Antiviral 1,3-di-oxo-indene compounds

Abstract

This invention provides compounds of formula (I) as described herein. And medically acceptable salts, pharmaceutical compositions containing such compounds, and methods of treating viral infections using such compounds, salts, and compositions.

Description

Antiviral 1,3-dioxoindene compounds The present invention relates to novel 1,3-dioxoindene compounds that are inhibitors of picornaviruses including Coxsackievirus, enterovirus, echovirus, poliovirus, and rhinovirus and are thus applicable to the treatment of viral infections including poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand, foot, and mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, colds, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis, or otitis media. The present invention provides novel tetracyclic pyridone compounds disclosed herein, pharmaceutical compositions containing such compounds, and methods of using such compounds and compositions for the treatment and prevention of viral diseases. Picornaviruses are non-enveloped positive single-stranded RNA viruses with an RNA genome length of 7.2 - 8.5 Kb. These viruses are extremely small and spherical in shape, with a size of about 22 - 30 nm, and were first identified a long time ago. Viruses belonging to the Picornaviridae family include enteroviruses, including rhinovirus, poliovirus, Coxsackievirus A, Coxsackievirus B, echovirus, and hepatitis A virus. The diseases caused by picornaviruses are diverse, ranging from respiratory diseases to digestive system diseases, to circulatory system diseases, and to dermal diseases. Examples of such diseases include poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand, foot, and mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, colds, herpangina, and foot-and-mouth disease. However, there is no therapy for curing these diseases. Most of the drugs under development are uncoating inhibitors. Viruses belonging to the Picornaviridae family cause various diseases, including the aforementioned respiratory diseases, which pose health, social, and economic problems. Picornaviruses are the main pathogens of waterborne diseases. Due to being extremely stable and difficult to disinfect, RNA viruses continuously cause related diseases. Human rhinovirus (hRV) has been associated with most asthma exacerbations in recent years and is known to be present even in the bronchial tissues of many stable asthma patients. Comparison of individual bronchial mucosal biopsy samples obtained from asthmatic and non-asthmatic patients showed that the frequency of detection of human rhinovirus in the lower respiratory tract of asthmatic patients was significantly higher compared to non-asthmatic patients. It has also been reported that there is a correlation between the presence of human rhinovirus and the clinical severity of asthma. In addition, rhinovirus causes chronic obstructive pulmonary disease, pneumonia, sinusitis, and otitis media as well as asthma. Rhinoviruses are the main pathogens of the common cold, and diseases induced by enteroviruses include meningitis, respiratory infections, etc. Extensive efforts to provide vaccination against poliovirus have significantly reduced the global incidence of polio, but cases have still been reported in Niger, Nigeria, Egypt, India, Pakistan, and Afghanistan. Thanks to the hepatitis A virus vaccine, hepatitis A is now to some extent controllable. However, no vaccines have been developed so far for coxsackieviruses, echoviruses, or rhinoviruses. Specifically, coxsackievirus B is the main cause of myocarditis, which can develop into idiopathic dilated cardiomyopathy requiring heart transplantation in severe cases. Enviroxime derivatives are considered the most promising candidates with broad anti-enterovirus and anti-rhinovirus activities. Enviroxime interferes with the synthesis of positive-strand RNA by binding to viral protein 3A required for the formation of RNA intermediates in viral replication (Heinz B A and Vance L M: J Virol, 1995, 69(7), 4189-97). However, in clinical studies, the therapeutic effects of this compound were observed to be insignificant or rare, and at the same time, adverse pharmacokinetics and unwanted side effects were detected (Miller F D et al: Antimicrob Agents Chemother, 1985, 27(1), 102-6). The protease inhibitor AG 7088 was developed based on the understanding of the fine structure and function of viral protease 2C. In cell cultures within the nanomolar concentration range, AG 7088 has effects on 48 rhinovirus types and coxsackievirus A21, B3, enterovirus 70, and echovirus 11 (Pattick A K et al: Antimicrobila Agents Chemother, 1999, 43(10), 2444-50). Thanks to the clarification of the molecular structure of the viral capsid, the prerequisites for the purposeful design of capsid blockers (the "WIN substances") have been obtained (Diana G D: Curr Med Chem 2003, 2, 1-12). These WIN substances inhibit the adsorption and / or uncoating of rhinoviruses and enteroviruses. Some WIN substances have a highly specific effect only on picornaviruses of individual genera or virus types. Other derivatives inhibit the replication of both rhinoviruses and enteroviruses. For example, arildone, disoxaril, and pirodavir belong to the WIN substances. These compounds exhibit excellent antiviral effects in cell culture. However, poor solubility (arildone), low bioavailability (arildone and disoxaril), rapid metabolism and excretion (disoxaril and WIN 54954), and side effects (such as rash (WIN 54954)) make clinical application impossible. Pleconaril (a WIN substance) has excellent oral bioavailability and, after binding to the hydrophobic pocket in the viral capsid, inhibits the penetration of rhinoviruses, echoviruses, and coxsackieviruses (Pevear D C et al: Antimicrob Agents Chemother 1999, 43(9), 2109-15; McKinlay M A et al: Annu Rev Microbiol 1992, 46, 635-54). Therefore, pleconaril may be effective against a wide range of viral diseases, from the common cold to viral meningitis or myocarditis. Resistance to rhinoviruses, enterovirus 71, and coxsackievirus B3 has been observed (Ledford R M et al: J Virol 2004, 78(7), 3663-74; Groarke J M et al: J Infect Dis 1999, 179(6), 1538-41). However, the proven therapeutic effect has not been sufficient to register pleconaril (Picovir, Viropharma, USA) in the United States as a drug for the treatment of rhinovirus infections. In March 2002, the US Food and Drug Administration (FDA) rejected the corresponding application because the success rate of the therapy was too low and side effects were observed. The antiviral activity of BTA-798 has been found to be higher than that of pleconaril, as evaluated in vitro and in vivo with rhinoviruses, and clinical tests are currently underway (Ryan, J. et al Antiviral Res [18th Intl Conf Antiviral Res (April 11-14, Barcelona) 2005] 2005, 65(3): abstract LB-11). However, to date, no antiviral drugs have been developed and approved for the treatment of enteroviruses or rhinoviruses. There is still a need for novel treatments and therapies for enteroviruses or rhinoviruses. The reason for the present invention is that in-depth and thorough research has been carried out on the effective viral inhibitory effect against picornaviruses including coxsackieviruses, enteroviruses, echoviruses, polioviruses, and rhinoviruses, and finally it has been found that novel 1,3-dioxoindene derivatives exhibit high inhibitory activity against picornaviruses including coxsackieviruses, enteroviruses, echoviruses, polioviruses, and rhinoviruses. The present invention provides novel compounds having potent antiviral activity in vitro. The present invention also provides pharmaceutical compositions containing the novel compounds, and methods of using such compounds and compositions to inhibit viral replication or reactivation, and to treat disease conditions related to or caused by viruses. Other objects of the present invention are described in the following description and examples. In one aspect, the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof: wherein, G 1 is selected from straight-chain or branched-chain C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl or straight-chain or branched-chain C 1 -C 4 alkoxy; wherein the C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl and C 1 -C 4 alkoxy may be substituted by one, two or three substituents independently selected from cyclopropyl and straight-chain or branched-chain C 1 -C 3 alkyl; L is a single bond or CH 2 ; E is a) -CH(CHOHCH 3 )(NMe 2 ) or b) a monocyclic 4- to 6-membered heterocyclic group containing one or two nitrogen atoms or a 5- to 6-membered heteroaryl group containing one nitrogen atom, wherein the 4- to 6-membered heterocyclic group and the 5- to 6-membered heteroaryl group are optionally substituted with one to three substituents independently selected from the group consisting of linear or branched C 1 -C 3 alkyl, -OH, =O, -SO 2 R; wherein each R is independently selected from linear or branched C 1 -C 3 alkyl, a monocyclic 5- to 6-membered heterocyclic group containing one or two nitrogen atoms, and NR 1 R 2 ; wherein the monocyclic 5- to 6-membered heterocyclic group is optionally substituted with C 1 -C 3 alkyl or NR 3 R 4 substituted; each R 1 and R 2 are independently selected from H and C 1 -C 3 alkyl, wherein the C 1 -C 3 alkyl is optionally substituted with NR 3 R 4 substituted; and each R 3 and R 4 are independently selected from H or methyl. In another aspect, the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the present invention and one or more pharmaceutically acceptable carriers. In another aspect, the present invention provides a combination, particularly a pharmaceutical combination, comprising a therapeutically effective amount of a compound of the present invention and one or more therapeutic active agents. For the purposes of interpreting this specification, the following definitions will apply, and terms used in the singular will also include the plural where appropriate. Unless the context clearly indicates otherwise, the terms used in this specification have the following meanings: As used herein, the term "subject" refers to an animal. In certain aspects, the animal is a mammal. A subject also refers to, for example, a primate (e.g., a human), a cow, a sheep, a goat, a horse, a dog, a cat, a rabbit, a rat, a mouse, a fish, a bird, and the like. In certain embodiments, the subject is a human. As used herein, "patient" refers to a human subject. As used herein, a subject "needs" a treatment if the subject would benefit biologically, medically, or in terms of quality of life from the treatment. As used herein, the term "inhibition" (inhibition / inhibiting) refers to reducing or curbing a given condition, symptom, or disorder, or disease, or significantly reducing the baseline activity of a biological activity or process. As used herein, the term "treating" (treating / treatment) of any disease or disorder in one embodiment refers to ameliorating the disease or disorder (i.e., slowing or arresting or reducing the development of the disease or at least one of its clinical symptoms). In another embodiment, "treating" refers to alleviating or ameliorating at least one physiological parameter, including physiological parameters that may not be discernible by the patient. In yet another embodiment, "treating" refers to modulating the disease or disorder physically (e.g., stabilizing a discernible symptom), physiologically (e.g., stabilizing a physiological parameter), or both. In yet another embodiment, "treating" refers to preventing or delaying the onset or development or progression of a disease or disorder. As used herein, unless otherwise indicated herein or clearly contradicted by the context, the terms "a / an", "the", and similar terms used in the context of the present invention (especially in the context of the claims) shall be construed to cover both the singular and the plural. Unless otherwise specified herein or clearly contradicted by the context, all methods described herein can be performed in any suitable order. The use of any and all examples or illustrative language (e.g., "such as") provided herein is merely intended to better illuminate the invention and does not impose a limitation on the scope of the invention otherwise claimed. "Optionally substituted" means that the group mentioned may be substituted at one or more positions with any one or any combination of the groups listed hereinafter. The number, position and choice of substituents are understood to cover only those substitutions that a skilled chemist would expect to be reasonably stable; thus, a "side oxy group" will not be a substituent on, for example, an aryl or heteroaryl ring, and a single carbon atom will not have three hydroxy or amino substituents. Unless otherwise specified, the substituents that may optionally be present are generally up to four groups selected from the following: halogen, side oxy group, CN, amino, hydroxy, -C 1-3 alkyl, -OR*, -NR* 2 、-SR*, -SO 2 R*, -COOR* and -CONR* 2 where each R* is independently H or C 1-3 alkyl. Unless otherwise stated, as used herein, "aryl" means phenyl or naphthyl. Unless otherwise specified, the aryl may optionally be substituted with up to four groups selected from the following: halogen, CN, amino, hydroxy, C 1-3 alkyl, -OR*, -NR* 2 、-SR*, -SO 2 R*, -COOR* and -CONR* 2 where each R* is independently H or C 1-3 alkyl. As used herein, "halogen" or "halide" may be fluorine, chlorine, bromine or iodine. As used herein, "C 1-6 alkyl" or "C 1 -C 6 alkyl" represents a straight-chain or branched-chain alkyl having 1-6 carbon atoms. If a different number of carbon atoms is specified, such as C 4 or C 3 then the definition is correspondingly amended, such as "C 1-4 alkyl" will represent methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl and tertiary butyl. As used herein, "C 1-6 "Alkoxy" means a straight-chain or branched-chain alkoxy group (-O-alkyl) having 1 to 6 carbon atoms. If a different number of carbon atoms is specified, such as C 4 or C 3 , the definition is correspondingly amended, such as "C 1-4 alkoxy" will mean methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy. As used herein, "C 1-4 haloalkyl" or "C 1 -C 4 haloalkyl" indicates a straight-chain or branched-chain alkyl group having 1 to 4 carbon atoms, wherein at least one hydrogen has been replaced by a halogen. The number of halogen substitutions can be from one to the number of hydrogen atoms on the unsubstituted alkyl group. If a different number of carbon atoms is specified, such as C 6 or C 3 , the definition is correspondingly amended. Thus, "C 1-4 haloalkyl" means methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl in which at least one hydrogen has been replaced by a halogen, such as where the halogen is fluorine: CF 3 CF 2 -, (CF 3 ) 2 CH-, CH 3 -CF 2 -, CF 3 CF 2 -, CF 3 , CF 2 H-, CF 3 CF 2 CH(CF 3 )- or CF 3 CF 2 CF 2 CF 2 -. As used herein, "C 3-8 cycloalkyl" means a saturated monocyclic hydrocarbon ring having 3 to 8 carbon atoms. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. If a different number of carbon atoms is specified, such as C 3 -C 6 , the definition is correspondingly modified. "4- to 8-membered heterocyclic group", "5- to 6-membered heterocyclic group", "3- to 10-membered heterocyclic group", "3- to 14-membered heterocyclic group", "4- to 14-membered heterocyclic group", and "5- to 14-membered heterocyclic group" respectively mean 4- to 8-membered, 5- to 6-membered, 3- to 10-membered, 3- to 14-membered, 4- to 14-membered, and 5- to 14-membered heterocycles; unless otherwise specified, these rings contain 1 to 7, 1 to 5, or 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur as ring members, and the rings can be saturated or partially saturated, but not aromatic. The heterocyclic group can be attached to another group at a nitrogen or carbon atom. The term "heterocyclic group" includes monocyclic groups, fused ring groups, and bridged groups. Examples of such heterocyclic groups include, but are not limited to, pyrrolidine, piperidine, piperazine, pyrrolidinone, morpholine, tetrahydrofuran, tetrahydrothiophene, tetrahydrothiopyran, tetrahydropyran, 1,4-dioxane, 1,4-oxathiane, 8-aza-bicyclo[3.2.1]octane, 3,8-diazabicyclo[3.2.1]octane, 3-oxa-8-aza-bicyclo[3.2.1]octane, 8-oxa-3-aza-bicyclo[3.2.1]octane, 2-oxa-5-aza-bicyclo[2.2.1]heptane, 2,5-diazabicyclo[2.2.1]heptane, azetidine, ethylene dioxy, oxetane, or thiazole. In certain embodiments, unless otherwise specified, the heterocyclic group has 1-2 heteroatoms selected from N, O, and S as ring members, and 4 to 7 ring atoms, and is optionally substituted with up to four groups selected from halo, side oxy, CN, amino, hydroxy, C 1-3 alkyl, -OR*, -NR* 2 、-SR*, -SO 2 R*, -COOR*, and -CONR* 2 : wherein each R* is independently H or C 1-3Alkyl. Specifically, a heterocyclic group containing a sulfur atom is optionally substituted on sulfur with one or two side oxygen groups. "Heteroaryl" is a completely unsaturated (aromatic) ring. The term "heteroaryl" refers to a 5- to 14-membered monocyclic, bicyclic, or tricyclic aromatic ring system having 1 to 8 heteroatoms selected from N, O, or S. Typically, heteroaryl is a 5- to 10-membered ring or ring system (e.g., a 5- to 7-membered monocyclic group or an 8- to 10-membered bicyclic group), usually a 5- to 6-membered ring containing up to four heteroatoms selected from N, O, and S, but usually the heteroaryl ring contains no more than one divalent O or S in the ring. Typical heteroaryls include furan, isothiazole, thiadiazole, oxadiazole, indazole, indole, quinoline, 2-thienyl or 3-thienyl, 2-furyl or 3-furyl, 2-pyrrolyl or 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl or 5-imidazolyl, 3-pyrazolyl, 4-pyrazolyl or 5-pyrazolyl, 2-thiazolyl, 4-thiazolyl or 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl or 5-isothiazolyl, 2-oxazolyl, 4-oxazolyl or 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl or 5-isoxazolyl, 3-(1,2,4-triazolyl) or 5-(1,2,4-triazolyl), 4-(1,2,3-triazolyl) or 5-(1,2,3-triazolyl), tetrazolyl, triazine, pyrimidine, 2-pyridyl, 3-pyridyl or 4-pyridyl, 3-pyridazinyl or 4-pyridazinyl, 3-pyrimidyl, 4-pyrimidyl or 5-pyrimidyl, 2-pyrimidyl. Heteroaryl is and optionally substituted with up to four groups selected from the following: halo, CN, amino, hydroxy, C 1-3 alkyl, -OR*, -NR* 2 、-SR*, -SO 2 R*, -COOR* and -CONR* 2 where each R* is independently H or C 1 - 3 alkyl. The term "hydroxy / hydroxyl" refers to -OH. Various embodiments of the present invention are described herein. It should be recognized that the features specified in each embodiment can be combined with other specified features to provide other embodiments. The following examples illustrate the present invention: Example 1. A compound of formula (I), or a pharmaceutically acceptable salt thereof: wherein, G 1 is selected from straight-chain or branched-chain C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl or straight-chain or branched-chain C 1 -C 4 alkoxy; wherein the C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl and C 1 -C 4 alkoxy may be substituted by one, two or three substituents independently selected from cyclopropyl and straight-chain or branched-chain C 1 -C 3 alkyl; L is a single bond or C 1 -C 4 a straight-chain or branched-chain alkylene linking group; E is a) -CH(CHOHCH 3 )(NMe 2 ); or b) a monocyclic 4-6 membered heterocyclic group containing one or two nitrogen atoms or a 5-6 membered heteroaryl group containing one nitrogen atom, wherein the 4-6 membered heterocyclic group and the 5-6 membered heteroaryl group are optionally substituted by one to three substituents independently selected from the group consisting of straight-chain or branched-chain C 1 -C 3 alkyl, -OH, =O, -SO 2 R; wherein each R is independently selected from straight-chain or branched-chain C 1 -C 3 alkyl, a monocyclic 5-6 membered heterocyclic group containing one or two nitrogen atoms and NR 1 R 2 ; wherein the monocyclic 5-6 membered heterocyclic group is optionally substituted by C 1 -C 3 alkyl or NR 3 R 4 substituted; each R 1 and R 2 is independently selected from H and C 1 -C 3 alkyl, wherein the C 1 -C 3 alkyl is optionally substituted by NR 3 R 4 substituted; and each R 3 and R 4 is independently selected from H or methyl. Example 2. A compound according to Example 1 or a pharmaceutically acceptable salt thereof, the compound having formula (II): . Example 3. A compound according to Example 1 or a pharmaceutically acceptable salt thereof, the compound having formula (III): . Example 4. A compound according to any one of the foregoing examples or a pharmaceutically acceptable salt thereof, wherein G 1 is a straight-chain or branched-chain C 1 -C 4 alkyl. Example 5. A compound according to any one of the foregoing examples or a pharmaceutically acceptable salt thereof, wherein G 1 is a C 3 -C 4 cycloalkyl. Example 6. A compound according to any one of the foregoing examples or a pharmaceutically acceptable salt thereof, wherein G 1 is a straight-chain or branched-chain C 1 -C 4 Alkoxy group. Example 7. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl and C 1 -C 4 alkoxy group may be substituted with one, two or three substituents. Example 8. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the substituents are independently selected from cyclopropyl and straight-chain or branched-chain C 1 -C 3 alkyl. Example 9. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein L is a single bond. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein L is a C 1 -C 4 straight-chain or branched-chain alkylene linking group. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein L is CH 2 . Example 10. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein E is -C(CHOHCH 3 )(NMe 2 ). Example 11. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein E is a monocyclic 4- to 6-membered heterocyclic group. Example 12. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein E is a monocyclic 4- to 6-membered heteroaryl group. Example 13. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the monocyclic 4- to 6-membered heterocyclic group contains one or two nitrogen atoms. Example 14. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the 5- to 6-membered heteroaryl group contains one nitrogen atom. Example 15. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the 4- to 6-membered heterocyclic group and the 5- to 6-membered heteroaryl group are optionally substituted with one, two or three substituents. Example 16. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the substituents are independently selected from the group consisting of linear or branched C 1 -C 3 alkyl, -OH, =O, -SO 2 R. Example 17. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein R is independently selected from linear or branched C 1 -C 3 alkyl, monocyclic 5- to 6-membered heterocyclic group and NR 1 R 2 . Example 18. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein the monocyclic 5- to 6-membered heterocyclic group is optionally substituted with C 1 -C 3 alkyl or NR 3 R 4 substituted. Example 19. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are independently selected from H and C 1 -C 3 alkyl. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein C 1 -C 3 alkyl is optionally substituted with NR 3 R 4 substituted. Example 20. A compound according to any one of the preceding examples or a pharmaceutically acceptable salt thereof, wherein each R 3 and R 4 is independently selected from H or methyl. Example 21. A compound or a pharmaceutically acceptable salt thereof according to any one of the foregoing examples, wherein G 1 is a straight-chain or branched-chain C 1 -C 4 alkyl group, which is optionally substituted by one, two or three substituents independently selected from cyclopropyl and straight-chain or branched-chain C 1 -C 3 alkyl group. Example 22. A compound or a pharmaceutically acceptable salt thereof according to any one of the foregoing examples, wherein G 1 is a C 3 -C 4 cycloalkyl group, which is optionally substituted by one, two or three substituents independently selected from straight-chain or branched-chain C 1 -C 3 alkyl group. Example 23. A compound or a pharmaceutically acceptable salt thereof according to any one of the foregoing examples, wherein G 1 is a straight-chain or branched-chain C 1 -C 4 alkoxy group, which is optionally substituted by one, two or three substituents independently selected from cyclopropyl and straight-chain or branched-chain C 1 -C 3 alkyl group. Example 24. A compound or a pharmaceutically acceptable salt thereof according to Example 1, the compound having the formula (Ia): wherein A 1 is selected from the group consisting of H, straight-chain or branched-chain C 1 -C 3 alkyl and SO 2 R; and A 2 selected from the group consisting of H and SO 2 R. Example 25. A compound as in the foregoing examples, wherein A 1 is methyl or SO 2 CH 3 . Example 26. A compound as in the foregoing examples, wherein A 2 is SO 2 R, and R is selected from the group consisting of: CH 3 ; a monocyclic 5- or 6-membered heterocyclic group containing one or two nitrogen atoms and substituted with CH 3 or N(CH 3 ) 2 ; and NR 1 R 2 . Example 27. A compound as in Example 1 or a pharmaceutically acceptable salt thereof, the compound having formula (Ib): wherein Y is H or CH 3 . Example 28. A compound as in Example 1 or a pharmaceutically acceptable salt thereof, the compound having formula (Ic): wherein X is selected from the group consisting of methyl, ethyl, and cyclopropyl. Example 29. A compound or a pharmaceutically acceptable salt thereof as in any one of the foregoing examples of any instance, the compound being selected from the group consisting of: N-((4bR,9bR)-1-amino-4b-hydroxy-7-((1R,2R)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-amino-4b-hydroxy-7-((1S,2R)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-2-(azetidin-1-yl)acetamide; N-((4bR,9bR)-1-amino-7-((S)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-6-hydroxypicolinamide; N-(1-amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-5-(N-(2-(dimethylamino)ethyl)sulfamoyl)-3,4-dimethyl-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-amino-7-((S)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-2-(azetidin-1-yl)acetamide; N-(1-amino-7-((1R,2S)-1,2-dimethylcyclopropyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide; N-(1-amino-4b-hydroxy-7-(2-methylcyclobutyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-6-hydroxypicolinamide; N-(1-amino-4b-hydroxy-7-((trans)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfamoyl)-1H-pyrrole-2-carboxamide;(2S,3S)-N-(1-Amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-2-(dimethylamino)-3-hydroxybutyramide; N-(1-Amino-4b-hydroxy-7-((1S,2S)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-5-(((S)-3-(dimethylamino)pyrrolidin-1-yl)sulfonyl)-3-methyl-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-Amino-4b-hydroxy-7-((trans)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,4-dimethyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide; N-(1-Amino-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-Amino-4b-hydroxy-7-((1S,2S)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide; (2S,3S)-N-((4bR,9bR)-1-Amino-7-((S)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-2-(dimethylamino)-3-hydroxybutyramide; N-(1-Amino-4b-hydroxy-7-((1R,2S)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-Amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-2-(azetidin-1-yl)acetamide; N-((4bR,9bR)-1-Amino-7-((S)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide;N-((4bR,9bR)-1-amino-4b-hydroxy-7-isopropoxy-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide; N-((4bS,9bS)-1-amino-4b-hydroxy-7-isopropoxy-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide; N-(1-amino-4b-hydroxy-7-((1S,2R)-2-methylcyclopropyl)-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-(methylsulfonyl)-1H-pyrrole-2-carboxamide; N-((4bR,9bR)-1-amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-1,5-dimethyl-2-formyloxy-2,3-dihydro-1H-imidazole-4-carboxamide; N-(1-amino-7-(sec-butyl)-4b-hydroxy-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide; N-(1-amino-4b-hydroxy-7-((1S,2R)-2-methylcyclopropyl)-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide; N-(1-amino-4b-hydroxy-7-isopropyl-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethyl-4-aminosulfonyl-1H-pyrrole-2-carboxamide; N-(1-amino-4b-hydroxy-7-((1R,2S)-2-methylcyclopropyl)-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-(methylsulfonyl)-1H-pyrrole-2-carboxamide;N-(1-Amino-4b-hydroxy-7-((1S,2R)-2-methylcyclopropyl)-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide and N-((4bR,9bR)-1-amino-4b-hydroxy-7-((1S,2S)-2-methylcyclopropyl)-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide. This example includes each and every example represented in the bioactivity data table herein.; Example 30. A compound comprising each or any one of the examples represented in the bioactivity data table herein. Example 31. A compound of Formula I to III or any one of the examples herein, its pharmaceutically acceptable salt or its optical isomer, which is used for preventing or treating viral diseases. Example 32. A pharmaceutical composition for preventing or treating viral diseases, which comprises a compound of Formula I to III or any one of the examples herein, its pharmaceutically acceptable salt or its optical isomer and a pharmaceutically acceptable diluent or excipient. Example 33. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is caused by a Coxsackievirus. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is caused by a poliovirus. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is caused by an echovirus. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is caused by an enterovirus. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is caused by a rhinovirus. