TW201109028A - HCV protease inhibitors - Google Patents

Abstract

This invention relates to macrocyclic compounds of formula (I) shown in the specification. These compounds can be used to treat hepatitis C virus infection.

Description

201109028 VI. Description of the invention: c Inventive technology field 3 The present invention relates to hepatitis C virus protease inhibitors.

H ^tr才支四标J Background of the invention Hepatitis C virus (HCV) is a (+) sense single-stranded RNA ((+)-sense single-stranded RNA) ' also mainly causes non-A, non-B The causative factor of hepatitis. HCV infection is a problem that threatens human health. See, for example, WO 05/007681; WO 89/04669; EP 381216; Alberti et al, J. Hepatology, 31 (Supp. 1), 17-24 (1999); Alter, J. Hepatology, 31 (Supp. 1), 88- 91 (1999); and Lavanchy, J. Viral Hepatitis, 6, 35-47 (1999). Hepatitis caused by HCV infection is difficult to treat because of rapid mutation of the virus and avoidance of an innate immune response. The only anti-HCV therapeutics currently available are interferon-alpha, interferon-alpha/ribavirin combinations, and pegylated interferon-alpha. However, the sustained response rate of the interferon-α or interferon-α/ribavirin combination was found to be < 50%, and the patient was greatly affected by the side effects of these therapeutic agents. See, for example, Walker, DDT, 4, 518-529 (1999); Weiland, FEMS Microbial. Rev., 14, 279-288 (1994); and WO 02/18369. Therefore, there is still a need to develop more effective and acceptable anti-HCV drugs. The HCV protease required for viral replication contains approximately 3000 amino acids. It includes nucleocapsid protein (C), envelope proteins (E1 and E2), and some non-structural proteins (NS2, NS3, NS4a, NS5a and NS5b). 201109028 N S 3 protein has serine protease activity and is considered essential for viral replication and infection. This is evidenced by the fact that the mutation of the yellow fever virus NS3 protease reduces viral infectivity and that the variation of the active site of the HCV NS3 protease completely inhibits HCV infection in the chimpanzee model. See, for example, Chamber et al., Proc. Natl. Acad. Sci. USA 87, 8898-8902 (1990) and Rice et al, J. Virol. 74(4) 2046-51 (2000). In addition, the HCV NS3 protease was found to promote proteolysis at the NS3/NS4a, NS4a/NS4b, NS4b/NS5a, NS5a/NS5b junctions. Therefore, HCV NS3 serine protease is thought to be involved in the production of four viral proteins during viral replication. See, for example, US 2003/0207861. Therefore, the HCV NS3 protease is an attractive target for the treatment of HCV infection. Possible NS3 HCV protease inhibitors can be found in WO 02/18369, WO 00/09558, WO 00/09543, WO 99/64442, WO 99/07733, WO 99/07734, WO 99/50230, WO 98/46630, WO 98/17679, WO 97/43310, US 5,990,276, Dunsdon et al, Biorg. Med. Chem. Lett. 10, 1571-1579 (2000); Llinas-Brunet et al. Biorg. Med. Chem Lett. 10, 2267-2270 (2000); and S. LaPlante et al., Biorg. Med. Chem. Lett. 10, 2271-2274 (2000). SUMMARY OF THE INVENTION The present invention is based on the surprising discovery that certain macrocyclic compounds are capable of blocking NS3-4A protease activity, reducing HCV RNA levels, inhibiting HCV protease mutants against other inhibitors, and in circulating blood. The half-length of the 201109028 is extended. In one aspect, the invention relates to compounds of formula (1):

Alkyl, cM〇heterocycloalkyl, aryl, heteroaryl, _Z R or _nh_z_r; wherein R is deuterium or a moiety selected from the group consisting of Ci 6 alkyl, cycloalkyl, CM{) heterocycle An alkyl group, an aryl group and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by a substituent: a cyclin, a nitro group, a cyano group, an amino group, a Cl. , C2_6 refining group, C2·6 block group, aryl group or heteroaryl; Z is χ(〇)-, -c(o)o-, -c(o)c(o)〇_, -C(0 C(0)NH_, -C(0)NR'-, -OC(S)-, -C(S)NR,- or -C(NH)〇_, R, is H, Ci 6 alkyl, Cwo cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R2 is H, or is selected from the group consisting of Cw alkyl, C3_1Q cycloalkyl, C| |()heterocycloalkyl, aryl And a heteroaryl group, each of which is optionally monosubstituted, disubstituted or disubstituted by the following substituents: iS, nitro, cyano, amino, C16 alkyl, 6 alkoxy, C2·6 alkenyl, C2- 6 alkynyl, aryl or heteroaryl; A*N or cH; u is -Ο, -NH-, -NH(CO)-, -NHS(O). or -NHS〇2_ ; w is -(CH2 M_ NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n·, _(cH2)n〇-, -S(CH2)n-, -(CH 2) nS-, -S(O)-, -SO(CH2)n-, -(CH2)nS(0)-, -S〇2(CH2)n- or -(CH2)nS〇2- 'm疋1,2 or 3,n;^〇,i or 2; x is 201109028 -〇-, -S-, -NH- or -OCH2-;

Wherein v and τ are each independently _CH_n octagonal and octa 2 are each independently selected from the group consisting of c4_10 cycloalkyl, c M 〇heterocyclic alkyl, aryl and heteroaryl, each of which is optional Monosubstituted, disubstituted or trisubstituted by the following substituents: halogen, nitro, cyano, amino, c 1 -6 alkyl, Cm alkoxy, C2·6, C2.6, aryl or a heteroaryl group, or optionally fused to a fluorene 3-? anthracene group, a CM hydrazine heterocyclic group, an aryl group or a heteroaryl group; and Ri is an anthracene, a cycline, a nitro group, a fluorenyl group or an amino group, or Is selected from the following: Ci_6 alkyl, C!.6 alkoxy, C2-6 dilute, C2-6 alkynyl, () 3-10 cycloalkyl, Cmq heterocyclic, aryl and hetero An aryl group, the C|.6 alkyl group, a hydrazine: |6 alkoxy group, a C2-6 alkenyl group and a C2. 6 alkynyl group are each optionally monosubstituted, disubstituted or trisubstituted by the following substituents: Nitro, cyano, amino, Cm alkyl, CM methoxy*, €2.6, [2-6, 匚3.1. Cycloalkyl, oxime 1.1 () heterocycle. Hyun (aryl, aryl) Or a heteroaryl group, each of a C3_l() cycloalkyl group, a CM()heterocycloalkyl group, an aryl group and a heteroaryl group, optionally taken as follows Mono-, di- or tri-substituted: halogen, nitro, cyano 'amino, Cm alkyl, Cw alkoxy, C2-6 alkenyl, C2-6 block, C3.10 cycloalkyl, CNI ( a heterocycloalkyl, aryl or heteroaryl group, or optionally fused to a C3_l() cycloalkyl, CM()heterocycloalkyl, aryl or heteroaryl; diterpene early or double bond. The groups designated by U, W, X and Z are divalent groups. The orientation of each group of 6 201109028 shown above is the same as the orientation shown in the formula. The -NHSO- group is specified by the variable U. For example, as shown in the structural formula, it is inserted between C=〇 and R2. The N atom of the -NHS(O)- group is connected to C=0, and the S atom is connected to R2. Another example is a variable. Z-specified -C(0)0- is interposed between NH and R (ie, -NH-ZR). The C atom in -C(0)0- is connected to NH, and the deuterium atom is connected to R. I), the subgroup of compounds is characterized by RiS-NH-ZR, where Z is -C(O)-, -C(0)0-, -C(0)C(0)0- or -C( 0) C(0)NH- ; R2 '4 > VCH3 is Δ or Δ; X is Ο; A is CH; w is -CH2CH2-, -OCH2-, -SCH2- or -SOCH--, U is - NHS〇2- ; is a double bond; or γ is

Riv 'wherein T is CH or N; Ri is phenyl or thioazolyl optionally substituted by halogen, amino, Ck alkyl or Cl-6 alkoxy; Rb's, Riv&R;Rv Independently η, halogen, nitrate-based, cyano, amino, Ck alkyl, C, 6 alkoxy, c2_6 alkenyl or C2.6 alkynyl, or a moiety selected from the group consisting of C3_1() Alkyl, indenyl 11 ()heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro, cyano, amino, Ci 6 a thiol group, a Ci 6 alkoxy group, a CM dilute group, a C2·6 alkynyl group, an aryl group or a heteroaryl group, or optionally fused to a ring-based group, a CM fluorene heterocyclic group, an aryl group or a heteroaryl group. Examples are -NH-C(0)0-t-Bu, -NH-C(0)0-cyclopentyl^0_NH_c(〇xyl. Another subgroup of the compound is characterized as follows, γ is 201109028

Rii

Riii

or

Rh

Riv~丨Rv, wherein Ri, Rii, Riii, Riv, R> Rvi are each independently H, halogen, schlossyl, cyano, amino, C|_6 alkyl, Ci.6 methoxy, C2-6 A dilute group, an alkynyl group, a c3.1()cycloalkyl group, a CM(,heterocycloalkyl group, an aryl group or a heteroaryl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group and a heteroaryl group are each optionally selected Substituted monosubstituted, disubstituted or trisubstituted: halogen, nitro, cyano, amino, C1-6 alkyl, C|-6 alkoxy, C2-6 alkyl, C2.6 fast radical, aryl or heteroaryl And optionally fused to a C3-10 ring pit group, a Cl.10 heterocycloalkyl group, an aryl group or a heteroaryl group. Among the above compounds, Ri may be, for example, the following: 201109028

(CH2)n

Where n is 1 or 2. The compounds of the invention also have the feature that the second is a single bond and R2 is

, or ^ is -H, -OH, C1-6 alkyl, C, -6 alkoxy, (: 3-10 cycloalkyl, Cmq heterocycloalkyl, aryl or heteroaryl, or -ZR. "Alkyl" means a saturated straight or branched hydrocarbyl moiety such as -CH3 or -CH(CH3)2. The term "alkoxy" denotes a -CKCkalkyl) group. The term "alkenyl" denotes a straight or branched hydrocarbyl moiety containing at least one double bond, such as -CH=CH-CH3. The term "alkynyl" means a straight or branched hydrocarbyl moiety containing at least one triple bond, such as -OC-CH3. The term "cycloalkyl" denotes a saturated cyclic hydrocarbyl moiety, such as cyclohexyl. The term "cycloalkenyl" denotes a non-aromatic cyclic hydrocarbyl moiety containing at least one double bond. The term "heterocycloalkyl" denotes a saturated cyclic moiety having at least one ring heteroatom (e.g., N, 0 or S), such as 4-tetrahydropyranyl. The term "heterocyclenyl" denotes a non-aromatic cyclic moiety having at least one ring heteroatom (e.g., fluorene, fluorene or S) and at least one ring double bond, such as a pyranyl group. The term "aryl" means a hydrocarbon moiety having one or more aromatic rings. Examples of the aryl moiety include phenyl (Ph), phenylene, naphthyl, naphthylene, anthracenyl, fluorenyl and phenanthryl. The term "heteroaryl" means a moiety comprising one or more aromatic rings having at least one hetero atom (e.g., N, 0 or S). Examples of the heteroaryl 201109028 base moiety include furyl, furanyl, fluorenyl, pyridyl, porphinyl, oxazolyl, imidazolyl, thiazolyl, pyridyl, pyrimidinyl, sulfhydryl, sulfinyl , isoquinolinyl and 吲β-based. The group "amino," means -NtHCk alkyl) or -Νβκalkyl) 2 Unless otherwise specifically indicated, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, hetero Cycloalkyl, heterocycloalkenyl, aryl and heteroaryl groups include substituted and unsubstituted moieties. Possible for cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl groups. Substituents include, but are not limited to: q-Ch) alkyl group c2-c1(), c2-c10 alkynyl, c3-c2 anthracenyl, C3_C2 anthracenyl, C|-C2 anthracene Anthracene, crC2 fluorene heterocyclic, C|-C1Q; j^oxy, aryl, aryloxy, heteroaryl, heteroaryloxy, amino, crc1Q, alkylamino, crC2〇dialkylamino, Arylamino, diarylamino, CrC|decylalkylsulfonyl, arylsulfamoyl, C1 „C1G alkylimino, arylimino, (^-(:1()alkyl sulfonate Imino, arylsulfoimino, hydroxy, halogen, halogenated, CrCl() alkylthio, arylthio, CrC|G alkylsulfonic acid, arylsulfonyl, decylamino, aminoguanidine Base, aminothiononyl, fluorenyl, fluorenyl, ureido'cyano a nitro group, a nitroso group, an azido group, a fluorenyl group, a thioindenyl group, a decyloxy group, a carboxyl group, and a carboxylate group. On the other hand, a substituent on an alkyl group, an alkenyl group or an alkynyl group includes all of the above substitutions. a group, except for a C1_CI() alkyl group. The cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl and heteroaryl groups may also be fused to each other. 281 examples of the invention are listed below. Sex compounds. 10 201109028

Compound 3

Compound 10

Compound 11

Compound 15 11 tjtl: 201109028

Compound 20

Compound 29

Compound 27

12 201109028

Compound 45 13 201109028

Compound 50

Compound 51 compound 49

F

Compound 60 14 201109028

Compound 62

Compound 63

Compound 64

Compound 65

Compound 66

Compound 67

Compound 68

Compound 69

Compound 73

Compound 75 15 201109028

Compound 84

Compound 87

16 201109028

Compound 99

Compound 101

17 201109028

Compound 109

Compound 107

Compound 110

Compound 118 Compound 119

Compound 117

Compound 120 201109028

Compound 121

Compound 122

^νΗΛ

Compound 127

>

Compound 131 Compound 129

Compound 130

19 201109028

Compound 141

20 201109028

Compound 157

Compound 152

Compound 162

21 201109028

22 201109028

Compound 194

Compound 195 23 201109028

Ν Ν compound 199

"iNHOCS

Compound 201

Compound 202

Compound 203

Compound 204

24 201109028

》slv

ΎΎ

, Κ

Compound 218

Compound 223

Compound 222

Compound 225 25 201109028

Compound 239

Compound 237

Compound 240 26 201109028

Compound 242

&

Compound 245

σ 丫 compound 249

V νκΛ〇〇

m^TV

Compound 252

27 201109028

Compound 257

F

Compound 263

V° Compound 269 彳丫:

Compound 272

28 201109028

Compound 275

Compound 276

In another aspect, the invention relates to a method of treating an HCV infection, the method comprising administering to a patient in need thereof an effective amount of a compound of formula (I) above. In still another aspect, the invention relates to a pharmaceutical composition for treating an HCV infection. The composition comprises an effective amount of at least one compound of formula (I) and a pharmaceutically acceptable carrier. Inhibitors of targets other than the HCV NS3 protease in the HCV life cycle, such as NS5B polymerase, NS5A, NS4B or p7, may be included. Examples of such inhibitors include, but are not limited to, N-[3-(l-cyclobutylindolyl-4-yl-2-oxo-1,2-dimur-indolyl-3-yl)- 1,1-dioxo-1,4-diazo 29 201109028 -116-benzo[1,2,4]thiadiazin-7-yl]-indolesulfonamide (W004041818), anti-1,2 -Di-4-[(phenylethenylpyrrolidine-2-(S)-carbonyl)amino]-phenylethene (W00401413) and 1-amino-gumamine^Amentadine, Griffin, 2004, J. Gen· Virol 85: p451). The pharmaceutical composition may also comprise an immunomodulatory agent or a second antiviral agent. An immunomodulator refers to an active agent capable of mediating an immune response. Examples of immunomodulators include, but are not limited to, Nov-205 (Novelos Therapeutics Inc., W002076490) and IMO-2125 (Idala) Drug Company (Idera Pharmaceuticals Inc.), W005001055). An antiviral agent refers to an active agent that kills a virus or inhibits viral replication. Examples of antiviral agents include, but are not limited to, ribavirin, ribamidin, interferon-a, Pegylated interferon, and HCV protease inhibitors, such as 2-(2-{2-cyclohexyl-2- [〇bazine-2-carbonyl)-amino]-ethionylamino}-3,3-dimethyl-butanyl)-octahydro-cyclopenta[c]pyrrole-1·carboxylic acid (1-cyclopropyl) Aminoglycol-butyl), guanamine (Telaprevir, top pharmaceutical company (Vertex Pharmaceuticals lnc.), WO02018369), 3-[2-(3-tert-butyl-ureido)-3,3-didecyl -Butyl]-6,6-dimercapto-3.-azabicyclo[3.1.0]hexane-2-carboxylic acid (2-carbamoyl-1-cyclobutylmethyl-2-oxo- Ethyl)-decylamine (Boceprevir, Schering-Plough Research Institute, WO03062265) and 4-fluoro-1,3-dihydro-isoindole-2-carboxylic acid 14-tert-butoxy Carbonylamino-4-cyclopropanesulfonylaminocarbonyl-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]dodecyl-.7-ene-18-yl ester (ITMN-] 91, InterMune Inc., US 2005/0267018). The use of the composition in the treatment of HCV infection or in the manufacture of a medicament for use in such a treatment is also within the scope of the invention. One or more embodiments of the present invention are described in detail below. Other features, objects, and advantages of the invention will be apparent from the description and appended claims. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The compounds of the present invention can be prepared from commercially available starting materials by methods well known in the art. For example, the compounds of the invention can be synthesized by the path shown in the following illusion:

31 201109028 As shown in Process 1, the polycyclic compound (1) is first coupled with ^^_(tert-butoxycarbonyl)-L-valine (ii) and then methylated to form an intermediate (丨丨丨) . The intermediate (m) is subjected to a deprotection reaction to remove the N-butoxycarbonyl group to form the N-free compound (iv) which is coupled with the carboxylic acid (v) to form the intermediate (vi). By hydrolyzing the intermediate (vi), an acid (vii) is obtained which is coupled with an amine compound (viy) to obtain a pyrrolidine compound (ix) having two alkenyl end groups. The intermediate (ix) is subjected to an olefin displacement reaction in the presence of a groude catalyst to obtain the desired macrocyclic compound (X). The double bond of the macrocyclic analog (xi) can be further hydrogenated in the presence of pd_c to obtain saturation. Macrocyclic compound (X丨). The following Schemes 2 and 3 show alternative synthetic routes for the two compounds of the invention. History 2

32 201109028 History 3

The above process also includes the steps carried out after the steps specifically described in Schemes 1-3 to add or remove suitable protecting groups to synthesize the desired compound. In addition, the different synthetic steps can be carried out in the order or sequence to obtain the desired compound. Synthetic chemical transformation and protecting group methods for the synthesis of (丨) applicable compounds (Baoyan ‧1 R. machine protection) are known in the art and include, for example, those described in the following literature: Larock, Comprehensive Organic Transformations (combined with #允人VCH Press (1989); TW Greene and PGM Wuts

Protective Groups in Organic Synthesis 'Second Edition' John Power and Sasun Press (John Wiley and 33 201109028

Sons) (1991); L. Fieser and M. Fieser,

Reagents for Organic Synthesis (Fahrenheit and Fei's Test #9 in Organic Synthesis, John Power and Sasun Press (1994); and Encyclopedia of Reagents for Organic Synthesis by L. Paquette (Test for Organic Compounds # / Full Magic, John Power and Sasun Press (1995), and subsequent editions. The following is a detailed description of the actual preparation of compound 1-281. The compounds described herein contain non-aromatic doubles. Bonds and asymmetric centers. Thus, the compounds can be a variety of racemates and racemic mixtures, simple enantiomers, individual diastereomeric 'diastereomeric mixtures, tautomers' and cis-iso In the form of a conformation or a trans-isomer. All such isomeric forms are contemplated. For example, the compound of formula (1) shown above may have the following stereochemical configuration (II):

The above compounds include the compound itself, if applicable, including its salts, prodrugs and solvates. For example, the salt may be formed of an anion and a positively charged group (e.g., an amino group) on the compound of formula (1). Suitable anions include: gas ion, bromide ion, sulfate ion, nitrate ion, phosphate ion, screw 34 201109028 citrate ion, sulfonate ion, trifluoroacetate ion, acetate ion, malate ion, strontium Benzoate ion, tartrate ion, fumarate ion, glutamate ion, glucuronide ion, lactate ion, sebacate ion and maleate ion. Similarly, the salt may also be formed from a cation and a negatively charged group (e.g., a diacidate) on the compound of formula (I). Suitable cations include sodium ions, potassium ions, magnesium ions, calcium ions, and cations such as tetradecyl hydroxy ions. The compounds of formula (I) also include those containing a quaternary nitrogen atom. Examples of prodrugs include esters and other pharmaceutically acceptable derivatives which, upon administration to a patient, provide the active compound of formula (1). Solvate refers to a complex formed between the active compound of formula (I) and a pharmaceutically acceptable solvent. Examples of pharmaceutically acceptable solvents include water, ethanol, isopropanol, ethyl acetate, acetic acid and ethanolamine. One method of treating HCV infection within the scope of the present invention is by administering to a patient an effective amount of one or more compounds of formula (I). The term "therapeutic" or "treatment" means the administration of a compound to a subject infected with HCV, exhibiting symptoms of HCV infection, or susceptible to HCV infection, to achieve a therapeutic effect, such as healing, ameliorating, altering, affecting, ameliorating or Prevention of HCV infection, symptoms of HCV infection, or a predisposition to HCV infection. The term "effective amount" means the amount of active compound of the invention required to achieve a therapeutic effect in a subject being treated. Those skilled in the art will recognize that effective The dosage may vary depending on the type of disease being treated, the route of administration, the excipients employed, and other treatments which may be employed in parallel. The compounds of the present invention may remain in the blood circulation 35 201109028 at an effective level for a long time. Therefore, these compounds may An effective amount is administered once a day to provide a therapeutic effect. In order to practice the methods of the invention, compositions comprising one or more compounds of the invention may be administered parenterally, orally, intranasally, rectally, topically or Contains the service. The term "parenteral" means subcutaneous injection, intradermal injection, intravenous Injection, intramuscular injection, intra-articular injection, intra-arterial injection, intrasynovial injection, intrasternal injection, intrathecal injection, wound injection or intracranial injection, and any suitable injection technique. Sterile injectable composition can be located in non-toxic a solution or suspension in a parenterally acceptable diluent or solvent, for example, in 1,3-butanediol. Acceptable vehicles and solvents that may be employed are mannitol, water, Ringer's solution and Isotonic sodium chloride solution. In addition, non-volatile oils are usually used as a solvent or suspension medium (for example, synthetic monoglycerides or diglycerides). Fatty acids, such as oleic acid and its glycerin derivatives, can be used to prepare injectable preparations. For example, pharmaceutically acceptable natural oils such as olive oil or castor oil, especially in their polyoxyethylated form, may be employed. These oil solutions or suspensions may also contain a long-chain alcohol diluent or suspending agent, carboxy Methylcellulose or similar dispersing agents. Other commonly used surfactants, such as Tween or Span, or commonly used to produce pharmaceutically acceptable solids, Other similar emulsifiers or bioavailability enhancers for body or other dosage forms may also be used to formulate pharmaceutical compositions. Compositions for oral administration may be in any acceptable oral dosage form including capsules, tablets, lotions and Aqueous suspensions, dispersions and solutions. For tablets, commonly used carriers include lactose and corn starch. It is usually also possible to add 36 201109028 to a lubricant such as magnesium stearate. For oral administration in capsule form, available release The agent comprises lactose and dried corn starch. When the aqueous suspension or emulsion is administered orally, the active ingredient can be suspended or dissolved in the oil phase combined with the emulsifier or suspending agent. If desired, certain sweeteners can be added. , perfume or colorant. Nasal sprays or inhalation compositions can be prepared according to techniques well known in the art of pharmaceutical formulation. For example, benzyl alcohol or other suitable preservatives, absorption enhancers that increase bioavailability, fluorohydrocarbons, and / or other solubilizing or dispersing agents known in the art, such compositions are prepared as solutions in saline. The compositions of the various active compounds of the invention may also be administered in the form of a suppository' for rectal administration. The carrier in the pharmaceutical composition must be "acceptable, that is, compatible with the active ingredients of the composition (preferably capable of stabilizing the active ingredient), and = will cause a discomfort to the treated subject. A pharmaceutical excipient that delivers the active compound of the present invention as a silk. Examples of other carriers include colloidal oxygen, hard magnesium, cellulose, sodium lauryl sulfate, and D&C#10 yellow. The compounds of the invention can be used to treat HCV with a second anti-HCV agent, including, for example, a dry-labeled inhibitor of the HCV NS3 protease in the Hcv life cycle, an immunomodulator and a second antiviral agent. The compound of the present invention and the second anti-Hcv agent may be administered as the same or at different times. For simultaneous administration, the two agents may be mixed to form a single-pill or separately into a pill. Two reagents ^ 37 201109028 They are administered in a quantity such that their total amount is an effective amount for the treatment of HCV as recognized by the skilled artisan. Initial screening can be performed by in vitro assays (see Examples 282 and 283). The efficacy of the compounds of the invention in the treatment of HCV infection is then determined by animal and clinical trials. Other methods will be apparent to those of ordinary skill in the art. The following examples are illustrative only and are not intended in any way. The other parts of the specification constitute limitations. It is believed that those skilled in the art, based on the description herein, may use the present invention to the fullest extent without additional work. The entire disclosure of all publications cited herein is hereby incorporated by reference in its entirety Reference Example 1: Synthesis of {4-cyclopropanediaminocarbamicin-2,15-dioxo-18-[2-(4-difluoroindolyl-phenyl)-benzo[4,5 Furano[3,2-d]pyrimidin-4-yloxy:indole-3,16-diazatricyclo[14.3.0.04,6]nonadecane-14-yl}-carbamic acid cyclopentyl ester (Compound 1) Compound 1-3 was first prepared from the commercially available ethyl 1-tert-butoxycarbonylamino-2-vinyl-cyclopropanecarboxylate by the following route:

HATU, DIPEA, DBU DMAP, CH2CI2

38 201109028 To a solution of ethyl 1-tert-butoxycarbonylamino-2-vinyl-cyclopropanecarboxylate (0.34 g, 1-3 mmol) in THF (5 mL) A suspension of 11 (0.13 g '5.3 mmol) of water. After stirring overnight at room temperature, the reaction was quenched with 10% EtOAc (2 mL). The resulting solid powder was washed with water (10 ml) to give compound EtOAc (m.sup.27 g, 90%), MS m/z 249.9 (M++23); NMR (CDC13) δ 10.35 (brs, 1H), 5.84-5.71(m, 1H), 5.29(d, J = 17.4 Hz, 1H), 5.12(d, J = 10.2 Hz, 1H), 2.23-2.14(m, 1H), 1.87-1.65(m, 1H) , 1.58-1.41 (m, 1H), 1.43 (s, 9H). Stir compound Il (0-52 g, 2.3 mmol), 2-(lH-7-azabenzotriene.sodium-1-yl)-l,l,3,3-tetradecyl gland cation (uronium) at room temperature Hexafluoro-salt ammonium methanaminium (HATU, 1.74 g, 4.6 mmol) and 4-dimethylamino group (1.39 g, 11.6 mmol) at (1^2〇!12 ( The solution in 40 ml), followed by the slow addition of cyclopropanesulfonamide (0.57 g, 4.7 mmol), diisopropylethylamine (1.81 ml, 14_0 mmol) and 1,8-diaza in 15 minutes. Bicyclo[5,4,0]undec-7-ene (1.80 g, 11.7 mmol). After stirring the reaction mixture at rt overnight, solvent was evaporated in vacuo. Compound 1-2 (0.51 g, 66%) MS m/z 353.1 (M++23); NMR (CDC13) δ 9.75 (brs, 1H), 5.64-5.51 (m, 1H), 5.30 (d) , J = 17.4 H), 5.l6(d, J = 10.2 Hz, 1H), 2.95-2.89(m, 1H), 2.19-2.10(m, 1H), 1.93-1.88(m, 1H), 1.47( s, 9H), 1.46-1.38 (m, 1H), 1.32-1.23 (m, 2H), 1.15-1.00 (m, 2H). Compound 1-2 (0.50 g, 1.5 mmol) at room temperature In MeOH (8 39 201109028 ml) The solution was added to EtOAc (EtOAc (EtOAc) (EtOAc). MS m/z (M++l); 'H NMR (CD3COD) δ 5.77-5.65 (m, 1 Η), 5.43 (d, J = 17.4 Hz, 1H), 5.32 (d, J = 10.2 Hz, 1H ), 3.06-2.97(m, 1H), 2.45(dd, J = 17.4 Hz, J = 7.8, 1H), 2.16(dd, J = 8.0 Hz, J = 7.8 Hz, 1H), 1.75(dd, J = 10.1 Hz, J = 7.8 Hz, 1H), 1.32-0.86 (m, 4H) 〇 Compound 1 was prepared by the following route: 40 201109028

