nh2 VII-11-6 ch3 H H CH2-indol-3-yl Et H F H OH H H nh2 VII-11-7 ch3 H H ch2ch2sch3 Et H F H OH H H nh2 VII-11-8 ch3 * H * Et H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-12. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-12-1 Et H H H Et H F H OH H H nh2 VII-12-2 Et H H ch3 Et H F H OH H H nh2 VII-12-3 Et H H CH(CH3)2 Et H F H OH H H nh2 VII-12-4 Et H H CH2CH(CH3)2 Et H F H OH H H nh2 VII-12-5 Et H H CH2Ph Et H F H OH H H nh2 VII-12-6 Et H H CH2-indol-3-yl Et H F H OH H H nh2 VII-12-7 Et H H ch2ch2sch3 Et H F H OH H H nh2 VII-12-8 Et * H * Et H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 5 Table VII-13. No R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-13-1 !Pr H H H Et H F H OH H H nh2 VII-13-2 !Pr H H ch3 Et H F H OH H H nh2 VII-13-3 !Pr H H CH(CH3)2 Et H F H OH H H nh2 VII-13-4 !Pr H H CH2CH(CH3)2 Et H F H OH H H nh2 VII-13-5 zpr H H CH2Ph Et H F H OH H H nh2 VII-13-6 zpr H H CH2-indol-3-yl Et H F H OH H H nh2 VII-13-7 zpr H H ch2ch2sch3 Et H F H OH H H nh2 VII-13-8 zpr * H * Et H F H OH H H nh2 *R2 and R3b joined together by (CH2)3 to form five-membered ring. 2023263496   09 Nov 2023 Ns      R1 R2 B L R3b R4 R5 R6 X Y R7 R8 R9 3< VII- rBu H F I H Et H F H OH H H NH2 14-1 VII- 'Bu H F I ch3 Et H F H OH H H NH2 14-2 VII- 'Bu H F I CH(CH3)2 Et H F H OH H H NH2 14-3 VII- 'Bu H F I CH2CH(CH3)2 Et H F H OH H H NH2 14-4 VII- 'Bu H F I CH2Ph Et H F H OH H H NH2 14-5 VII- 'Bu H F I CH2-indol-3-yl Et H F H OH H H NH2 14-6 VII- rBu H F I CH2CH2SCH3 Et H F H OH H H NH2 14-7 VII- rBu * F I * Et H F H OH H H NH2 14-8 *R2 and R3b joined together by (CH2)3 to form five-membered ring. Table VII-15. Ns        R1 R2 R3a R3b R4 R5 R6 X Y R7 R8 R9 VII-15-1 Ph H H H Et H F H OH H H NH2 VII-15-2 Ph H H CH3 Et H F H OH H H NH2 VII-15-3 Ph H H CH(CH3)2 Et H F H OH H H NH2 VII-15-4 Ph H H CH2CH(CH3)2 Et H F H OH H H NH2 VII-15-5 Ph H H CH2Ph Et H F H OH H H NH2 VII-15-6 Ph H H CH2-indol-3-yl Et H F H OH H H NH2 VII-1...

Claims

1. A compound, or a stereoisomer thereof, represented by formula (I):OH(?        “F5                                                         (I)wherein P* is a chiral phosphorous atom,and wherein(a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, or a substituted or unsubstituted phenyl, where the substitutent of the substituted phenyl is at least one of a CH3, OCH3, F, 10 Cl, Br, I, nitro, cyano, and a CH3-qXq, where X is F, Cl, Br, or I, and q is 1-3;(b) R2 is hydrogen or CH3;(c-i) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, 15 CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl, or(c-ii) R3a is CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl and R3b is H;20   (d) R4 is hydrogen, CH3, Et, !Pr, ”Pr, ”Bu, 2-butyl, 'Bu, 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; and2023263496   09 Nov 2023(e) R7 and R8 are independently H, F, Cl, Br, I, OH, OCH3, SH, SCH3, NH2, NHCH3, N(CH3)2, CH3, CHs-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2H, CO2CH3, CONH2, CONHCH3, or CON(CH3)2, wherein R' is a C1-20 alkyl; a C1-20 cycloalkyl; a C2-C6 alkenyl, a C2-C6 alkynyl.5   2. (Previously Presented): The compound according to claim 1, wherein:(a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl; and(c-i) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, CH2-indol-3-yl, -CH2CH2SCH3, CH2CO2H, CH2C(O)NH2, CH2CH2COOH, 10 CH2CH2C(O)NH2, CH2CH2CH2CH2NH2, -CH2CH2CH2NHC(NH)NH2, CH2-imidazol-4-yl, CH2OH, CH(OH)CH3, CH2((4'-OH)-Ph), CH2SH, or lower cycloalkyl.

3. The compound according to claim 1, wherein:(a) R1 is hydrogen, methyl, ethyl, n-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;15   (c-i) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, orlower cycloalkyl; and(e) R7 and R8 are independently H, F, Br, SCH3, CH3, CHs-qXq, where X is F, Cl, Br, or I and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2.

4. The compound according to claim 1, wherein:20   (a) R1 is hydrogen, methyl, ethyl, zz-propyl, z-propyl, phenyl, p-tolyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;(b) R2 is hydrogen;(c-i) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; and25   (e) R7 and R8 are independently H, F, Br, SCH3, CH3, CHs-qXq, where X is F, Cl, Br, or Iand q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2.

5. The compound according to claim 1, wherein:(a) R1 is hydrogen, methyl, phenyl, p-bromo-phenyl, p-chloro-phenyl, p-fluorophenyl;2023263496   09 Nov 2023(b) R2 is hydrogen;(c-i) R3a is H and R3b is H, CH3, CH(CH3)2, CH2CH(CH3)2, CH(CH3)CH2CH3, CH2Ph, or lower cycloalkyl; and(e) R7 and R8 are independently H, F, Br, SCH3, CH3, CH3.qXq, where X is F, Cl, Br, or I 5 and q is 1 to 3, vinyl, CO2CH3, CONH2, CONHCH3, or CON(CH3)2.

6. A composition comprising the compound according to any one of claims 1 to 5.

7. A composition comprising the compound according to any one of claims 1 to 5 and apharmaceutically acceptable medium.

8. A composition comprising an effective amount of the compound according to any 10 one of claims 1 to 5 to treat a hepatitis C virus infection and a pharmaceutically acceptable medium.

9. A method of treating a subject infected by a virus selected from among 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, which comprises15 administering to the subject an effective amount of the compound according to any one of claims 1 to 5.

10. The method of claim 9, wherein the virus is hepatitis C virus.

11. The method of claim 10, which further comprises administering to the subject aneffective amount of another antiviral agent.20   12.    The method of claim 10 or 11, wherein the subject is a human.

13. A process for preparing the compound according to any one of claims 1 to 5comprising reacting a compound 4" with a nucleoside analog 5':4"                                     5'wherein25 X' is a leaving group.2023263496   09 Nov 202314. Use of a compound according to any one of claims 1 to 5 in the preparation of a medicament for treating a subject infected by a virus selected from among 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.5   15. Use of a compound according to any one of claims 1 to 5 in the preparation of amedicament for treating a hepatitis C infection.