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is caused by a picornavirus. A compound, a pharmaceutically acceptable salt thereof, or an optical isomer thereof as described in the examples herein, or a pharmaceutical composition as described in the examples herein, wherein the viral disease is poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand, foot and mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, influenza, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media. Example 34. Use of a compound of Formula I to III or any one of the compounds in the examples herein, or a pharmaceutically acceptable salt thereof, or an optical isomer thereof, for the prevention or treatment of a viral disease. Example 35. Use as in the examples herein, wherein the viral disease is caused by a Coxsackievirus. Example 36. Use as in the examples herein, wherein the viral disease is caused by a poliovirus. Example 37. Use as in the examples herein, wherein the viral disease is caused by an echovirus. Example 38. Use as in the examples herein, wherein the viral disease is caused by an enterovirus. Example 39. Use as in the examples herein, wherein the viral disease is caused by a rhinovirus. Example 40. Use as in the examples herein, wherein the viral disease is caused by a picornavirus. Example 41. The use as described in the examples herein, wherein the viral disease is poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand, foot and mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, influenza, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis or otitis media. These compounds are novel and suitable for use as intermediates in the preparation of the compounds of formulas (I)-(III) described herein. Another embodiment of the present invention provides a compound as described above, or a pharmaceutically acceptable salt thereof, as an agent. The use of the compound of formula (I) or a pharmaceutically acceptable salt thereof is also within the scope of the present invention. It is used in the manufacture of an agent for the treatment or prevention of viral diseases and / or infections in humans. The scope of the present invention includes a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. According to another aspect of this embodiment, the pharmaceutical composition according to the present invention further comprises a therapeutically effective amount of at least one other antiviral agent. The present invention also provides the use of the pharmaceutical composition as described above for the treatment of a viral infection or other virus in a human who is suffering from or at risk of suffering from an infection. The present invention also provides the use of the pharmaceutical composition as described above for the treatment of a viral disease or other viral infection in a human who is suffering from or at risk of suffering from a disease. Another aspect of the present invention relates to a method for treating or preventing a viral disease and / or infection in a human by administering to the human an antiviral effective amount of the compound of the present invention, a pharmaceutically acceptable salt thereof, or the composition described above, alone or in combination with at least one other antiviral agent, either together or separately. Another aspect of the present invention refers to a product comprising a composition that can effectively treat a herpesvirus disease and / or infection; and a packaging material comprising a label indicating that the composition can be used to treat a disease and / or infection caused by a virus; wherein the composition comprises a compound of formula (I) according to the present invention or a pharmaceutically acceptable salt thereof. Another aspect of the present invention relates to a method for inhibiting virus replication, which comprises exposing a virus to an effective amount of a compound of formula (I) or a salt thereof under conditions that inhibit virus replication. This method can be carried out in vitro or in vivo. The scope of the present invention further includes the use of a compound of formula (I) or a salt thereof for inhibiting virus replication. In one embodiment, the present invention provides a pharmaceutical composition comprising a compound of the present invention and an additional (multiple) therapeutic agent. As described above, the pharmaceutical composition may optionally comprise a pharmaceutically acceptable carrier. In some embodiments, the compound of formula (I) is co-administered with at least one additional agent selected from including another antiviral agent. These additional agents can be combined with the compound of the present invention to produce a single pharmaceutical dosage form. Alternatively, these additional agents can be part of a multi-dose form, for example, administered to a patient separately using a kit. Such additional agents can be administered to the patient before, simultaneously with, or after the administration of the compound of the present invention or its pharmaceutically acceptable salt. The daily applicable dosage range of the compound of the present invention is generally 0.01 to 100 mg / kg body weight, for example, 0.1 to 50 mg / kg body weight. Each dosage unit preferably may contain 5% to 95% active compound (w / w). Sometimes such preparations contain 20% to 80% active compound. Of course, the actual pharmaceutically effective amount or therapeutic dosage will depend on factors known to those skilled in the art, such as the age and weight of the patient, the route of administration, and the severity of the disease. In any case, the combination will be administered in a dosage and manner that permits delivery of a pharmaceutically effective amount based on the unique condition of the patient. When the composition of the present invention comprises a combination of a compound of the present invention and one or more additional therapeutic or prophylactic agents, both the compound and the additional agent should be present in a dosage content between about 10% and 100%, and sometimes between about 10% and 80% of the dosage normally administered in a single therapy regimen. Antiviral agents contemplated for such combination therapies include agents (compounds or biologics) that are effective in inhibiting the formation and / or replication of viruses in humans, including (but not limited to) agents that interfere with host or viral mechanisms necessary for virus formation and / or replication in humans. The various compounds of the present invention contain one or more chiral centers. These compounds can be made and used as single isomers or mixtures of isomers. Methods for separating isomers, including diastereoisomers and enantiomers, are known in the art, and examples of suitable methods are described herein. In certain embodiments, the compounds of the present invention are used as substantially pure single isomers, meaning that at least 90% of the compound sample is the designated isomer and less than 10% of the sample is any other isomer or mixture of isomers. In some embodiments, at least 95% of the sample is a single isomer. The selection of the appropriate isomer is within the scope of ordinary skill in the art, as one isomer typically has higher activity in the in vitro assay of herpesvirus DNA polymerase described herein and will be the single isomer. When the difference in in vitro activity between isomers is relatively small, for example, less than about 4-fold, a single isomer can be selected based on the degree of activity against virus replication in cell culture using methods such as those described herein: for example, the isomer with the lower IC-50 or EC-50. The compounds of the present invention can be synthesized by the following general synthetic routes, specific examples of which are described in more detail in the examples. The present invention also provides methods for preparing the compounds of formula I as described herein and intermediates suitable for the preparation of compounds of formula (I). Accordingly, the present invention also includes a method for preparing a compound of formula (I). The present invention further includes any variations of the methods of the present invention, where intermediate products obtainable at any stage thereof are used as starting materials and the remaining steps are carried out, or where the starting materials are formed in situ under the reaction conditions, or where the reaction components are used in the form of their salts or optically pure substances. The present invention also relates to methods in which compounds obtainable as intermediates at any stage of the method are used as starting materials and the remaining method steps are carried out, or where the starting materials are formed under the reaction conditions or used in derivative form (e.g., in protected form or in the form of salts), or in forms that produce compounds obtainable by the methods of the present invention under the method conditions and are further processed in situ. The term "optical isomer" or "stereoisomer" refers to any of the various stereoisomeric configurations that can exist for a given compound of the invention and includes geometric isomers. It is understood that substituents can be attached at the chiral centers of carbon atoms. The term "chiral" refers to a molecule that has the property of non-superimposability on its mirror image counterpart, while the term "achiral" refers to a molecule that can be superimposed on its mirror image counterpart. Thus, the invention includes enantiomers, diastereomers or racemates of the compounds. "Enantiomers" are a pair of stereoisomers that are non-superimposable mirror images of each other. A 1:1 mixture of a pair of enantiomers is a "racemic" mixture. This term is used to indicate a racemic mixture when appropriate. "Diastereomers" are stereoisomers that have at least two asymmetric atoms but are not mirror images of each other. Absolute stereochemistry is assigned according to the Cahn-Ingold-Prelog R-S system. When the compound is a pure enantiomer, the stereochemistry at each chiral carbon can be designated as R or S. An analytical compound of unknown absolute configuration can be designated as (+) or (-) depending on the direction (right or left) in which it rotates plane-polarized light at the wavelength of the sodium D line. Some of the compounds described herein contain one or more asymmetric centers or axes and can thus give rise to enantiomers, diastereomers and other stereoisomeric forms, which in terms of absolute stereochemistry can be defined as (R)- or (S)-. Depending on the choice of starting materials and procedures, the compounds may exist in the form of one or more of the possible isomers or mixtures thereof, for example in the form of pure optical isomers, or in the form of mixtures of isomers such as racemates and mixtures of diastereomers (depending on the number of asymmetric carbon atoms). The invention is intended to include all such possible stereoisomers, including racemic mixtures, mixtures of diastereomers and optically pure forms. The optically active (R)- and (S)-isomers can be prepared using chiral synthons or chiral reagents or resolved using conventional techniques. If the compound contains a double bond, the substituents can be in the E or Z configuration. If the compound contains a disubstituted cycloalkyl group, the cycloalkyl substituents can have a cis or trans configuration. All tautomeric forms are also intended to be included. Any resulting mixture of isomers can be separated into pure or substantially pure geometric or optical isomers or diastereomers based on the physicochemical differences of the components, for example by chromatography and / or fractional crystallization. Any racemate of the final product or intermediate can be resolved into its enantiomers by known methods, for example, by separating its diastereomeric salts (which are obtained with an optically active acid or base), and releasing the optically active acidic or basic compound. In particular, the basic moiety can thus be used to resolve the compounds of the present invention into their enantiomers, for example, by fractional crystallization of salts formed from an optically active acid (such as tartaric acid, dibenzoyl tartaric acid, diacetyl tartaric acid, di - O,O'-p - toluoyl tartaric acid, mandelic acid, malic acid or camphor - 10 - sulfonic acid). The racemic product can also be resolved by chiral chromatography, for example, by high - performance liquid chromatography (HPLC) using a chiral adsorbent. In addition, the compounds of the present invention (including their salts) can also be obtained in the form of their hydrates, or include other solvents used for their crystallization. The compounds of the present invention can inherently or be designed to form solvates with pharmaceutically acceptable solvents (including water); thus, the present invention is intended to cover both solvated and non - solvated forms. The term "solvate" refers to a molecular complex of a compound of the present invention (including its pharmaceutically acceptable salts) with one or more solvent molecules. Such solvent molecules are those commonly used in pharmaceutical technology and are known to be harmless to the recipient, such as water, ethanol and the like. The term "hydrate" refers to a complex in which the solvent molecule is water. The compounds of the present invention, including their salts, hydrates and solvates, can inherently or be designed to form polymorphs. As used herein, the term "salt" refers to an acid addition salt or a base addition salt of a compound of the present invention. "Salt" particularly includes "pharmaceutically acceptable salts". The term "pharmaceutically acceptable salts" refers to salts that retain the biological utility and properties of the compounds of the present invention and are generally biologically or otherwise desirable. In many cases, the compounds of the present invention are capable of forming acid salts and / or base salts by virtue of the presence of amino and / or carboxyl groups or their analogs. Pharmaceutically acceptable acid addition salts can be formed from inorganic acids and organic acids, such as acetates, aspartates, benzoates, benzenesulfonates, bromides / hydrobromides, bicarbonates / carbonates, bisulfates / sulfates, camphorsulfonates, chlorides / hydrochlorides, chlortheophyllonates, citrates, edisylates, fumarates, glucoheptonates, glucuronates, lactates, lactobionates, lauryl sulfates, malates, maleates, malonates, mandelates, mesylates, methyl sulfates, naphthoates, naphthalenesulfonates, nicotinates, nitrates, octadecanoates, oleates, oxalates, palmitates, pamoates, phosphates / hydrogen phosphates / dihydrogen phosphates, polygalacturonates, propionates, stearates, succinates, sulfosalicyclates, tartrates, toluenesulfonates, and trifluoroacetates. Inorganic acids from which the salts can be derived include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and similar acids. Organic acids from which the salts can be derived include, for example, acetic acid, propionic acid, glycolic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, sulfosalicylic acid, and similar acids. Pharmaceutically acceptable base addition salts can be formed from inorganic bases and organic bases. Inorganic bases from which the salts can be derived include, for example, ammonium salts and metals from rows I through XII of the periodic table. In certain embodiments, the salts are derived from sodium, potassium, ammonium, calcium, magnesium, iron, silver, zinc, and copper; particularly suitable salts include ammonium salts, potassium salts, sodium salts, calcium salts, and magnesium salts. Organic bases from which the salts can be derived include, for example, primary amines, secondary amines, and tertiary amines; substituted amines including naturally occurring substituted amines; cyclic amines; basic ion exchange resins, and the like. Some organic amines include isopropylamine, benzathine, choline, diethanolamine, diethylamine, lysine, meglumine, piperazine, and tromethamine. The pharmaceutically acceptable salts of the present invention can be synthesized from basic or acidic moieties by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid form of these compounds with a stoichiometric amount of a suitable base, such as hydroxides, carbonates, bicarbonates or the like of Na, Ca, Mg or K, or by reacting the free base form of these compounds with a stoichiometric amount of a suitable acid. These reactions are generally carried out in water or an organic solvent, or in a mixture of both. Generally, when practicable, a non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile is used. A listing of other suitable salts can be found, for example, in "Remington's Pharmaceutical Sciences", 20th Edition, Mack Publishing Company, Easton, Pa., (1985); and in "Handbook of Pharmaceutical Salts: Properties, Selection, and Use", Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002). Any formula given herein is intended to represent both the unlabeled and isotopically labeled forms of the compounds of the present invention having at most three atoms in a non-natural isotopic distribution, e.g., deuterium-rich or 13 C or 15 sites of N. Except that one or more atoms are replaced by atoms having a selected atomic mass or mass number (other than the natural abundance mass distribution), the isotopically labeled compounds have the structures depicted by the chemical formulas given herein. Examples of isotopes that can be beneficially incorporated into the compounds of the present invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as 2 H, 3 H, 11 C, 13 C, 14 C, 15 N, 18 F, 31 P, 32 P, 35 S, 36Cl, 125 I. The present invention includes various isotopically labeled compounds of the present invention, such as radioactive isotopes (such as 3 H and 14 C) or non-radioactive isotopes (such as 2 H and 13 C) present at substantially higher levels than normal isotope distributions. Such isotopically labeled compounds are suitable for metabolic studies (using, for example, 14 C); reaction kinetics studies (using, for example, 2 H or 3 H); detection or imaging techniques, such as positron emission tomography (PET) or single photon emission computed tomography (SPECT), including drug or substrate tissue distribution analysis; or suitable for radioactive treatment of patients. In particular, the 18 F-labeled compounds of the present invention may be particularly required for PET or SPECT studies. The isotopically labeled compounds of the present invention can generally be prepared by conventional techniques known to those skilled in the art or by methods similar to those described in the accompanying examples and preparations, using appropriate isotopically labeled reagents in place of the unlabeled reagents usually used. The labeled samples can be applicable at relatively low isotope incorporations, such as when radioactive labeling is used to detect trace amounts of the compound. In addition, more broadly, heavier isotopes (especially deuterium (i.e., 2Replacement with H or D)) can result in certain therapeutic advantages due to greater metabolic stability, such as an extended in vivo half-life or reduced dose requirements or improved therapeutic index. It should be understood that deuterium is considered a substituent of the compounds of the present invention in this context, and a sample of a compound having deuterium as a substituent typically has at least 50% deuterium incorporation at the labeled position. The concentration of such heavier isotopes (especially deuterium) can be defined by the isotopic enrichment factor. As used herein, the term "isotopic enrichment factor" means the ratio between the isotopic abundance of a specified isotope and its natural abundance. If a substituent in a compound of the present invention is labeled with deuterium, the isotopic enrichment factor for each specified deuterium atom in such a compound is respectively at least 3500 (52.5% deuterium incorporation at each specified deuterium atom), at least 4000 (60% deuterium incorporation), at least 4500 (67.5% deuterium incorporation), at least 5000 (75% deuterium incorporation), at least 5500 (82.5% deuterium incorporation), at least 6000 (90% deuterium incorporation), at least 6333.3 (95% deuterium incorporation), at least 6466.7 (97% deuterium incorporation), at least 6600 (99% deuterium incorporation) or at least 6633.3 (99.5% deuterium incorporation). Pharmaceutically acceptable solvates according to the present invention include solvates in which the solvent of crystallization can be isotopically substituted, such as D 2 O, d 6 -acetone, d 6 -DMSO. Compounds of the present invention containing groups capable of acting as donors and / or acceptors of hydrogen bonds may be capable of forming co-crystals with suitable co-crystal formers. Such co-crystals can be prepared from the compounds of the present invention by known co-crystal formation procedures. Such procedures include grinding, heating, co-sublimation, co-melting or contacting the compounds of the present invention with a co-crystal former together under crystallization conditions in solution, and separating the co-crystals thus formed. Suitable co-crystal formers include those described in WO 2004 / 078163. Accordingly, the present invention further provides co-crystals comprising the compounds of the present invention. Unless otherwise specified herein or clearly inconsistent with the context, all methods described herein can be carried out in any suitable order. Use of any and all examples or illustrative language (such as "such as") provided herein is merely intended to better illustrate the invention and does not impose a limitation on the scope of the invention otherwise claimed. The compounds of the present invention can be administered by known methods, including oral, parenteral, inhalation and similar methods. In certain embodiments, the compounds of the present invention are administered orally in the form of pills, lozenges, tablets, capsules, solutions or suspensions. In other embodiments, the compounds of the present invention are administered by injection or infusion. Infusion is usually carried out intravenously, usually over a period of between about 15 minutes and 4 hours. In other embodiments, the compounds of the present invention are administered intranasally or by inhalation; inhalation methods are particularly suitable for treating respiratory infections. The compounds of the present invention exhibit oral bioavailability, and thus in some embodiments, the compounds can be administered orally. The compounds of the present invention can also be used in combination with other agents (combination formulations), such as other antiviral agents of formula I or non-formula I, to treat viral infections in an individual. The term "combination" means a fixed combination of a unit dosage form, individual dosage forms suitable for simultaneous or sequential use, or a kit of aliquots for combined administration, wherein the compound of the present invention and the combination formulation can be administered independently simultaneously or separately at time intervals that particularly allow the combination formulation to exhibit a cooperative (e.g., synergistic) effect, or any combination thereof. In certain embodiments of the present invention, the compounds of the present invention are used in combination with a second antiviral agent, such as those presented herein. The second antiviral agent can be administered in combination with the compound of the present invention, wherein the second antiviral agent is administered before, simultaneously with or after one or more compounds of the present invention. When it is necessary to administer the compound of the present invention and the second agent simultaneously and by the same route of administration, the compound of the present invention can be formulated into the same dosage form with the second agent. Examples of dosage forms containing the compound of the present invention and the second agent are tablets or capsules. In some embodiments, the combination of the compound of the present invention and the second antiviral agent can provide synergistic activity. The compound of the present invention and the second antiviral agent can be administered together, separately but simultaneously or sequentially. An "effective amount" of a compound is an amount necessary or sufficient to treat or prevent a viral infection and / or the diseases or conditions described herein. In one example, an effective amount of a viral inhibitor of formula I is an amount sufficient to treat a viral infection in an individual. In another example, an effective amount of an inhibitor is an amount sufficient to treat a viral infection in an individual in need of such treatment. The effective amount can vary depending on factors such as the size and weight of the individual, the type of disease or the particular compound of the present invention. For example, the selection of the compound of the present invention can affect the elements that constitute an "effective amount". One of ordinary skill in the art will be able to study the factors contained herein and determine the effective amount of the compound of the present invention without undue experimentation. The dosing regimen can affect the elements that constitute an effective amount. The compounds of the present invention can be administered to an individual before or after the onset of a viral infection. In addition, several divided doses and staggered doses can be administered daily or sequentially, or the dose can be continuously infused, or a single rapid injection can be given. Further, the dose of the compounds of the present invention can be increased or decreased proportionally as indicated by the exigencies of the treatment or prophylactic situation. The compounds of the present invention can be used to treat the conditions, disorders or diseases as described herein, or for manufacturing a pharmaceutical composition for treating such diseases. The present invention provides methods of using the compounds of the present invention to treat such diseases or to prepare a pharmaceutical composition having the compounds of the present invention for treating such diseases. The term "pharmaceutical composition" includes formulations suitable for administration to a mammal (such as a human). When the compounds of the present invention are administered to a mammal, such as a human, as a pharmaceutical composition, they can be provided by themselves or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (such as 0.5 to 90%) of at least one compound of formula (I) or any subgenus thereof as an active ingredient and a pharmaceutically acceptable carrier, or optionally two or more pharmaceutically acceptable carriers. The phrase "pharmaceutically acceptable carrier" is recognized in the art and includes pharmaceutically acceptable materials, compositions or media suitable for administering the compounds of the present invention to a mammal. Carriers include liquid or solid fillers, diluents, excipients, solvents or encapsulating materials that participate in carrying or transporting an individual agent from one organ or part of the body to another organ or part of the body. Each carrier should be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to its patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository wax; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; diols, such as propylene glycol; polyols, such as glycerol, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethanol; phosphate buffer solution; and other non-toxic compatible substances used in pharmaceutical formulations. Generally, pharmaceutically acceptable carriers are sterile and / or substantially pyrogen-free. Wetting agents, emulsifying agents and lubricants (such as sodium lauryl sulfate and magnesium stearate), as well as coloring agents, release agents, coating agents, sweetening agents, flavoring agents and fragrances, preservatives and antioxidants may also be present in the composition. Examples of pharmaceutically acceptable antioxidants include: water-soluble antioxidants such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite and the like; oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol and the like; and metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid and the like. The formulations of the present invention include formulations suitable for oral, nasal, inhalation, topical, transdermal, buccal, sublingual, rectal, vaginal and / or parenteral administration. The formulations are preferably presented in unit dosage forms and can be prepared by any method well known in the pharmaceutical art. The amount of the active ingredient that can be combined with the carrier material to produce a single dosage form will generally be the amount of the compound that produces a therapeutic effect. Generally, in 100%, this amount will be in the range of about 1% to about 99%, often about 5% to about 70%, often about 10% to about 30% of the active ingredient. The methods for preparing such formulations or compositions include the step of combining the compounds of the present invention with a carrier and optionally one or more accessory ingredients. Generally, the formulations are prepared by uniformly and intimately combining the compounds of the present invention with a liquid carrier or a finely divided solid carrier or both and then shaping the product if necessary. The formulations of the present invention suitable for oral administration can be in the form of capsules, cachets, pills, tablets, lozenges (using a flavoring base such as usually sucrose and acacia or tragacanth), powders, granules, or in the form of solutions or suspensions in aqueous or non-aqueous liquids, or in the form of water-in-oil or oil-in-water liquid emulsions, or in the form of elixirs or syrups, or in the form of tablets (using an inert base such as gelatin and glycerol, or sucrose and acacia) and / or in the form of mouthwashes and the like, each containing a predetermined amount of the compound of the present invention as the active ingredient. The compounds of the