HATU. HOBt, NNM CH2C12

Ml

H:, PdC

MeOH

A solution of 3-amino-p-furanfuran-2-carboxylic acid decylamine (1.00 g, 5.7 mmol) and pyridine (1 mL, 12.26 mmol) in THF (25 mL) was stirred for 10 min. To the resulting solution was slowly added 4-trifluorodecyl-benzhydrazene 41 201109028 (1·48 g, 7.1 mmol). The temperature was then raised to room temperature and the mixture was stirred for 12 hours. After removing the solvent under reduced pressure, the solid formed was collected, washed with water and dried to give 1-4 (1.92 g, 96.0%). MS: m/z 349.0 (M++1) 〇 1-4 (1.92 g, 5.5 mmol) and 2\\3 〇 13 13 ml) in a suspension of 玢 011 (25 ml) at 85 ° C 12 hours. After cooling, the mixture was acidified and then EtOH was removed. The solid which formed was collected, filtered, washed with water and dried to give 1-5 (1.71 g, 95.0%). MS m/z 331 (M++1). A solution of 1-5 (1.71 g, 5.2 mmol) and excess phosphorus argon (POCl3) was refluxed for 2 hours. After cooling and complete concentration, the mixture was extracted with dichloromethane and 10% sodium hydroxide. The organic layer was dried with EtOAc (EtOAc) (EtOAc) (HHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH , 2Η), 8.34(d, 1H), 7·82·7_75(ητ, 4H), 7.57 (ddd, 1H). To a suspension of Boc-trans-4-hydroxy-L-proline (0.53 g, 2.3 mmol) in DMSO (25 mL) was added t-BuOK (0.82 g, 5.1 mmol). After the mixture was allowed to warm to room temperature and stirred for 1 hour, the compound oxime-6 (0.81 g, 2.3 mmol) was slowly added to 0 °C. Continue stirring overnight. Iodine (1. 02 g, 6.9 mmol) was added. The reaction mixture was further stirred at room temperature for 30 minutes. The reaction mixture was neutralized to a pH of 6-7 with a 10% aqueous HCl solution and extracted with di-methane. The organic layer was dried with EtOAc (EtOAc m.) MS m/z 557.8 (M++1); 'H NMR (CDC13) δ 8.63 (d, 2 Η), 8.28 (d, 1H), 7.80-7.74 (m, 2H), 7.70 (d, 2H), 7.51 (ddd, 1H) 〇42 201109028 </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; The reaction mixture was returned to the hour to remove Me〇H and S〇Cl2. The residue was ground with a pen. The suspension was filtered to give a compound (yield: 87 g, 95%). MS m/z 458·1 (Μ++1). To the brew, to HATU (1.12 g '3_〇 mmol), p-benzotriazole (HOBT, 41.41 g '3.0 mmol), work, Buick, i 9 mmol) and 2 · tert-butoxy N-methylmorpholine (NMM, 2 g, 9-9 mmol) was added to a solution of carbonylamino-indole-8-enoic acid (1.21 g, 19 mmol) in CH2C12 (40 mL). After stirring overnight, the compound was concentrated under vacuum. The residue was purified by column chromatography eluted to afford compound </RTI> -9 (m. MS m/z 711.3 (Μ++1). To a solution of compound 1-9 (1.01 g, 1.4 mmol) in EtOAc (2 mL), EtOAc. After stirring overnight, the reaction mixture was neutralized to pH with 丨〇% HCl. &lt; 7, and concentrated with vacuum. The resulting residue is filtered and washed with water to give compound 1-10 (0. 91 grams, 92%). MS: m/z 697·3 (Μ++1). At room temperature, it will be ΝΜΜ (0. 12 grams, 1. 2 mmol) is added to compound 1-3 (0. 28 grams ’ 0. 4 mmol), HATU (0. 31 grams, 0. 8 mmol), ΗΟΒΤ (0. 08 g, 〇·6 mmol) and compound 1-10 (0. 〇 9 grams, 0. 4 mmol) in a solution of CH2Cl2 (10 mL). After stirring overnight, the reaction mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography to give compound 1-11 (0. 10 grams, 85%) ° MSm / z921. 3(M++l); HNMWCDCh) δ 10. 24 (8, 1Η), 8. 61(d, 2H), 8. 26(d, 1H), 7. 77(d, 2H), 7. 73- 43 201109028 7. 64(m, 2H), 7. 54-7. 47(m, 1H), 7. 11(s, 1H), 6. 19(d, 1H), 5. 88-5. 70 (m, 2H), 5. 38-5. 25(m, 2H), 5. 16(d, 1H), 5. 00-4. 90 (m, 2H), 4. 60 (dd, 1H), 4. 88-4. 34(m, 2H), 4. 18-4. 10 (m, 1H), 2. 98-2. 89 (m, 1H), 2. 68 (dd, 2H), 2. 18-1. 96 (m? 6H), 1. 50-1. 32 (m, 7H), 1. 28(s,9H), 1. 09-1. 25 (m, 2H). At room temperature, under the N2 atmosphere to the compound M 丨 (0. 10 grams, 0. 11 mmol) Add the Hoveyda-Grubbs II (35 mg, 0.) solution in milliliters). 056 mmol). Then, the reaction mixture was stirred at 40 C for 24 hours to carry out metathesis cyclization. The reaction was quenched and the reaction mixture was purified mpjjjjjjj MS: m/z 893. 3(M++1) ; lH NMR(CDC13) δ 10. 39(s,1H), 8. 59(d, 2H), 8. 21 (d, 1H), 7. 77 (d, 2H), 7. 69-7. 57(m, 2H), 7. 46 (dd, 1H), 7. 20(s, 1H), 6. 12(s, 1H), 5. 69(q, 1H), 5. 12(d, 1H), 4. 97 (dd, 1H), 4. 81-4. 68(m, 2H), 4. 28-4. 07(m, 2H), 2. 96-2. 49(m, 3H), 2. 30(q, 1H), 1. 96-1. 12(m, 14H), 1. 08(s, 9H), 0. 96-0. 82 (m, 2H) ° room temperature, under the A atmosphere to the compound 142 (30 mg, 0. 034 mmol.) 5% pd-C (5 mg) was added to a solution of MeOH (1 mL). Then, the reaction mixture was stirred at room temperature under a hydrogen pressure of 60 psi' for 4 hours. The reaction mixture was filtered and purified by column chromatography to give Compound 1 (16. 5 mg ' 55%) ° MS: m/z 895. 3(M++1); 'H NMR(CDC13) δ 10. 79(s, 1H), 8. 57(d, 2H), 8. 21(d, 1H), 7. 75(d, 2H), 7. 64(m, 2H), 7. 46(d, 1H), 7. 11(s, 1H), 6. 11(s&gt; ih), 5. 29(d, 1H), 4. 72(m, 2H), 4. 38(m, 2H), 4. 12 (m, 1H), 3. 〇 2-2. 58(m, 3H), 1. 98-0. 86 (m, 44 201109028 29H). Example 2-141: Synthesis of Compound 2-141 Compound 2-141 was each prepared in a similar manner to that described in Example 1. Compound 2: MS: m/z 883. 3(M++1) ; NMR(CDC13) δ 10. 51(s, 1H), 8. 53(d, 2H), 8. 16(d, 1H), 7. 73(d, 2H), 7. 62(m, 2H), 7. 22(m, 2H), 6. 07(s, 1H), 5. 23(d, 1H), 4. 77 (dd, 1H), 4. 49(d, 1H), 4. 35 (m, 1H), 4. 13(m, 1H), 3. 02-2. 57(m, 3H), 1. 99-0. 91 (m, 30H). Compound 3: MS: m/z 823. 2(M++1) ; 'H NMR(CDC13) δ 10. 38(s, 1H), 8. 53(d, 2H), 8. 16(d, 1H), 7. 73(d, 2H), 7. 61(m, 2H), 7. 41(m, 2H), 6. 13(m, 2H), 5. 69(q, 1H), 4. 98 (dd, 1H), 4. 78(m, 1H), 4. 55 (m, 1H), 4. 42 (m, 1H), 4. 19 (m, 1H), 2. 89 (m, 1H), 2. 78(m, 2H), 2. 52(m, 1H), 2. 23(q, 1H), 1. 96-0. 84 (m, 15H), 1. 90 (s, 3H). Compound 4: MS: m/z 882. 3(M++1) ; 4 NMR(CDC13) δ 10. 47(s, 1H), 8. 64(d, 1H), 8. 52(m, 3H), 7. 70(d, 2H), 7. 44 (dd, 1H), 6. 07(s, 1H), 5. 63(q, 1H), 5. 01-4. 73(m, 3H), 4. 07-4. 01(m, 2H), 2. 90-2. 22(m, 4H), 1. 97-1. 09(m, 17H), 0. 94(s, 9H), 0. 90-0. 88 (m, 1H). Compound 5: MS: m/z 840. 2(M++1) ; 'H NMR(CDC13) δ 10. 42(s, 1H), 8. 64-8. 47(m, 4H), 7. 80(d, 2H), 7. 50-7. 27(m, 2H), 6. 15(s, 1H), 5. 69(q, 1H), 5. 23(d, 1H), 5. 02(dd, 1H), 4. 84 (dd, 1H), 4. 53(d, 1H), 4. 25-4. Ll(m, 2H), 3. 32(s, 3H), 45 201109028 2. 93- 2. 15 (m, 4H), 1. 92-0. 83 (m, 16H). Compound 6: MS: m/z 824. 2(M++1) ; 4 NMR(CDC13) δ 10. 48(s, 1H), 8. 63(d, 1H), 8. 62-8. 48(m, 3H), 7. 78(d, 2H), 7. 44_7. 4〇(m&gt; ih), 6. 16-6. 14(m, 2H), 5. 73(q, 1H), 5. 04 (dd, 1H), 4. 85 (dd, 1H), 4. 55(s,1H), 4. 51(s,1H), 4. 15(d,1H), 2. 93- 2. 89(m, 2H), 2. 77-2. 22 (m, 3H), 1. 95-1. 85(m, IK), 1. 79(s,3H), 1. 76-0. 83 (m,] 5H). Compound 7: MS: m/z 839. 2 (M++1); NMR (C: DC13) δ 10. 39(s, 1H), 8. 46(d, 2H), 8. 15(d, 1H), 7. 71(d, 2H), 7. 62-7. 37(m, 3H)5 7. 16(s, 1H), 6. 08(s, 1H), 5. 71(q, 1H), 5. 25(d, 1H), 4. 96 (dd, 1H), 4. 75 (dd, 1H), 4. 44(d, 1H), 4. 35-4. 09(m, 2H), 3. 34(s, 3H), 2. 96-2. 71(m, 2H), 2. 57(brs, 1H), 2. 28(q, 1H), 2. 08-0. 87 (m, 16H). Compound 8: MS: m/z 849. 3(M++1) ; 'H NMR(CDC13) δ 10. 54(s, 1H), 8. 45(d, 2H), 8. 06(d, 1H), 7. 71(d, 2H), 7. 57(m, 3H), 7. 35(s, 1H), 6. 28(d, 1H), 6. 04(s, 1H), 5. 71(q, 1H), 4. 96 (dd, 1H), 4. 67(dd, 1H), 4. 47(d, 1H), 4. 45(brs, 1H), 4. 11 (m, 1H), 2. 92-2. 45 (m, 4H), 2. 32(q, 1H), 1. 96-0. 84 (m, 20H). Compound 9: MS: m/z 880. 3(M++1) ; 4 NMR(CDC13) δ 10. 45(s, 1H), 8. 40(d, 2H), 8. 14(s, 1H), 7. 97(d, 1H), 7. 64(d, 2H), 7. 48-7. 41(m, 2H), 7. 25-7. 20 (m, 1H), 5. 96(s, 1H), 5. 63(q, 1H), 4. 92-4. 86(m, 2H), 4. 77(d, 1H), 4. 44(s, 1H), 4. 20 (dd, 1H), 4. 03(dd, 1H), 2. 90-2. 84(m, 2H), 2. 80-2. 63(m, 1H), 46 201109028 2. 38-2. 32(m, 1H), 1. 98-1. 02(m, 15H), 0. 91(s, 9H), 0. 90-. 086 (m, 1H). Compound 10: MS: m/z 911·2 (Μ++1); *H NMR (CDC13) δ 10. 23(s, 1H), 8. 54(d, 2H), 7. 87-7. 80 (m, 1H), 7. 71(d, 2H), 7. 56(dd, 1H), 7. 33-7. 20 (m, 1H), 6. 88(s, 1H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 07-4. 94(m, 2H), 4. 69 (dd, 1H), 4. 57(d, 1H), 4. 43-4. 38(m, 1H), 4. 24-4. 01(m, 2H), 2. 91-2. 80 (m, 2H), 2. 74 (s, 3H), 2. 65-2. 63(m, 1H), 2. 60-2. 41 (m, 1H), 2. 22(q, 1H), 1. 98-0. 86 (m, 20H). Compound 11: MS: m/z 907. 3 (M++1). Compound 12: MS: m/z 923·3 (Μ++1); NMR (CDC13) δ 10. 42(s, 1H), 8. 57(d, 2H), 8. 06(d, 1H), 7. 76(d, 2H), 7. 51(s, 1H), 7. 14-6. 93(m, 2H), 6. 13(s, 1H), 5. 80-5. 60 (m, 1H), 5. 31(d, 1H), 4. 97-4. 83(m, 2H), 4. 79 (dd, 1H), 4. 64-4. 04(m, 3H), 3. 88(s, 3H), 2. 94-2_43(m, 3H), 2. 36-0. 86 (m, 25H). Compound 13: MS: m/z 852. 3(M++1) ; 'H NMR(CDC13) δ 10. 68(s, 1H), 8. 38(d, 2H), 7. 95(d, 1H), 7. 72-7. 58(m, 3H), 7. 47(d, 2H), 7. 24-7. 19(m, 1H), 6. 01(s, 1H), 5. 69(q, 1H), 4. 94 (dd, 1H), 4. 78(dd, 1H), 4. 70(d, 1H), 4. 46(d, 1H), 4. 22- 3. 98(m, 2H), 2. 97-2. 80 (m, 2H), 2. 57(s, 6H), 2. 67-2. 41 (m, 1H), 2. 23(q, 1H), 1. 85-0. 84 (m, 16H). Compound 14: MS: m/z 766·2 (Μ++1); 'H NMR (CDC13) δ 10. 30(s, 1H), 8. 62 (m, 2H), 8. 24(m, 1H), 7. 77(d, 2H), 7. 67(m, 2H), 7. 48 (m, 1H), 6. 90(s, 1H), 6. 18(s, 1H), 5. 72(q, 1H), 47 201109028 4. 98 (dd, 1H), 4. 65 (dd, 1H), 4. 24(m, 1H), 4. 05(m, 1H), 2. 92 (m, 1H), 2. 76(m, 2H), 2. 58-2. 28(m, 4H), 1. 94-1. 05(m, 13H), 0. 97-0. 86 (m, 2H). Compound 15: MS: m/z 893. 3 (M++1); NMR (CDC13) δ 10. 33(s, 1H), 8. 88(s, 1H), 8. 68(d, 1H), 8. 26(d, 1H), 7. 80-7. 65 (m, 4H), 7. 35-7. 