present invention can also be administered in the form of boluses, pastilles or pastes. In the solid dosage forms for oral administration (capsules, tablets, pills, dragees, powders, granules and the like) of the present invention, the active ingredient is admixed with one or more pharmaceutically acceptable carriers such as sodium citrate or dibasic calcium phosphate and / or any of the following: fillers or extenders such as starch, lactose, sucrose, glucose, mannitol and / or silicic acid; binders such as carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose and / or acacia; humectants such as glycerol; disintegrants such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; solution retarders such as paraffin; absorption promoters such as quaternary ammonium compounds; wetting agents such as cetyl alcohol and glycerol monostearate; adsorbents such as kaolin and bentonite; lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate and mixtures thereof; and coloring agents. In the case of capsules, tablets and pills, the pharmaceutical compositions may also contain buffering agents. Excipients such as lactose (lactose / milk sugar) and high molecular weight polyethylene glycols and the like can also be used to use solid compositions of a similar type as fillers in soft-fill and hard-fill gelatin capsules. Tablets can be manufactured by compressing or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared using binders (such as gelatin or hydroxypropylmethyl cellulose), lubricants, inert diluents, preservatives, disintegrants (such as sodium starch glycolate or croscarmellose sodium), surfactants or dispersing agents. Molded tablets can be manufactured by molding in a suitable machine a mixture of powdered compounds moistened with an inert liquid diluent. Tablets and other solid dosage forms (such as dragees, capsules, pills and granules) of the pharmaceutical compositions of the present invention can optionally be scored or prepared with coatings and shells such as enteric coatings and other coatings well known in pharmaceutical formulation techniques. It can also be formulated using, for example, hydroxypropylmethyl cellulose, other polymeric matrices, liposomes and / or microspheres in different proportions to provide the desired release characteristics so as to provide slow or controlled release of the active ingredient therein. It can be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporating a sterilizing agent, in the form of a sterile solid composition that is soluble in sterile water or some other sterile injectable medium immediately before use. These compositions may also optionally contain emulsifying agents and can be compositions that release the active ingredient only, or for example in a delayed manner, in a part of the gastrointestinal tract. Examples of embedding compositions that can be used include polymeric materials and waxes. The active ingredient can also be in microencapsulated form, if appropriate, together with one or more of the above excipients. Liquid dosage forms for oral administration of the compounds of the present invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. Besides the active ingredient, the liquid dosage forms may also contain inert diluents commonly used in the art (such as water or other solvents), solubilizers, and emulsifying agents, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3 - butanediol, oils (specifically, cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan and their mixtures. In addition to the inert diluent, the oral compositions may also include adjuvants such as wetting agents, emulsifying agents, and suspending agents, sweetening agents, flavoring agents, coloring agents, aromatic agents, and preservatives. In addition to the active compound, the suspension may contain suspending agents in the form of, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol, and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar - agar, and tragacanth and their mixtures. The pharmaceutical compositions of the present invention for rectal or vaginal administration may be presented in the form of suppositories, which may be prepared by mixing one or more compounds of the present invention with one or more suitable non - irritating excipients or carriers (including, for example, cocoa butter, polyethylene glycol, suppository wax, or salicylate esters), and which are solid at room temperature but liquid at body temperature and thus melt in the rectal or vaginal cavity and release the active compound. The formulations of the present invention suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams, or spray formulations containing suitable carriers known in the art. Dosage forms for topical or transdermal administration of the compounds of the present invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compound can be mixed under sterile conditions with a pharmaceutically acceptable carrier and with any preservatives, buffers, or propellants that may be required. In addition to the active compounds of the present invention, ointments, pastes, creams, and gels may contain excipients such as animal and vegetable fats, oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, polysiloxane, bentonite, silica, talc, and zinc oxide, or mixtures thereof. In addition to the compounds of the present invention, powders and sprays may contain excipients such as lactose, talc, silica, aluminum hydroxide, calcium silicate, and polyamide powder or mixtures of these substances. Sprays may additionally contain conventional propellants such as chlorofluorocarbons and volatile unsubstituted hydrocarbons such as butane and propane. The transdermal patch has the additional advantage of providing controlled delivery of the compounds of the present invention to the body. Such dosage forms can be manufactured by dissolving or dispersing the compounds in a suitable medium. Penetration enhancers can also be used to increase the amount of the compound that penetrates the skin. The rate of the flux can be controlled by providing a rate-controlling membrane or by dispersing the active compound in a polymeric matrix or a gel. Ophthalmic formulations, eye ointments, powders, solutions and the like are also covered by the scope of the present invention. The pharmaceutical compositions of the present invention suitable for parenteral administration can comprise one or more compounds of the present invention in combination with one or more pharmaceutically acceptable carriers (such as sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions or emulsions) or sterile powders that can be reconstituted into sterile injectable solutions or dispersions only immediately before use. Such compositions can contain antioxidants, buffers, bacteriostatic agents, solutes or suspending or thickening agents that render the formulation isotonic with the blood of the intended recipient. Examples of suitable aqueous and non-aqueous carriers that can be used in the pharmaceutical compositions of the present invention include water, ethanol, glycol ethers, polyols (such as glycerol, propylene glycol, polyethylene glycol and the like) and their suitable mixtures, vegetable oils (such as olive oil) and injectable organic esters (such as ethyl oleate). Appropriate fluidity can be maintained, for example, by using coating materials (such as lecithin), by maintaining the desired particle size in the case of dispersions and by using surfactants. These compositions can also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of microbial action can be ensured by including various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid and the like. It may also be necessary to include isotonic agents such as sugars, sodium chloride and the like in the composition. In addition, prolonged absorption of injectable pharmaceutical forms can be achieved by including agents that delay absorption (such as aluminum monostearate and gelatin). In some cases, to prolong the action of a drug, it is necessary to slow down the absorption of the drug injected subcutaneously or intramuscularly. This can be achieved by using a liquid suspension of crystalline or amorphous substances with poor water solubility. The rate of drug absorption depends on its dissolution rate, which in turn can depend on crystal size and crystalline form. Alternatively, delayed absorption of parenterally administered drug forms is achieved by dissolving or suspending the drug in an oily vehicle. Injectable depot forms are manufactured by forming a microcapsule matrix of the subject compound in a biodegradable polymer such as poly(lactide-co-glycolide). Depending on the ratio of the drug to the polymer and the nature of the particular polymer used, the drug release rate can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Injectable depot formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues. The preparation of the present invention can be administered orally, parenterally, topically or rectally. It is of course administered in a form suitable for each administration route. For example, it is administered in the form of tablets or capsules, by injection, inhalation, eye wash, ointment, suppository, etc., by injection, infusion or inhalation; topically administered by wash or ointment; and rectally administered by suppository. As used herein, the phrase "parenteral administration / administered parenterally" means a mode of administration other than enteral and topical administration, usually by injection, and includes (but is not limited to) intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, intratracheal, subcutaneous, subepidermal, intra-articular, subcapsular, subarachnoid, intraspinal and intrasternal injections and infusions. Intravenous infusion is sometimes the preferred method for delivering the compounds of the present invention. Infusion can be used to deliver a single daily dose or multiple doses. In some embodiments, the compounds of the present invention are administered by infusion at time intervals between 15 minutes and 4 hours, typically between 0.5 and 3 hours. The infusion can be used once a day, twice a day or up to three times a day. As used herein, the phrases "systemic administration / administered systemically" and "peripheral administration / administered peripherally" mean that a compound, drug or other material is not directly administered to the central nervous system, such that it enters the patient's system and is thus subject to metabolism and other similar processes, such as subcutaneous administration. These compounds can be administered to humans and other animals by any suitable route of administration for treatment, including orally, nasally (such as by aerosol, for example), rectally, intravaginally, parenterally, intracisternally and topically (such as by powder, ointment or drops, including buccal and sublingual). Regardless of the selected route of administration, the compounds of the present invention and / or the pharmaceutical compositions of the present invention in a suitable hydrated form are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those skilled in the art. The actual dosage content of the active ingredient in the pharmaceutical composition of the present invention can be varied so that the amount of the active ingredient is effective to achieve the desired therapeutic response for a particular patient, composition and mode of administration and is non-toxic to the patient. The selected dosage amount depends on various factors, including the activity of the specific compound of the present invention or its ester, salt or amide used; the route of administration; the time of administration; the excretion rate of the specific compound used; the duration of treatment; other drugs, compounds and / or materials used in combination with the specific compound; the age, sex, weight, condition, general health and previous medical history of the patient being treated; and similar factors well known in the medical arts. A physician or veterinarian of ordinary skill in the art can readily determine and prescribe the effective amount of the required pharmaceutical composition. For example, a physician or veterinarian can start with a dose of the compound of the present invention for the pharmaceutical composition that is less than the amount required to achieve the desired therapeutic effect and gradually increase the dose until the desired effect is achieved. Generally, the suitable daily dose of the compound of the present invention is the amount of the compound that is the lowest dose effective to produce a therapeutic effect. This effective dose generally depends on the above factors. Generally, the intravenous and subcutaneous doses of the compound of the present invention for a patient range from about 0.0001 to about 100 mg / kg body weight / day, often about 0.01 to about 50 mg / kg / day, and still often about 0.1 to about 20 mg / kg / day when used for the designated effect. The effective amount is the amount that prevents or treats a viral infection. If necessary, the effective daily dose of the active compound can be administered as a single dose per day, or, as appropriate, in unit dosage forms at appropriate intervals within a day in two, three, four, five, six or more sub-doses. Compounds delivered orally or by inhalation are usually administered in one to four doses per day. Compounds delivered by injection are usually administered once a day or once every other day. Compounds delivered by infusion are usually administered in one to three doses per day. When multiple doses are administered within a day, the doses can be administered at intervals of about 4 hours, about 6 hours, about 8 hours or about 12 hours. Although the compounds of the present invention are potentially administered alone, the compounds are sometimes administered in the form of a pharmaceutical composition, such as the pharmaceutical compositions described herein. Accordingly, methods of using the compounds of the present invention include administering the compound in a pharmaceutical composition, wherein at least one compound of the present invention is admixed with a pharmaceutically acceptable carrier prior to administration. General synthetic procedures The compounds described herein can be synthesized by the following general synthetic routes, specific examples of which are described in more detail in the examples. All starting materials, building blocks, reagents, acids, bases, dehydrating agents, solvents, and catalysts used for synthesizing the compounds of the present invention are commercially available or can be produced by organic synthesis methods known to those of ordinary skill in the art (Houben-Weyl, 4th Edition, 1952, Methods of Organic Synthesis, Thieme, Volume 21). List of Abbreviations Ac Acetyl ACN or MeCN Acetonitrile AcOEt / EtOAc Ethyl acetate AcOH Acetic acid Aq Aqueous / aqueous solution Bn Benzyl Bu Butyl (nBu = n-butyl, tBu = tert-butyl) CDI Carbonyl diimidazole CH 3 CN Acetonitrile DBU 1,8-Diazabicyclo[5.4.0]-undec-7-ene Boc 2 O Di-tert-butyl dicarbonate DCE 1,2-Dichloroethane DCM Dichloromethane DIAD Diisopropyl azodicarboxylate DiBAl-H Diisobutylaluminum hydride DIPEA or DIEA N-Ethyldiisopropylamine DMA N,N-Dimethylacetamide DMAP 4-Dimethylaminopyridine DMF N,N-Dimethylformamide DMSO Dimethyl sulfoxide EDC 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide EI Electrospray ionization Et 2 O Diethyl ether Et 3 N Triethylamine Ether Diethyl ether EtOAc Ethyl acetate EtOH Ethanol FC Flash chromatography h Hour HATU O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyl HBTU O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyl HCl Hydrochloric acid HMPA Hexamethylphosphoramide HOBt 1-Hydroxybenzotriazole HPLC High performance liquid chromatography H 2 O Water IPA Isopropyl alcohol L Liter LC-MS Liquid chromatography-mass spectrometry LiHMDS Lithium bis(trimethylsilyl)amide MgSO 4 Magnesium sulfate Me Methyl MeI Methyl iodide MeOH Methanol mg Milligram min Minutes mL Milliliter MS Mass spectrometry MsCl Methanesulfonyl chloride NaHCO 3 Sodium hydrogen carbonate Na 2 SO 4 Sodium sulfate NH 2 OH Hydroxylamine Pd / C Palladium on carbon Pd(OH) 2 Palladium hydroxide PG Protecting group Ph Phenyl Ph 3 P Triphenylphosphine Prep Preparative Rf Front ratio RP Reverse phase Rt Retention time RT Room temperature SFC Supercritical fluid chromatography SiO 2 Silica gel SOCl 2 Thionyl chloride T3P® Propylphosphonic anhydride TBAF Tetrabutylammonium fluoride TBDMS Tert-butyldimethylsilyl TBTU O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyl TEA Triethylamine TFA Trifluoroacetic acid THF Tetrahydrofuran TLC Thin layer chromatography TsCl Tosyl chloride TsOH p-Toluenesulfonic acid The compounds of the present invention are prepared from commonly available compounds using procedures known to those skilled in the art in view of the examples and protocols provided herein. Within the scope of this text, unless the context indicates otherwise, only those removable groups that are not components of the specific desired end products of the compounds of the invention are designated as "protecting groups". The protection of functional groups by such protecting groups, the protecting groups themselves, and their cleavage reactions are described, for example, in standard reference works such as: Science of Synthesis: Houben-Weyl Methods of Molecular Transformation. Georg Thieme Verlag, Stuttgart, Germany. 2005. p. 41627 (URL: http: / / www.science-of-synthesis.com (Electronic Version, Vol. 48)); J. F. W. McOmie, "Protective Groups in Organic Chemistry", Plenum Press, London and New York 1973, in T. W. Greene and P. G. M. Wuts, "Protective Groups in Organic Synthesis", 3rd Edition, Wiley, New York 1999, in "The Peptides"; Vol. 3 (editors: E. Gross and J. Meienhofer), Academic Press, London and New York 1981, in "Methoden der Organischen Chemie" (Methods of Organic Chemistry), Houben Weyl, 4th Edition, Vol. 15 / I, Georg Thieme Verlag, Stuttgart 1974, in H.-D. Jakubke and H.Jeschkeit, 「Aminosäuren, Peptide, Proteine」 (Amino acids, Peptides, Proteins), Verlag Chemie, Weinheim, Deerfield Beach, and Basel 1982, and in Jochen Lehmann, 「Chemie der Kohlenhydrate: Monosaccharide und Derivate」 (Chemistry of Carbohydrates: Monosaccharides and Derivatives), Georg Thieme Verlag, Stuttgart 1974. The protecting groups are characterized in that they can be removed easily, for example, by solvolysis, reduction, photolysis or under physiological conditions (e.g., by enzymatic cleavage) (i.e., without occurring unwanted side reactions). The salts of the compounds of the invention having at least one salt-forming group can be prepared in a manner known per se. For example, the salts of the compounds of the invention having an acid group can be formed, for example, by treating the compounds of the invention with a metal compound (such as an alkali metal salt of a suitable organic carboxylic acid, e.g., the sodium salt of 2-ethylhexanoic acid), an organic alkali metal or alkaline earth metal compound (such as the corresponding hydroxide, carbonate or bicarbonate, such as sodium hydroxide or potassium hydroxide, and the corresponding calcium compound or ammonia or the carbonate or bicarbonate of a suitable organic amine), often using stoichiometric amounts or only a small excess of the salt-forming reagent. The acid addition salts of the compounds of the invention are obtained in a conventional manner, for example, by treating the compound with an acid or a suitable anion exchange reagent. The internal salts of the compounds of the invention containing acid and basic salt-forming groups (such as free carboxyl and free amino groups) can be formed, for example, by neutralizing a salt (such as an acid addition salt) to the isoelectric point (e.g., by neutralizing with a weak base), or by treating with an ion exchanger. The salts can be converted into the free compounds in a conventional manner; the metal and ammonium salts can be converted, for example, by treating with a suitable acid, and the acid addition salts, for example, by treating with a suitable basic reagent. Mixtures of isomers obtainable according to the invention can be separated into the individual isomers in a manner known per se; diastereoisomers can be separated, for example, by partitioning between multiphase solvent mixtures, recrystallization and / or chromatography (e.g., via silica gel) or by medium-pressure liquid chromatography, for example, via a reversed-phase column; and racemates can be separated, for example, by forming salts with an optically pure salt-forming reagent and separating the resulting mixture of diastereoisomers, for example, by fractional crystallization or by chromatography via an optically active column material. Intermediates and final products can be processed and / or purified according to standard methods, such as using chromatography, distribution, (re)crystallization, and the like. By LC-MS high-resolution mass spectrometry ESI-MS data was recorded using an LTQ-XL Orbitrap mass spectrometer (ThermoFisher Scientific) with an electrospray ionization source. The resolution of the MS system was approximately 30,000. Candidate drugs were infused from a sample probe into the mass spectrometer by UPLC (Acquity, Waters). Separation was performed on an Acquity UPLC BEH C18 1x50 mm column at a flow rate of 0.15 mL / minute in a 5% to 95% gradient over 3 minutes. Solvent A was water with 0.1% trifluoroacetic acid, and solvent B was 75% methanol and 25% isopropanol with 0.1% trifluoroacetic acid. The mass accuracy of the system was found to be <5 ppm. Examples The present invention is further illustrated by the following examples, which should not be construed as limiting. The analyses used throughout the examples are well-established in the art: the demonstration of efficacy in such analyses is generally regarded as a prediction of efficacy in an individual. The compounds of the present invention can be prepared by organic synthesis methods known to those of ordinary skill in the art with reference to the following reaction schemes and examples. The general synthetic method for the compounds of formula (I) is provided in the following scheme. Examples 1 : N-((4bR,9bR)-1- amino -4b- hydroxy -7-((1R,2R)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -4-( methylsulfonyl )-1H- Pyrrole -2- Formamide (33) : Process - 1 4- Nitroisobenzofuran -1,3- Dione (2) : The initial suspension of 3-nitrophthalic acid 1 (1.0 kg, 4.7 moles) in Ac 2 O (1 liter) was refluxed at 140 °C for 2.5 hours. Subsequently, it was cooled to 80 °C and slowly added dropwise to diethyl ether (4 liters) with vigorous stirring. The precipitate was collected by filtration through a Buckner funnel and washed with Et 2 O to obtain the product. 4- Nitro -1,3- Dioxo -2,3- Dihydro -1H- Indene -2- Ethyl carboxylate (3) : At ambient temperature, ethyl acetoacetate (42 mL, 0.31 moles) and Ac 2 O (48.5 mL, 0.52 moles) were added to a suspension of acid anhydride 2 (50 g, 0.26 moles) in dry DCM (260 mL). This suspension was charged dropwise with Et 3N (108 mL, 0.78 mol) (exothermic). Add a few mL of TEA. Stir it for an additional 15 minutes at the same temperature and then evaporate the DCM. Subsequently, dissolve the resulting crude material in 2 L of water and cool to 0 °C. Fix it with a overhead stirrer and, under vigorous stirring conditions, add dropwise 300 mL of 2 N HCl thereto, keeping the temperature below 0 °C. The precipitate begins to form slowly. Stir it for an additional 15 minutes at 0 °C and then filter it through a Buckner funnel and wash with ice-cold water (500 mL). Subsequently, air dry it for three days to obtain the solid as the product. 4- nitro -1H- indene -1,3(2H)- dione (4 ) : Place ethyl 4-nitro-1,3-dioxo-2,3-dihydro-1H-indene-2-carboxylate 3 (272.5 g, 1.04 mol) in 1 L of MeCN:water (20:1, 1.0 M). At room temperature, slowly charge TFA (60 mL, 1.14 mol) to this suspension and then maintain heating at 50 °C. After 4 hours, the reaction mass is concentrated by a rotary evaporator until approximately 100 mL of solvent remains. Subsequently, filter the precipitated solid through a Buckner funnel and wash with (1:1) CHCl 3 :hexane. The product is thus obtained and the filtrate is concentrated again to obtain more product in the second batch. 2,2- dihydroxy -4- nitro -1H- indene -1,3(2H)- dione (5) : Place 4-nitro-1H-indene-1,3(2H)-dione 4 (10.0 g, 52.3 mmol) in AcOH:dioxane (1:10, 105 mL, 0.5 M). Charge SeO 2(12.77 g, 115.1 mmol) and refluxed at 105 °C to 110 °C for 5 hours. Subsequently, the reaction mass was filtered through diatomaceous earth under hot conditions, and then the volatiles were concentrated to obtain the crude substance 2,2-dihydroxy-4-nitro-1H-indene-1,3(2H)-dione. 7- bromo -4b,9b- dihydroxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one (7) : The crude substance 2,2-dihydroxy-4-nitro-1H-indene-1,3(2H)-dione 5 was then placed in glacial acetic acid (210 mL, 0.25 mmol), and 3-bromophenol 6 (9.96 g, 57.5 mmol) was charged thereto and refluxed for an additional 12 hours. The reaction mass was concentrated and placed in EA (500 - 600 mL). It was filtered through diatomaceous earth and the residue was washed with EA. The filtrate was washed with water (200 mL × 2) and brine (100 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (35 - 40% EA / hexane) twice to obtain the pure product. 7- bromo -9b- chloro -4b- hydroxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one (8) : At room temperature, 7-bromo-4b,9b-dihydroxy-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 7 (39.5 g, 0.105 mol) was placed in DCM (520 mL, 0.2 M) and oxalyl chloride (11 mL, 0.13 mol) was charged thereto. DMF (40 mL, 0.53 mol) was slowly added thereto (0.05 mL / min for 30 min and 0.1 mL / min for 30 min, and then rapidly), and it was stirred at ambient temperature (30 °C). Subsequently, the reaction mixture was stirred at room temperature (20 °C) for another 12 hours. The reaction mixture was diluted with water (about 300 mL). The aqueous layer was extracted with DCM (about 500 mL × 2). The combined organic layers were washed with water (about 300 ml) and brine (about 300 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (10 - 30% EA / hexane) to obtain a pure product. 9b- amino -7- bromo -4b- hydroxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one (9) : 9b-Chloro-4b-hydroxy-4-nitro-8-(trifluoromethyl)-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 8 (21.2 g, 53.4 mmol) was placed in THF (530 mL, 0.1 M) and cooled to -40 o °C. At the same temperature, 2.0 M NH 3IPA (54 mL, 0.11 mmol) was added thereto and the mixture was stirred for another 3 hours. The reaction mixture was diluted with water (about 150 mL) and brine (150 mL). The aqueous layer was extracted with EA (about 300 mL × 2). The combined organic layers were washed with brine (about 100 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude material was purified by silica gel column chromatography (20 - 30% EA / hexane, with 20% DCM as co - solvent) to obtain the pure product. (7 - bromo -4b - hydroxy -4 - nitro -10 - side - oxy -4b,10 - dihydro -9bH - indeno [1,2 - b] benzofuran -9b - yl ) tert - butyl carbamate (10) : Boc anhydride (8.74 g, 40 mmol) and molecule I 2 (0.69 g, 2.67 mmol) were added to a solution of the racemic mixture of 9b - amino - 7 - bromo - 4b - hydroxy - 4 - nitro - 4b,9b - dihydro - 10H - indeno[1,2 - b]benzofuran - 10 - one 9 (10.1 g, 31 mmol) in THF (5.0 mL, 5.0 M) and the mixture was stirred at 30 °C for another 72 hours. The reaction mixture was concentrated and purified. The crude product was purified by silica gel column chromatography (10% - 30% EA / hexane, with 5 - 10% DCM) to obtain the pure product. (1 - amino -7 - bromo -4b - hydroxy -10 - side - oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) tert-Butyl carbamate (11) : The mixture of racemic (7-bromo-4b-hydroxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl) tert-butyl carbamate 10 (10.3 g, 21.5 mmol) was placed in EtOH:water (10:1, 110.0 mL, 0.20 M), and Fe powder (3.57 g, 63.9 mmol) was charged thereto, followed by concentrated HCl (0.8 mL, catalytic amount). It was refluxed at 90 °C for another 3 hours. The reaction material was filtered through diatomaceous earth using warm EA (50 - 100 mL). The filtrate was concentrated and placed in EA (about 1000 - 1200 mL), and washed with water (about 300 - 500 mL) and brine (about 300 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (10 - 30% EA / hexane) to obtain the pure product. ((4bR,9bR)-1- amino -7- bromo -4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) tert-Butyl carbamate (12) and ((4bS,9bS)-1- amino -7- bromo -4b- hydroxy -10- lateral oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group ) tert-butyl carbamate (13) :(1-Amino-7-bromo-4b-hydroxy-10-lateral oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)tert-butyl carbamate(11) (7000 mg) was purified by chiral chromatography using (AD column, HPLC = 20 ml / min, heptane / EtOH = 70 / 30, 724 psi) to obtain 3010 mg of ((4bR,9bR)-1-amino-7-bromo-4b-hydroxy-10-lateral oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)tert-butyl carbamate(12) as (peak 2, tR 15.59 min); 1H NMR (500 MHz, METHANOL-d4) δ: 7.48 (br t, J = 7.7 Hz, 1H), 7.37 (br s, 1H), 7.11 (br s, 1H), 7.02 (br d, J = 7.1 Hz, 1H), 6.95 (s, 1H), 6.72 (br s, 1H), 1.42 (br s, 5H), 1.13 (br s, 4H) LCMS: 447.2 / 449.2 [M + H] +And 3060 mg of tert-butyl ((4bS,9bS)-1-amino-7-bromo-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)carbamate (13) as (Peak 1, tR 8.97 min); 1H NMR (500 MHz, METHANOL-d4) δ: 7.48 (br t, J=7.6 Hz, 1H), 7.37 (br s, 1H), 7.11 (br s, 1H), 7.02 (br d, J=6.9 Hz, 1H), 6.95 (s, 1H), 6.72 (br s, 1H), 1.42 (br s, 5H), 1.13 (br s, 4H) LCMS: 447.2 / 449.2 [M + H] + 。 Process - 2 The intermediates (14 and 18) were prepared according to the literature reported in the following: J. Am. Chem. Soc. 2013, 135, 82−85. ((1S,2S)-2- methylcyclopropyl ) acid (15) : A solution of (4S,5S)-N4,N4,N5,N5-tetramethyl-2-((1S,2S)-2-methylcyclopropyl)-1,3,2-dioxaborolane-4,5-dicarboxamide 14 (4.21 g, 14.4 mmol) in water (145 mL) was stirred at room temperature for 12 h. The aqueous layer was extracted with ether (100 mL×3), and the combined ether layers were washed with water and dried over Na 2 SO 4 and the solvent was evaporated at low temperature to give the product. The crude material was used in the next step without purification. 6- methyl -2-((1S,2S)-2- methylcyclopropyl )-1,3,6,2- dioxazaborocane -4,8- dione (17) : To a solution of ((1S,2S)-2-methylcyclopropyl) acid 15 (800 mg, 8.0 mmol) in toluene:DMSO (80 mL) was added 2,2'-(methylazanediyl)diacetic acid 16 (1.766 mg, 12 mmol), and the resulting reaction mixture was refluxed under Dean-Stark conditions for 3 h. The toluene was evaporated in vacuo, the organic layer was diluted with water and the aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with water and dried over Na 2 SO 4 dried and the solvent was evaporated to give the crude product. The crude material was triturated with ether, the solid was filtered off and washed with ether to give the product. ((1R,2R)-2- methylcyclopropyl ) acid (19) : A solution of (4R,5R)-N4,N4,N5,N5-tetramethyl-2-((1R,2R)-2-methylcyclopropyl)-1,3,2-dioxaborinan-4,5-dicarboxamide 18 (11.3 g, 31.7 mmol, based on the starting material of the previous step) in distilled water (317 mL, 0.1 M) was stirred at room temperature for 12 h. The reaction mixture was extracted with diethyl ether (500 mL×3), the combined organic layers were washed with water (×1), dried over anhydrous Na 2 SO 4 dried and concentrated at low temperature to give the crude product. The crude product was used in the next step without purification. 6- methyl -2-((1R,2R)-2- methylcyclopropyl )-1,3,6,2- dioxazaborocane -4,8- dione (20) : To ((1R,2R)-2-methylcyclopropyl) A solution of acid 19 (6.03 g, 60.3 mmol) in toluene / DMSO (10 / 1, 300 mL / 30 mL) was added to 2,2'-(methylazanediyl)diacetic acid 16 (13.3 g, 90.5 mmol), and the mixture was then refluxed for 3 h under Dean-Stark conditions. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (500 mL). The organic layer was washed with water (200 ml×4), dried over anhydrous Na 2 SO 4 dried, filtered and concentrated. Diethyl ether was added to the residue, and the desired product was then obtained. 1 1H NMR (300 MHz, CDCl 3 ) δ 3.92 (d, J = 16.6 Hz, 2H), 3.72 (dd, J = 16.6, 4.8 Hz, 2H), 3.04 (s, 3H), 1.10 (d, J = 5.8 Hz, 3H), 0.70 (dt, J = 11.3, 5.7 Hz, 1H), 0.47 - 0.35 (m, 1H), 0.34 - 0.22 (m, 1H), -0.61 (dt, J = 9.2, 6.1 Hz, 1H). Procedure - 3 Methyl tosylglycinate (23) : Glycine methyl ester hydrochloride 21 (50.0 g, 398.2 mmol) was dissolved in DCM (800 mL). p-Toluenesulfonyl chloride 22 (75.9 g, 398.2 mmol) was then added slowly. The reaction mixture was cooled to 0 °C. DIPEA (208 mL, 1194.7 mmol) was then added slowly and the reactants were stirred at 0 °C for 10 min. The reactants were warmed to 30 °C and stirred for 18 h. The reaction was quenched with 1 N HCl, the aqueous layer was extracted with DCM (500 mL×3), and the combined organic layers were washed with water (500 mL) and brine (200 mL). The organic layer was dried over Na 2 SO 4Dry and evaporate the solvent to obtain the crude product. The crude product is purified by wet grinding with DCM:hexane to obtain the product. 3- hydroxy -3- methyl -1- tosyl pyrrolidine -2- methyl carboxylate (25) : Dissolve methyl tosylglycinate 23 (58.50 g, 240.5 mmol) and methyl vinyl ketone 24 (26 mL, 529.0 mmol) in THF (241 mL), then slowly add DBU (79 mL, 529.0 mmol), and stir the reaction mixture at room temperature (30 °C) for 12 hours. Dilute the reaction mixture with ether (1000 mL). Wash the organic phase with a solution of 1 N HCl. Once the pH of the aqueous phase is acidic, wash the organic phase with 5% Na 2 CO 3 solution and wash the organic phase with water until the pH is neutral. The organic phase is dried over anhydrous Na 2 SO 4 dried and evaporated in vacuo to obtain the product. The crude material is used in the next step without purification. 3- methyl -1- tosyl -4,5- dihydro -1H- pyrrole -2- methyl carboxylate (26) : Dissolve methyl 3-hydroxy-3-methyl-1-tosylpyrrolidine-2-carboxylate 25 (69 g, 220 mmol) in anhydrous pyridine (550 mL), and slowly add POCl 3(61 mL, 660 mmol), and the reactants were stirred at room temperature (30 °C) for 12 h. The reaction mixture was poured into ice water, and the aqueous layer was extracted with diethyl ether (5 times), and the combined organic layers were washed with 5% HCl solution. Once the pH of the aqueous layer was acidic, the organic layer was washed with a solution of 5% Na 2 CO 3 and then washed with water until neutral pH. The organic layer was dried over anhydrous Na 2 SO 4 and evaporated in vacuo. The crude product was purified by silica gel column chromatography to give the product. 3- Methyl -1H- Pyrrole -2- Methyl Carboxylate (27) : Methyl 3-methyl-1-tosyl-4,5-dihydro-1H-pyrrole-2-carboxylate 26 (30 g, 102 mmol) was dissolved in THF (204 mL) and DBU (46 mL, 306 mmol) was added slowly. The resulting reaction mixture was stirred at 50 °C for 20 h. The reaction mixture was cooled to room temperature and diluted with diethyl ether. The organic layer was washed with 1N HCl and then with 5% NaHCO 3 and then with water. The organic layer was dried over Na 2 SO 4 and evaporated to give the crude product. The crude material was filtered through a silica plug and the solvent was evaporated to give the product. 3- Methyl -4-( Methylthio )-1H- Pyrrole -2- Methyl Carboxylate (28) : Methyl 3-methyl-1H-pyrrole-2-carboxylate 27 (460 mg, 3.3 mmol) and CuI (314 mg, 0.5 mmol) were placed in DMSO (3.3 mL, 1.0 M). Subsequently, dimethyl disulfide (0.531 mL, 6.0 mmol) was added thereto, and the mixture was heated at 110 °C for another 48 hours. The reaction mixture was quenched with water (50 mL) and EA (50 mL). Each layer was filtered through diatomaceous earth and then separated. The aqueous layer was extracted with EA (50 mL), and the combined organic layers were washed with water (30 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (10 - 15% EA / hexane) to obtain the product. 3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Methyl Carboxylate (29) : Methyl 3-methyl-5-(methylthio)-1H-pyrrole-2-carboxylate 28 (185 mg, 1.0 mmol) was placed in MeOH (10 mL) at room temperature, and a solution of OXONE (1.85 g, 2.0 mmol) in water (10 mL) was added dropwise thereto. Subsequently, the reaction mixture was stirred at room temperature (25 °C) for another 3 hours. Subsequently, the volatiles were removed under reduced pressure, and a suspension of the solid in water was extracted with EA (70 mL × 2) using a certain amount of water to dissolve only the inorganic matter. The combined organic layers were washed with water (30 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (30 - 40% EA / hexane) to obtain the pure product. 3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Carboxylic Acid (30) : To a solution of ethyl 3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxylate 29 (390 mg, 1.68 mmol) in H 2 O:THF (17 mL) was added LiOH·H 2 O (353 mg, 8.4 mmol). The resulting reaction mixture was then stirred at 80 °C for 12 h. The reaction mixture was acidified with 1 N HCl, and the precipitated solid was extracted with ethyl acetate (100 mL × 2). The combined organic layers were washed with water and brine. The organic layer was dried over anhydrous Na 2 SO 4 and the solvent was evaporated to give the product, which was used without purification in the next step. Scheme-4 ((4bR,9bR)-1- amino -4b- hydroxy -7-((1R,2R)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) tert-butyl carbamate (31) : ((4bR,9bR)-1-Amino-7-bromo-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)tert-butyl carbamate 12 (112 mg, 0.25 mmol) was placed in nitrogen-purged toluene:water (5 mL). To this was added Pd(OAc) 2 (6 mg, 0.03 mmol), RuPhos (24 mg, 0.05 mmol), K 3 PO 4 (213 mg, 1.0 mmol) and 6-methyl-2-((1R,2R)-2-methylcyclopropyl)-1,3,6,2- dioxazaborocane-4,8-dione 20 (79 mg, 0.38 mmol). The reactants were refluxed at 100 °C for 2 hours, and the reaction mixture was filtered through a bed of diatomaceous earth. The filtrate was evaporated to give the crude product. The crude product was purified by silica gel column chromatography to give the product. (4bR,9bR)-1,9b- diamino -4b- hydroxy -7-((1R,2R)-2- methylcyclopropyl )-4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one hydrochloride (32) : ((4bR,9bR)-1-Amino-4b-hydroxy-7-((1R,2R)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamic acid tert-butyl ester 31 (70 mg, 0.21 mmol) was dissolved in DCM (2 mL). To this was added 1,4-dioxane containing 4 N HCl (0.6 mL, 2.1 mmol). The reaction mixture was stirred at room temperature (30 °C) for 12 hours. The solvent was evaporated in vacuo to give the crude product. The crude product was used without purification. N-((4bR,9bR)-1- amino -4b- hydroxy -7-((1R,2R)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] Benzofuran -9b- yl )-3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Formamide (33) : 3-Methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxylic acid 30 (48 mg, 0.23 mmol) was placed in DMF (4 mL, 0.05 M). To this was added HATU (111 mg, 0.3 mmol) and DIPEA (0.1 mL, 0.6 mmol), and the mixture was stirred for 20 minutes, and then (4bR,9bR)-1,9b-diamino-4b-hydroxy-7-((1R,2R)-2-methylcyclopropyl)-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one hydrochloride 32 (70 mg, 0.2 mmol) was added, and the mixture was stirred at 30 °C for 36 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and with brine, and the organic layer was dried over Na 2 SO 4 dried and the solvent was evaporated to give the crude product. The crude product was purified by silica gel column chromatography and again by chiral column chromatography using ADH to give the product. 1 1H-NMR (300 MHz, MeOD) δ 0.66 - 0.72 (m, 1H), 0.78 - 0.84 (m, 1H), 0.95 - 1.03 (m, 1H), 1.13 (d, J = 6.0 Hz, 3H), 1.49 - 1.55 (m, 1H), 2.48 (s, 3H), 3.05 (s, 3H), 6.45 (s, 1H), 6.63 - 6.67 (m, 1H), 6.76 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 7.2 Hz, 1H), 2.27 (d, J = 8.1 Hz, 1H), 7.38 (s, 1H), 7.43 - 7.49 (m, 1H). LCMS: 508.4 [M+H] + 。 Example 2 : N-((4bR,9bR)-1- amino -4b- hydroxy -7-((1S,2R)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-2-( azetidin-1- yl yl ) acetamide This compound was prepared similar to the above compound. LCMS: 420.2 [M+H] + 。 Example 3 : N-((4bR,9bR)-1- amino -7-((S)-1- cyclopropylethyl )-4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-6- hydroxypicolinamide This compound was prepared similar to Example 1 above. LCMS: 458.2 [M+H] + 。 Example 4 : N-(1- amino -4b- hydroxy -7- isopropyl -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-5-(N-(2-( dimethylamino ) ethyl ) aminosulfonyl )-3,4- dimethyl -1H- pyrrole -2- formamide (51) : Process - 5: 4b,9b- dihydroxy -7- isopropyl -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- ketone (35) : 4-Nitro-1H-indene-1,3(2H)-dione (4) (250 g, 1.31 mol) was placed in 1,4-dioxane (2 L) and AcOH (200 ml). To this was added SeO 2 (291 g, 2.62 mol) at room temperature, and the mixture was kept refluxing at 110 °C for 4 h. It was stirred at room temperature for an additional 12 h. Subsequently, 500 g - 600 g of diatomaceous earth was charged thereto. The mixture was stirred and filtered through a diatomaceous earth pad. The residue was washed with ethyl acetate (300 - 500 mL). The resulting filtrate was concentrated to obtain the crude product 5, which was used as such without further purification. 2,2-Dihydroxy-4-nitro-1H-indene-1,3(2H)-dione 5 (crude, 1.31 mol) was placed in glacial acetic acid (2 L), 3-isopropylphenol 34 (196 g, 1.44 mol) was charged thereto, and the mixture was kept refluxing for 10 h. Subsequently, it was concentrated and purified by silica gel column chromatography (30% EA / hexane) to obtain the pure product. 9b- chloro -4b- hydroxy -7- isopropyl -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one (36) : 4b,9b-Dihydroxy-7-isopropyl-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 35 (50 g, 0.147 mol) was placed in DCM (500 mL), and a single batch of oxalyl chloride (1.2 equiv) was charged to this suspension. Subsequently, DMF (50 mL) was slowly charged thereto. The reaction mixture was then stirred at room temperature for 6 h. It was quenched with water (500 ml), and the layers were separated. The aqueous layer was extracted with DCM (300 mL × 2). The combined organic layers were washed with water (300 mL) and brine (300 mL). It was dried over sodium sulfate and concentrated to obtain the crude material, which was then purified by silica gel short pad (30% ethyl acetate / hexane) to obtain the pure product. 1H-NMR (300 MHz, CDCl 3 ): δ 1.18 (dd, J = 3.6 Hz, J = 6.9 Hz, 6H), 2.84 (septet, J = 6.9 Hz, 1H), 6.34 (s, 1H), 6.70 (s, 1H), 6.94 (dd, J = 1.0 Hz, J = 7.8 Hz, 1H), 7.45 (d, J = 7.8 Hz, 1H), 7.81 - 7.83 (m, 1H), 8.21 (m, 1H), 8.52 (m, 1H). 9b- amino -4b- hydroxy -7- isopropyl -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one (37) : Place 9b-chloro-4b-hydroxy-7-isopropyl-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 36 (36.0 g, 0.1 mol) in THF (350 mL) and cool to -40 o °C. Using a dropping funnel, add a 2.0 M solution of NH 3 in IPA (100 mL, 0.20 mol) and maintain the temperature below -20 °C. Monitor the reaction mixture at -20 °C for one hour and then warm to room temperature. Stir it at room temperature until the reaction is complete and then concentrate it completely. Dissolve the crude product in ethyl acetate (500 mL) and wash with water (200 mL × 2) and brine (100 mL). Dry it over anhydrous Na 2 SO 4 It was dried and then concentrated to obtain a crude material, which was purified by a short silica pad to obtain a pure product. 1 H-NMR (300 MHz, CDCl 3 ) δ 1.18 (d, J = 6.9 Hz, 6H), 2.84 (septet, J = 6.9 Hz, 1H), 3.46 (s, 1H), 6.25 (s, 1H), 6.74 (s, 2H), 6.90 (dd, J = 1.2 Hz, J = 7.8 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.77 (t, J = 8.1 Hz, 1H), 8.22 (dd, J = 1.2 Hz, J = 8.4 Hz, 1H), 8.52 (dd, J = 1.2 Hz, J = 8.1 Hz, 1H). Process - 6 Acetic acid 3 - Nitro But -2 - Ester (39) : 3 - Nitrobutan - 2 - ol 38 (7.5 g, 63 mmol) was placed in DCM (37.5 mL, 1.7 M), and acetic anhydride (11.3 mL, 120 mmol) and DMAP (305 mg, 2.52 mmol) were sequentially charged. After stirring at room temperature (20 °C) for another 24 hours, the reaction mixture was quenched with MeOH (8 mL) and stirred for 1 hour. Subsequently, it was placed in DCM (250 mL) and washed with saturated NaHCO 3 (100 mL×2), water (100 mL) and brine (about 100 mL). It was dried over anhydrous Na 2 SO 4 Dry and concentrate to obtain the pure product as an oil. Ethyl formylglycinate (41) : Add pTSA (1.36 g, 7.2 mmol) to a solution of glycinate hydrochloride 40 (20.0 g, 0.143 mol) in ethyl formate (90 mL, 1.6 M). Reflux it and add TEA (22.0 mL, 0.157 mol) dropwise at this temperature. Let the reaction mixture reflux for another 24 hours or as monitored by TLC. Then cool it to room temperature (20 °C) and then concentrate. The crude product is then filtered through a short pad of silica gel using 50% EA / hexane (3000 mL). Then concentrate it to obtain the product, which is used as such in the next step. The product contains TEA by NMR. Since an excess of TEA is used in the next step, it is used as such in the next step. 2- Ethyl isocyanoacetate (42) : Slowly add POCl 3 (7.5 mL, 80 mmol) dropwise to a solution of ethyl formylglycinate 41 (9.40 g, 80 mmol) and TEA (28 mL, 0.2 mol) in DCM (80 mL, 1.0 M) at 0 °C. The solution turns red, and then let it reach room temperature after the addition is complete and stir for another 4 hours. Then slowly quench the reaction mixture on Na 2 CO 3 solution and solid Na 2 CO 3 and stir for another 30 minutes at room temperature. Separate the organic layer and extract the aqueous layer with DCM (200 mL × 2). The combined organic layers are then washed with water (100 mL) and brine (100 mL). Let it pass through anhydrous Na 2 SO 4 Dry and concentrate to obtain the pure product as a liquid. 3,4- Dimethyl -1H- Pyrrole -2- Ethyl carboxylate (43) : 3-Nitrobutan-2-yl acetate 39 (8.9 g, 55.0 mmol) and ethyl 2-isocyanoacetate 42 (8.1 g, 71.5 mmol) were placed in THF:water (1:1, 110 mL, 0.5 M), and anhydrous K 2 CO 3 (12.2 g, 88.0 mmol) was slowly added portionwise thereto with vigorous stirring, and the reaction mixture was then stirred at room temperature for another 3 days. The reaction mixture was then concentrated to give a thick slurry. This was then diluted with ice-cold water (100 mL) and then slowly neutralized with 5% HCl (2 N, pH = 5) at 0 °C. It was then extracted with EA (150 mL × 3). The combined organic layers were washed with 5% brine (100 mL × 2). It was then dried over anhydrous Na 2 SO 4 and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (0 - 10% EA / hexane) to give the pure product. 5-( Chlorosulfonyl )-3,4- Dimethyl -1H- Pyrrole -2- Ethyl carboxylate (44) : Ethyl 3,4-dimethyl-1H-pyrrole-2-carboxylate 43 (1.67 g, 10.0 mmol) was placed in CHCl 3 (40 mL, 0.25 M), and chlorosulfonic acid (10.0 mL, 150.0 mmol) was added thereto at 0 °C. The reaction mixture was stirred at 0 °C for another 3 hours. The reaction mixture was quenched with crushed ice (120 mL) and extracted with DCM (100 mL × 3). The combined organic layers were washed with water (100 mL) and brine (100 mL). It was dried over anhydrous Na 2 SO 4 and concentrated to give the crude product. The crude product was passed through a short pad of silica gel using DCM, and the filtrate was concentrated to give the pure product. 5-(N-(2-(( tert-Butoxycarbonyl ) Amino ) Ethyl ) Sulfamoyl )-3,4- Dimethyl -1H- Pyrrole -2- Ethyl Carboxylate (46) : At room temperature, 5-(chlorosulfonyl)-3,4-dimethyl-1H-pyrrole-2-carboxylic acid ethyl ester 44 (530 mg, 2.0 mmol) was placed in DCM (20 mL, 0.1 M), and to this was added (2-aminoethyl)carbamic acid tert-butyl ester 45 (385 mg, 2.4 mmol), followed by DIPEA (0.52 mL, 3.0 mmoL). Subsequently, the reaction mixture was stirred at room temperature (25 °C) for another 2 hours. The reaction mixture was quenched with water (50 mL), and then extracted with DCM (70 mL×2). The combined organic layers were washed with water (30 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (30% EA / hexane) to obtain the pure product. 5-(N-(2-(( tert-Butoxycarbonyl ) Amino ) Ethyl ) Sulfamoyl )-3,4- Dimethyl -1H- Pyrrole -2- Carboxylic Acid (47) : Ethyl 5-(N-(2-((tert-butoxycarbonyl)amino)ethyl)sulfamoyl)-3,4-dimethyl-1H-pyrrole-2-carboxylate 46 (682 mg, 1.75 mmol) was placed in THF:MeOH:H 2 O (1:1:10, 18.0 mL, 0.1 M) and charged with LiOH.H 2 O (367 mg, 5.0 mmol), and the reaction mixture was refluxed at 80 °C for 5 h. The reaction mixture was concentrated to remove volatiles. It was then acidified with 1 N HCl (pH < 2 - 3). The precipitated solid was then filtered, washed with cold water and dried to give the pure product. Scheme - 7 (2-((5-((4b- hydroxy -7- isopropyl -4- nitro -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) carbamoyl )-3,4- dimethyl -1H- pyrrole )-2- sulfonamido ) ethyl ) tert-butyl carbamate (48) : 5-(N-(2-((tert-Butoxycarbonyl)amino)ethyl)sulfamoyl)-3,4-dimethyl-1H-pyrrole-2-carboxylic acid 47 (452 mg, 1.25 mmol) was placed in DMF (5 mL, 0.25 M) and cooled to 0 °C. To this were sequentially charged EDCI (360 mg, 1.88 mmol) and HOBt (254 mg, 1.88 mmol). After 10 min, 9b-amino-4b-hydroxy-7-isopropyl-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 37 (425 mg, 1.25 mmol) and DIPEA (0.55 mL, 3.13 mmol) were sequentially charged thereto and allowed to reach room temperature (35 °C) for 18 hours. The reaction mixture was then quenched with water (60 mL) and extracted with EA (100 mL × 2). The combined organic layers were washed with water (50 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to give a crude product. The crude product was purified by silica gel column chromatography (40% EA / hexane) to give the product. 5-(N-(2- aminoethyl ) sulfamoyl )-N-(4b- hydroxy -7- isopropyl -4- nitro -10- oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,4- dimethyl -1H- pyrrole -2- formamide (49) : tert-Butyl (2-((5-((4b-hydroxy-7-isopropyl-4-nitro-10-sulfooxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)-3,4-dimethyl-1H-pyrrol)-2-sulfonamido)ethyl)carbamate 48 (275 mg, 0.4 mmol) was placed in DCM (8 mL, 0.05 M), and 4 M HCl in dioxane (1.0 mL, 4.0 mmol) was added thereto. It was stirred at room temperature (25 °C) for an additional 15 hours. The reaction mixture was diluted with DCM (20 mL) and stirred with saturated NaHCO 3 (20 mL) for 10 min. The free amine was not released sufficiently and thus 0.5 mL of TEA was added. It was then diluted with DCM (100 mL), and the layers were then separated. The organic layer was washed with saturated NaHCO 3 (20 mL), water (30 mL), and brine (30 mL). It was dried over anhydrous Na 2 SO 4 and concentrated to give a solid. 5-(N-(2-( dimethylamino ) ethyl ) aminosulfonyl )-N-(4b- hydroxy -7- isopropyl -4- nitro -10- sulfooxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,4- dimethyl -1H- pyrrole -2- formamide (50) : 5-(N-(2-Aminoethyl)sulfamoyl)-N-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,4-dimethyl-1H-pyrrole-2-carboxamide 49 (88 mg, 0.15 mmol) was placed in MeCN: glacial acetic acid (2:1, 3 mL, 0.05 M) and cooled to 0 o °C. 35% Aqueous HCHO solution (0.125 mL, 1.5 mmol) was charged thereto, and then NaBH 3 CN (33 mg, 0.53 mmol) was added. It was stirred at 0 °C for another 0.5 hour. The reaction mixture was quenched with water (40 mL) and extracted with EA (40 mL × 2). The combined organic layers were washed with water (30 mL) and brine (10 mL). It was dried over anhydrous Na 2 SO 4 and concentrated to give the crude product. The crude was purified by column chromatography (0.05% TEA in 0-10% MeOH / DCM) to give the pure product. N-(1- amino -4b- hydroxy -7- isopropyl -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-5-(N-(2-( dimethylamino ) ethyl ) sulfamoyl )-3,4- dimethyl -1H- Pyrrole -2- formamide (51) : 5-(N-(2-Aminoethyl)sulfamoyl)-N-(4b-hydroxy-7-isopropyl-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,4-dimethyl-1H-pyrrole-2-carboxamide 50 (46 mg, 0.075 mmol) was placed in EtOH:water (10:1, 5.0 mL, 0.015 M), and iron powder (13 mg, 0.23 mmol) and 1 M HCl (3 drops) were successively charged thereto. It was refluxed at 90 °C for 1.5 hours. The reaction mixture was cooled to 50 °C and then neutralized with TEA (1 drop). Subsequently, the reaction mixture was filtered through celite using EA (20 ml) under warm conditions. The filtrate was concentrated and placed in EA (100 mL) and washed with water (20 mL) and brine (20 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain a crude product. The crude product was purified by preparative thin-layer chromatography (10% MeOH / DCM) to obtain a pure product. 1 H-NMR (300 MHz, CD 3 OD) δ 1.19 (d, J = 6.9 Hz, 6H), 2.17 (s, 3H), 2.20 (s, 3H), 2.43 (s, 6H), 2.65 (t, J = 6.6 Hz, 2H), 2.82 (septet, J = 6.9 Hz, 1H), 3.06 (t, J = 6.6 Hz, 2H), 6.69 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 7.03 (d, J = 7.2 Hz, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.45 - 7.50 (m, 1H). LCMS: 582.3 [M+H] + 。 Example 5 : N-((4bR,9bR)-1- amino -7-((S)-1- cyclopropylethyl )-4b- hydroxy -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-2-( azetidine -1- yl ) acetamide (62) : Process-8 2-(1- cyclopropylviny )-4,4,5,5- tetramethyl -1,3,2- dioxaborolane (54) : Under nitrogen, anhydrous lithium chloride (7.06 g, 166.5 mmol), CuCl (16.5 g, 166.5 mmol) and dry N,N-dimethylformamide (500 mL) were added to the reaction flask, and the mixture was stirred at room temperature for 1 hour. Subsequently, potassium acetate (16.4 g, 166.5 mmol), B 2 Pin 2 53 (42.3 g, 166.5 mmol) and cyclopropylacetylene 52 (10 g, 151.3 mmol) were added, and stirring was continued at room temperature for 20 hours. The reaction mass was treated with NH 4 The saturated solution of Cl (100 mL) was quenched, ethyl acetate (100 mL) was added and filtered through a diatomaceous earth bed. The filtrate was extracted with hexane (200 mL×3), and the combined organic layers were collected, washed with water (100 mL×3) and with brine (100 mL), and dried over Na 2 SO 4 dried, and the solvent was evaporated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography (hexane) to obtain the product as an oil. Process - 9 2 - ( azetidinyl -1- yl ) tert - butyl acetate (57) : Azetidine hydrochloride 56 (73 g, 78 mmol) was placed in THF:water (4:1, 170 mL, 0.3 M) and cooled to 0 °C. To this was added 2N aqueous NaOH solution (78 mL, 157 mmol) and stirred for 10 minutes. Subsequently, 2 - bromo - tert - butyl acetate 55 (7.2 mL, 49 mmol) was added dropwise thereto at 0 °C and stirred at 30 °C for another 1 hour. Subsequently, the reaction mixture was extracted with EA (150 mL×2), and the combined organic layers were washed with saturated brine (about 50 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product as a liquid. 2 - ( azetidinyl -1- yl ) acetate hydrochloride (58) : 2 - (Azetidin - 1 - yl) - tert - butyl acetate 57 (6.7 g, 39 mmol) was cooled to 0 °C and slowly added to dichloromethane containing 4 M HCl (98 mL, 0.4 M). Subsequently, the reaction mixture was stirred at room temperature (30 °C) for another 24 hours. Subsequently, the precipitated solid was filtered out, washed with cold 1,4 - dichloromethane (about 20 - 30 mL) and dried to obtain the pure product. Process - 10 ((4bR,9bR)-1 - Amino -7-(1- Cyclopropylethylene )-4b- Hydroxy -10- Lateral oxygen group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group ) Tert-butyl carbamate (59) : Add (tert-butyl (1-amino-7-bromo-4b-hydroxy-10-lateral oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamate) 12 (3.36 g, 7.50 mmol), Pd(dppf)Cl 2 (613 mg, 0.75 mmol) and K 2 CO 3 (3.11 g, 22.5 mmol) into a sealed tube and charged with toluene:water (5:1, 75 mL, 0.10 M), which has been purged with nitrogen. The reaction mixture is purged again with N 2 (for 10 minutes), and then charged with 2-(1-cyclopropylethylene)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 54 (2.15 g, 11.3 mmol) and maintained at 90 °C for another 3 hours. Pass the reaction mixture through a bed of diatomaceous earth and concentrate. Place this in EA and water and separate the layers. The organic layer is dried over anhydrous Na 2 SO 4 and concentrated to obtain the crude product. The crude product is purified by silica gel column chromatography (20 - 30% EA / hexane) to obtain the pure product. ((4bR,9bR)-1- Amino -7-((S)-1- Cyclopropylethyl )-4b- hydroxy -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group ) tert-butyl carbamate (60) : Under nitrogen, (1-amino-7-(1-cyclopropylethylene)-4b-hydroxy-10-side oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl) tert-butyl carbamate 59 (5.43 g, 12.5 mmol) was placed in DCM (125 mL, 0.10 M) and loaded with [((4 S, 5 S)-Cy2-UBaphox)Ir(COD)]BARF (433 mg, 0.25 mmol). Subsequently, it was flushed with H 2 gas, and then maintained at room temperature (20 °C) for 4 hours under an H 2 atmosphere (60 psi). Subsequently, the reaction mass was concentrated to obtain a crude product. The crude product was purified by silica gel column chromatography (0-10-30% EA / hexane, with 10% DCM as a co-solvent) to obtain a pure product. (4bR,9bR)-1,9b- diamino -7-((S)-1- cyclopropylethyl )-4b- hydroxy -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- ketone (61) : ((4bR,9bR)-1-Amino-7-((S)-1-cyclopropylethyl)-4b-hydroxy-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamic acid tert-butyl ester 60 (2.18 g, 5.00 mmol) was placed in DCM (50 mL, 0.1 M) and immediately charged with 4.0 M HCl in dioxane (12.5 mL, 50.0 mmol). The reaction mixture was then stirred at room temperature (20 °C) for an additional 6 hours. The reaction mixture was diluted with EA (ca. 150 mL) and stirred with saturated NaHCO 3 (ca. 100 mL) for 5 - 10 min. The layers were separated and the aqueous layer was extracted with EA (ca. 100 mL). The combined organic layers were washed with water (100 ml) and brine (ca. 100 mL). It was dried over anhydrous Na 2 SO 4 and concentrated to give the product, which was used as such in the next step without further purification. N-((4bR,9bR)-1- Amino -7-((S)-1- Cyclopropylethyl )-4b- Hydroxy -10- Formyloxy -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- yl )-2-( Azetidin-1- yl yl ) acetamide (62) : At 0 °C, HATU (2.57 g, 6.75 mmol) and DIPEA (2.35 mL, 13.5 mmol) were charged into 45 mL of anhydrous DMF (0.1 M) containing 2-(azetidin-1-yl)acetic acid hydrochloride 58 (1.02 g, 6.75 mmol). After 10 min, (4bR,9bR)-1,9b-diamino-7-((S)-1-cyclopropylethyl)-4b-hydroxy-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 61 (1.51 g, 4.50 mmol) was charged thereto and stirred at room temperature (20 °C) for 15 hours. The reaction mass was quenched with water (about 100 mL) and saturated NaHCO 3 (about 100 mL). It was extracted with EA (100 mL × 3). The combined organic layers were washed with water (100 mL × 2), brine (100 mL) and dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (0 - 10% MeOH / DCM) to obtain the crude substance. 1 1H-NMR (500 MHz, MeOD) δ 7.50 - 7.39 (m, 1H), 7.29 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 7.3 Hz, 1H), 6.85 (dd, J = 8.0, 1.3 Hz, 1H), 6.72 (d, J = 8.5 Hz, 1H), 6.69 (d, J = 1.3 Hz, 1H), 3.37 (t, J = 7.3 Hz, 4H), 3.18 (s, 2H), 2.09 (p, J = 7.1 Hz, 2H), 1.91 - 1.83 (m, 1H), 1.25 (d, J = 7.0 Hz, 3H), 0.94 - 0.79 (m, 1H), 0.55 - 0.47 (m, 1H), 0.40 - 0.26 (m, 1H), 0.17 - 0.13 (m, 1H), 0.07 - 0.03 (m, 1H). LCMS: 432.3 [M - H] - . LCMS: 434.2 [M+H] + . Example 6 : N-(1- amino -7-((1R,2S)-1,2- dimethylcyclopropyl )-4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -4-( methylsulfonyl )-1H- pyrrole -2- formamide. This compound was prepared similar to Example 5 above. LCMS: 522.2 [M+H] + . Example 7 : N-(1- amino -4b- hydroxy -7-(2- methylcyclobutyl )-10- oxo -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- yl )-3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Formamide This compound was prepared similar to Example 5 above. LCMS: 522.2 [M+H] + 。 