26(m, 1H), 6. 98(d, 1H), 6. 20(d, 1H), 5. 71(q, 1H), 5. 18(d, 1H), 5. 00 (dd, 1H), 4. 77 (dd, 1H), 4. 64(d, 1H), 4. 46(s, 1H), 4. 25(dd, 1H), 4. 15(dd, 1H), 2. 92-2. 28(m, 4H), 2. 17-0. 82 (m, 24H). Compound 16: MS: m/z 877. 3(M++1) ; 4 NMR(C:DC13) δ 10. 40(s, 1H), 8. 45(d, 2H), 8. 04(d, 1H), 7. 62(d, 2H), 7. 58-7. 50 (m, 2H), 7. 44(s, 1H), 7. 35 (dd, 1H), 6. 02(s, 1H), 5. 95(d, 1H), 5. 63(q, 1H), 4. 81 (dd, 1H), 4. 70 (dd, 1H), 4. 49(d, 1H), 4. 42-4. 38(m, 1H), 4. 04(dd, 1H), 2. 90-2. 20(m, 6H), 1. 96-0. 83 (m, 23H) » Compound 17: MS: m/z 907. 3(M++1) ; 4 NMR(CDC13) δ 10. 42(s, 1H), 8. 73(s, 1H), 8. 62(d, 1H), 7. 96(s, 1H), 7. 71(d, 1H), 7. 64 (dd, 1H), 7. 59-7. 25(m, 3H), 6. 11(s, 1H), 5. 62(q, 1H), 5. 21(d, 1H), 4. 99(dd, 1H), 4. 79 (dd, 1H), 4. 61(d, 1H), 4. 52(s, 1H), 4. 25-4. 10(m, 2H), 2. 95-2. 51(m, 3H), 2. 47(s , 3H), 2. 31(q,]H), 2. 03-0_91 (m, 24H). Compound 18: MS: m/z 767. 2(M++1) ; NMR(CDC13) δ 10. 38(s, 1H), 8. 49(d, 2H), 8. 15(d, 1H), 7. 77(d, 2H), 7. 64-7. 58(m, 2H), 7. 41-7. 32(m, 1H), 7. 29(s, 1H), 6. 08(s, 1H), 48 201109028 5. 78(q, 1H), 5. 08(dd, 1H), 4. 66(dd, 1H), 4. 42(d, 1H), 4. 09-4. 06(m, 1H), 3. 85-3. 62 (m, 4H), 2. 93-2. 45 (m, 4H), 2. 04-0. 87 (m, 13H). Compound 19: MS: m/z 899·3 (Μ++1); Η NMR (CDC13) δ 10. 28(s, 1H), 8. 51(d, 2H), 7. 80 (dd, 1H), 7. 70(d, 2H), 7. 51-7. 42(m, 1H), 7. 37-7. 23(m, 1H), 6. 97(s, 1H), 6. 06(s, 1H), 5. 63(q, 1H), 4. 96-4. 85(m, 2H), 4. 75-4. 63(m, 2H), 4. 09-4. 02 (m, 2H), 2. 93-2. 43(m, 4H), 2. 21(q,1H), 1. 96-0. 76 (m, 24H). Compound 20: MS: m/z 895. 3(M++1) ; 4 NMR(CDC13) δ 10. 42(s, 1H), 8. 43(d, 2H), 7. 81(s, 1H), 7. 67(d, 2H), 7. 51(s, 1H), 7. 35-7. 28(m, 2H), 5. 92(s, 1H), 5. 57(q, 1H), 5. 19(d, 1H), 4. 88-4. 61(m, 3H), 4. 14-4. 00 (m, 2H), 2. 83-2. 41 (m, 4H), 2. 38(s, 3H), 2. 24(q, 1H), 1. 96-1. 16 (m, 15H), 1. 05(s, 9H), 0. 97-0. 78 (m, 1H). Compound 21: MS: m/z 923·3 (Μ++1); 'H NMR (CDC13) δ 10. 33(s, 1H), 8. 50(d, 2H), 7. 67(d, 2H), 7. 59(s, 1H), 7. 41(d, 1H), 7. 34(s, 1H), 7. 16(d, 1H), 6. 06(s, 1H), 5. 64(q, 1H), 5. 23(d, 1H), 4. 94 (dd, 1H), 4. 87 (dd, 1H), 4. 58-4. 42 (m, 2H), 4. 30-4. 02(m, 2H), 3. 84(s, 3H), 2. 88-2. 44(m, 4H), 2. 21(q, 1H), 1. 84-0. 78 (m, 23H). Compound 22: MS: m/z 752. 2(M++1) ; 4 NMR(CDC13) δ 10. 76(s, 1H), 8. 61(d, 2H), 8. 25(m, 1H), 7. 79(d, 2H), 7. 67(d, 2H), 7. 52(m, 1H), 6. 70(s, 1H), 6. 19(s, 1H), 5. 69(q, 1H), 5. 08(m, 1H), 4. 65 (dd, 1H), 4. 23(dd, 1H), 4. 02(m, 1H), 49 201109028 3. 05-1. 98 (m, 7H), 1. 96-0. 82 (m, 13H). Compound 23: MS: m/z 907·3 (Μ++1); if! NMR (CDC13) δ 10. 40(s, 1H), 8. 56(d, 2H), 8. 08(d, 1H), 7. 73(d, 2H), 7. 29(s, 1H), 7. 26-7. 20(m, 2H), 6. 13(s, 1H), 5. 71(q, 1H), 5. 22(d, 1H), 4. 95 (dd, 1H), 4. 82-4. 73 (m, 1H), 4. 63-4. 51(m, 1H), 4. 33-4. 06 (m, 2H), 2. 96-2. 51(m, 4H), 2. 53(s, 3H), 2. 24(q, 1H), 1. 96-0. 94 (m, 24H). Compound 24: MS: m/z 916. 3(M++1) ; 4 NMR(CDC13) δ 10. 37(s, 1H), 8. 48(d, 2H), 8. 08(s, 1H), 7. 68(d, 2H), 7. 50-7. 37(m, 3H), 6. 01(s, 1H), 5. 59(q, 1H), 5. 13(d, 1H), 4. 83 (dd, 1H), 4. 74-4. 63(m, 2H), 4. 15(dd, 1H), 4. 05(d, 1H), 2. 94-2. 41 (m, 4H), 2. 21(q, 1H), 1. 89-1. 14(m, 14H), 1. 03(s, 9H), 0. 96-0. 85 (m, 1H). Compound 25: MS: m/z 923. 3 (M++1). Compound 26: MS: m/z 923. 3(M++1) ; 4 NMR(CDC13) δ 1035(s, 1H), 8. 50(d, 2H), 7. 69(d, 2H), 7. 52 (dd, 1H), 7. 40(s, 1H), 7. 12(d, 1H), 6. 75(d, 1H), 6. 05(s, 1H), 5. 63(q, 1H), 5. 27(d, 1H), 4. 97-4. 83 (ms 1H), 4. 75 (dd, 1H), 4. 42 (brs, 1H), 4. 28-4. 08(m, 2H), 4. 08(s, 3H), 2. 91-2. 38(m, 4H), 2. 23(q, 1H), 1. 96-0. 82 (m, 24H). Compound 27: MS: m/z 894_3 (M++1); "H NMR (CDC13) δ 10. 38(s,]H), 8. 47(d, 2H), 8. 08(d,lH), 7. 62 (d, 2: H), 7. 58-7. 54(m, 2H), 7. 40-7. 33(m, 1H), 7. 3 l(s, 1H), 6. 07(s, 1H), 5. 63(q, 1H), 4. 95 (dd, 1H), 4. 83(d, 1H), 4. 87 (dd, 1H), 4. 58(d, 50 201109028 1H), 4. 31-4. 19(m, 1H), 4. 09(dd, 1H), 3. 40-3. 32(m, 4H), 3. 01-2. 41 (m, 8H), 2. 19(q, 1H), 1. 92-0. 83 (m, 15H). Compound 28: MS: m/z 878·3 (Μ++1); &apos;H NMR (CDC13) δ 10. 56(s, 1H), 8. 41(d, 2H), 8. 02(d, 1H), 7. 74(s, 1H), 7. 68(d, 2H), 7. 53-7. 47(m, 2H), 7. 35-7. 32(m, 1H), 6. 01(s, 1H), 5. 62(q, 1H), 4. 90 (dd, 1H), 4. 78(dd, 1H), 4. 59-4. 43(m, 2H), 4. 35-4. 25 (m, 1H), 4. 05(dd, 1H), 3. 61-3. 49(m, 1H), 3. 01-2. 45 (m, 8H), 2. 21(q, 1H), 1. 85-0. 83 (m, 18H). Compound 29: MS: m/z 909·3 (Μ++1); 4 NMR (CDC13) δ 10. 27(s, 1H), 8. 53(d, 2H), 8. 16(d, 1H), 7. 67(d, 2H), 7. 64-7. 43(m, 4H), 6. 03(s, 1H), 5. 61(q, 1H), 5. 22-5. 19(m, 1H), 4. 87 (dd, 1H), 4. 66(dd, 1H), 4. 57(d, 1H), 4. 19-4. 01(m, 3H), 3. 71-3. 42 (m, 4H), 3. 19-2. 97(m, 2H), 2. 91-2. 43(m, 4H), 2. 20(q, 1H), 1. 95-0. 81 (m, 17H). Compound 30: MS: m/z 906. 3(M++1) ; !H NMR(CDC13) δ 10. 18(s, 1H), 8. 62(d, 2H), 8. 25(d, 1H), 7. 78(d, 2H), 7. 70-7. 61(m, 2H), 7. 55-7. 46(m, 1H), 7. 01(1H), 6. 18(1H), 5. 71(q, 1H), 5. 12(d, 1H), 5. 02(dd, 1H), 4. 77 (dd, 1H), 4. 64(d, 1H), 4. 53-4. 43(lH), 4. 31-4. 18(m, 2H), , 2. 83-2. 44(m, 3H), 2. 28(q, 1H), 1. 95-1. 22(m, 23H), 0. 83 (s, 3H). Compound 31: MS: m/z 907. 3(M++1); 丨11 NMR (CDC13) δ 10. 39(s, 1H), 8. 57(d, 2H), 8. 05(d, 1H), 7. 77(d, 2H), 7. 42-7. 26(m, 3H), 6. 15(s, 1H), 5. 69(q, 1H), 5. 29(d, 1H), 4. 96 (dd, 1H), 4. 78(dd, 1H), 4. 63-4. 56(m, 1H), 4. 40-4. 13(m, 3H), 51 201109028 2. 91-2. 64 (m, 3H), 2. 62(s, 3H), 2. 56-2. 22(m, 2H), 1. 89-0. 96 (m, 23H). Compound 32: MS: m/z 895. 2(M++1) ; rH NMR(CDC13) δ 10. 45(s, 1H), 8. 60(d, 2H), 8. 22(d, 1H), 7. 55(d, 2H), 7. 67-7. 60 (m, 2H), 7. 45 (dd, 1H), 7. 20(s, 1H), 6. 12(s, IH), 5. 65(q, 1H), 5. 13(d, 1H), 4. 97 (dd, 1H), 4. 81-4. 71(m, 2H), 4. 14-4. 10 (m, 2H), 2. 82-2. 45 (m, 3H), 2. 27(q, 1H), 1. 97-1. 21(m, 14H), 1. 08(s, 9H), 0. 89-0. 80 (m, 4H). Compound 33: MS: m/z 853. 3(M++1) ; NMR(CDC13) δ 10. 22(s, 1H), 8. 58(s, 1H), 8. 48(d, 2H), 8. 08(d, 1H), 7. 57(d, 2H), 7. 53-7. 44(m, 2H), 7. 39-7. 26(m, 1H), 6. 05(s, 1H), 5. 65(q, 1H), 5. 21(d, 1H), 4. 95 (dd, 1H), 4. 82 (dd, 1H), 4. 40(d, 1H), 4. 21-4. 03(m, 2H), 3. 27(s, 3H), 2. 81-2. 40 (m, 3H), 2. 22(q, 1H), 1. 95-l_20(m, 15H), 0. 81(s, 3H). Compound 34: MS: m/z 923. 3(M++1); 丨14 NMR(CDC13) δ 10. 17(s, 1H), 8. 61(d, 2H), 8. 25(d, 1H), 7. 80(d, 2H), 7. 65-7. 50 (m, 2H), 7. 41 (dd, 1H), 6. 97(s, 1H), 6. 18(s, 1H), 5. 72(q, 1H), 5. 15(d, 1H), 5. 05(dd, 1H), 4. 77 (dd, 1H), 4. 65(d, 1H), 4. 29-4. 10 (m5 2H), 3. 78-3. 52(m, 2H), 3. 23-3. 03(m, 2H), 2. 79-2. 85 (ms 2H), 2. 56(brs, 1H), 2. 27(q, 1H), 1. 98-1. 19(m, 20H), 0. 88 (s, 3H). Compound 35: MS: m/z 894·2 (Μ++1); NMR (CDC13) δ 10. 45(s, 1H), 8. 47(d, 2H), 8. 12(s, 1H), 8. 05(d, 1H), 7. 70(d, 2H), 7. 53-7. 46(m, 2H), 7. 31-7. 22 (m, 1H), 6. 03(s, 1H), 5. 70(q, 52 201109028 1H), 5. 03-4. 84(m, 4H), 4. 24(d, 1H), 2. 95-2. 47(m, 3H), 2. 38(q,1H), 1. 94-1. Ll(m, 25H), 0. 85(s, 3H). Compound 36: MS: m/z 889. 3(M++1) ; 'H NMR(CDC13) δ 10. 26(s, 1H), 8. 47(d, 2H), 8. 07(d, 1H), 7. 65(d, 2H), 7. 57(s, 1H), 7. 55-7. 42(m, 2H), 7. 38-7. 27(m, 2H), 6. 82(d, 1H), 6. 62(d, 1H), 5. 63(dd, 1H), 6. 15(s, 1H), 5. 63(q, 1H), 4. 92(dd, 1H), 4. 74-4. 59(m, 2H), 4. 42(d, 1H), 4. 17(dd, 1H), 2. 79-2. 42 (m, 3H), 2. 23(q,1H), 1. 95-1. 05(m, 15H), 0. 76(s, 3H). Compound 37: MS: m/z 837·3 (Μ++1); 4 NMR (CDC13) δ 10. 16(s, 1H), 8. 48(d, 2H), 8. 11(d, 1H), 7. 69(d, 2H), 7. 58(d, 2H), 7. 36(dd, 1H), 7. 17(s, 1H), 6. 15(s, 1H), 6. 04(d, 1H), 5. 64(q, 1H), 4. 94 (dd, 1H), 4. 67(dd, 1H), 4. 47 (dd, 1H), 4. 41(d, 1H), 4. 12 (dd, 1H), 2. 78-2. 68 (m, 1H), 2. 43(brs, 1H), 2. 22(q, 1H), 1. 98-1. 64 (m, 7H), 1. 53-l. Ll(m,12H), 0. 78(s, 3H). Compound 38: MS: m/z 863·3 (Μ++1); 4 NMR (CDC13) δ 10. 52(s, 1H), 8. 38(d, 2H), 7. 92(d, 1H), 7. 88(s, 1H), 7. 65(d, 2H), 7. 58-7. 52(m, 2H), 7. 35-7. 21 (m, 1H), 6. 19(d, 1H), 5. 92(s, 1H), 5. 71(q, 1H), 5. 01(dd, 1H), 4. 81 (dd, 1H), 4. 62(d, 1H), 4. 37(brs, 1H), 4. 11-4. 01(m, 1H), 2. 98-2. 87 (m, 1H), 2. 74-2. 52 (m, 2H), 2. 33(q, 1H), 1. 98-1. 19(m, 16H), 0. 88(s, 3H), 0. 68-0. 41 (m, 4H). Compound 39: MS: m/z 908. 3(M++1) ; 4 NMR(CDC13) δ 10. 26(s, 1H), 8. 48(d, 2H), 8. 15(d, 1H), 7. 67(d, 2H), 7. 57-7. 46(m, 2H), 7. 39-7. 35 (m, 2H), 6. 07(s, 1H), 5. 62(q, 1H), s 53 201109028 4. 98-4. 86(m, 2H), 4. 77 (dd, 1H), 4. 58(d, 1H), 4. 02(dd, 1H), 3. 38-3. 24(m, 4H), 2. 99-2. 81(m, 4H), 2. 82-2. 42 (m, 3H), 2. 19 (q, 1H), 1. 88-1. 04(m, 15H), 0. 92-0. 72 (m, 4H). Compound 40: MS: m/z 866. 3(M++1); 丨H NMR(CDC13) δ 10. 51(s, 1H), 8. 37(d, 2H), 7. 91(d, 1H), 7. 69(s, 1H), 7. 61(d, 2H), 7. 53-7. 42(m, 2H), 7. 23-7. 14(m, 1H), 6. 01(s, 1H), 5. 67(q, 1H), 4. 94 (dd, 1H), 4. 72 (dd, 1H), 4. 61(d, 1H), 4. 43(d, 1H), 4. 30-4. 02(m, 2H), 2. 94-2. 60 (m, 3H), 2. 57(s, 6H), 2. 20(q, 1H), 1. 80-l_15(m,]5H),0. 77 (s, 3H). Compound 4]: MS: m/z 892. 3(M'+1) ; 4 NMR(CDC13) δ 10. 40(s, 1H), 8. 51(d, 2H), 8. 16(d, 1H), 7. 85(d, 2H), 7. 65(s, 1H), 7. 58(d, 1H), 7. 41-7. 37(m, 1H), 6. 14(s, 1H), 5. 59(q, 1H), 4. 99(dd, 1H), 4. 80 (dd, 1H), 4. 62(d, 1H), 4. 57(d, 1H)? 4. 45-4. 37(m, 1H), 4. 17(dd, 1H), 3. 75-3. 65(m, 2H), 3. 60-3. 48 (m, 2H), 2. 80-2. 45 (m, 3H), 2. 24(q, 1H), 1. 89-1. 41 (m, 20H), 0. 8(s, 3H). Compound 42: MS: m/z 907. 3(M++1) ; NMR(CDC13) δ 10. 20(s, 1H), 8. 43(d, 2H), 8. 10(d, 1H), 7. 65(d, 2H), 7. 60-7. 55(m, 2H), 7. 39-7. 35 (m, 1H), 7. 25(s, 1H), 6. 05(s, 1H), 5. 98(d, 1H), 5. 66(q, 1H), 4. 93(dd, 1H), 4. 72 (dd, 1H), 4. 52-4. 42 (m, 2H), 4. 08(dd, 1H), 3. 78-3. 60 (m, 2H), 3. 21-3. 11 (m, 2H), 3. 81-2. 43(br,3H), 2. 19-2. 05(m, 2H), l_85-1. 09(m, 19H), 0. 