Example 8 : N-((4bR,9bR)-1- Amino -7-((R)-1- Cyclopropylethyl )-4b- Hydroxy -10- Oxo -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- yl )-6- Hydroxypicolinamide This compound was prepared similar to Example 5 above. LCMS: 458.1 [M+H] + 。 Example 9 : N-(1- Amino -4b- Hydroxy -7-(( trans )-2- methylcyclopropyl )-10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-((4- methylpiper idin -1- yl ) sulfonyl )-1H- pyrrole -2- formamide (83) : Process-11 3-(( tert-butyldimethylsilyl ) oxy ) benzaldehyde (64) : To a solution of 3-hydroxybenzaldehyde (30 g, 0.25 mol) and imidazole (21.7 g, 0.32 mol) in dry dichloromethane (250 mL) at 0 °C was slowly added tert-butylchlorodimethylsilane (44.4 g, 0.30 mol). The reaction mixture was stirred overnight at room temperature. The reaction mixture was filtered and washed with DCM. The organic layer was washed with water, dried over anhydrous MgSO 4 dried, filtered and concentrated. The residue was purified on a silica gel column, eluting with EA / hexane (0 / 100 -> 1 / 10), to give the desired product. 1 H NMR (300 MHz, CDCl 3) δ 9.95 (s, 1H), 7.40 (tdd, J= 21.4, 12.8, 9.5 Hz, 3H), 7.11 (ddd, J = 7.9, 2.5, 1.2 Hz, 1H), 1.00 (s, 9H), 0.23 (d, J= 3.0 Hz, 6H). (E)- tertiary - butyldimethyl (3-( prop -1- ene -1- yl ) phenoxy ) silane (66) : At room temperature, acetic acid (13.7 mL, 0.24 mol) was added dropwise to a solution of 3-((tert-butyldimethylsilyl)oxy)benzaldehyde 64 (30 g, 0.13 mol), propionaldehyde 65 (11.5 mL, 0.16 mol), and malononitrile (20.95 g, 0.17 mol) in acetonitrile (630 mL, 0.2 M). The reaction mixture was stirred for 10 minutes, and then ammonium acetate (12.2 g, 0.16 mol) was added. The resulting solution was stirred overnight at 80 °C. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, filtered, concentrated, and purified on a silica gel column, eluting with n-hexane, to give the desired product. 1 H NMR (300 MHz, CDCl 3 ) δ 7.14 (td, J= 7.8, 2.8 Hz, 1H), 6.92 (d, J= 7.5 Hz, 1H), 6.81 (s, 1H), 6.68 (d, J= 8.0 Hz, 1H), 6.35 (d, J= 15.9 Hz, 1H), 6.22 (m, 1H), 1.88 (d, J = 6.1 Hz, 3H), 0.99 (d, J = 2.6 Hz, 9H), 0.20 (d, J = 2.6 Hz, 6H). tert-Butyldimethyl (3-(( trans )-2- methylcyclopropyl ) phenoxy ) silane (67) : At -40 °C with stirring, diethylzinc (50 mL, 1.0 M / hexane, 0.05 mol) was added dropwise via cannula to dry dichloromethane (150 mL). After 10 minutes, a solution of diiodomethane (8 mL, 0.1 mol) in dry dichloromethane (25 mL) was added dropwise to this reaction mixture at -40 °C. The reaction mixture was stirred at -40 °C for 1 hour. A solution of trichloroacetic acid (0.82 g, 0.005 mol), DME (2.59 mL, 0.025 mol) in dry dichloromethane (25 mL) was added dropwise to this reaction mixture at -40 °C. The reaction mixture was stirred at -15 °C for 1 hour. A solution of (E)-tert-butyldimethyl(3-(prop-1-en-1-yl)phenoxy)silane 66 (6.21 g, 0.025 mol) in dry dichloromethane (25 mL) was added dropwise to this reaction mixture at -15 °C. After 10 min, the reaction mixture was warmed to room temperature and stirred overnight at room temperature. At 0 °C, the reaction mixture was carefully poured into ice water. The resulting solid was filtered off and the filtrate was extracted with dichloromethane, dried over MgSO 4 dried, concentrated and purified on a silica gel column, eluting with n-hexane / EA (100 / 0 -> 50 / 1) to give the desired racemic product of the trans geometric structure as an oil. 1 1H NMR (300 MHz, CDCl 3 ) δ 7.08 (t, J = 7.8 Hz, 1H), 6.60 (m, 2H), 6.48 (t, J = 2.0 Hz, 1H), 1.87 (dd, J = 6.4, 1.3 Hz, 0.20H), 1.51 (dt, J = 8.9, 3.3 Hz, 1H), 1.19 (dd, J = 15.5, 5.8 Hz, 3H), 1.01 (m, 9H), 0.81 (m, 2H), 0.71 (m, 1H), 0.18 (m, 6H). 3-(( trans- )-2- methylcyclopropyl ) phenol (68) : To a stirred solution of racemic tert-butyldimethyl(3-((trans)-2-methylcyclopropyl)phenoxy)silane 67 (32.93 g, 0.12545 mol) in ethanol (300 mL) was added dropwise concentrated HCl (30 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated and purified on a silica gel column, eluting with EA / hexane (1 / 20 -> 1 / 15), to give 3-((1S,2S)-2-methylcyclopropyl)phenol (the product). 1 H NMR (300 MHz, CDCl 3 ) δ 7.10 (t, J = 7.9 Hz, 1H), 6.59 (m, 2H), 6.49 (m, 1H), 4.66 (d, J = 8.7 Hz, 1H), 1.52 (dt, J = 8.9, 4.6 Hz, 1H), 1.15 (t, J = 10.4 Hz, 3H), 1.04 (tdd, J = 10.3, 5.7, 4.5 Hz, 1H), 0.86 (m, 1H), 0.72 (m, 1H). 4b,9b- dihydroxy -7-(( trans- )-2- methylcyclopropyl )-4- Nitro -4b,9b- Dihydro -10H- Indeno [1,2-b] Benzofuran -10- Ketone (69) : To a solution of 4-nitro-1H-indene-1,3(2H)-dione 4 (16.4 g, 0.086 mol) in dioxane:AcOH (10:1, v / v, 140 mL / 14 mL, 0.6 M) was added selenium dioxide (19 g, 0.17 mol). The reaction mixture was refluxed at 130 °C for 3 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate, filtered through a pad of diatomaceous earth, concentrated, and the crude product 5 was obtained, which was used in the next step without purification. To a solution of 2,2-dihydroxy-4-nitro-1H-indene-1,3(2H)-dione 5 (crude) in glacial acetic acid (140 mL) was added a racemic mixture of 3-((trans)-2-methylcyclopropyl)phenol (12.7 g, 0.085 mol). The reaction mixture was refluxed at 80 °C for 3 h, cooled to room temperature, diluted with EA, filtered, and concentrated. The residue was purified on a silica gel column, eluting with EA / hexane (1 / 2 -> 2 / 3), to give the desired product. 1 H NMR (300 MHz, CDCl 3 ) δ 8.48 (dd, J= 8.0, 0.9 Hz, 1H), 8.16 (dd, J= 7.6, 1.0 Hz, 1H), 7.77 (t, J= 7.8 Hz, 1H), 7.40 (d, J= 7.9 Hz, 1H), 6.72 (ddd, J= 7.9, 3.9, 1.4 Hz, 1H), 6.45 (m, 1H), 1.50 (m, 1H), 1.12 (m, 3H), 0.98 (m, 1H), 0.81 (dt, J= 14.8, 5.5 Hz, 1H), 0.75 (m, 1H). 9b- Chlorine -4b- Hydroxy -7-(( trans )-2- Methylcyclopropyl )-4- Nitro -4b,9b- Dihydro -10H- Indeno [1,2-b] Benzofuran -10- Ketone (70) : At room temperature, oxalyl chloride (2.90 mL, 0.03 mol) was added dropwise to a solution of racemic 4b,9b-dihydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 69 (10.1 g, 0.03 mol) in dry dichloromethane (143 mL). Dry DMF (10 mL) was added dropwise to the reaction mixture with stirring at room temperature (about 2 hours). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with dichloromethane, washed with water, and the organic layer was dried over MgSO 4 dried, filtered, concentrated and purified on a silica gel column, eluting with EA / hexane (1 / 4 -> 1 / 2) to give the desired product. 1 H NMR (300 MHz, CDCl 3 ) δ 8.49 (dd, J = 8.0, 1.1 Hz, 1H), 8.19 (dd, J = 7.7, 1.1 Hz, 1H), 7.80 (t, J = 7.9 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 6.75 (dt, J = 8.1, 1.6 Hz, 1H), 6.44 (t, J = 1.4 Hz, 1H), 6.29 (s, 1H), 1.50 (m, 1H), 1.13 (dd, J = 5.7, 1.2 Hz, 3H), 0.99 (m, 1H), 0.82 (dt, J = 12.4, 4.4 Hz, 1H), 0.76 (m, 1H). 9b- Amino -4b- Hydroxyl -7-(( trans )-2- Methylcyclopropyl )-4- Nitro -4b,9b- Dihydro -10H- Indeno [1,2-b] Benzofuran -10- Ketone (71) : At -40 o C, a solution of racemic 9b-chloro-4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one (6.47 g, 0.017 mol) in dry THF (90 mL) was added dropwise with ammonia solution (26.1 mL, 0.052 mol, 2.0 M / IPA) (about 10 min). The reaction mixture was stirred at -40 °C for 1 hour and at -20 °C for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with brine and water. The organic layer was dried over MgSO 4 Dried, filtered, concentrated and purified on a silica gel column, eluting with EA / hexane (1 / 2 -> 2 / 3), to give the desired product. 1 H NMR (300 MHz, CDCl 3 ) δ 8.48 (m, 1H), 8.10 (d, J = 7.6 Hz, 1H), 7.73 (dd, J= 13.5, 5.6 Hz, 1H), 7.27 (d, J= 7.4 Hz, 1H), 6.68 (m, 1H), 6.45 (d, J = 2.7 Hz, 1H), 1.48 (d, J = 5.1 Hz, 1H), 1.13 (t, J = 5.0 Hz, 3H), 0.98 (d, J = 6.7 Hz, 1H), 0.81 (dd, J= 5.0, 1.9 Hz, 1H), 0.73 (dd, J = 7.3, 4.9 Hz, 1H). Scheme-12 3- methyl -1-( Phenylsulfonyl )-1H- Pyrrole -2- Methyl carboxylate (73) : At 0 o To a solution of methyl 3-methyl-1H-pyrrole-2-carboxylate 27 (3.5 g, 25.2 mmol) in dry DMF (63 mL) was added NaH (1.51 g, 37.8 mmol) followed by benzenesulfonyl chloride 72 (4.82 mL, 37.8 mmol) at 4 °C. The reaction mixture was stirred at 0 °C to room temperature for 15 h. The reaction was quenched with ice water (300 mL), the aqueous layer was extracted with ethyl acetate (3×100 mL), the combined organic layers were purified by Na 2 SO 4 Dry and evaporate under vacuum. The crude material was purified by silica gel column chromatography (ethyl acetate:hexane) and the obtained product was recrystallized using DCM and HX. 5-( Methoxycarbonyl )-4- methyl -1-( Phenylsulfonyl )-1H- pyrrole -2- sulfinic acid (74) : Dissolve methyl 3-methyl-1-(phenylsulfonyl)-1H-pyrrole-2-carboxylate 73 (5.03 g, 18 mmol) in THF (180 mL). Cool the resulting solution to -78 °C, and dropwise add lithium diisopropylamide (18 mL, 36 mmol) at -78 °C, and stir the reaction mass at -78 °C for an additional 1 hour. Bubble sulfur dioxide (gas) slowly into the cold solution at -78 °C for 30 min. Allow the resulting reaction mass to warm slowly to room temperature and stir at room temperature for 12 hours. Remove THF under vacuum, dissolve the resulting residue in water and wash with ethyl acetate (50 mL×2). Acidify the aqueous layer to pH about 1 with 1N HCl, extract the aqueous layer with ethyl acetate (200 mL×3), wash the combined organic layers with water and brine, and dry the organic layer over Na 2 SO 4 dry and evaporate the solvent to obtain the product, which is used as such without purification in the next step. 5-( chlorosulfonyl )-3- methyl -1-( phenylsulfonyl )-1H- pyrrole -2- methyl carboxylate (75) : Place 5-(methoxycarbonyl)-4-methyl-1-(phenylsulfonyl)-1H-pyrrole-2-sulfinic acid 74 (3.9 g, 11.4 mmol) in THF (115 mL) and cool to 0 °C. Add NCS (1.83 g, 13.7 mmol) thereto. Stir the reaction mass at room temperature for 15 hours. Remove THF under vacuum to obtain a residue. Purify the residue by silica gel column chromatography (ethyl acetate:hexane) to obtain the product. 4-((5-( methoxycarbonyl )-4- methyl -1-( Phenylsulfonyl )-1H- Pyrrole -2- base ) Sulfonyl ) Piperidone 𠯤 -1- Tributyl carboxylate (77) : 5-(Chlorosulfonyl)-3-methyl-1-(phenylsulfonyl)-1H-pyrrole-2-carboxylic acid methyl ester 75 (491.2 mg, 1.3 mmol) was dissolved in DCM (13 mL). To this was added tributyl piperidine-1-carboxylate 76 (290.6 mg, 1.56 mmol) followed by DIPEA (0.340 mL, 1.95 mmol). The reaction mass was stirred at room temperature for 12 h. The reaction mass was diluted with DCM (100 mL) and washed with water (50 mL×3) and washed with Na 2 SO 4 The residue was dried and the solvent was evaporated to obtain a crude product. The crude product was purified by silica gel column chromatography (ethyl acetate:hexane) to obtain the product. 4-((5-( Methoxycarbonyl )-4- methyl -1H- Pyrrole -2- base ) Sulfonyl ) Piperidone 𠯤 -1- Tributyl carboxylate (78) : 4-((5-(Methoxycarbonyl)-4-methyl-1-(phenylsulfonyl)-1H-pyrrol-2-yl)sulfonyl)piperidinium-1-carboxylic acid tributyl ester 77 (660 mg, 1.25 mmol) was dissolved in MeOH:H 2in O (13 mL). K was added to this solution 2 CO 3 (518.3 mg, 3.75 mmol). The reactants were stirred at 50 °C for 12 hours. The methanol was evaporated and the resulting residue was dissolved in water (100 mL). The aqueous layer was extracted with ethyl acetate (100 mL × 3), and the combined organic layers were washed with water and with brine. The organic layer was dried over Na 2 SO 4 dried and the solvent was evaporated to give the crude product. The crude product was purified by silica gel column chromatography (ethyl acetate:hexane) to give the product. 5-((4-( tert-Butoxycarbonyl ) piper azin -1- yl ) sulfonyl )-3- methyl -1H- pyrrole -2- carboxylic acid (79) : 4-((5-(Methoxycarbonyl)-4-methyl-1H-pyrrol-2-yl)sulfonyl)piperazin-1-carboxylic acid tert-butyl ester 78 (360 mg, 0.93 mmol) was placed in MeOH:H 2 O (1:10) (10 mL) and LiOH·H 2 O (195 mg, 4.65 mmol) was added thereto. The reactants were heated at 70 °C for 8 hours. The MeOH was removed under vacuum, and the aqueous layer was diluted with water (10 mL) and acidified to pH ~1 with 1N HCl. The product was extracted with ethyl acetate (100 mL × 3). The combined organic layers were washed with water and brine, dried over Na 2 SO 4 dried, and the solvent was evaporated to give the product (79), which was used without purification in the next step. Scheme-13 4-((5-((4b- Hydroxyl -7-(( trans )-2- Methylcyclopropyl )-4- Nitro -10- Side oxy group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group ) Carbamoyl )-4- Methyl -1H- Pyrrole -2- Group ) Sulfonyl ) Piper 𠯤 -1- Tert-butyl carboxylate (80) : At 0 °C, EDCI (306 mg, 1.6 mmol) was added to a solution of 5-((4-(tert-Butoxycarbonyl)piperazin-1-yl)sulfonyl)-3-methyl-1H-pyrrole-2-carboxylic acid 79 (397 mg, 1.1 mmol) in DMF (11 mL), followed by the addition of HOBt (216 mg, 1.6 mmol). The mixture was stirred for 30 min, and then the racemic mixture of 9b-amino-4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 71 (375 mg, 1.1 mmol) was added, followed by the addition of DIPEA (0.6 mL, 3.2 mmol). The reaction mass was stirred at 30 °C for 20 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with water and with brine. The organic layer was dried over Na 2 SO 4 Dry and evaporate the solvent to obtain the crude product. The crude material is purified by silica gel column chromatography to obtain the solid product. N-(4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-4- nitro -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-( piper azin -1- sulfonyl )-1H- pyrrole -2- formamide (81) : To a solution of racemic tert-butyl 4-((5-((4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)-4-methyl-1H-pyrrole-2-yl)sulfonyl)piperazin-1-carboxylate 80 (250 mg, 0.35 mmol) in DCM (7 mL, 0.05 M) was added 1,4-dioxane containing 4 N HCl (0.9 mL, 3.5 mmol) and the reaction mixture was stirred at room temperature (30 °C) for 12 hours. The solvent was evaporated under vacuum, water (10 mL) was added and the residue was obtained, and the mixture was basified with 10% NaHCO 3 The solution was alkalized. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and with brine. The organic layer was dried over Na 2 SO 4 The solvent was dried and evaporated to obtain a solid product, which was used as such in the next step without further purification. N-(4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-4- nitro -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-((4- methylpiperazin- 1- yl ) ) sulfonyl )-1H- pyrrole -2- carboxamide (82) : To a solution of racemic N-(4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-(piperazin-1-ylsulfonyl)-1H-pyrrole-2-carboxamide 81 (100 mg, 0.16 mmol) in glacial acetic acid:MeCN (1:1) (4 mL) was added aqueous formaldehyde solution (35%) (0.15 mL, 1.6 mmol), followed by addition of NaBH 3 CN (36 mg, 0.6 mmol). The reaction mixture was stirred at 0 °C for 2 h. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate and washed with water and brine. The organic layer was dried over Na 2 SO 4 Dry and evaporate the solvent to obtain a crude product. The crude material is purified by silica gel column chromatography to obtain a solid product. N-(1- amino -4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-((4- methylpiperazin- 𠯤 -1- yl ) sulfonyl )-1H- pyrrole -2- formamide (83) : To a solution of racemic N-(4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide 82 (36 mg, 0.06 mmol) in EtOH : H 2 O (10 : 1) (6 mL) was added Fe powder (10 mg, 0.2 mmol) and concentrated HCl (1 drop), and the reaction mixture was stirred at 90 °C for 3 h. The hot reaction mixture was filtered through a bed of diatomaceous earth. The filtrate was evaporated in vacuo. The residue was dissolved in water and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and with brine. The organic layer was dried over Na 2 SO 4 Dry and evaporate the solvent. The crude product was purified by silica gel column chromatography to obtain a solid product. 1 H-NMR (300 MHz, MeOD) δ 0.70 - 0.76 (m, 1H), 0.81 - 0.89 (m, 1H), 0.98 - 1.02 (m, 1H), 1.16 (d, J = 5.7 Hz, 1H), 1.53 - 1.59 (m, 1H), 2.29 (s, 3H), 2.30 (s, 3H), 2.50 - 2.53 (m, 4H), 2.99 - 3.12 (m, 4H), 6.48 (s, 1H), 6.54 (s, 1H), 6.69 - 6.78 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 7.33 (d, J = 6.3 Hz, 1H), 7.46 - 7.51 (m, 1H). LCMS: 592.2 (M+H] + 。 Example 10 : (2S,3S)-N-(1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-2-( dimethylamino )-3- hydroxybutyramide This compound was prepared similar to Example 9 above. LCMS: 466.4 [M+H] + 。 Example 11 : N-(1- amino -4b- hydroxy -7-((1S,2S)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-5-(((S)-3-( dimethylamino ) pyrrolidin- -1- yl ) sulfonyl )-3- methyl -1H- pyrrole -2- formamide (89) Process -14 (S)-5-((3-(( tert-butoxycarbonyl ) amino ) pyrrolidin- -1- yl ) sulfonyl )-3- methyl -1-( phenylsulfonyl )-1H- pyrrole -2- methyl carboxylate (84) : Dissolve methyl 5-(chlorosulfonyl)-3-methyl-1-(phenylsulfonyl)-1H-pyrrole-2-carboxylate 75 (985 mg, 2.6 mmol) in DCM (26 mL). To this, add tert-butyl (S)-pyrrolidin-3-ylcarbamate (583 mg, 3.1 mmol), followed by DIPEA (0.7 mL, 3.9 mmol). Stir the reaction mixture at 30 °C for 15 h. Dilute the reaction mixture with DCM and wash with water and brine. The organic layer is dried over anhydrous Na 2 SO 4 dry and evaporate the solvent to obtain the crude product. Purify the crude material by silica gel column chromatography to obtain the solid product. (S)-5-((3-(( tert-Butoxycarbonyl ) amino ) pyrrolidine -1- yl ) sulfonyl )-3- methyl -1H- pyrrole -2- carboxylic acid (85) : To a solution of methyl (S)-5-((3-((tert-butoxycarbonyl)amino)pyrrolidin-1-yl)sulfonyl)-3-methyl-1-(phenylsulfonyl)-1H-pyrrole-2-carboxylate 84 (1.10 g, 2.1 mmol) in MeOH:THF:H 2 O (1:1:10) (42 mL), add LiOH.H 2 O (855 mg, 20.8 mmol) and stir the reaction mixture at 80 °C for 15 h. Evaporate the organic solvents. Acidify the reaction mixture with 1 N HCl solution, extract the aqueous layer with ethyl acetate, and wash the combined organic layers with brine. The organic layer is dried over Na 2 SO 4 dry and evaporate the solvent under vacuum to obtain the solid product. ((3S)-1-((5-((4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-4- nitro -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group ) carbamoyl )-4- methyl -1H- pyrrole -2- group ) sulfonyl ) pyrrolidine -3- group ) tert-butyl carbamate (86) : At 0 °C, EDCI (212 mg, 1.1 mmol) was added to a solution of (S)-5-((3-((tert-butoxycarbonyl)amino)pyrrolidin-1-yl)sulfonyl)-3-methyl-1H-pyrrole-2-carboxylic acid 85 (276 mg, 0.7 mmol) in DMF (7 mL), followed by the addition of HOBt (149 mg, 1.1 mmol). The mixture was stirred for 30 min, and then a racemic mixture of 9b-amino-4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 71 (260 mg, 0.7 mmol) was added, followed by DIPEA (0.4 mL, 2.2 mmol). The reaction mass was stirred at room temperature (30 °C) for 20 hours. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and with brine, and the organic layer was dried over Na 2 SO 4 and evaporated under vacuum to give the crude product. The crude material was purified by silica gel column chromatography to give the product. 5-(((S)-3- aminopyrrolidine -1- yl ) sulfonyl )-N-(4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-4- nitro -10- oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -1H- pyrrole -2- formamide (87) : To a stirred solution of the racemic mixture of tert-butyl ((3S)-1-((5-((4b-hydroxy-7-((E)-2-methylcyclopropyl)-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)-4-methyl-1H-pyrrol-2-yl)sulfonyl)pyrrolidin-3-yl)carbamate 86 (170 mg, 0.24 mmol) in DCM (5 mL, 0.05 M) was added 1,4-dioxane containing 4 N HCl (0.6 mL, 2.4 mmol), and the reaction mixture was stirred at room temperature (30 °C) for 12 h. The solvent was evaporated, the residue was dissolved in water (10 mL), and the solution was basified with 10% NaHCO 3 solution. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with water and brine, and the organic layer was dried over Na 2 SO 4 and evaporated in vacuo to give the product. 5-(((S)-3-( dimethylamino ) pyrrolidine -1- yl ) sulfonyl )-N-(4b- hydroxy -7-(( E )-2- methylcyclopropyl )-4- nitro -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -1H- Pyrrole -2- formamide (88) : At 0 °C, formaldehyde (35% aqueous solution) (0.34 mL, 3.9 mmol) was added to a stirred solution of the racemic mixture of 5-(((S)-3-aminopyrrolidin-1-yl)sulfonyl)-N-(4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrrole-2-carboxamide 87 (120 mg, 0.2 mmol) in glacial acetic acid:MeCN = 1:1 (7 mL, 0.03 M), and then NaBH 3 CN (62 mg, 1.0 mmol) was added. The reaction mixture was stirred at 0 °C for 2 hours. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate, and washed with water and brine. The organic layer was dried over Na 2 SO 4 dried and the solvent was evaporated in vacuo to give the crude product. The crude material was purified by silica gel column chromatography to give the product. N-(1- amino -4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-5-(((S)-3-( dimethylamino ) pyrrolidine -1- yl ) sulfonyl )-3- Methyl -1H- Pyrrole -2- Formamide (89) : To a stirred solution of the racemic mixture of 5-(((S)-3-(dimethylamino)pyrrolidin-1-yl)sulfonyl)-N-(4b-hydroxy-7-((trans)-2-methylcyclopropyl)-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-1H-pyrrole-2-carboxamide 88 (32 mg, 0.05 mmol) in EtOH:H2O (10:1) (5 mL) was added Fe powder (8 mg, 0.2 mmol) and concentrated HCl (1 drop) and the reaction mass was stirred at 90 °C for 3 hours. The hot reaction mass was filtered through a bed of diatomaceous earth. The filtrate was evaporated in vacuo, the resulting residue was dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over Na 2 SO 4 dried and the solvent was evaporated in vacuo to give the crude product. The crude product was purified by silica gel column chromatography to give the solid product. 1 1H-NMR (300 MHz, MeOD) δ 0.70 - 0.76 (m, 1H), 0.82 - 0.89 (m, 1H), 0.97 - 1.07 (m, 1H), 1.16 (d, J = 5.7 Hz, 3H), 1.53 - 1.59 (m, 1H), 1.62 - 1.72 (m, 1H), 2.02 - 2.08 (m, 1H), 2.22 (s, 6H), 2.31 (s, 3H), 2.64 - 2.75 (m, 1H), 2.98 - 3.05 (m, 1H), 3.16 - 3.27 (m, 1H), 3.41 - 3.53 (m, 2H), 6.48 (s, 1H), 6.58 (s, 1H), 6.69 - 6.77 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 7.33 (d, J = 7.2 Hz, 1H), 7.47 - 7.52 (m, 1H). LCMS: 606.3 (M+H] + . Example 12 : N-((4bR,9bR)-1- amino -4b- hydroxy -7-(( trans )-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,4- dimethyl -5-((4- methylpiper idin -1- yl ) sulfonyl )-1H- pyrrole -2- formamide Process-15 4-((5-( ethoxycarbonyl )-3,4- dimethyl )-1H- pyrrole -2- yl ) sulfonyl ) piper idin -1- tert-butylcarboxylate (123) : At room temperature, ethyl 5-(chlorosulfonyl)-3,4-dimethyl-1H-pyrrole-2-carboxylate (530 mg, 2.0 mmol) was placed in DCM (20 mL, 0.1 M), and tert-butyl piperazin-1-carboxylate (448 mg, 2.4 mmol) was added thereto, followed by the addition of DIPEA (0.52 mL, 3.0 mmoL). Subsequently, the reaction mixture was stirred at room temperature (25 °C) for an additional 18 hours. The reaction mixture was quenched with water (50 mL) and then extracted with DCM (70 mL × 2). The combined organic layers were washed with water (30 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to give the crude product. The crude product was purified by silica gel column chromatography (10 - 20% EA / hexane) to give the pure product. 5-((4-( tert-Butoxycarbonyl ) piper azin -1- yl ) sulfonyl )-3,4- dimethyl -1H- pyrrole -2- carboxylic acid (124) : 4-((5-(Ethoxycarbonyl)-3,4-dimethyl-1H-pyrrol-2-yl)sulfonyl)piperazin-1-carboxylic acid tert-butyl ester (580 mg, 1.4 mmol) was placed in THF:MeOH:H 2 O (1:1:10, 28.0 mL, 0.05 M), and LiOH.H 2 O (294 mg, 7.0 mmol) was charged, and the reaction was refluxed at 80 °C for 5 hours. The reaction mixture was concentrated to remove volatiles. Subsequently, it was acidified with 1 N HCl (pH < 2 - 3). The precipitated solid was then filtered out, washed with cold water and dried to give the product. 4-(5-((4b- hydroxy -7- Isopropyl -4- Nitro -10- Lateral oxy group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group ) Carbamoyl )-3,4- Dimethyl -1H- Pyrrole -2- Carbonyl ) Piper 𠯤 -1- Tert-butyl carboxylate (125) : 5-(4-(tert-Butoxycarbonyl)piperidin-1-carbonyl)-3,4-dimethyl-1H-pyrrole-2-carboxylic acid (264 mg, 0.75 mmol) was placed in DMF (4 mL, 0.2 M) and cooled to 0 °C. To this was charged EDC·HCl (216 mg, 1.125 mmol) and HOBt (152 mg, 1.125 mmol). After 10 min, 9b-amino-4b-hydroxy-7-isopropyl-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one (255 mg, 0.75 mmol) was charged thereto, followed by addition of DIPEA (0.33 mL, 1.875 mmol) and allowing it to reach room temperature (35 °C) by itself. It was stirred for another 18 h. The reaction mixture was then quenched with water (30 mL) and extracted with EA (50 mL × 2). The organic layer was washed with brine (30 mL), dried over anhydrous Na 2 SO 4 dried and concentrated. The crude product was purified by silica gel column chromatography (20 - 50% EA:MeOH (4:1) / hexane) to obtain an impure product, which was purified again with the MeOH / DCM system to obtain the pure product. N-(4b- hydroxy -7- isopropyl -4- nitro -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,4- dimethyl -5-( piper azin -1- carbonyl )-1H- pyrrole -2- formamide (126) : 4-(5-((4b-Hydroxy-7-isopropyl-4-nitro-10-side oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)-3,4-dimethyl-1H-pyrrole-2-carbonyl)piperazin-1-carboxylic acid tert-butyl ester (135 mg, 0.2 mmol) was placed in DCM (2.0 mL, 0.1 M), and 4 M HCl in dioxane (0.50 mL, 2.0 mmol) was added thereto. It was stirred at room temperature (25 °C) for 15 hours. The reaction material was concentrated and the residue was placed in EA (20 - 30 mL) and stirred with saturated NaHCO 3 (about 20 mL) for 5 - 10 min. It was extracted with EA (50 mL × 2). The combined organic layers were washed with water (30 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to give the crude product. The crude material was used in the next step without further purification. N-(4b- Hydroxyl -7- Isopropyl -4- Nitro -10- Lateral oxygen group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group )-3,4- Dimethyl -5-(4- Methylpiperidine 𠯤 -1- Carbonyl )-1H- Pyrrole -2- Formamide (127) : Dissolve N-(4b-Hydroxy-7-isopropyl-4-nitro-10-lateral oxygen group-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,4-dimethyl-5-(piperidine-1-carbonyl)-1H-pyrrole-2-carboxamide (90 mg, 0.15 mmol) in MeCN: glacial acetic acid (2:1, 3 mL, 0.05 M), and cool to 0 °C. Charge 35% aqueous HCHO solution (0.13 mL, 1.5 mmol) into this, and then add NaBH 3 CN (33 mg, 0.525 mmol). Stir it at 0 °C for another 2 hours. Quench the reaction mixture with water (20 mL) and saturated NaHCO 3 (20 mL), and extract with EA (40 mL×2). Wash the combined organic layers with water (30 mL) and brine (10 mL). Dry it over anhydrous Na 2 SO 4 Dry and concentrate to obtain the crude product. Purify the crude product by flash silica gel column chromatography (0-5% MeOH / DCM) to obtain the pure product. N-(1- amino -4b- hydroxy -7- isopropyl -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,4- dimethyl -5-(4- methylpiperazin- 1-yl -1- carbonyl )-1H- pyrrole -2- formamide (128) : Dissolve N-(4b-hydroxy-7-isopropyl-4-nitro-10-side oxy group-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,4-dimethyl-5-(4-methylpiperazin-1-ylcarbonyl)-1H-pyrrole-2-formamide (60 mg, 0.1 mmol) in EtOH : water (10:1, 5.0 mL, 0.02 M), add Fe powder (17 mg, 0.3 mmol) to it, and then add 6.0 M HCl (1 drop). Reflux the mixture at 90 °C for 2.0 h. Filter the reaction mixture through diatomaceous earth using EA (30 mL) under warm conditions. Concentrate the filtrate and dissolve it in EA (100 mL), and wash it with saturated NaHCO 3 (20 mL×2), water (20 mL×2), and brine (20 mL). Dry it over anhydrous Na 2 SO 4It was dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (0 - 10% MeOH / DCM) to obtain the pure product. 1H NMR (500 MHz, METHANOL-d4) δ: 7.48 (br s, 2H), 7.05 (br s, 1H), 6.89 (br s, 1H), 6.70 (br s, 2H), 3.10 (br s, 4H), 2.87 (dt, J = 13.4, 6.6 Hz, 1H), 2.51 (br t, J = 4.4 Hz, 4H), 2.29 (s, 3H), 2.22 (s, 3H), 2.21 (s, 3H), 1.21 (d, J = 6.9 Hz, 6H); LCMS: 594.2 (M+H] + Example 13 : N-(1- amino -4b- hydroxy -7- isopropyl -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-((4- methylpiper yl -1- yl ) sulfonyl )-1H- pyrrole -2- formamide The above compound was prepared by the following procedure. Procedure - 16 4-((5-((4b- hydroxy -7- isopropyl -4- nitro -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group ) carbamoyl )-4- methyl -1H- pyrrole -2- group ) sulfonyl ) piper azepane -1- tert-butyl carboxylate (122) : 5 - ((4 - (tert-Butoxycarbonyl)piperazin-1-yl)sulfonyl)-3-methyl-1H-pyrrole-2-carboxylic acid 79 (384 mg, 1.0 mmol) was placed in DMF (10 mL, 0.1 M) and cooled to 0 o °C. To this were sequentially charged EDCI (288 mg, 1.5 mmol), HOBt (203 mg, 1.5 mmol). After 10 min, 9b-amino-4b-hydroxy-7-isopropyl-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 37 (340 mg, 1.0 mmol), DIPEA (0.43 mL, 2.5 mmol) were sequentially charged thereto and allowed to reach room temperature (35 °C) for an additional 12 hours. The reaction mixture was then quenched with water (30 mL) and extracted with EA (50 mL × 2). The combined organic layers were washed with water (30 mL) and brine (30 mL). It was dried over anhydrous Na 2 SO 4Dry and concentrated. The crude product was purified by silica gel column chromatography (25 - 30% EA / hexane) to obtain the product. N-(4-((l1- amino ) peroxy )-4b- hydroxy -7- isopropyl -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-( piper il -1- yl sulfonyl )-1H- pyrrole -2- formamide (122-1) At room temperature, 4N HCl in dioxane (1.2 mL, 4.9 mmol) was added to a stirred solution of tert-butyl 4-((5-((4b-hydroxy-7-isopropyl-4-nitro-10-side oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamoyl)-4-methyl-1H-pyrrol-2-yl)sulfonyl)piperidin-1-carboxylate (340 mg, 0.49 mmol) in DCM (10 mL). The resulting reaction mixture was stirred at room temperature for 15 hours. The reaction mixture was evaporated to dryness, and the resulting residue was dissolved in water (50 mL) and basified with saturated NaHCO 3 solution. The product was extracted with EA (50 mL × 3), and the combined organic layers were washed with water and brine. The organic layer was dried over anhydrous Na 2 SO 4Dry to evaporate the solvent to obtain the crude product. The crude material was purified by silica gel column chromatography (MeOH:DCM = 1:20) to obtain the desired product. N-(4-((l1- amino ) peroxy )-4b- hydroxy -7- isopropyl -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group )-3- methyl -5-((4- methylpiper ylidene -1- group ) sulfonyl )-1H- pyrrole -2- formamide (122-2) At 0 °C, 35% formaldehyde solution (0.15 mL, 1.7 mmol) was added to a stirred solution of N-(4-((l1-amino)peroxy)-4b-hydroxy-7-isopropyl-10-side oxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-(piper ylidene-1-ylsulfonyl)-1H-pyrrole-2-formamide 122-1 (100 mg, 0.17 mmol) in glacial acetic acid:MeCN (4 mL), and then NaBH 3 CN (36 mg, 0.6 mmol) was added. The resulting reaction mixture was stirred at 0 °C for 2 hours. The reaction mixture was quenched with water and the desired product was extracted with EA (50 mL×3). The combined organic layers were washed with water and brine. The organic layer was dried over anhydrous Na 2 SO 4 Dry and evaporate the solvent to obtain the crude product. The crude material was purified by silica gel column chromatography (MeOH:DCM = 1:20) to obtain the desired product. N-(1- amino -4b- hydroxy -7- isopropyl -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-((4- methylpiper azin -1- yl ) sulfonyl )-1H- pyrrole -2- formamide (122-3) Add Fe powder (14 mg, 0.25 mmol) to N-(4-((11-amino)peroxy)-4b-hydroxy-7-isopropyl-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-formamide (51 mg, 0.08 mmol) in a stirred solution of EtOH:H 2 O (3 mL), then add concentrated HCl (1 drop). The resulting reaction mixture was refluxed at 90 °C for 3 h. The hot reaction mixture was filtered through a bed of diatomaceous earth and washed with EA. The organic layer was evaporated to dryness, and the resulting residue was dissolved in EA (100 mL) and washed with water (50 mL × 2) and brine. The organic layer was dried over anhydrous Na 2 SO 4 Dry, evaporate the solvent to obtain the crude product. The crude material was purified by silica gel column chromatography to obtain the desired product. 