77 (s, 3H). Compound 43: MS: m/z 890. 3(M++1) ; NMR(CDC13) δ 54 201109028 10. 16(s, 1H), 8. 55(d, 2H), 8. 21(d, 1H), 8. 14(s, 1H), 7. 68(d, 2H), 7. 58-7. 41(m, 4H), 7. 21(s, 1H), 6. 40(s, 1H), 6. 18(s, 1H), 5. 63(q, 1H), 4. 95 (dd, 1H), 4. 78-4. 62(m, 2H), 4. 44(d, 1H), 4. 16(dd, 1H), 2. 69-2. 44(m, 3H), 2. 24(q, 1H), 1. 98-1. 15(m, 15H), 0. 79 (s, 3H). Compound 44: MS: m/z 879. 3(M++1) ; W NMR(CDC13) δ 10. 22(s, 1H), 8. 59(d, 2H), 8. 22(d, 1H), 7. 76(d, 2H), 7. 75-7. 60 (m, 2H), 7. 48-7. 42(m, 1H), 7. 17(s, 1H), 6. 20(s, 1H), 6. 16(d, 1H), 5. 71(q, 1H), 5. 02(dd, 1H), 4. 77 (dd, 1H), 4. 60-4. 52(m, 2H), 4. 20 (dd, 1H), 2. 79-2. 45 (m, 3H), 2. 21(q, 1H), 1. 96-1. 07(m, 15H), 1. 03(s,9H), 0. 82 (s, 3H). Compound 45: MS: m/z 933_3 (M++1); NMR (CDC13) δ 10. 22(s, 1H), 8. 56(d, 2H), 8. 19(d, 1H), 7. 88(d, 2H), 7. 69-7. 42(m, 3H), 7. 19(s, 1H), 6. 81-6. 62 (m, 4H), 6. 11(s, 1H), 5. 68 (q, 1H), 5. 00 (dd, 1H), 4. 77 (dd, 1H), 4. 55(d, 2H), 4. 41-4. 12 (m, 2H), 2. 82-2. 42 (m, 3H), 2. 28(q, 1H), 2. 01-l. Ll(m, 15H), 0. 83 (s, 1H). Compound 46: MS: m/z 891. 3(M++1); 丨11 NMR (CDC13) δ 10. 34(s, 1H), 8. 35(d, 2H), 7. 94(d, 1H), 7. 66(s, 1H), 7. 62(d, 2H), 7. 54-7. 46(m, 2H), 7. 22 (dd, 1H), 5. 93-5. 84(m, 2H), 5. 61(q, 1H), 4. 92(dd, 1H), 4. 87 (dd, 1H), 4. 58(d, 1H), 4. 41-4. 36(m, 1H), 4. 04(dd, 1H), 2. 82-2. 75 (m, 1H), 2. 65-2. 50 (m, 2H), 2. 24(q,1H), 1. 80-1. 00 (m, 24H), 0. 81 (s, 3H). Compound 47: MS: m/z 867_3 (M++1); iH NMR (CDC13) δ 55 201109028 l〇. 35(s, 1H), 8. 54(d, 2H), 8. 18(d, 1H), 7. 86(d, 1H), 7. 66(d, 2H), 7. 6] (m, 2H), 7. 46 (m, 2H), 6. 13(s,1H), 5. 67(q,ΠΙ), 4. 94 (dd, 1H), 4. 77(m, 1H), 4. 61 (m, 1H), 4. 40(d, 1H), 4. 20 (m, 1H), 3. 72(s, 3H), 2. 91 (m, 1H), 2. 72-2. 39(m, 3H), 2. 25(q, 1H), 1. 96-0. 82 (m, 15H). Compound 48: MS: m/z 908. 2(M++1) ; 'H NMR(CDC13) δ 10. 28(s, 1H), 8. 44(d, 1H), 8. 23(d, 1H), 7. 67(m, 3H), 7. 52(m, 1H), 7. 07(s, 1H), 6. 04(s, 1H), 5. 68(q, 1H), 5. 12(d, 1H), 4. 98(dd, 】H), 4. 79-4. 68 (m, 2H), 4. 34(s, 1H), 4. 20 (dd, 1H), 4. 00 (m, 1H), 2. 95(s, 3H), 2. 93(m, 1H), 2. 72(m, 2H), 2. 52(m, 1H), 2. 26(q,1H), 1. 94-0. 82 (23H). Compound 49: MS: m/z 920. Compound 50: MS: m/z 806. 2(M++1) ; rH NMR(CDC13) δ 10. 47(s, 1H), 8. 77-8. 53 (ra, 2H), 8. 19(d, 1H), 8. 13(d, 1H), 7. 73(s, 1H), 7. 53-7. 30 (m, 2H), 7. 26-7. 18(m, 1H), 6. 07(s, 1H), 5. 70-5. 40 (m, 2H), 4. 98-4. 61(m, 2H), 4. 40-4. 03(m, 3H), 3. 47 (s, 3H), 2. 95-2. 90 (m, 1H), 2. 87-2. 50 (m, 3H), 2. 20 (dd, 1H), 2. 10-1. 86(m,3H), 1. 61-1. 08(m,11H),0. 96 (m, 1H). Compound 51: MS: m/z 822. 3, 824. 3(M++1); iHNMRXCDCh) δ 10. 42(s, 1H), 8. 69-8. 44 (m, 3H), 8. 34(d, 2H), 7. 65(s, 1H), 7. 42-7. 30 (m, 3H), 6. 04(s, 1H), 5. 70-5. 45 (m, 2H), 4. 91-4. 63 (m, 2H), 4. 35-4. 03(m, 3H), 3. 42(s, 3H), 2. 84(s, 1H), 2. 72-2. 50 (m, 3H), 2. 22 (dd, 1H), 2. 19 (m, 3H), 1. 54-0. 78 (m, 11Hb compound 52: MS: m/z 774. 2(M++1) ; 4 NMR(CDC13) δ 56 201109028 10. 33(s, 1H), 8. 65-8. 58 (m, 1H), 8. 46(d, 1H), 8. 18(d, 1H), 8. 06(d, 1H), 7. 46-7. 38 (m, 3H), 7. 19-7. 11 (m, 1H), 6. 13(s, 1H), 6. 04(d, 1H), 5. 66 (dd, 1H), 5. 27-5. 08(m, 1H), 5. 07-4. 67(m, 2H), 4. 52-4. 39(m, 2H), 4. 13-4. 09(m, 1H), 3. 62-3. 60 (m, 1H), 2_95-2. 10 (m, 4H), 1. 98(s,3H), 1. 90-0. 81 (m, 14H). Compound 53: MS: m/z 825. 3 (M++1). Compound 54: MS: m/z 805. 3, 807. 3(M++1); h NMR(CDC13) δ 10. 46(s, 1H), 8. 28-8. 19(m, 1H), 7. 98(s, 1H), 7. 88-7. 85(m, 1H), 7. 63-7. 39(m, 6H), 6. 07(s, 1H), 5. 67-5. 46(m, 2H), 4. 96-4. 79(m, 2H), 4. 41-4. 09(m, 3H), 3. 37(s, 3H), 2. 97-0. 88 (m, 20H). Compound 55: MS: m/z 789. 2(M++1) ; NMR(CDC13) δ 10. 61(s, 1H), 8. 49(s, 1H), 8. 39-8. 24(m, 2H), 8. 05-7. 94(m, 2H), 7. 56-7. 04(m, 5H), 5. 90(s, 1H), 5. 47(br, 1H), 4. 93-4. 69 (br, 2H), 4. 40-4. 07(m, 3H), 3. 46(s, 1H), 3. 23(s, 3H), 2. 91-2. 07(m, 11H), 1-99-1. 54(m, 4H), 1. 32-0. 81 (m, 5H). Compound 56: MS: m/z 839. 3, 843_3 (M++1); 〗 〖HNMR (CDC13) δ 10. 27(s, 1H), 8. 24(d, 1H), 7. 89(d, 1H), 7. 63(d, 1H), 7. 56(s, 1H), 7. 52-7. 40 (m, 2H), 7. 14(brs, 1H), 6. 08(s, 1H), 5. 69(q, 1H), 5. 30 (brs, 1H), 4. 97 (dd, 1H), 4. 74 (dd, 1H), 4. 46(d, 1H), 4. 40-4. 22 (m, 1H), 4. 13-4. 08(m, 1H), 3. 36(s, 3H), 2. 99-2. 05 (m, 5H), l_90-1. 10(m, 15H), 0. 99-0. 88 (m, 1H). Compound 57: MS: m/z 827·2 (Μ++1); NMR (CDC13) δ 10. 17(s, 1H), 8. 42(d, 2H), 7. 84(d, 1H), 7. 49-7. 41(m, 4H), 57 201109028 7. 28(m, 1H), 7. 13(brs, 1H), 6. 16(s, 1H), 5. 63(q, 1H), 4. 95 (m, 1H), 4. 70 (dd, 1H), 4. 63(m, 1H), 4. 31-4. 11 (m, 2H), 2. 97-2. 70 (m, 3H), 2. 50-1. 06 (m, 17H), 0. 91 (m5lH). Compound 58: MS: m/z 803. 3 (M++1). Compound 59: MS: m/z 789·2 (Μ++1); NMR (CDC13) δ 10. 39(s, 1H), 8. 53-8. 41(m, 3H), 7. 81(d, 1H), 7. 59-7. 42(m, 4H), 7. 26(m, 1H), 7. 18(s, 1H), 6. 17(s, 1H), 5. 17(q, 1H), 5. 28(dd, 1H), 4. 95 (dd, 1H), 4. 75 (m, 1H), 4. 43(d, 1H), 4. 38-4. 04(m, 2H), 3. 40(s, 3H), 2. 96-2. 67(m, 3H), 2. 60-2. 41 (m, 1H), 2. 37-2. 22 (m, 1H), 1. 99-0. 85 (m, 14H). Compound 60: MS: m/z 773. 2(M*&gt;1) ; 'H NMR(CDC13) δ 10. 33(s, 1H), 8. 46(d, 2H), 7. 88-7. 84(m, 1H), 7. 60-7. 50 (m, 4H), 7. 35-7. 17(m, 1H), 6. 20(s, 1H), 6. 08(d, 1H), 5. 72(q, 1H), 4. 98 (dd, 1H), 4. 72 (dd, 1H), 4. 56(m, 1H), 4. 41(d, 1H), 4. 21 (m, 1H), 2. 94-2. 90 (m, 1H), 2. 80-2. 77(m, 1H), 2. 55-2. 52(m, 1H), 2. 23(q, 1H), 1. 98-1. 90 (m, 1H), 1. 84(s, 3H), 1. 80-0. 80 (m, 16H). Compound 61: MS: m/z 845. 3(M++1) ; NMR(CDC13) δ 10. 41(s, 1H), 8. 34(d, 2H), 7. 84(d, 1H), 7. 53-7. 44(m, 1H), 7. 40-7. 33(m, 3H), 7. 19(s, 1H), 6. 14(s, 1H), 5. 71(q, 1H), 5. 15 (d, 1H), 4. 98 (dd, 1H), 4. 89~4. 80 (m, 2H), 4. 25-4. 19(m, 2H), 2. 95-2. 90 (m, 1H), 2. 88-2. 42 (m, 3H), 2. 44(s, 3H), 2. 29 (m, 1H), 1. 98-1. 20 (m, 14H), 1. 1 l(s, 9H), 1. 00-0. 87 (1H). Compound 62: MS: m/z 841. 2(M++1) ; h NMR(CDC13) δ 58 201109028 10. 21(s, 1H), 8. 35(d, 2H), 7. 89(d, 1H), 7. 60-7. 57(m, 1H), 7. 33(d, 2H), 7. 17(d, 1H), 7. 05(s, 1H), 6. 22(s, 1H), 5. 68(q, 1H), 4. 97 (dd, 1H), 4. 77-4. 64 (m, 2H), 4. 33-4. 17(m, 2H), 2. 93-2. 74 (m, 3H), 2. 44(s, 3H), 2. 21 (m, 1H), 1. 95-0. 91 (m, 17H). Compound 63: MS: m/z 903. 3; 905. 3(M++1); h NMR(CDC13) δ 10. 18(s, 1H), 8. 45(d, 2H), 8. 23(d, 1H), 7. 64(m, 2H), 7. 49(d, 3H), 7. 01(s, 1H), 6. 17(s, 1H), 5. 72(q, 1H), 5. 13(d, 1H), 4. 99(dd, 1H), 4. 77 (dd, 1H), 4. 58(d, 1H), 4. 53(brs, 1H), 4. 27(m, 1H), 4. 14(m, 1H), 2. 83-2. 44(m, 3H), 2. 27(q, 1H), 1. 95-1. 22 (m, 23H), 0. 83(s, 3H). Compound 64: MS: m/z 787. 3(M++1);]H NMR(CDC13) δ 10. 45(s, 1H), 8. 25(d, 2H), 7. 75(d, 1H), 7. 67(s, 1H), 7. 53-7. 52(m, 1H), 7. 26(d, 2H), 6. 29(d, 1H), 6. 19(s, 1H), 5. 67(q, 1H), 4. 94 (dd, 1H), 4. 75 (dd, 1H), 4. 52(brs, 1H), 4. 42(d, 1H), 4. 10-4. 18(m, 1H), 2. 89-2. 50 (m, 3H), 2. 43(s, 3H), 2. 35-2. 20 (m, 1H), 1. 98-1. 85(m, 1H), 1. 82(s, 3H), 1. 62-0. 81 (m, 16H). Compound 65: MS: m/z 803. 2(M++1) ; h NMR(CDC13) δ 10. 46(s, 1H), 8. 30(d, 1H), 8. 17(d, 2H), 7. 63(d, 1H), 7. 55(s, 1H), 7. 45-7. 41 (m, 1H), 7. 25-7. 20(m, 2H), 5. 97(s, 1H), 5. 65-5. 59(m, 1H), 5. 36(d, 1H), 4. 91-4. 87(m, 1H), 4. 73 (dd, 1H), 4. 37-4. 05(m, 3H), 3. 30(s, 3H), 2. 84-2. 47(m, 3H), 2. 38(s, 3H), 2. 40-2. 16 (m, 1H), 1. 90-0. 87 (m, 16H). Compound 66: MS: m/z 871. 3(M++1) ; 'H NMR(CDC13) δ 59 201109028 10. 42(s, 1H), 8. 19-8. 02(m, :2H), 7. 93(s, 1H), 7. 67(s, 1H), 7. 47-7. 26(m, 3H), 6. 05(s, 1H), 5. 62(q, 1H), 5. 34(d, 1H), 4. 96- 4. 42 (m, 4H), 4. 36-4. 10(m, 2H), 2. 95-2. 90 (m, 1H), 2. 77(s, 3H), 2. 76-2. 48 (m, 3H), 2. 35(s, 3H), 2. 30-0. 87 (m, 24H). Compound 67: MS: m/z 875. 3 (M++1). Compound 68: TG-2379: MS: m/z 871. 3(M++1) ; 4 NMR (CDC13) δ 10. 33(s, 1H), 8. 34(d, 2H), 7. 85(d, 1H), 7. 73(s, 1H), 7. 54-7. 46(m, 1H), 7. 38-7. 22 (m, 3H), 6. 12(s, 1H), 5. 65(q, 1H), 5. 35(d, 1H), 4. 93(dd, 1H), 4. 78(dd, 1H), 4. 62-4. 50 (m, 2H), 4. 32-4. 08(m, 2H), 2. 81-2. 42 (m, 3H), 2. 40(s, 3H), 2. 2. 6(q, 1H), 1. 93-1. l](m, 23H), 0. 80 (s, 3H). Compound 69: MS: m/z 861. 3 (M++1). Compound 70: MS: m/z 857. 2(M++1) ; 4 NMR(CDC13) δ 10. 23(s, 1H), 8. 09(s, H), 8. 05(s, 1H), 7. 96(dd, 1H), 7. 58 (dd, 1H), 7. 47-7. 19(m, 3H), 7. 06(d, 1H), 6. 21(s, 1H), 5. 69(q, 1H), 4. 95 (dd, 1H), 4. 81-4. 60 (m, 2H), 4. 35-4. 17(m, 2H), 3. 94(s, 3H), 2. 92-2. 41 (m, 3H), 2. 23(q, 1H), 1. 92-0. 82 (m, 17H). Compound 7]: MS: m/z 8] 9. 2(Mf+l) ; NMR(CDC13) δ 10. 36(s,1H), 8. 01-7. 81 (m, 3H), 7. 71 (d, 1H), 7. 34-7. 22 (m, 3H), 6. 96(d, IH), 6. 01(s, 1H), 5. 61(q, 1H), 5. 27(dd, 1H), 4. 90 (dd, 1H), 4. 69 (dd, 1H), 4. 38(d, 1H), 4. 22-4. 03(m, 2H), 3. 87(s, 3H)S 3. 28(s, 3H), 2. 86-2. 42 (m, 3H), 2. 20(q, 1H), 1. 97- 0. 88 (m, 16H). 60 201109028 Compound 72: MS: m/z 861. 3(M++1) ; 'H NMR(CDC13) δ 10. 38(s, 1H), 8. 10-7. 98(m, 2H), 7. 86(d,1H), 7. 54-7. 22(m, 3H), 7. 20(s, 1H), 7. 06(d, 1H), 6. 10(s, 1H), 5. 70(q, 1H), 5. 29(d, 1H), 4. 97 (dd, 1H), 4. 79-4. 67(m, 2H), 4. 18-4. 04(m, 2H), 3. 94(s, 3H), 2. 95-2. 57(m, 3H), 2. 28(q, 1H), 1. 91-0. 87 (m, 25H). Compound 73: MS: m/z 803. 2(M++1) ; 4 NMR(CDC13) δ 10. 37(s, 1H), 8. 12-8. 96(m, 2H), 7. 85(d, 1H), 7. 56-7. 26(m, 4H), 7. 05(d, 1H), 6. 19-6. 15(m, 2H), 5. 71(q, 1H), 4. 96 (dd, 1H), 4. 74(s, 1H), 4. 53-4. 42 (m, 2H), 4. 19(d, 1H), 3. 93(s, 3H), 2. 91-2. 20 (m, 4H), 2. 10-0. 82 (m, 19H). Compound 74: MS: m/z 861·3 (Μ++1); 'H NMR (CDC13) δ 10. 42(s, 1H), 8. 39(d, 2H), 7. 81(d, 1H), 7. 50-7. 26(m, 3H), 7. 00(d, 2H), 6. 05(s, 1H), 5. 65(q, 1H), 5. 21(d, 1H), 4. 95 (dd, 1H), 4. 84 (dd, 1H), 4. 68(d, 1H), 4. 21-4. 07(m, 2H), 3. 90(s, 3H), 2. 90-2. 45 (m, 4H), 2. 