1 H NMR (300 MHz, MeOD) δ 7.42 - 7.33 (m, 1H), 7.03 (d, J = 7.4 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.81 - 6.72 (m, 1H), 6.69 (s, 1H), 6.52 (s, 1H), 3.11 - 2.98 (m, 4H), 2.89 - 2.80 (m, 1H), 2.59 - 2.46 (m, 4H), 2.28 (s, 3H), 1.19 (d, J = 6.9 Hz, 6H). Mass: [M + H] + : 580.1 Example 14 : N - ((4bR,9bR) - 1 - amino - 4b - hydroxy - 7 - ((1S,2S) - 2 - methylcyclopropyl ) - 10 - oxo - 4b,10 - dihydro - 9bH - indeno [1,2 - b] benzofuran - 9b - yl ) - 3 - methyl - 5 - ((4 - methylpiper idin - 1 - yl ) sulfonyl ) - 1H - pyrrole - 2 - formamide Process - 17 This compound was prepared according to the above procedure using 3,4-dimethylpyrrole derivatives similar to Example 12. (300 MHz, MeOD) δ 0.70 - 0.76 (m, 1H), 0.81 - 0.89 (m, 1H), 0.98 - 1.02 (m, 1H), 1.16 (d, J = 5.7 Hz, 1H), 1.53 - 1.59 (m, 1H), 2.29 (s, 3H), 2.30 (s, 3H), 2.50 - 2.53 (m, 4H), 2.99 - 3.12 (m, 4H), 6.48 (s, 1H), 6.54 (s, 1H), 6.69 - 6.78 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 7.33 (d, J = 6.3 Hz, 1H), 7.46 - 7.51 (m, 1H). LCMS: 592.1 [M+H]+, HPLC purity: 95.4% Example 15 : (2S,3S)-N-((4bR,9bR)-1- amino -7-((S)-1- cyclopropylethyl )-4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-2-( dimethylamino )-3- hydroxybutyramide This compound was prepared similar to Example 12 above. LCMS: 466.3 [M+H] + . Example 16 : N-(1- amino -4b- Hydroxy -7-((1R,2S)-2- Methylcyclopropyl )-10- Lateral oxygen -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group )-3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Formamide This compound was prepared similar to Example 12 above. LCMS: 508.3 [M+H] + . Example 17 : N-((4bR,9bR)-1- Amino -7-((R)-1- Cyclopropylethyl )-4b- Hydroxy -10- Lateral oxygen -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group )-2-( Azetidine -1- Group ) Acetamide (92) Process-18 ((4bR,9bR)-1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) tert-butyl carbamate (90) : Under nitrogen, ((4bR,9bR)-1-amino-7-(1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl) tert-butyl carbamate 59 (174 mg, 0.40 mmol) was placed in DCM (8.0 mL, 0.05 M) and loaded with [((4 R, 5 R)-Cy2-UBaphox)Ir(COD)]BARF (13.9 mg, 0.008 mmol). Subsequently, it was flushed with H 2 gas, and then maintained at room temperature (20 °C) for 4 hours under an H 2 atmosphere (60 psi). Subsequently, the reaction mixture was concentrated and passed through a short plug of silica gel. It was concentrated to give a crude product. The crude product was purified by silica gel column chromatography and then by preparative HPLC (ADH column (Diacel 250×20 mm, EtOH:MeOH:hexane = 36:4:60). (4bR,9bR)-1,9b- diamino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -4b,9b- dihydro -10H- Indeno [1,2-b] benzofuran -10- one (91) : The enantiopure ((4bR,9bR)-1-amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-formyloxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl) carbamic acid tert-butyl ester 90 (70 mg, 0.16 mmol) was placed in DCM (1.6 mL, 0.1 M) and immediately charged with 4.0 M HCl in dioxane (0.40 mL, 1.60 mmol). The reaction mixture was then stirred at room temperature (20 °C) for an additional 6 hours. The reaction mixture was diluted with EA (ca. 50 mL) and stirred with saturated NaHCO 3 (ca. 30 mL) for 5 - 10 min. The layers were separated and the aqueous layer was extracted with EA (ca. 30 mL × 2). The combined organic layers were washed with water (30 mL) and brine (ca. 30 mL). It was dried over anhydrous Na 2 SO 4 dried and concentrated to give the crude solid product, which was used as such without further purification in the next step. N-((4bR,9bR)-1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- formyloxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-2-( azetidine -1- yl ) acetamide (92) : At 0 °C, HATU (87.5 mg, 0.23 mmol) and DIPEA (79 μL, 0.23 mmol) were charged into 1.5 mL of anhydrous DMF (0.1 M) containing 2-(azetidin-1-yl)acetic acid hydrochloride 58 (34 mg, 0.23 mmol). After 10 min, (4bR,9bR)-1,9b-diamino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 91 (51 mg, 0.15 mmol) was charged into this and stirred at room temperature (20 °C) for 15 hours. The reaction mixture was quenched with water (about 20 mL) and saturated NaHCO 3 (about 30 mL). It was extracted with EA (50 mL × 3). The combined organic layers were washed with water (30 mL × 2), brine (30 mL) and dried over anhydrous Na 2 SO 4 dried and concentrated to obtain the crude product. The crude product was purified by silica gel column chromatography (0 - 10% MeOH / DCM) to obtain the solid product. 1 1H-NMR (300 MHz, MeOD) δ 7.51 - 7.39 (m, 1H), 7.28 (d, J = 7.9 Hz, 1H), 6.99 (d, J = 7.0 Hz, 1H), 6.85 (dd, J = 7.9, 1.3 Hz, 1H), 6.78 - 6.65 (m, 2H), 3.38 (t, J = 7.2 Hz, 4H), 3.19 (s, 2H), 2.14 - 2.03 (m, 2H), 1.91-1.84 (m, 1H), 1.25 (d, J = 7.0 Hz, 3H), 0.96 - 0.80 (m, 1H), 0.54-0.49 (m, 1H), 0.37-0.32 (m, 1H), 0.23 - 0.12 (m, 1H), 0.10-0.02 (m, 1H). LCMS: 432.2 [M - H] -。LCMS: 434.3 [M+H] + 。 Example 18 : N-((4bR,9bR)-1- amino -7-((S)-1- cyclopropylethyl )-4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-1,5- dimethyl -2- oxo -2,3- dihydro -1H- imidazole -4- formamide This compound was prepared similar to Example 15 above. LCMS: 475.1 [M+H] + 。 Example 19 and 20 : N-((4bR,9bR)-1- amino -4b- hydroxy -7- isopropoxy -10- oxo -4b,10- dihydro -9bH- Indocyanine [1,2-b] Benzofuran -9b- base )-3- methyl -5-((4- Methylpiperidone 𠯤 -1- base ) Sulfonyl )-1H- Pyrrole -2- Formamide (101) and N-((4bS,9bS)-1- Amine -4b- Hydroxyl -7- Isopropoxy -10- Pendant -4b,10- Dihydrogen -9bH- Indocyanine [1,2-b] Benzofuran -9b- base )-3- methyl -5-((4- Methylpiperidone 𠯤 -1- base ) Sulfonyl )-1H- Pyrrole -2- Formamide (102) : Process-19 4b,9b- Dihydroxy -7- isopropoxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- ketone (94) : Dissolve 4-nitro-1H-indene-1,3(2H)-dione 4 (10.0 g, 52.3 mmol) in AcOH:dioxane (1:10, 105 mL, 0.5 M). Charge SeO 2 (12.77 g, 115.1 mmol) and reflux at 105 - 110 °C for 5 hours. Subsequently, filter the reaction mass through diatomaceous earth under hot conditions, and then concentrate the volatiles to obtain the crude 2,2-dihydroxy-4-nitro-1H-indene-1,3(2H)-dione 5. Dissolve this crude product in acetic acid (106 mL) and add 3-isopropoxyphenol 93 (8.1 g, 53 mmol) thereto. Heat the resulting reaction mass at 80 °C for 4 hours. Cool the reaction mass to room temperature and dilute with ethyl acetate. Filter the reaction mass through a diatomaceous earth bed and wash with ethyl acetate. Evaporate the solvent to dryness. Purify the residue by silica gel column chromatography (ethyl acetate:hexane) to obtain the solid product. 9b- chloro -4b- hydroxy -7- isopropoxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- ketone (95) : Dissolve 4b,9b-dihydroxy-7-isopropoxy-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 94 (5.4 g, 15 mmol) in DCM (75 mL). To this, add oxalyl chloride (2.6 mL, 30 mmol), and then add DMF (5.4 mL) dropwise. Stir the reaction mixture at room temperature for 18 h. The reaction mixture is diluted with DCM (300 mL) and the organic layer is washed with water (200 mL×2) and with brine, and then dried over Na 2 SO 4 2. Evaporate the solvent to obtain the crude product. The crude material is purified by silica gel column chromatography (ethyl acetate:hexane) to obtain the solid product. 9b- amino -4b- hydroxy -7- isopropoxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one (96) : This compound was prepared similar to the above compound 37. 4-((5-((4b- hydroxy -7- isopropoxy -4- nitro -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) carbamoyl )-4- methyl -1H- Pyrrole -2- base ) Sulfonyl ) Piperidone 𠯤 -1- Tributyl carboxylate (97) : 5-((4-(tributyloxycarbonyl)piperidin-1-yl)sulfonyl)-3-methyl-1H-pyrrole-2-carboxylic acid 79 (240 mg, 0.65 mmol) was dissolved in DMF (6.5 mL). The resulting solution was cooled to 0 °C, and EDCI (187 mg, 0.975 mmol), HOBT (132 mg, 0.975 mmol) and DIPEA (0.283 mL, 1.625 mmol) were added at 0 °C. The reaction mass was stirred for 30 min. 9b-amino-4b-hydroxy-7-isopropoxy-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 96 (232 mg, 0.65 mmol) was then added and the reaction was stirred at 30°C for 15 hours. The reaction was quenched with water (100 ml) and the aqueous layer was extracted with ethyl acetate (3×100 ml). The organic layers were combined, washed with water and brine solution and purified by Na 2 SO 4 The mixture was dried. The solvent was evaporated under vacuum. The residue was purified by silica gel column chromatography (methanol: DCM) to obtain a solid product. N-(4b- Hydroxyl -7- Isopropoxy -4- Nitro -10- Pendant -4b,10- Dihydrogen -9bH- Indocyanine [1,2-b] Benzofuran -9b- base )-3- methyl -5-( Piperidone 𠯤 -1- Sulfonyl )-1H- Pyrrole -2- Formamide (98) : Tributyl 4-((5-((4b-hydroxy-7-isopropoxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamyl)-4-methyl-1H-pyrrol-2-yl)sulfonyl)piperidin-1-carboxylate 97 (145 mg, 0.2 mmol) was dissolved in DCM (4 mL). To this solution was added 4 M HCl in dioxane (0.5 mL). The clear solution was stirred at room temperature for 15 h. The DCM was evaporated under vacuum. The residue was dissolved in water (100 mL) and the aqueous solution was treated with saturated NaHCO 3 The solution was neutralized. The aqueous layer was extracted with ethyl acetate (100 mL×2), and the organic layers were combined and washed with water and saline solution. 2 SO 4 Drying and evaporation of the solvent gave a crude solid product. The crude material was used as is in the next step without further purification. N-(4b- Hydroxyl -7- Isopropoxy -4- Nitro -10- Pendant -4b,10- Dihydrogen -9bH- Indocyanine [1,2-b] Benzofuran -9b- base )-3- methyl -5-((4- Methylpiperidone 𠯤 -1- base ) Sulfonyl )-1H- Pyrrole -2- Formamide (99) : N-(4b-Hydroxy-7-isopropoxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-(piperidin-1-ylsulfonyl)-1H-pyrrole-2-carboxamide 98 (115 mg, 0.188. mmol) was dissolved in glacial acetic acid: MeCN (1:1) (5 mL). The solution was cooled to 0 °C and formaldehyde (0.161 mL, 1.88 mmol) was added to it, followed by NaBH 3 CN (41 mg, 0.658 mmol). The resulting suspension was stirred at 0°C to 5°C for 1.5 hours. Acetonitrile was evaporated and the residue was quenched with water and the aqueous layer was extracted with ethyl acetate (50 mL×3). The organic layers were combined and washed with water and then with saline solution. The organic layer was purified by Na 2 SO 4 The residue was dried and the solvent was evaporated to give a crude product. The crude product was purified by silica gel column chromatography (methanol:DCM) to give a solid product. N-(1- Amine -4b- Hydroxyl -7- Isopropoxy -10- Pendant -4b,10- Dihydrogen -9bH- Indocyanine [1,2-b] Benzofuran -9b- base )-3- methyl -5-((4- Methylpiperidone 𠯤 -1- base ) Sulfonyl )-1H- Pyrrole -2- Formamide (100) : N-(4b-Hydroxy-7-isopropoxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperidin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide 99 (66 mg, 0.105 mmol) was dissolved in EtOH-water mixture (1:1, 3.5 mL), Fe powder (18 mg, 0.315 mmol) and concentrated HCl (1 drop) were added. The clear solution was refluxed at 90 °C for 3 hours. The hot reaction mass was filtered through a celite pad and washed with ethyl acetate. The organic layer was evaporated under vacuum. The residue was dissolved in ethyl acetate (200 mL) and washed with water (75 mL x 2), and then with a saline solution. 2 SO 4 Drying and evaporation under vacuum gave a crude product. The crude material was purified by silica gel column chromatography (methanol:DCM) to give a solid product. 1 H-NMR (300 MHz, CD3OD) δ 1.28 (dd, J = 6 Hz, J = 1.6 Hz, 6H), 2.29 (s, 6H), 2.51 - 2.54 (m, 4H), 3.06 (br, 4H),4.51 - 4.59 (m, 1H) 6.38 (d, J = 1.9 Hz, 1H), 6.54 (br, 2H), 6.79(br, 1H), 7.04 (d, J = 7.2 Hz, 1H), 7.34 (br, 1H), 7.47 - 7.52 (m, 1H). LCMS:596.5[M+1] + . N-((4bR,9bR)-1- Amine -4b- hydroxy -7- isopropoxy -10- lateral oxygen group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group )-3- methyl -5-((4- methylpiper 𠯤 -1- group ) sulfonyl )-1H- pyrrole -2- formamide (101) and N-((4bS,9bS)-1- amino -4b- hydroxy -7- isopropoxy -10- lateral oxygen group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group )-3- methyl -5-((4- methylpiper 𠯤 -1- group ) sulfonyl )-1H- Pyrrole -2- Formamide (102) : N-(1-Amino-4b-hydroxy-7-isopropoxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide (100) (90 mg) as a racemate was purified by chiral chromatography using (IA column, HPLC = 20 ml / min, heptane / EtOH = 30 / 70, 2562 psi) to give 37.5 mg of N-((4bR,9bR)-1-amino-4b-hydroxy-7-isopropoxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide (101) as (peak 2, tR 16.32 min.), 1H NMR (METHANOL-d4) δ: 7.43-7.53 (m, 1H), 7.39 (br d, J = 12.3 Hz, 1H), 7.02 (br s, 1H), 6.72 (br s, 1H), 6.55 (s, 2H), 6.36 (br s, 1H), 4.54 (dt, J = 12.0, 5.9 Hz, 1H), 3.11 (br s, 4H), 2.75 (br s, 4H), 2.45 (br s, 3H), 2.29 (s, 3H), 1.25-1.28 (m, 6H); LCMS: 596.6 [M + H] +And 36.4 mg of N-((4bS,9bS)-1-amino-4b-hydroxy-7-isopropoxy-10-sideoxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-((4-methylpiperazin-1-yl)sulfonyl)-1H-pyrrole-2-carboxamide (102) as (peak 1, tR 5.70 min); 1H NMR (METHANOL-d4) δ: 7.48 (br s, 1H), 7.24 - 7.42 (m, 1H), 7.03 (br d, J = 5.9 Hz, 1H), 6.67 - 6.82 (m, 1H), 6.53 (s, 2H), 6.36 (br s, 1H), 4.54 (dt, J = 11.9, 6.1 Hz, 1H), 3.07 (br s, 4H), 2.59 (br s, 4H), 2.33 (s, 3H), 2.28 (s, 3H), 1.24 - 1.31 (m, 6H); LCMS: 596.0 [M + H] + 。 Example 21 : N-(1- amino -4b- hydroxy -7-((1S,2R)-2- methylcyclopropyl )-10- sideoxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-( methylsulfonyl )-1H- pyrrole -2- carboxamide Process-19B N-[9- Hydroxyl -5-[(1S,2R)-2- Methylcyclopropyl ]-11- Nitro -16- Side oxy group -8- Oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] Hexadecane -2(7),3,5,10,12,14- Hexaene -1- Group ]-5- Methanesulfonyl -3- Methyl -1H- Pyrrole -2- Formamide (19B-1) : Place 5-methanesulfonyl-3-methyl-1H-pyrrole-2-carboxylic acid (259 mg, 1.27 mmol, 1.50 equivalents), HOBt (172 mg, 1.27 mmol, 1.50 equivalents), EDCI (243 mg, 1.27 mmol, 1.50 equivalents), N,N-dimethylformamide (5 mL), 1-amino-9-hydroxy-5-[(1S,2R)-2-methylcyclopropyl]-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadecane-2(7),3,5,10,12,14-hexaen-16-one (300 mg, 0.85 mmol, 1.00 equivalent) and triethylamine (257 mg, 2.54 mmol, 3.00 equivalents) in a 50 mL round-bottom flask. The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane / methanol (25 / 1). This gave 250 mg (55%) of a yellow solid of N-[9-Hydroxy-5-[(1S,2R)-2-methylcyclopropyl]-11-nitro-16-sidemethyloxy-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadecane-2(7),3,5,10,12,14-hexaen-1-yl]-5-methanesulfonyl-3-methyl-1H-pyrrole-2-carboxamide (19B-1). N-[14- Amino -9- Hydroxy -5-[(1S,2R)-2- Methylcyclopropyl ]-16- Sidemethyloxy -8- Oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] Hexadecane -2(7),3,5,10,12,14- Hexaene -1- yl ]-5- Methanesulfonyl -3- Methyl -1H- Pyrrole -2- Carboxamide (19B-2) : Place in a 50 mL round-bottom flask N-[9-Hydroxy-5-[(1S,2R)-2-methylcyclopropyl]-11-nitro-16-oxo-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-1-yl]-5-methanesulfonyl-3-methyl-1H-pyrrole-2-carboxamide (19B-1) (250 mg, 0.47 mmol, 1.00 equivalent), Fe (78 mg, 3.00 equivalents), ethanol (10 mL), water (1 mL), hydrogen chloride (0.1 mL). The resulting solution was stirred in an oil bath at 85 °C for 2 h. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane / methanol (20 / 1). This gave 108 mg (46%) of N-(1-amino-4b-hydroxy-7-((1S,2R)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-5-(methylsulfonyl)-1H-pyrrole-2-carboxamide (19B-2). 1 H NMR (300 MHz, CD 3 OD) δ 7.54-7.43 (m, 1H), 7.41-7.35 (m, 1H), 7.08-7.00 (m, 1H), 6.90-6.80 (m, 1H), 6.80-6.75 (m, 1H), 6.69-6.60 (m, 2H), 3.13 (s, 3H), 2.29 (s, 3H), 2.12-1.98 (m, 1H), 1.23-1.05 (m, 1H), 1.03 -0.88 (m, 1H), 0.81-0.72 (m, 3H), 0.64-0.52 (m, 1H); LC-MS (ES, m / z): [M+H] + 508.0 (The stereochemistry on the cyclopropane is relative and absolutely unknown) Example 22 , 29 and 30 : N-(1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group )-1,5- dimethyl -2- side oxy group -2,3- dihydro -1H- imidazole -4- formamide (29) , N-((4bR,9bR)-1- amino -7-((R)-1- cyclopropyl ethyl )-4b- hydroxy -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group )-1,5- dimethyl -2- side oxy group -2,3- dihydro -1H- imidazole -4- formamide (22) and N-((4bS,9bS)-1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- side oxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-1,5- dimethyl -2- side oxy -2,3- dihydro -1H- imidazole -4- formamide (30) Process-19C (1R)-1-[3-( benzyloxy ) phenyl ] ethyl -1- alcohol (19C-1) : Place 1-[3-(benzyloxy)phenyl]ethan-1-one (10 g, 44.19 mmol, 1.00 equivalent), MeCN (30 mL), triethylamine (6.7 g, 66.21 mmol, 1.50 equivalent), [Ru(p-cymene)Cl 2 2 (136 mg, 0.22 mmol, 0.01 equivalent), (1R,2R)-TsDpen (330 mg, 0.89 mmol, 0.02 equivalent), HCO 2H (6.1 g, 3.00 equivalents). The resulting solution was stirred at room temperature for 12 h. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (20 / 80). This gave 4 g (40%) of (1R)-1-[3-(benzyloxy)phenyl]ethan-1-ol as a colorless oil. N,N- bis ( prop -2- yl ) carbamic (1R)-1-[3-( benzyloxy ) phenyl ] ethyl ester (19C-2) : To a 50 mL round-bottom flask was placed (1R)-1-[3-(benzyloxy)phenyl]ethan-1-ol (3.5 g, 15.33 mmol, 1.00 equivalent), CH 3 CN (15 mL), N,N-bis(prop-2-yl)carbamoyl chloride (2.9 g, 17.72 mmol, 1.15 equivalents), and TEA (1.9 g, 18.78 mmol, 1.20 equivalents). The resulting solution was stirred at 80 °C for 12 h. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (15 / 85). This gave 5.3 g (97%) of N,N-bis(prop-2-yl)carbamic (1R)-1-[3-(benzyloxy)phenyl]ethyl ester as a yellow oil. 2-[(1R)-1-[3-( benzyloxy ) phenyl ]-1- cyclopropylethyl ]-4,4,5,5- tetramethyl -1,3,2- dioxaborolane (19C-3) : Place N,N-bis(prop-2-yl)carbamic acid (1R)-1-[3-(benzyloxy)phenyl]ethyl ester (5.3 g, 14.91 mmol, 1.00 equivalent), diethyl ether (100 mL), and 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5 g, 29.75 mmol, 2.00 equivalents) into a 500 mL three-necked round-bottom flask. Subsequently, add LDA (14.9 mL, 2 mol / L, 2.00 equivalents) dropwise at -20 °C. Stir the resulting solution at room temperature for 12 h. Then quench the reactants by adding methanol. Concentrate the resulting mixture in vacuo. Apply the residue onto a silica gel column with ethyl acetate / petroleum ether (15 / 85). This gives 4.1 g (73%) of 2-[(1R)-1-[3-(benzyloxy)phenyl]-1-cyclopropylethyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as a yellow oil. 1-( benzyloxy )-3-[(1R)-1- cyclopropylethyl ] benzene (19C-4) : Place 2-[(1R)-1-[3-(benzyloxy)phenyl]-1-cyclopropylethyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4 g, 10.57 mmol, 1.00 equivalent), n-pentane (50 mL), and TBAF·3H 2 O (5 g, 15.87 mmol, 1.50 equivalents) into a 100 mL round-bottom flask. Stir the resulting solution at 45 °C for 12 h. Concentrate the resulting mixture in vacuo. Apply the residue onto a silica gel column with ethyl acetate / petroleum ether (10 / 90). This gives 2.4 g (90%) of 1-(benzyloxy)-3-[(1R)-1-cyclopropylethyl]benzene as a yellow oil. 3-[(1R)-1- cyclopropylethyl ] phenol (19C-5) : Place 1-(benzyloxy)-3-[(1R)-1-cyclopropylethyl]benzene (2.1 g, 8.32 mmol, 1.00 equivalent), methanol (20 mL), and palladium on carbon (200 mg) into a 100 mL round-bottom flask. Stir the resulting solution at room temperature under H 2Stir for 2 h under the atmosphere. Filter out the solid. Concentrate the resulting mixture in vacuo. Apply the residue onto a silica gel column with ethyl acetate / petroleum ether (15 / 85). This gives 1.3 g (96%) of 3-[(1R)-1-cyclopropylethyl]phenol as a colorless oil. 5-[(1R)-1- cyclopropylethyl ]-1,9- dihydroxy -11- nitro -8- oxatricyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexaene -16- one (19C-6) : Place 3-[(1R)-1-cyclopropylethyl]phenol (1.3 g, 8.01 mmol, 1.00 equivalent), acetic acid (20 mL) and 2,2-dihydroxy-4-nitro-2,3-dihydro-1 H-indene-1,3-dione (1.8 g, 8.07 mmol, 1.00 equivalent) into a 100 mL round-bottom flask. Stir the resulting solution at 120 °C for 2 hours. Concentrate the resulting mixture in vacuo. Apply the residue onto a silica gel column with ethyl acetate / petroleum ether (30 / 70). This gives 2.2 g (75%) of 5-[(1R)-1-cyclopropylethyl]-1,9-dihydroxy-11-nitro-8-oxatricyclo[7.7.0.0^[2,7].0^[10,15]]hexadecane-2(7),3,5,10,12,14-hexaene-16-one as a yellow solid. 1- chloro -5-[(1R)-1- cyclopropylethyl ]-9- hydroxy -11- nitro -8- oxatricyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexaene -16- ketone (19C-7) : Place 5-[(1R)-1-cyclopropylethyl]-1,9-dihydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaene-16-one (4.1 g, 11.16 mmol, 1.00 equivalent), dichloromethane (20 mL), N,N-dimethylformamide (2 mL), and oxalyl chloride (16.7 mL, 3.00 equivalents) in a 100 mL round-bottom flask. Stir the resulting solution at 45 °C for 2 hours. Then quench the reaction by adding water / ice. Extract the resulting solution with dichloromethane. Combine the organic layers and concentrate under vacuum. This gives 4.5 g (crude) of 1-chloro-5-[(1R)-1-cyclopropylethyl]-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaene-16-one as a brown oil. 1- amino -5-[(1R)-1- cyclopropylethyl ]-9- hydroxy -11- nitro -8- oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexaene -16- ketone (19C-8) : Place 1-chloro-5-[(1R)-1-cyclopropylethyl]-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexen-16-one (4.5 g, 11.66 mmol, 1.00 equivalent) in a 250 mL round-bottom flask, and dropwise add IPA (17.5 mL, 3.00 equivalents) containing NH 3 in THF (30 mL) at -50 °C. Stir the resulting solution at -50 °C for 2 hours. Concentrate the resulting mixture under vacuum. Apply the residue to a silica gel column with ethyl acetate / petroleum ether (35 / 65). This gives 3.5 g (82%) of 1-amino-5-[(1R)-1-cyclopropylethyl]-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexen-16-one as a yellow solid. N-[5-[(1R)-1- cyclopropylethyl ]-9- hydroxy -11- nitro -16- oxo -8- oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexene -1- yl ]-1,5- dimethyl -2- oxo -2,3- dihydro -1H- imidazole -4- formamide (19C-9) : Place 1,5-dimethyl-2-oxo-2,3-dihydro-1 H-Imidazole-4-carboxylic acid (1.3 g, 8.33 mmol, 1.20 equivalents), EDCI (1.6 g, 8.35 mmol, 1.20 equivalents), HOBt (1.1 g, 8.14 mmol, 1.20 equivalents), N,N-dimethylformamide (5 mL), 1-amino-5-[(1R)-1-cyclopropylethyl]-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one (2.5 g, 6.82 mmol, 1.00 equivalent) and triethylamine (2.3 mL, 3.00 equivalents). The resulting solution was stirred at room temperature for 12 h. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane / methanol (20 / 1). This gave 1.4 g (41%) of N-[5-[(1R)-1-cyclopropylethyl]-9-hydroxy-11-nitro-16-oxo-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-1-yl]-1,5-dimethyl-2-oxo-2,3-dihydro-1 H-imidazole-4-carboxamide. N-(1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-1,5- dimethyl -2- oxo -2,3- dihydro -1H- imidazole -4- carboxamide (19C-10) : Place N-[5-[(1R)-1-cyclopropylethyl]-9-hydroxy-11-nitro-16-oxo-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-1-yl]-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (120 g, 237.86 mmol, 1.00 equivalent), ethanol (10 mL), iron (40 mg, 0.72 mmol, 3.00 equivalents), water (1 mL), and concentrated hydrochloric acid (0.01 mL) into a 25 mL round-bottom flask. Stir the resulting solution at 85 °C for 2 hours. Concentrate the resulting mixture under vacuum. Purify the residue by flash chromatography using DCM / MeOH (25 / 1). This gives 100 mg of N-(1-amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (19C-10, Example 29). 1 H NMR (300 MHz, CD 3 OD) 7.55 - 7.39 (m, 2H), 7.05 - 7.01 (m, 1H), 6.93 - 6.70 (m, 3H), 3.21 (s, 3H), 2.35 (s, 3H), 2.04 - 1.84 (m, 1H), 1.30 - 1.27 (m, 3H), 0.94 - 0.89 (m, 1H), 0.57 - 0.52 (m, 1H), 0.38 - 0.34 (m, 1H), 0.22 - 0.16 (m, 1H), 0.09 - 0.02 (m, 1H); LCMS: (ES, m / z): [M+H] + 475.2 N-((4bR,9bR)-1- amino -7-((R)-1- cyclopropylethyl )-4b- hydroxy -10- oxo -9b,10- Dihydro -4bH- Indeno [1,2-b] Benzofuran -9b- yl )-1,5- Dimethyl -2- Side oxy -2,3- Dihydro -1H- Imidazole -4- Formamide (19C-11 , example 22) And N-((4bS,9bS)-1- Amino -7-((R)-1- Cyclopropyl ethyl )-4b- Hydroxy -10- Side oxy -9b,10- Dihydro -4bH- Indeno [1,2-b] Benzofuran -9b- yl )-1,5- Dimethyl -2- Side oxy -2,3- Dihydro -1H- Imidazole -4- Formamide (19C-12 , example 30) : N-(1-Amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (19C-10) (103.9 mg) as a racemate was purified by chiral chromatography using (IA column, HPLC = 20 ml / min, heptane / IPA = 60 / 40) to obtain 42.8 mg of N-((4bR,9bR)-1-amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (19C-11) as (peak 1, tR 7.76 min.), 1H NMR (400 MHz, METHANOL-d4) δ: 8.32 - 8.47 (m, 2H), 7.97 (br d, J = 7.2 Hz, 1H), 7.86 (br d, J = 7.8 Hz, 1H), 7.62 - 7.71 (m, 2H), 4.17 (s, 3H), 3.31 (s, 3H), 2.80 - 2.93 (m, 1H), 2.24 (d, J = 7.0 Hz, 3H), 1.81 - 1.90 (m, 1H), 1.46 - 1.55 (m, 1H), 1.28 - 1.36 (m, 1H), 1.15 (dq, J = 9.4, 4.7 Hz, 1H), 1.04 (dq, J = 9.5, 4.8 Hz, 1H); LCMS: 475.2 [M + H]+ and 35.8 mg of N-((4bS,9bS)-1-amino-7-((R)-1-cyclopropylethyl)-4b-hydroxy-10-oxo-9b,10-dihydro-4bH-indeno[1,2-b]benzofuran-9b-yl)-1,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxamide (19C-12) as (peak 2, tR 16.43 min); 1H NMR (500 MHz, METHANOL-d4) δ: 7.38 - 7.51 (m, 2H), 7.01 (br d, J = 6.9 Hz, 1H), 6.85 - 6.94 (m, 1H), 6.70 (br s, 2H), 3.20 (s, 3H), 2.34 (s, 3H), 1.86 - 1.94 (m, 1H), 1.27 (d, J = 7.1 Hz, 3H), 0.85 - 0.93 (m, 1H), 0.50 - 0.55 (m, 1H), 0.31 - 0.38 (m, 1H), 0.18 (dq, J = 9.8, 4.8 Hz, 1H), 0.06 (dq, J = 9.4, 4.8 Hz, 1H); LCMS: 475.2 [M + H]+。. Example 23 : N-(1 - amino -7-( sec-butyl )-4b - hydroxy -10 - side oxy -4b,10 - dihydro -9bH - indeno [1,2 - b] benzofuran -9b - yl )-3 - methyl -4-( methylsulfonyl )-1H - pyrrole -2 - formamide Process - 19D 1 - [3 - ( benzyloxy ) phenyl ethyl -1 - ketone (19D - 1) : Place 1-(3 - hydroxyphenyl)ethan - 1 - one (20 g, 146.90 mmol, 1.00 equivalent), CH 3 ​A solution of CN (180 mL), (bromomethyl)benzene (20 mL, 1.20 equivalents), and potassium carbonate (40.8 g, 2.00 equivalents) was stirred in an oil bath at 80 °C for 2 h. The solid was filtered out. The reaction mixture was concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1:10). This gave 30.5 g (92%) of 1-[3-(benzyloxy)phenyl]ethan-1-one as a yellow oil. 2-[3-( benzyloxy ) phenyl ] but -2- ol (19D-2) : A solution of 1-[3-(benzyloxy)phenyl]ethan-1-one (5 g, 22.10 mmol, 1.00 equivalent) and THF (100 mL) was placed in a 250 mL round-bottom flask. Then bromo(ethyl)magnesium (22 mL, 3.00 equivalents) was added at 0 °C. The resulting solution was stirred overnight at room temperature. The reaction was then quenched by adding 300 mL of water. The resulting solution was extracted with 3 × 200 mL of chloroform. The combined organic layers were concentrated under vacuum. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1 / 1). This gave 3.1 g (55%) of 2-[3-(benzyloxy)phenyl]butan-2-ol as a colorless oil. 1-( benzyloxy )-3-( but -2- yl ) benzene (19D-3) : Place a solution of 2-[3-(benzyloxy)phenyl]butan-2-ol (6.2 g, 24.19 mmol, 1.00 equivalent) in dichloromethane (120 mL) into a 250 mL three-necked round-bottom flask purged and maintained with an inert nitrogen atmosphere. Subsequently, add triethylsilane (18.2 mL, 5.00 equivalents) and trifluoroacetic acid (18.05 mL, 1.00 equivalent). The resulting solution is stirred overnight at room temperature. The reaction is then quenched by adding 100 mL of water and extracted with 3 × 50 mL of dichloromethane. The combined organic layers are concentrated under vacuum. The residue is applied to a silica gel column with petroleum ether (100%). This gives 3.8 g (65%) of 1-(benzyloxy)-3-(butan-2-yl)benzene as a yellow oil. 3-( but -2- -yl ) phenol (19D-4) : Place a solution of 1-(benzyloxy)-3-(butan-2-yl)benzene (3.8 g, 15.81 mmol, 1.00 equivalent) in methanol (38 mL) and palladium on carbon (380 mg) into a 100 mL round-bottom flask. The resulting solution is stirred at room temperature for 2 h under H 2 . The solid is filtered out. The resulting mixture is concentrated under vacuum. The residue is applied to a silica gel column with ethyl acetate / petroleum ether (1 / 20). This gives 2.0 g (84%) of 3-(butan-2-yl)phenol as a yellow solid. 