22(q, 1H), 1. 98-1. 20 (m, 14H), 1. 13(s, 9H), 0. 99-0. 84 (m, 1H). Compound 75: MS: m/z 887. 3(M++1) ; 'H NMR(CDC13) δ 10. 33(s, 1H), 8. 38(d, 2H), 7. 82(d, 1H), 7. 61(s, 1H), 7. 59-7. 43(m, 1H), 7. 35-7. 20 (m, 1H), 7. 01(d, 2H), 6. 07(s, 1H), 5. 68(q, 1H), 5. 42(d, 1H), 4. 98 (dd, 1H), 4. 75 (dd, 1H), 4. 58(s, 1H), 4. 38-4. 13(m, 3H), 3. 88(s, 3H), 2. 86(br, 2H), 2. 59-2. 11 (m, 2H), 1. 96-1. 20(m, 22H), 0. 92-0. 78 (m, 4H). Compound 76: MS: m/z 903. 3, 905. 3 (M++1). 61 201109028 Compound 77: MS: m/z 887. 3 (M++1). Compound 78: MS: m/z 883. 4(M++1);丨]·! NMR(CDC13) δ 10. 19(s, 1H), 8. 46(d, 2H), 8. 25(d, 1H), 7. 62(m, 2H), 7. 46(m, 1H), 7. 04((1, 2H), 6. 96(s, 1H), 6. 19(s, 1H), 5. 73(q, 1H), 5. 15 (d, 1H), 5. 02(dd, 1H), 4. 77(m, 1H), 4. 58(m, 2H), 4. 30 (m, 1H), 4. 15(m, 3H), 2. 79(m, 2H), 2. 54 (m, 1H), 2. 26(q, 1H), 1. 92-0_83 (m, 26H), 0_83 (s, 3H). Compound 79: MS: m/z 869_4 (M++1); 4 NMR (CDC13) δ 10. 36(s, 1H), 8. 44(d, 2H), 8. 24(d, 1H), 7. 60 (m, 2H), 7. 44(m, 1H), 7. 04(s, 1H), 7. 00(d, :2H), 6. 16(s, 1H), 5. 71(q, 1H), 5. 21(d, 1H), 4. 97 (dd, 1H), 4. 74 (m, 1H), 4. 57(m, 2H), 4. 30 (m, 1H), 4. 15(m, 3H), 2. 91 (m, 1H), 2. 75(m, 2H), 2. 56(m, 1H), 2. 26(q, 1H), 1. 92-0. 83 (m, 26H). Compound 80: MS: m/z 883·4 (Μ++1); 'H NMR (CDC13) δ 10. 42(s,1H), 8_43(d,2H), 8. 23(d, 1H), 7. 61-7. 39(m, 4H), 7. 03(d, 2H), 6. 18(s, 1H), 5. 71(q, 1H), 5. 30(d, 1H), 4. 96 (dd, 1H), 4. 79-4. 57(m, 4H), 4. 41-4. 22 (m, 1H), 4. 15-4. 08(m, 1H), 2. 96-2. 67(m, 3H), 2. 57-2. 42 (m, 1H), 2. 25(q, 1H), 1. 98-0. 87 (m, 29H). Compound 81: MS: m/z 897. 4(M++1); 丨11 NMR (CDC13) δ 10. 31(s, 1H), 8. 42(d, 2H), 8. 21(d, 1H), 7. 57-7. 25(m, 4H), 7. 02(d, 2H), 6. 14(s, 1H), 5. 67-5. 64 (m, 1H), 5. 40(d, 1H), 5. 03-4. 93(m, 1H), 4. 79-4. 54(m, 4H), 4. 39-4. 12 (m, 2H), 2. 77-2. 72(m, 2H), 2. 54(br, 1H), 2. 26(q, 1H), 2. 03-1. 24(m, 29H), 62 201109028 0. 80 (s, 3H). Compound 82: MS: m/z 915. 2(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 8. 38(d, 2H), 7. 74(d, 1H), 7. 57-7. 24(m, 3H), 7. 27(d, 2H), 6. 14(s, 1H), 5. 66(q, 1H), 5. 32(d, 1H), 4. 98 (dd, 1H), 4. 76(dd, 1H), 4. 71-4. 48 (m, 3H), 4. 39-4. 08(m, 2H), 2. 85-2. 42 (m, 3H), 2. 31(q, 1H), 2. 03-1. 24(m, 29H), 0. 80 (s, 3H). Compound 83: MS: m/z 901_2 (M++1); 4 NMR (CDC13) δ 10. 42(s, 1H), 8. 46(d, 2H), 7. 82(d, 1H), 7. 54 (dd, 1H), 7. 42(s, 1H), 7. 32(m, 1H), 6. 98(d, 2H), 6. 14(s, 1H), 5. 65(q, 1H), 5. 33(d, 1H), 4. 97 (dd, 1H), 4. 76(dd, 1H), 4. 71-4. 50 (m, 3H), 4. 41-4. 08(m, 2H), 2. 93-2. 42 (m, 4H), 2. 31(q, 1H), 2. 03-0. 80 (m, 29H). Compound 84: MS: m/z 885. 3(M++1) ; W NMR(CDC13) δ 10. 26(s, 1H), 8. 42(d, 2H), 8. 23(d, 1H), 7. 58(m, 2H), 7. 44 (dd, 1H), 7. 22(s, 1H), 7. 01(d, 2H), 6. 17(s, 1H), 5. 67(q, 1H), 5. 16(d, 1H), 4. 98 (dd, 1H), 4. 75 (dd, 1H), 4. 62(m, 2H), 4. 38-4. 08(m, 2H), 2. 80-2. 42 (m, 3H), 2. 32(q, 1H), 1. 96-1. 20(m, 21H), 1. 13(s, 9H), 0. 81 (m, 3H). Compound 85: MS: m/z 923. 2 (M++1). Compound 86: MS: m/z 883_2 (M++1); 丨!·! NMR (CDC13) δ 10. 41(s, 1H), 8. 19(d, 1H), 8. 06(d, 1H), 7. 95(s, 1H), 7. 61-7. 41 (m, 4H), 6. 92(d, 1H), 6. 12(s, 1H), 6. 04(s, 2H), 5. 67(q, 1H), 5. 35(d, 1H), 4. 97 (dd, 1H), 4. 77 (dd, 1H), 4. 58(d, 1H), 63 201109028 4. 36-4. 11 (m, 2H), 2. 85-2. 43(m, 3H), 2. 27(q, 1H), 1. 98-1. 21 (m, 24H), 0. 81 (s, 3H). Compound 87: MS: m/z 869·2 (Μ++1); 4 NMR (CDC13) δ 10. 36(s, 1H), 8. 17(d, 1H), 7. 97(d, 1H), 7. 88(s, 1H), 7. 58-7. 32(m, 4H), 6. 85(d, 1H), 6. 02(s, 1H), 5. 98(s, 2H), 5. 59(q, 1H), 5. 37(d, 1H), 4. 87(d, 1H), 4. 68 (dd, 1H), 4. 52-4. 02(m, 3H), 2-90-2. 38 (m, 4H), 2. 23(q, 1H), 1. 91-0. 88 (m, 24H). Compound 88: MS: m/z 868. 5 (M++1). Compound 89: MS: m/z 882. 5 (M++1). Compound 90: MS: m/z 910. 3(M++1) ; NMR(CDC13) δ 10. 32(s, 1H), 8. 34(d, 2H), 8. 22(d, 1H), 7. 61-7. 43(m, 3H), 7. 44 (dd, 1H), 6. 76(d, 2H), 6. L4(s, 1H), 5. 62(q, 1H), 5. 39(d, 1H), 4. 96 (dd, 1H), 4. 72 (dd, 1H), 4. 63(brs, 1H), 4. 55(d, 1H), 4. 41-4. 〇4(m, 2H), 3. 42(q, 4H), 2. 80-2. 42 (m, 3H), 2. 32(q, 1H), 1. 98-1. 17(m,29H), 0. 83(s, 3H). Compound 91: MS: m/z 896·3 (Μ++1); !Η NMR (CDC13) δ 10. 46(s, 1H), 8. 33(d, 2H), 8. 21(d, 1H), 7. 62-7. 43(m, 3H), 7. 43(dd, 1H), 6. 77(d, 2H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 39(d, 1H), 4. 93(dd, 1H), 4. 73 (dd, 1H), 4. 64 (brs, 1H), 4. 53(d, 1H), 4. 43-4. 05(m, 2H), 3. 43(q, 4H), 2. 94-2. 42 (m, 4H), 2. 29(q, 1H), 2. 14-0. 83 (m, 29H). Compound 92: MS: m/z 901. 4, 903·4(Μ++1); 4 NMR(CDC13) δ 10. 40(s, 1H), 8. 36(d, 2H), 8. 23(s, 1H), 7. 58-7. 26(m, 5H), 6. 15(s, 1H), 5. 65(q, 1H), 5. 19(d, 1H), 4. 96 (dd, 1H), 4. 77 (dd, 64 201109028 1H), 4. 62-4. 52(m, 2H), 4. 33-4. 08(m, 2H), 3. 01-2. 42 (m, 5H), 2. 25(q, 1H), l_96-0. 89 (m, 29H). Compound 93: MS: m/z 915. 4, 917·4(Μ++1);丨11 NMR(CDC13) δ 10. 27(s, 1H), 8. 38(d, 2H), 8. 22(s, 1H), 7. 59-7. 34(m, 5H), 6. 13(s, 1H), 5. 70(q, 1H), 5. 29(d, 1H), 4. 98 (dd, 1H), 4. 78(dd, 1H), 4. 62-4. 55(m, 2H), 4. 35-4. 08(m, 2H), 3. 04-2. 96(m, 1H), 2. 80-2. 43(m, 3H), 2. 25(q, 1H), 1. 97-1. 20(m, 29H), 0. 81(s, 3H). Compound 94: MS: m/z 867_4 (M++1). Compound 95: MS: m/z 881. 3(M++1) ; 4 NMR(CDC13) δ 10. 31(s, 1H), 8. 41(d, 2H), 8. 22(d, 1H), 7. 63-7. 21(m, 4H), 7. 20(d, 2H), 6. 16(s, 1H), 5. 65(q, 1H), 5. 38(d, 1H), 4. 94 (dd, 1H), 4. 80 (dd, 1H), 4. 65-4. 56(m, 2H), 4. 38-4. 12(m, 2H), 3. 08-2. 92(m, 1H), 2. 83-2. 67(m, 2H), 2. 59-2. 41 (m, 1H), 2. 25(q, 1H), 1. 98-1. 08 (, m, 28H), 0-95-0. 86 (m, 4H). Compound 96: MS: m/z 881_4 (M++1); 4 NMR (CDC13) δ 10. 47(s, 1H), 8. 40(d, 2H), 8. 23(d, 1H), 7. 76(s, 1H), 7. 62-7. 41(m, 5H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 33(d, 1H), 5. 03-4. 87 (m, 2H), 4. 78(dd, 1H), 4. 57(d, 1H), 4. 38-4. 04(m, 2H), 2. 95-2. 43(m, 4H), 2. 21(q, 1H), 2. 01-1. 37(m, 20H), 1. 33(s, 9H), 1. 21-0. 86 (m, 3H). Compound 97: MS: m/z 895. 4 (M++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 40(d, 2H), 8. 23(d, 1H), 7. 59-7. 43(m, 5H), 6. 98(d, 1H), 6. 16(s, 1H), 5. 65(q, 1H), 5. 41(d, 1H), 4. 98 (dd, s 65 201109028 1H), 4. 79(q, 1H), 4. 62-4. 52(m, 1H), 4. 36-4. 09(m, 3H), 2. 75 (brs, 2H), 2. 59-2. 56(m, 1H), 2. 28(q, 1H), 1. 91-1. 18(m, 31H), 0. 89-0. 78 (m, 4H). Compound 98: MS: m/z 869·4 (Μ++1); NMR (CDC13) δ 10. 41(s, 1H), 8. 42(d, 2H), 8. 23(d, 1H), 7. 62-7. 43(m, 5H), 7. 44 (dd, IH), 6. 17(s, 1H), 5. 64(q, 1H), 5. 17(d, 1H), 4. 97 (dd, 1H), 4. 77-4. 63(m, 2H), 4. 21-4. 10(m, 2H), 2. 94-2. 55(m, 4H), 2. 27(q, 1H), 1. 891. 15(m, 23H), 1. 10(s, 9H), 0. 98-0. 87 (m, 1H). Compound 99: MS: m/z 925·4 (Μ++1); NMR (CDC13) δ 10. 28(s, 1H), 8. 37(d, 2H), 8. 03(d, 1H), 7. 50(d, 2H), 7. 48(s, 1H), 7. 01-6. 92(m, 2H), 6. 13(s, 1H), 5. 65(q, 1H), 5. 39(d, 1H), 4. 98 (dd, 1H), 4. 88(dd, 1H), 4. 64(s, 1H), 4. 53(d, 1H), 4. 41-4. 23(m, 1H), 4. 19-4. 1 l(m, 1H), 3. 88(s, 3H), 2. 78-2. 42 (m, 3H), 2. 26(q, 1H), 2. 04-1. 18(m, 31H), 0. 89-0. 78 (m, 4H). Compound 100: MS: m/z 925. 4 (M++1); W NMR (CDC13&gt; δ 10. 23(s, 1H), 8. 35(d, 2H), 7. 77(d, 1H), 7. 48(d, 2H), 7. 38-7. 22(m, 1H), 7. 04-6. 81(m, 2H), 6. 16(s, 1H), 5. 68(q, 1H), 5. 21(d, 1H), 4. 99(dd, 1H), 4. 78(dd, 1H), 4. 57(d, 1H), 4. 22-4. 03(m, 3H), 4. 00(s, 3H), 2. 80-2. 43(m, 3H), 2. 3 l(q, 1H), 1. 96-1. 20(m, 31H), 0. 95-(). 78 (m, 4H). Compound 101: MS: m/z 827. 3 (M++1). Compound 102: MS: m/z 897·4 (Μ++1); 4 NMR (CDC13) δ 10. 30(s, 1H), 8. 39(d, 2H), 8. 20(d, 1H), 7. 59-7. 37(m, 5H), 66 201109028 7. 14(s, 1H), 6. 04(s, 1H), 5. 61(q, 1H), 5. 21(d, 1H), 4. 87 (dd, 1H), 4. 77 (dd, 1H), 4. 57(d, 1H), 4. 19-4. 07(m, 4H), 3. 67-3. 42 (m, 2H), 3. 17-2. 40 (m, 6H), 2. 20(q,1H), 1. 93-0_78 (m, 27H). Compound 103: MS: m/z 866. 3(M++1) ; NMR(CDC13) δ 10. 45(s, 1H), 8. 31(d, 2H), 8. 12(d, 1H), 7. 51-7. 42 (m, 5H), 7. 32- 7. 25(m, 1H), 6. 09(s, 1H), 5. 61(q, 1H), 4. 90 (dd, 1H), 4. 81 (dd, 1H), 4. 59(d, 1H), 4. 50-4. 36(m, 2H), 4. 13(dd, 1H), 3. 69-3. 27(m, 3H), 3. 10(brs, 4H), 2. 90-2. 41 (m, 4H), 2. 19(q, 1H), 1. 98-0. 78 (m, 25H). Compound 104: MS: m/z 811·3 (Μ++1); 'H NMR (CDC13) δ 10. 38(s, 1H), 8. 38(d, 2H), 8. 19(d, 1H), 7. 60-7. 31(m, 5H), 7. 32- 7. 25(m, 1H), 6. 15(s, 1H), 5. 65(q, 1H), 4. 88(dd, 1H), 4. 70 (dd, 1H), 4. 57 (dd, 1H), 4. 40(d, 1H), 4. 21-4. 05(m, 2H), 2. 95-2. 41 (m, 4H), 2. 22(q, 1H), 2. 01(s, 3H), 1. 98-0. 79 (m, 24H). Compound 105: MS: m/z 868·4 (Μ++1); NMR (CDC13) δ 10. 57(s, 1H), 8. 37(d, 2H), 8. 15(d, 1H), 8. 09(s, 1H), 7. 58-7. 51(m, 4H), 7. 27(dd, 1H), 6. 09(s, 1H), 5. 61(q, 1H), 4. 98-4. 79(m, 4H), 4. 44(s, 1H), 4. 10(dd, 1H), 3. 79-3. 68(m, 2H), 2. 92-2. 45 (m, 4H), 2. 24(q,1H), 1. 98-0. 88 (m, 32H). Compound 106: MS: m/z 882. 4(M++1) ; 4 NMR(CDC13) δ 10. 37(s, 1H), 8. 35(d, 2H), 8. 16(d, 1H), 7. 56-7. 48(m, 2H), 7. 42(d, 2H), 7. 36-7. 33(m, 1H), 7. 30(s, 1H), 6. 09(s, 1H), 5. 63(q, 1H), 4. 97-4. 86(m, 2H), 4. 76(dd, 1H), 4. 58(d, 1H), 67 201109028 4. 28-4. 1 l(m, 2H), 3. 39-3. 25(m, 4H), 3. 01-2. 82(m, 5H), 2. 75-2. 44 (m, 2H), 2. 16(q,1H), 1. 95-0. 76 (m, 25H). Compound 107: MS: m/z 863_3 (M++1); 4 NMR (CDC13) δ 10. 34(s, 1H), 8. 33(d, 2H), 8. 32(d, 1H), 7. 59-7. 40 (m, 6H), 7. 37(s, 1H), 6. 81(d, 1H), 6. 65(d, 1H), 6. 25(s, 1H), 6. 13(s, 1H), 5. 62(q, 1H), 4. 87 (dd, 1H), 4. 69-4. 52(m, 2H), 4, 42(d, 1H), 4. 18 (dd, 1H), 2. 95-2. 40 (m, 4H), 2. 24-0. 78 (m, 25H). Compound 108: MS: m/z 840. 4(M++1); 卞1 NMR (CDC13) δ 10. 67(s, 1H), 8. 32(d, 2H), 8. 19(d, 1H), 7. 77(s, 1H), 7. 58-7. 44(m, 4H), 7. 34-7. 25(m, 1H), 6. 14(s, 1H), 5. 77(q, 1H), 4. 98 (dd, 1H), 4. 78-4. 71(m, 2H), 4. 44(d, 1H), 4. 29(brs, 1H), 4. 11-4. 05(m, 1H), 2. 96-2. 72(m, 2H), 2. 64(s, 6H), 2. 41(br, 1H), 2_20(q, 1H), 1. 96-0. 78 (m, 25H). Compound 109: MS: m/z 837. 4(M++1) ; "H NMR(CDC13) δ 10. 49(s, 1H), 8. 35-8. 25(m, 3H), 7. 71(s, 1H), 7. 55-7. 41(m, 4H), 7. 26(s5 1H), 6. 19(d, 1H), 6. 01(s, 1H), 5. 63(q, 1H), 4. 88(dd, 1H), 4. 71(brs, 1H), 4. 56(d, 1H), 4. 39(brs, 1H), 4. 06(d, 1H), 2. 81-2. 45 (m, 4H), 2. 23(q, 1H), 1. 99-1. 64 (m, 4H), 1. 58-0. 77(m, 21H), 0. 51 (brs, 4H). Compound 1]0: MS: m/z 865·4 (Μ++1); W NMR (CDC13) δ 10. 39(s, 1H), 8. 29(d, 2H), 8. 15(d, 1H), 7. 56-7. 42 (m, 5H), 7. 36-7. 24(m, 1H), 6. 05(s, 1H), 5. 98(d, 1H), 5. 64(q, 1H), 4. 87 (dd, 1H), 4. 69 (dd, 1H), 4. 55(d, 1H), 4. 42 (dd, 1H), 4. 04(dd, 1H), 2. 81-2. 05(m, 5H), 1. 95-1. 71(m, 4H), 1. 57-0. 76 (m, 68 201109028 29H). Compound 111: MS: m/z 881·4 (Μ++1); 'H NMR (CDC13) δ 10. 29(s, 1Η), 8. 33(d, 2H), 8. 30(s, 1H), 7. 58-7. 41(m, 4H), 7. 39(dd, 1H), 7. 22(s, 1H), 6. 10(s, 1H), 5. 98(d, 1H), 5. 62(q, 1H), 4. 91 (dd, 1H), 4. 68 (dd, 1H), 4. 46-4. 40 (m, 2H), 4. 05(dd, 1H), 3. 79-3. 62(m, 2H), 3. 21-3. 09(m, 2H), 2. 88-2. 40 (m, 3H), 2. 22-1. 72 (m, 6H), 1. 47-0. 78 (m, 25H). Compound 112: MS: m/z 864. 3(M++1) ; A NMR(CDC13) δ 10. 29(s, 1H), 8. 38(d, 2H), 8. 23(d, 1H), 8. 09(s, 1H), 7. 57-7. 45 (m, 5H), 7. 41 (dd, 1H), 7. 28(s, 1H), 6. 42(s, 1H), 6. 15(s, 1H), 5. 62(q, 1H), 4. 86 (dd, 1H), 4. 75-4. 66(m, 2H), 4. 49(d, 1H), 4. 17(dd, 1H), 2. 83-2. 43(m, 3H), 2. 25(q, 1H), 1. 99-0. 78 (m, 25H). Compound 113: MS: m/z 853·4 (Μ++1); 'H NMR (CDC13) δ 10. 34(s, 1H), 8. 36(d, 2H), 8. 30(d, 1H), 7. 62-7. 46(m, 4H), 7. 41-7. 36(m, 1H), 7. 17(s, 1H), 6. 19(s, 1H), 6. 17(d, 1H), 5. 68(q, 1H), 4. 92(dd, 1H), 4. 73 (dd, 1H), 4. 58-4. 43(m, 2H), 4. 19 (dd, 1H), 2. 89-2. 43(m, 3H), 2. 22(q, 1H), 1. 99-1. 82(m, 6H), 1. 59-0. 83 (m, 28H). Compound 114: MS: m/z 907. 3(M++1) ; 'H NMR(CDC13) δ 10. 30(s, 1H), 8. 39(d, 2H), 8. 21(d, 1H), 7. 56(dd, 1H), 7. 48(d, 2H), 7. 40 (dd, 1H), 7. 24(s, 1H), 7. 18(d, 2H), 7. 03(d, 2H), 6. 92(s, 1H), 6. 06(s, 1H), 5. 74(d, 1H), 5. 61(q, 1H), 4. 87 (dd, 1H), 4. 70 (dd, 1H), 4. 42(d, 1H), 4. 31 (dd, 1H), 4. 08(dd, 1H), 69 5 201109028 2. 84-2. 79(m, 1H), 2. 65-2. 43(m, 2H), 2. 23(q, 1H), 1. 88-1. 62 (m, 6H), 1. 49-0. 78 (m, 19H). Compound 115: MS: m/z 895. 4(M++1) ; 'H NMR(CDC13) δ 10. 42(s,lH), 8. 40 (d, 2H), 8. 01(s,lH), 7. 55(d, 2H), 7. 46-7. 32(m, 3H), 6. 13(s, 1H), 5. 61(q, 1H), 5. 32(brs, 1H), 5. 01-4. 87(m, 1H), 4. 89 (dd, 1H), 4. 62-4. 55(m, 2H), 4. 34-4. 08 (m, 2H), 2. 94-2. 55(m, 4H), 2. 50(s, 3H), 2. 23(q, 1H), 1. 95-1. 10 (m, 32H). Compound 1]6: MS: m/z 9() 9. 4(M++1) ; !H NMR(CDC13) δ 10. 29(s, ΓΗ), 8. 40(d, 2H), 8. 01(s, 1H), 7. 55(d, 2H), 7. 47-7. 26(m, 3H)5 6. 14(s, 1H), 5. 69(q, 1H), 5. 37(d, 1H), 4. 99(dd, 1H), 4. 78(dd, 1H), 4. 60(d, 1H), 4. 40-4. 05(m, 3H), 2. 80-2. 51 (m, 3H), 2. 50(s, 3H), 2. 29(q, 1H), 1. 98-1. 12(m, 32H), 0. 82. (s, 3H). Compound 117: MS: m/z 855. 2(M++1) ; rH NMR(CDC13) δ 10. 08(s, 1H), 8. 22(d, 2H), 8. 03(d, 2H), 7. 44-7. 18(m, 3H), 7. 26-7. 17(m, 1H), 7. 13(d, 1H), 6. 12(s, 1H), 5. 65(q, 1H), 4. 89 (dd, 1H), 4. 77 (dd, 1H), 4. 49(d, 1H), 4. 42-4. 36(m, 1H), 4. 13(dd, 1H), 3. 16(s, 1H), 2. 84-2. 46(m, 4H), 2. 16(q, 1H), 1. 95-0. 77 (m, 31H). Compound 1]8: MS: m/z 895·4 (Μ++1). Compound 1]9: MS: m/z 895. 4 (M++1). Compound 120: MS: m/z 840·2 (Μ++1); 4 NMR (CDC13) δ 10. 26(s, 1H), 8. 38(d, 2H), 8. 20(d, 1H), 8. 00(d, 1H), 7. 61- 70 201109028 7. 54(m, 2H), 7. 50(d, 2H), 7. 41-7. 35 (m, 1H), 7. 15(s, 1H), 6. 72(d, 1H), 6. 10(d, 1H), 5. 63(q, 1H), 5. 27(d, 1H), 4. 89 (dd, 1H), 4. 68 (dd, 1H), 4. 51-4. 42 (m, 2H), 4. 12 (dd, 1H), 2. 84-2. 43 (m, 4H), 2. 22(q,1H), 1. 98-0. 84 (m, 24H). Compound 121: MS: m/z 829. 3 (M++1). Compound 122: MS: m/z 833. 3 (M++1). Compound 123: MS: m/z 821. 3(M++1) ; NMR(CDC13) δ 10. 27(s, 1H), 7. 90 (dd, 1H), 7. 60(s, 1H), 7. 27(dd, 1H), 7. 32-7. 20(m, 2H), 6. 91(s, 1H), 6. 53 (dd, 1H), 6. 03(s, 1H), 5. 64(q, 1H), 4. 98-4. 89(m, 2H), 4. 71-4. 58(m, 2H), 4. 14-4. 03 (m, 2H), 2. 86-2. 80 (m, 1H), 2. 67-2. 40 (m, 2H), 2. 22(q, 1H), 1. 98-1. 10 (m, 15H), 1. 05(s,9H),0. 98-0. 82 (m, 1H). Compound 124: MS: m/z 779·2 (Μ++1); NMR (CDC13) δ 10. 31(s, 1H), 7. 93(dd, 1H), 7. 70(s, 1H), 7. 65-7. 55 (dd, 1H), 7. 41-7. 26(m, 2H), 7. 04(s, 1H), 6. 61(s, 1H), 6. 15(s, 1H), 5. 72(q, 1H), 5. 37(d, 1H), 5. 01-4. 91(m, 1H), 4. 77 (dd, 1H), 4. 46(d, 1H), 4. 37-4. 09(m, 2H), 3. 36(s, 3H), 2. 92-2. 53(m, 3H), 2. 23(q,1H), 1. 99-0. 86 (m, 16H). Compound 125: MS: m/z 817_2 (M++1); 'H NMR (CDC13) δ 10. 28(s, 1H), 7. 98(d, 1H), 7. 66(s, 1H), 7. 60 (dd, 1H), 7. 40-7. 09(m, 3H), 6. 11(s, 1H), 6. 60(s, 1H), 6. 17(s, 1H), 5. 72(q, 1H), 4. 99(dd, 1H), 4. 76-4. 67(m, 2H), 4. 31-4. 18(m, 2H), 2. 91-2. 75 (m, 2H), 2. 45(br,1H), 2. 22-0. 84 (m, 17H). Compound 126: MS: m/z 763·2 (Μ++1); 4 NMR (CDC13) δ 71 201109028 10. 29(s, 1H), 7. 81 (dd, 1H), 7. 60(s, 1H), 7. 52 (dd, 1H), 7. 35-7. 18(m, 3H), 6. 52(d, 1H), 6. 13-6. 01(m, 2H), 5. 61(q, 1H), 4. 83 (dd, 1H), 4. 62 (dd, 1H), 4. 45 (dd, 1H), 4. 38(d, 1H), 4. 17(dd, 1H), 2. 85-2. 79(m, 1H), 2. 67(d, 1H), 2. 41 (m, 1H), 2. 21-0. 84 (m, 20H). Compound 127: MS: m/z 821·3 (Μ++1); NMR (CDC13) δ 10. 37(s, 1H), 8. 15(s, 1H), 7. 79(d, 1H), 7. 45-7. 42(m, 3H), 7. 35-7. 25(m, 1H), 7. 01(s, IH), 5. 89(s, 1H), 5. 54(q, 1H), 5. 19(d, 1H), 4. 85 (dd, 1H), 4. 67(dd, 1H), 4. 54(d, 1H), 4. 20 (dd, 1H), 4. 04(d, 1H), 2. 91-2. 44(m, 3H), 2. 24(q, 1H), 2. 01-1. Ll(m, 15H), 1. 06(s,9H),0. 83-0. 78 (m, 1H). Compound 128: MS: m/z 833. 3(M++1) ; rH NMR(CDC13) δ 10. 37(s, 1H), 8. 07(d, 1H), 7. 56-7. 22(m, 5H), 6. 89(d, 1H), 5. 96(s, 1H), 5. 57-5. 49 (m, 1H), 5. 21-5. 17(m, 1H), 4. 96-4. 83 (m, 1H), 4. 72 (dd, 1H), 4. 67(d, 1H), 4. 18-4. 03(m, 2H), 2. 90-2. 79(m, 1H), 2. 69(s, 3H), 2. 64-2. 46(m, 2H), 2. 22(q, 1H), 1. 97-1. 04(m, 15H), 1. 04(s,9H), 0. 96-0. 87 (m, 1H). Compound 129: MS: m/z 836. 3(M++1) ; NMR(CDC13) δ 10. 29(s, 1H), 7. 88(d, 1H), 7. 53-7. 50 (m, 1H), 7. 49 (dd, 1H), 7. 19(s, 1H), 6. 65(s, 1H), 6. 04(s, 1H), 5. 70-5. 50 (m, IH), 5. 12-4. 48 (m, 4H), 4. 19-3. 98(m, 2H), 2. 95-2. 58(m, 3H), 2. 48(s, 3H)S 2. 32-2. 12(m, 1H), 1. 97-1. 18(m, 15H), 1. 00(s, 9H), 0. 98-0. 86 (m, 1H). Compound 130: MS: m/z 832. 2(M++1); NMR(CDC13) δ 72 201109028 10. 20(s, 1H), 7. 84 (dd, 1H), 7. 52 (dd, 1H), 7. 39(, 1H), 7. 38-7. 26(m, 2H), 6. 62(s, 1H), 6. 05(s, 1H), 5. 60(q, 1H), 4. 83 (dd, 1H), 4. 67(dd, 1H), 4. 55 (dd, 1H), 4. 36(d, 1H), 4. 08 (dd, 1H), 2. 81-2. 50 (m, 3H), 2. 48(s, 3H), 2. 45-2. 37 (m, 1H), 2. 18(q, 1H), 1. 99-0_87 (m, 15H). Compound 131: MS: m/z 888. 3(M++1) ; NMR(CDC13) δ 10. 36(s, 1H), 8. 23(d, 1H), 7. 41(s, 1H), 7. 30 (m, 2H), 7. 11(s, 1H), 6. 16(s, 1H), 5. 68(q, 1H), 5. 23(d, 1H), 4. 98 (dd, 1H), 4. 75(brs, 1H), 4. 54(d, 1H), 4. 36-4. 11(m, 3H), 3. 39-3. 27(m, 1H), 2. 96-2. 63(m, 3H), 2. 54(s, 3H), 2. 25(q, 1H), 1. 89-0. 93 (m, 30H). Compound 132: MS: m/z 888. 3(M++1) ; 'H NMR(CDC13) δ 10. 24(s, 1H), 8. 37(d, 1H), 7. 74-7. 51(m, 2H), 7. 48-7. 42(m, 1H), 7. 22(s, 1H), 7. 12(s, 1H), 6. 17(s, 1H), 5. 70(q, 1H), 5. 28 (d, 1H), 4. 99(dd, 1H), 4. 76(dd, 1H), 4. 58(d, 1H), 4. 52(brs, 1H), 4. 35-4. 16(m, 2H), 3. 40-3. 35 (m, 1H), 2. 79-2. 43 (m, 3H), 2. 25(q, 1H), 1. 95-1. 23(m, 29H), 0. 87-0. 76 (m, 3H). Compound 133: MS: m/z 887·3 (Μ++1); 4 NMR (CDC13) δ 10. 37(s, 1H), 8. 59(s, 1H), 8. 22(d, 1H), 7. 81(d, 1H), 7. 58-7. 42 (m, 3H), 6. 95-6. 89(m, 2H), 6. 09(s, 1H), 5. 68(q, 1H), 5. 32(d, 1H), 4. 99(m, 1H), 4. 74 (m, 1H), 4. 54(d, 1H), 4. 39-4. 22 (m, 1H), 4. 14-4. 11 (m, 1H), 2. 90 (m, 1H), 2. 78(m, 2H), 2. 55 (m, 1H), 2. 27(q, 1H), 1. 90-1. 10(m, 21H), 1. 45(s, 9H), 0_94-0. 83 (m, 2H). 73 201109028 Compound 134: MS: m/z 901. 3(M++1);]H NMR(CDC13) δ 10. 21(s,lH), 8. 8. 51(s,lH), 8. 23(d,lH), 7. 81 (d, lH), 7. 59-7. 43(m, 3H), 7. 13(s, 1H), 6. 90(d, 1H), 6. 09(s, 1H), 5. 68(q, 1H), 5. 22(d, 1H), 4. 99(dd, 1H), 4. 76(m, IH), 4. 55(d, 1H), 4 39-4. 22 (m, 1H), 4. 14-4. 1 l(m, 1H), 2. 78(m, 2H), 2. 55(m, 1H), 2_27(q, 1H), 1. 90-0_83 (m, 23H), 1. 46(s, 9H). Compound 135: MS: m/z 888. 3 (M++1). Compound 136: MS: m/z 902. 3 (M++1). Compound 137: MS: m/z 899. 4 (M++1). Compound 138: MS: m/z 885. 3(M++1) ; 4 NMR(CDC13) δ 10. 36(s, 1H), 8. 17(d, 1H), 7. 58(m, 2H), 7. 42-7. 33(m, 2H), 6. 63(m, 1H), 6. 07(s, 1H)} 5. 67(q, 1H), 5. 29(d, 1H), 4. 97 (dd, 1H), 4. 77(m, 1H), 4. 57(m, 1H), 4. 42-4. 03(m, 3H), 2. 89 (m, 1H), 2. 75 (m, 5H), 2. 52(m, 1H), 2. 27(q, 1H), 1. 91-0. 82 (m, 32H). Compound 139: MS: m/z 803. 3 (M++1). Compound 140: MS: m/z 817. 3 (M++1). Compound 14L MS: m/z 831. 3(M++1) ; 4 NMR(CDC13) δ 10. 33(s, 1H), 8. 05(s, 1H), 7. 56-7. 48 (m, 3H), 6. 06(s, 1H), 5. 62(q, 1H), 5. 15(dd, 1H), 4. 91 (dd, 1H), 4. 75 (dd, 1H), 4. 59(d, 1H), 4. 35-4. 02(m, 3H), 2. 96-2. 88(m, 1H), 2. 74-2. 65 (m, 2H), 2. 53(s,3H), 2. 24(q,1H), 1. 96-0. 89 (m, 24H). Examples 142 and 143: Synthesis of [4-3⁄4 propyl-based aryl-based benzyl-2,15-di-lacto-18-(2-phenyl-74 201109028 benzo[4,5]furo[3, 2-b] acridine-4-yloxy)-3,16-diazatricyclo[14. 3·0·04,6]dodecyl-7-en-14-yl]-carbamic acid tert-butyl ester (Compound 142) and [4-cyclopropionylaminoamino-2,15-dioxo -18-(2-stupyl-stupid [4,5]pyrano[3,2-b] ate-4-yloxy)_316_diazatricyclo[14. 3. 0. 04,6] Nineteen carbon-7-thin-14-yl]-carbamic acid cyclopentyl ester (Compound 143) Compounds I42 and I43 were prepared by the following synthetic route: 75 201109028