5-( but -2- -yl )-1,9- -dihydroxy -11- -nitro -8- -oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- -hexaene -16- -one (19D-5) : Place 3-(butan-2-yl)phenol (1.5 g, 9.99 mmol, 1.00 equivalent) in a solution of acetic acid (35 mL) and 2,2-dihydroxy-4-nitro-2,3-dihydro-1H-indene-1,3-dione (1.85 g, 8.29 mmol, 1.00 equivalent) in a 100 mL round-bottom flask. Stir the resulting solution in an oil bath at 120 °C for 2 h. Concentrate the resulting mixture in vacuo. Apply the residue to a silica gel column with ethyl acetate / petroleum ether (1 / 2). This gives 1.37 g (39%) of 5-(butan-2-yl)-1,9-dihydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one as a yellow solid. 5-( but -2- yl )-1- chloro -9- hydroxy -11- nitro -8- oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexaene -16- one (19D-6) : Place 5-(butan-2-yl)-1,9-dihydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one (1.37 g, 3.86 mmol, 1.00 equivalent) in a 50 mL round-bottom flask in dichloromethane (20 mL), oxalyl chloride (1.1 mL, 3.00 equivalents) and N, Solution in N,N-dimethylformamide (2 mL). The resulting solution was stirred in an oil bath at 40 °C for 2 h. The reaction was then quenched by the addition of 50 mL of water / ice. The resulting solution was extracted with 3 × 100 mL of dichloromethane. The combined organic layers were concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1 / 5). This gave 1.2 g (83%) of 5-(butan-2-yl)-1-chloro-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one as a brown oil. 1- Amino -5-( But -2- yl )-9- Hydroxy -11- Nitro -8- Oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] Hexadecane -2(7),3,5,10,12,14- Hexaene -16- One (19D-7) : To a 50 mL round-bottom flask was placed a solution of 5-(butan-2-yl)-1-chloro-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one (1.2 g, 3.21 mmol, 1.00 equiv) in tetrahydrofuran (18 mL). Then, IPA (4.8 mL, 3.00 equiv) containing NH 3 was added at -50 °C. The resulting solution was stirred at -40 - 10 °C for 1.5 h. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with ethyl acetate / petroleum ether (1 / 2). This gave 630 mg (55%) of 1-amino-5-(butan-2-yl)-9-hydroxy-11-nitro-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one as a yellow solid. N-[5-( butyl -2- yl )-9- hydroxy -11- nitro -16- oxo -8- oxatricyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexaene -1- yl ]-4- methanesulfonyl -3- methyl -1H- pyrrole -2- formamide (19D-8) : Place 4-methanesulfonyl-3-methyl-1H-pyrrole-2-carboxylic acid (122 mg, 0.60 mmol, 1.50 equiv) in N, N-dimethylformamide (2 mL), EDCI (115 mg, 0.60 mmol, 1.50 equiv), HOBt (81 mg, 0.60 mmol, 1.50 equiv), 1-amino-5-(butan-2-yl)-9-hydroxy-11-nitro-8-oxatricyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-16-one (150 mg, 0.42 mmol, 1.00 equiv) and triethylamine (121 mg, 1.20 mmol, 2.50 equiv) in a 25 mL round-bottom flask. The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane / methanol (25 / 1). This gave 140 mg (61%) of a yellow solid N-[5-(butan-2-yl)-9-hydroxy-11-nitro-16-sulfooxy-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-1-yl]-4-methylsulfonyl-3-methyl-1 H-pyrrole-2-carboxamide. N-[14- amino -5-( but -2- yl )-9- hydroxy -16- sulfooxy -8- oxatetracyclo [7.7.0.0^[2,7].0^[10,15]] hexadecane -2(7),3,5,10,12,14- hexaene -1- yl ]-4- methylsulfonyl -3- methyl -1H- pyrrole -2- carboxamide (19D-9) : Place in a 50 mL round-bottom flask N-[5-(butan-2-yl)-9-hydroxy-11-nitro-16-sulfooxy-8-oxatetracyclo[7.7.0.0^[2,7].0^[10,15]]hexadec-2(7),3,5,10,12,14-hexaen-1-yl]-4-methylsulfonyl-3-methyl-1 A solution of H-pyrrole-2-carboxamide (140 mg, 0.26 mmol, 1.00 equivalent) in ethanol (5 mL), water (0.5 mL), Fe (40.32 mg, 3.00 equivalents), and hydrogen chloride (0.05 mL). The resulting solution was stirred in an oil bath at 85 °C for 2 h. The solid was filtered off. The resulting mixture was concentrated in vacuo. The residue was applied to a silica gel column with dichloromethane / methanol (20 / 1). This gave 22.1 mg (17%) of N-(1-amino-7-(sec-butyl)-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxamide (19D-9). 1 HNMR (300 MHz, CD 3 OD) δ 7.61-7.35 (m, 3H), 7.18-7.05 (m, 1H), 6.90-6.63 (m, 3H), 3.01 (s, 3H), 2.62-2.40 (m, 4H), 1.65-1.50 (m, 2H), 1.19 (d, J = 6.9 Hz, 3H), 0.90-0.78 (m, 3H); LC-MS: (ES, m / z): [M+H] + : 510.1 Example 24 : N-(1- amino -4b- hydroxy -7-((1S,2R)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-((4- Methylpiperidone 𠯤 -1- base ) Sulfonyl )-1H- Pyrrole -2- Formamide This compound was prepared similarly to Example 18 above. LCMS: 592.3 [M+H] + . Examples 25 : N-(1- Amine -4b- Hydroxyl -7- Isopropyl -10- Pendant -4b,10- Dihydrogen -9bH- Indocyanine [1,2-b] Benzofuran -9b- base )-3,5- Dimethyl -4- Sulfonamide -1H- Pyrrole -2- Formamide (111) : Process-20 2-( Hydroxyimide ) Dimethyl malonate (104) : While stirring, dimethyl malonate 103 (21.7 mL, 190 mmol) was added to glacial acetic acid (55 mL), and then a solution of sodium nitrite (26.2 g, 380 mmol) in 70 mL of water was added dropwise (over about 2 hours). The resulting mixture was stirred at room temperature for 16 h. The reaction mass was extracted with ethyl acetate. The combined extracts were washed with water and with 5% sodium bicarbonate solution until the aqueous solution became weakly basic. The organic layer was dried over Na 2 SO 4 dried, the solvent was evaporated, and a solid product was obtained. The crude material was used in the next step without further purification. 3,5- Dimethyl -1H- Pyrrole -2- Carboxylate methyl ester (106) : To a solution of acetylacetone 105 (10.3 mL, 100 mmol) in acetic acid (40 mL) at 95 °C was gradually added a solution of 2-(hydroxyimino)dimethyl malonate 104 (17 g, 105 mmol) in 20 mL of acetic acid and 10 mL of water (simultaneously with zinc powder (26 g, 400 mmol)). The reaction mixture was stirred at the same temperature for 2 h. The hot reaction mass was poured into 1000 mL of water. The solid precipitate was filtered out, washed with water, dried in air at room temperature, dissolved in DCM, filtered from the zinc powder residue, concentrated and dried in air at room temperature. The product was dissolved in DCM and filtered through a silica pad and washed with DCM. The solvent was evaporated to give the product. 4-( Chlorosulfonyl )-3,5- Dimethyl -1H- Pyrrole -2- Carboxylate methyl ester (107) : Methyl 3,5-dimethyl-1H-pyrrole-2-carboxylate 106 (383 mg, 2.5 mmol) was dissolved in chloroform (0.25 M) and the clear solution was cooled to 0 °C. Chlorosulfonic acid (2.5 mL, 37.5 mmol) was slowly added to the cold solution. The reaction was stirred at 0 °C for 2.5 h. The reaction mass was slowly poured into ice-cold water. The product was extracted with DCM (50 mL×2). The combined organic layers were washed with water (50 mL) and brine solution (50 mL), dried over anhydrous Na 2 SO 4 and the solvent was evaporated to give the crude. The crude was dissolved in DCM and filtered through a silica plug and washed with DCM to give the product. 3,5- Dimethyl -4- Aminosulfonyl -1H- Pyrrole -2- Carboxylic acid methyl ester (108) : 4-(Chlorosulfonyl)-3,5-dimethyl-1H-pyrrole-2-carboxylic acid methyl ester 107 (377.5 mg, 1.5 mmol) was placed in THF (15 mL) and cooled to -10 °C. To this was added a solution of NH 3 in THF (5 mL) (prepared by sweeping ammonia gas into THF at -20 °C). The reaction mass was slowly warmed to room temperature and stirred for 2 h. THF was removed under vacuum to give the residue. The residue was dissolved in ethyl acetate (100 mL) and washed with water (50 mL×3) and dried over Na 2 SO 4 The solvent was evaporated to give the crude product. The residue was purified by wet grinding with DCM and filtered to give the product. 3,5- Dimethyl -4- Aminosulfonyl -1H- Pyrrole -2- Carboxylic acid (109) : To a solution of methyl 3,5-dimethyl-4-sulfamoyl-1H-pyrrole-2-carboxylate 108 (255 mg, 1.1 mmol) in MeOH : H 2 O (1:10) (11 mL) was added LiOH.H 2 O (461.6 mg, 11 mmol). The reaction mixture was stirred at room temperature for 12 h. MeOH was removed under vacuum, and the aqueous layer was diluted with water (10 mL) and acidified to pH ~1 with 1N HCl. The aqueous layer was extracted with ethyl acetate (50 mL × 3). The combined organic layers were washed with water and with brine, dried over Na 2 SO 4 and the solvent was evaporated to give the solid product, which was used without purification in the next step. N-(4b- hydroxy -7- isopropyl -4- nitro -10- lateral oxygen group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,5- dimethyl -4- sulfamoyl -1H- pyrrole -2- formamide (110) : Dissolve 3,5-dimethyl-4-sulfamoyl-1H-pyrrole-2-carboxylic acid 109 (200 mg, 0.91 mmol) in DMF (9 mL) and cool the resulting solution to 0 °C. Add EDCI (216.7 mg, 1.365 mmol), HOBT (184.5 mg, 1.365 mmol), and DIPEA (0.396 mL, 2.275 mmol) at 0 °C and stir the reaction mixture for 30 min. Then add 9b-amino-4b-hydroxy-7-isopropyl-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 37 (312 mg, 0.91 mmol) and stir the reaction mixture at 30 °C for 15 h. Quench the reaction with water (100 mL) and extract with ethyl acetate (3 × 50 ml). Wash the combined organic layers with brine solution and dry over Na 2 SO 4 2SO4, and evaporate in vacuo. Purify the crude material by column chromatography (MeOH:DCM) to give (110). N-(1- amino -4b- hydroxy -7- isopropyl -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3,5- dimethyl -4- sulfamoyl -1H- pyrrole -2- carboxamide (111) : To a solution of N-(4b-hydroxy-7-isopropyl-4-nitro-10-sideoxy-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3,5-dimethyl-4-sulfamoyl-1H-pyrrole-2-carboxamide 110 (110 mg, 0.2 mmol) in an EtOH - water mixture (1:1, 7 mL) was added Fe powder (33.5 mg, 0.6 mmol) and concentrated HC (1 drop). The resulting solution was refluxed at 90 °C for 3 hours. The hot reaction mass was filtered through a pad of diatomaceous earth and washed with ethyl acetate. The organic layer was evaporated under vacuum. The resulting residue was dissolved in ethyl acetate (100 mL) and washed with water (50 mL × 2), followed by washing with brine. The combined organic layers were dried over Na 2 SO 4 dried and the solvent was evaporated under vacuum to give the crude material. The crude material was purified by silica gel column chromatography (methanol: DCM) to give the product. (300 MHz, CD3OD) δ 1.2 (dd, J = 6.2 Hz, J = 0.9 Hz, 6H), 2.44 (s, 3H), 2.49 (s, 3H), 2.84 - 2.87 (m, 1H), 6.70 (m, 2H), 6.89(m 1H), 7.04 (m 1H), 7.48 (m, 2H). LCMS: 510.78 [M+1] + 。LCMS: 511.5 [M+H] + 。 Example 26 : N-(1- amino -4b- hydroxy -7-((1R,2S)-2- methylcyclopropyl )-10- sideoxy -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -5-( methylsulfonyl )-1H- pyrrole -2- formamide This compound was prepared similar to Example 26 above. LCMS: 508.0 [M+H] + . Example 27 : N-(1- amino -4b- hydroxy -7-((1S,2R)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- methyl -4-( methylsulfonyl )-1H- pyrrole -2- formamide This compound was prepared similar to Example 26 above. LCMS: 508.2 [M+H] + . Example 28 : N-((4bR,9bR)-1- amino -4b- hydroxy -7-((1S,2S)-2- methylcyclopropyl )-10- Side oxy group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group )-3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Formamide Process 22 ((S)-1-(((4bS,9bS)-7- Bromo -4b- Hydroxy -4- Nitro -10- Side oxy group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group ) Amino )-1- Side oxy group -3- Phenylpropyl -2- Group ) tert-Butyl carbamate (113) : (tert-Butoxycarbonyl)-L-phenylalanine 112 (4.80 g, 16.4 mmol) was placed in DMF (110 mL, 0.15 M) and cooled to 0 °C. Subsequently, EDCI (4.73 g, 24.7 mmol) was added thereto, followed by HOBt (3.33 g, 24.7 mmol). It was stirred for another 20 min and 9b-amino-7-bromo-4b-hydroxy-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 9 (6.20 g, 16.4 mmol) was added, followed by the addition of DIPEA (8.6 mL, 49.3 mmol). It was stirred at 30 °C for another 24 hours. The reaction mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and with brine. The organic layer was dried over Na 2 SO 4 dried and the solvent was evaporated to give the crude product. The crude material was purified by silica gel column chromatography to give the product and other isomers. (S)-2- amino -N-((4bS,9bS)-7- bromo -4b- hydroxy -4- nitro -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- phenylpropanamide (114) : Dissolve tert-butyl ((S)-1-(((4bS,9bS)-7-bromo-4b-hydroxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 113 (1.475 g, 2.36 mmol) in DCM (47 mL). Add dichloromethane containing HCl (5.9 mL, 23.6 mmol) to the resulting solution, and stir the reaction mixture at room temperature for 18 h. Evaporate the reaction mixture to dryness, dissolve the residue in water, and basify the aqueous layer. Extract the aqueous layer with ethyl acetate (150 mL × 2), and wash the combined organic layers with water (100 mL) and then with brine. Dry the combined organic layers over Na 3 SO 2 SO 4 4, and evaporate the solvent under vacuum to obtain the crude product, which is used in the next step without purification. (S)-N-((4bS,9bS)-7- bromo -4b- hydroxy -4- nitro -10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl )-3- phenyl -2-(3- phenylthioureido ) propionamide (116) : At 0 °C, isothiocyanatobenzene 115 (0.425 mL, 3.54 mmol) was added to a solution of (S)-2-amino-N-((4bS,9bS)-7-bromo-4b-hydroxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-phenylpropanamide 114 (1.25 g, 2.36 mmol) in DCM (24 mL). Subsequently, the reaction mixture was warmed to room temperature and the resulting mixture was stirred at 28 °C for 24 h. The reaction mixture was evaporated to dryness to give a crude product. The crude product was purified by short silica gel column chromatography (ethyl acetate:hexane) to give the product. (4bS,9bS)-9b- amino -7- bromo -4b- hydroxy -4- nitro -4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- oxo (117) : (S)-N-((4bS,9bS)-7-Bromo-4b-hydroxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)-3-phenyl-2-(3-phenylthioureido)propanamide 116 (1.70 g, 2.58 mmol) was dissolved in DCM (260 mL). To this solution was added TFA (8.8 mL, 77.4 mmol) at room temperature. Subsequently, the reaction mixture was warmed to 50 °C for 12 h. The DCM was evaporated and the resulting residue was dissolved in water. The aqueous layer was basified with saturated NaHCO 3 solution and then the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over Na 2 SO 4 and the solvent was evaporated to give a crude product. The crude product was purified by silica gel column chromatography (ethyl acetate:hexane) to give the product. ((4bS,9bS)-7- bromo -4b- hydroxy -4- nitro -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group ) tert-butyl carbamate (118) : Dissolve (4bS,9bS)-9b-amino-7-bromo-4b-hydroxy-4-nitro-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one 117 (472 mg, 1.25 mmol) in THF (1.25 mL). Add Boc anhydride (546 mg, 2.5 mmol) thereto, and then add iodine (32 mg, 0.125 mmol). Stir the reaction mixture at room temperature for 36 h. Evaporate the reaction mixture to dryness. Purify the residue by silica gel column chromatography (ethyl acetate:hexane) to obtain the product. ((4bR,9bR)-1- amino -7- bromo -4b- hydroxy -10- side oxy group -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- group ) tert-butyl carbamate (12) : Dissolve tert-butyl ((4bS,9bS)-7-bromo-4b-hydroxy-4-nitro-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamate 118 (460 mg, 0.96 mmol) in an EtOH-water mixture (1:1, 10 mL). Add Fe powder (161 mg, 2.88 mmol) and concentrated HCl (2 drops). Reflux the clear solution at 90 °C for 3 h. Filter the hot reaction mixture through a Celite pad and wash with ethyl acetate. Evaporate the organic layer in vacuo. Dissolve the resulting residue in ethyl acetate (250 mL) and wash with water (100 mL×2) and then with brine. Combine the organic layers, dry over Na 2 SO 4 dry and evaporate the solvent in vacuo to give the crude material. Purify the crude product by silica gel column chromatography (ethyl acetate:hexane) to give the product. ((4bR,9bR)-1- amino -4b- hydroxy -7-((1S,2S)-2- methylcyclopropyl )-10- oxo -4b,10- dihydro -9bH- indeno [1,2-b] benzofuran -9b- yl ) tert-butyl carbamate (119) : To a degassed solution of tert-butyl ((4bR,9bR)-1-amino-7-bromo-4b-hydroxy-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamate 12 (326 mg, 0.73 mmol) in toluene (12.5 mL) add water (2.5 mL), Pd(OAc) 2 (16.4 mg, 0.073 mmol), RuPhos (68 mg, 0.146 mmol) and K 3 PO 4 (620 mg, 2.92 mmol). Subsequently, 6-methyl-2-((1S,2S)-2-methylcyclopropyl)-1,3,6,2- dioxazaborocane-4,8-dione 17 (231 mg, 1.095 mmol) was added. The resulting reaction mass was purged with N 2 for 10 min and then the reaction mass was stirred at 100 °C for 1 h. The reaction mass was cooled to room temperature and diluted with ethyl acetate (100 mL). The organic layer was washed with water (50 mL × 2), dried over Na 2 SO 4 and the solvent was evaporated to give the crude material. The crude material was purified by silica gel column chromatography (ethyl acetate:hexane) to give the product. (4bR,9bR)-1,9b- diamino -4b- hydroxy -7-((1S,2S)-2- methylcyclopropyl )-4b,9b- dihydro -10H- indeno [1,2-b] benzofuran -10- one hydrochloride (120) : ((4bR,9bR)-1-Amino-4b-hydroxy-7-((1S,2S)-2-methylcyclopropyl)-10-oxo-4b,10-dihydro-9bH-indeno[1,2-b]benzofuran-9b-yl)carbamic acid tert-butyl ester 119 (250 mg, 0.59 mmol) was dissolved in DCM (12 mL). To this solution, dichloromethane containing HCl (1.5 mL, 5.9 mmol) was added and the reaction mass was stirred for 12 h. The reaction mass was evaporated to dryness to give the product (crude), which was used as such in the next step. N-((4bR,9bR)-1- amino -4b- Hydroxyl -7-((1S,2S)-2- Methylcyclopropyl )-10- Side oxy group -4b,10- Dihydro -9bH- Indeno [1,2-b] Benzofuran -9b- Group )-3- Methyl -4-( Methylsulfonyl )-1H- Pyrrole -2- Formamide (121) : Dissolve 3-methyl-4-(methylsulfonyl)-1H-pyrrole-2-carboxylic acid 30 (97.6 mg, 0.48 mmol) in DMF (8 mL). Cool the resulting solution to 0 o °C. Add HATU (28.2 mg, 0.60 mmol) and DIPEA (0.210 mL, 1.2 mmol) at 0 °C and stir the reaction mixture for 30 min. Then add (4bR,9bR)-1,9b-diamino-4b-hydroxy-7-((1S,2S)-2-methylcyclopropyl)-4b,9b-dihydro-10H-indeno[1,2-b]benzofuran-10-one hydrochloride 120 (144 mg, 0.4 mmol) and stir the reaction at 30 °C for 15 hours. Quench the reaction with water (100 ml) and extract the aqueous layer with ethyl acetate (2 × 100 mL). Wash the combined organic layers with water and with brine solution, and dry over Na 2 SO 4Dry and evaporate the solvent under vacuum. The crude product was purified by silica gel column chromatography (MeOH: DCM) and subsequently by preparative HPLC (ethanol: hexane) to obtain the product. (300 MHz, MeOD) δ 0.66 - 0.72 (m, 1H), 0.78 - 0.84 (m, 1H), 0.95 - 1.03 (m, 1H), 1.13 (d, J = 6.0 Hz, 3H), 1.49 - 1.55 (m, 1H), 2.48 (s, 3H), 3.05 (s, 3H), 6.45 (s, 1H), 6.63 - 6.67 (m, 1H), 6.76 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 7.2 Hz, 1H), 2.27 (d, J = 8.1 Hz, 1H), 7.38 (s, 1H), 7.43 - 7.49 (m, 1H). LCMS: 508.1 [M+H] + . The biological activity of the compounds of the present invention was determined using the following method. Using the cytopathic effect (CPE) inhibition assay to determine against minute RNA virus drug efficacy In the assay, HeLa (human cervical cancer cells), MRC-5 (human fetal lung fibroblasts) and RD cells (derived from human rhabdomyosarcoma) were used. For comparison, ribavirin (Riv), pleconaril (pleco) and BTA-798 (BTA) were used as controls. The reagents were dissolved in 100% dimethyl sulfoxide (DMSO) at a concentration of 10 - 40 mg / ml. The water-soluble reagents were dissolved in PBS (-) solution and stored at -20 °C. On the day of the experiment, they were used at a 3- to 5-fold concentration such that the concentration of DMSO in each well was between 0.5% and 1%. The pharmaceutical efficacy was determined using virus-induced cytopathic effect (CPE) inhibition assay. In this regard, after growing cells suitable for the virus in 96-well plates, a virus dilution in DME (DME / 2% FBS) supplemented with 2% FBS or MEM (MEM / 2% FBS) supplemented with 2% FBS was inoculated in an amount of 100 μl into each well of the plate at a concentration corresponding to 100 CCID50 (50% cell culture infective dose), and incubated at 33 °C or 37 °C for 30 minutes to 1 hour to allow the virus to adsorb onto the cells. The culture medium was removed, and thereafter aliquots of drug dilutions at various concentrations were added in an amount of 100 μl to each well. HRV (human rhinovirus) was grown at 33 °C, while other viruses were grown in a 37 °C CO 2 incubator for 2 to 3 days. Alternatively, after adding 50 μl of each drug dilution with a 2-fold higher concentration to the cells and then adding 50 μl of the virus dilution, the cells were cultured for 2 to 3 days without removing the culture medium. The virus was cultured in host HeLa cells at 37 °C in DME / 2% or MEM / 2% FBS for 2 to 3 days. For HeLa cells, MTT assay was used to measure the EC 50 (50% maximum effective concentration), which is the drug concentration that induces half the response between baseline and maximum. For RD and MRC-5 cells, CPE was determined using FDA (fluorescein diacetate) or MTT. To determine the effect of drug toxicity on the efficacy results, mock infection was also included when inoculating with the virus. Virus-free culture medium was added to the cell culture, and then it was treated in the same way as the mock-infected cells inoculated with the virus. That is, after incubating for one hour, the culture medium was removed, and the drug dilution in the culture medium was added again. After incubating for 2 to 3 days, the cells were observed under a microscope, and MTT assay comparing the number of live cells in the mock-infected wells containing the drug with the number of live cells in the drug-free control wells was used to determine the CC 50 (50% cytotoxic concentration), at which 50% of the cells are killed. In the FDA hydrolysis assay, FDA was added to each well after removing the culture medium, and incubated for 20 - 30 min, and then the fluorescence intensity was measured using a spectrofluorometer to determine CPE in the same way as in MTT. That is, the survival rate (survival rate %) of mock-infected cells for cytotoxicity measurement was calculated using the following mathematical formula 1: Cell drug = survival rate calculated as [A (drug) - A (background solution) / A (cell control) - A (background × 100% solution)] 100% cell viability means the drug has no cytotoxicity to cells, while the highest cytotoxicity is reflected by 0% cell viability. The 50% cytotoxic concentration is defined as the concentration required to reduce the cell number by 50%. This drug concentration is expressed as CC50. The higher the value, the lower the cytotoxicity. In addition, the antiviral effect can be calculated using the following mathematical formula 2: Antiviral effect = [A (drug / virus) - A (virus control) / A (cell control) - A (virus control)] If the viability is 100%, its antiviral effect is 100%, and if the viability is 0%, its antiviral effect is none. When the drug concentration at which the cells in the wells infected with the virus can exhibit 50% viability is calculated as EC 50 the lower this value, the stronger the antiviral effect. The LC 50 concentration showing cytotoxicity against the compounds in some examples and the EC 50 concentration showing activity against various rhinoviruses belonging to picornavirus are listed in Table 1 below. Using multi-cycle cytopathic effect (CPE) reduction analysis to determine the anti- RNA virus drug effect The drug efficacy against picornavirus was determined using multi-cycle CPE reduction analysis. Initially, the antiviral activity of the compound was determined by CPE reduction analysis based on MIS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium]. Specifically, cells grown to confluence in a 96-well plate were infected with a dose (CCID 50 ) of virus at 100 50% cell culture infectivity. After a 2-hour adsorption period at 37 °C, the virus was removed and serial dilutions of the compound were added. The cultures were further incubated at 37 °C for 3 days until complete CPE was observed in the infected and untreated virus control (VC). After removing the medium, 90 μl of medium and 10 μl of MTS - phenazine methosulfate (Promega, Leiden, The Netherlands) were added to each well. After a 2-hour incubation period at 37 °C, the optical density (OD) of each well was read at 498 nm in a microplate reader. The CPE% value for evaluating antiviral activity was calculated using the following Mathematical Equation 3: CPE% = 100 x [OD(CC) - OD(virus + compound) / OD(CC) - OD(VC)] The CPE% value for measuring drug cytotoxicity was calculated by the following Mathematical Equation 4: CPE% = 100 x [OD(CC) - OD(virus + compound) / OD(CC) - OD(blank)] In the above Mathematical Equations 3 and 4, OD(CC) represents the OD of the background cell culture that is neither induced by virus nor treated with chemicals, OD(VC) represents the OD of the control cell culture induced by virus but not treated with chemicals, OD(virus + compound) represents the OD of the cell culture infected with virus treated with concentrated compound, OD(compound) represents the OD of the cell culture treated only with concentrated compound, and OD(blank) represents the OD of the well with only cell culture added. The effective concentration (EC 50 ) represents the drug concentration that enables 50% of the cells to survive the CPE of the induced virus, and the cytotoxic concentration (CC 50 ) represents the drug concentration at which the compound has killed 50% of the cells, and these concentrations were calculated by logarithmic interpolation. The cytotoxic concentrations (CC 50 ) and effective concentrations (EC 50 ) of various viruses for some compounds of the examples are listed in Table 1 below. Table 1: Table of Biological Activity Data As indicated in Table 1 above, most of the compounds according to the present invention showing higher CC 50 concentrations were thus found to have lower cytotoxicity. Additionally, the compounds according to the present invention were mainly found to have higher antiviral activity against various human rhinoviruses (HRV). Therefore, since the compounds in the examples according to the present invention show lower cytotoxicity and higher antiviral activity against various human rhinoviruses, they can be effectively used in pharmacological compositions for preventing or treating diseases caused by the picornaviruses to which they belong. Thus, since the compounds in the examples according to the present invention have low cytotoxicity and exhibit antiviral activity against picornaviruses belonging to Coxsackievirus, Poliovirus, and Rhinovirus, they can be effectively used for preventing or treating diseases caused by such viruses, such as respiratory diseases, cardiovascular diseases, and nervous system diseases, including poliomyelitis, acute hemorrhagic conjunctivitis, viral meningitis, hand, foot, and mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, influenza, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis, and otitis media. Since the compounds expressed in the formula according to the present invention, which are in balance with each other, not only have low cytotoxicity but also have high antiviral activity against picornaviruses including Coxsackievirus, Enterovirus, Echovirus, Poliovirus, and Rhinovirus, they can be effectively used as a pharmaceutical composition for preventing or treating viral diseases such as poliomyelitis, acute hemorrhagic conjunctivitis, viral meningitis, hand, foot, and mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, diabetes, epidemic myalgia, encephalitis, influenza, herpangina, foot-and-mouth disease, asthma, chronic obstructive pulmonary disease, pneumonia, sinusitis, or otitis media.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein, G1 is selected from straight-chain or branched C1-C4 alkyl, C3-C4 cycloalkyl, or straight-chain or branched C1-C4 alkoxy groups; wherein the C1-C4 alkyl, C3-C4 cycloalkyl, and C1-C4 alkoxy groups may be substituted by one, two, or three independent substituents selected from cyclopropyl and straight-chain or branched C1-C3 alkyl groups; L is a single bond or CH2; E is a) -CH(CHOHCH3)(NMe2); or b) A monocyclic 4- to 6-membered heterocyclic group containing one or two nitrogen atoms, or a 5- to 6-membered heteroaryl group containing one nitrogen atom, wherein the 4- to 6-membered heterocyclic group and the 5- to 6-membered heteroaryl group are optionally substituted by one to three substituents independently selected from the group consisting of straight-chain or branched C1-C3 alkyl, -OH, =O, -SO2R; wherein each R is independently selected from straight-chain or branched C1-C3 alkyl, a monocyclic 5- to 6-membered heterocyclic group containing one or two nitrogen atoms, and NR1R2; wherein the monocyclic 5- to 6-membered heterocyclic group is optionally substituted by C1-C3 alkyl or NR3R4; each R1 and R2 is independently selected from H and C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted by NR3R4; and each R3 and R4 is independently selected from H or methyl; the limitation is that when E is option b), (i) G1 is a C3-C4 cycloalkyl group, wherein the C3-C4 cycloalkyl group may be substituted by one, two or three independent substituents selected from cyclopropyl and straight-chain or branched C1-C3 alkyl groups; or (ii) G1 is a straight-chain or branched C1-C4 alkyl group or a straight-chain or branched C1-C4 alkoxy group, wherein the C1-C4 alkyl group and the C1-C4 alkoxy group are substituted by one, two or three cyclopropyl groups.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound has formula (II): .

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound has formula (III): .

4. A compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, wherein L is a single bond.

5. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, wherein E is -CH(CHOHCH3)(NMe2).

6. A compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, wherein E is a monocyclic 5 to 6-membered heteroaryl group containing a nitrogen atom, wherein the 5 to 6-membered heteroaryl group is, as appropriate, substituted by one to three independent substituents selected from the group consisting of straight-chain or branched C1-C3 alkyl groups, -OH, =O, and -SO2R.

7. A compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, wherein G1 is a straight-chain or branched C1-C4 alkyl group, which, as appropriate, is substituted by one, two, or three independent substituents selected from cyclopropyl and straight-chain or branched C1-C3 alkyl groups.

8. A compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, wherein G1 is a C3-C4 cycloalkyl group, which, as appropriate, is substituted by one, two, or three independent substituents selected from straight-chain or branched-chain C1-C3 alkyl groups.

9. A compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, wherein G1 is a straight-chain or branched C1-C4 alkoxy group, which, as appropriate, is substituted by one, two, or three independent substituents selected from cyclopropyl and straight-chain or branched C1-C3 alkyl groups.

10. The compound of claim 1 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound has formula (Ia): wherein A1 is selected from the group consisting of H, straight-chain or branched C1-C3 alkyl groups and SO2R; and A2 is selected from the group consisting of H and SO2R.

11. The compound of claim 10 or its pharmaceutically acceptable salt or any of the aforementioned stereoisomers, wherein A1 is methyl or SO2CH3.

12. The compound of claim 10 or its pharmaceutically acceptable salt or any of the aforementioned stereoisomers, wherein A2 is SO2R and R is selected from the group consisting of: CH3; a monocyclic 5- to 6-membered heterocyclic group containing one or two nitrogen atoms and substituted with CH3 or N(CH3)2; and NR1R2.

13. The compound of claim 1 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound has the formula (Ib): where Y is H or CH3.

14. The compound of claim 1 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound has the formula (Ic): wherein X is selected from the group consisting of methyl, ethyl and cyclopropyl.

15. A compound or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound is selected from the group consisting of:

16. The compound of claim 1 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, wherein the compound is selected from the group consisting of:

17. A pharmaceutical composition for treating viral diseases, comprising a compound of any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, and a pharmaceutically acceptable diluent or excipient.

18. A combination comprising a compound of any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers or a pharmaceutical composition of claim 17, and one or more therapeutic agents.

19. Use of any compound of claims 1 to 15 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers or a pharmaceutical composition of claim 17 or a combination of claims 18, for the preparation of a medicament for treating viral diseases.

20. As claimed in claim 19, wherein the compound or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers is as defined in claim 15.

21. As requested in paragraphs 19 or 20, wherein the viral disease is caused by coxsackievirus.

22. As requested in paragraphs 19 or 20, wherein the viral disease is caused by the poliovirus.

23. As requested in paragraphs 19 or 20, wherein the viral disease is caused by echovirus.

24. As requested in paragraphs 19 or 20, wherein the viral disease is caused by an enterovirus.

25. As requested in paragraphs 19 or 20, wherein the viral disease is caused by a rhinovirus.

26. As used in claims 19 or 20, wherein the viral disease is caused by a picovirus.

27. As claimed in claim 19 or 20, wherein the viral disease is poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, epidemic myalgia, encephalitis, influenza, herpetic pharyngitis, foot-and-mouth disease, pneumonia, sinusitis, or otitis media.

28. A pharmaceutical composition comprising a compound as claimed in claim 16 or a pharmaceutically acceptable salt thereof or any of the aforementioned stereoisomers, and a pharmaceutically acceptable diluent or excipient.

29. A combination comprising a compound as claimed in claim 16 or a pharmaceutically acceptable salt or optical isomer thereof, and one or more therapeutically active agents.

30. Use of a compound as claimed in claim 16, or a pharmaceutically acceptable salt thereof, or any of the aforementioned stereoisomers, for the preparation of a medicament for treating viral diseases.

31. As requested in claim 30, wherein the viral disease is caused by Coxsackievirus.

32. As claimed in claim 30, wherein the viral disease is caused by the poliovirus.

33. As requested in claim 30, wherein the viral disease is caused by echovirus.

34. As requested in claim 30, wherein the viral disease is caused by an enterovirus.

35. As requested in claim 30, wherein the viral disease is caused by a rhinovirus.

36. As claimed in claim 30, wherein the viral disease is caused by a microRNA virus.

37. As claimed in claim 30, wherein the viral disease is poliomyelitis, paralysis, acute hemorrhagic conjunctivitis, viral meningitis, hand-foot-mouth disease, vesicular disease, hepatitis A, myositis, myocarditis, pancreatitis, epidemic myalgia, encephalitis, influenza, herpetic pharyngitis, foot-and-mouth disease, pneumonia, sinusitis, or otitis media.

38. The pharmaceutical composition of claim 17, wherein the viral disease is caused by Coxsackievirus.

39. The pharmaceutical composition of claim 17, wherein the viral disease is caused by poliovirus.

40. The pharmaceutical composition of claim 17, wherein the viral disease is caused by echovirus.

41. The pharmaceutical composition of claim 17, wherein the viral disease is caused by an enterovirus.

42. The pharmaceutical composition of claim 17, wherein the viral disease is caused by a rhinovirus.

43. The pharmaceutical composition of claim 17, wherein the viral disease is caused by a microRNA virus.