76 143 201109028 To a solution of 2-hydroxybenzonitrile (30 g, 251.6 mmol) in ethyl methyl ketone (32 mL) was added a carbonic acid (69.6 g, 755.5 mmol). After stirring at room temperature for 30 minutes, air acetone (34.95 g, 3718 mmol) was added to the resulting mixture, which was then heated at 100 ° C overnight. Finally, the reaction solvent was removed under reduced pressure, and the resulting solid was washed with water and then washed.

1_13 (31 g' yield: 70.3%). MS: m/z 176.0 (M++1); 4 NMR (CDCI3) δ 7.59 (d, 1H), 7.46 (dd, 1H), 7.41 (d, 1H), 7.24 (dd, out), 2.50 (s) , 3H). To 2-ethylhydrazino-3-aminobenzofuran 1-13 (2.17 g, 12.38 mmol) and claudaldehyde (1.31 g, 12.38 mmol) at 5-10 ° C with constant stirring Aqueous sodium hydroxide (7 〇0/〇, 5 mL) was added dropwise to a solution of ethanol (30 mL). After stirring overnight, the crude product of the bright yellow solid was suspended in the reaction mixture. The solid was filtered, collected, and recrystallized from ethanol to give a filamentous needle 1-14 (2.7 g, 90%). MS: m/z 264.0 (M++1); 'H NMR (CDC13) δ 7.83 (d, 1H), 7.71 (dd, 2H), 7.64 (d, 1H), 7.62 (d, 1H)» 7.58- 7.39(m, 5H), 7.29-7.24 (m, 1H), 5.83 (ms 2H) ° Intermediate IM (1.32 g, 5.0 mmol) was suspended in acetic anhydride (10 mL) and in a hot water bath Stir. After stirring overnight, the reaction mixture was poured into ice and water. The suspended crude product was separated and collected, and then reconstituted with ethanol to obtain I-15 (1.52 g, 90 〇/〇). MS: m/z 306·0 (Μ++1); 丨H NMR (CDc!3) δ 8.58 (d, 1 Η), 7.91 (d, 1 Η), 7.72 (m, 3 Η), 7.54-7.44 , 5H), 7.34.7.7 28 (m, 1H), 2.35 (s, 3H). Intermediate 1-15 (1.22 g of '4.0 mmol) in celite of CHC13 (20 mL) was slowly added dropwise to bromo (〇72 g 4 5 mmol) in CHCb (15 mL) in sol. 77 201109028 . After stirring overnight, the reaction mixture was quenched with ice water. The suspended solids were separated, collected and recrystallized from ethanol/h2o to give 1-16 (1·12 g ' 60%). MS: m/z 465.9 (M++1); 'HNMR (CDC13) δ l 〇.22 (brs, 1 Η), 8.63 (d, 1H), 7.61-7.25 (m, 8H), 5.92 (d, 1H) ), 5.62(d, 1H), 2.37(s, 3H). Anhydrous potassium acetate (0.2 g, 2.0 mmol) was added to a solution of 1-16 (0.93 g, 2.0 mmol). After stirring overnight, the reaction mixture was poured into cold water. The suspended solid was separated, collected and recrystallized from ethanol to give monobromide-compound 1-17 (0.46 g, 60%). MS: m/z 385.9 (M++1); 'HNMR (CDC13) δ 10.50 (brs, 1H), 8.54 (d, 1H), 8.48 (s, 1H)} 7.93 (m, 2H), 7.56-7.46 (m, 5H), 7.36-7.3l (m, lH), 2.35 (s, 3H). The compound Μ7 (0. 35 g, 1.0 mmol) was refluxed in acetic acid (5 ml) and then. The reaction mixture was cooled to room temperature, poured into ice water and stirred for 30 min. The suspended solids were separated 'collected and recrystallized from DMF to give 1-18 (0.2 g, 80%). 1^: 111^ 262.0(]^++1). A solution of 1-18 (1.0 g, 3.8 mmol) and phosphonium chloride (?? (: 13) (10 ml) was refluxed for 2 hours. After the solution was cooled and completely concentrated, the resulting residue was treated with 10% hydr. The sodium was quenched and extracted with di-methane (20 mL EtOAc). The organic layer was collected and dried with sodium sulfate and concentrated. The crude product was recrystallized from CH2C12 and hexanes to obtain Ι-19 (〇.7 g, 75%) °MS: m/z 279·9(Μ++1); ,H NMR(CDC13) δ 8.45(d, 1Η), 8.09(d, 2H), 7.84(s, 1H), 7.71-7.64(m , 2H), 7.56-7.47(m, 4H) «= to °C to Boc-trans- 4-hydroxy-L-proline (0.53 g, 2.3 mmol) 78 201109028 Suspension in DMSO (10 ml) i_BuONa (0.49 g, 5-10 mmol) was added to the solution. After heating to room temperature and mixing for 1 hour, intermediate 1-19 (0.64 g '2.3 mmol) was slowly added at 1 ° C. The reaction mixture was stirred 4 </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; ; 'H NMR(CDC13) δ 8.27(d5 1Η), 7.97(m, 2H), 7.86-7.76(m,3H), 7.66-7.44(ms 4H), 5.81(s, 1H), 4 .47 (m, 1H), 4.03-3.89 (m, 2H), 2-81 (m, lH), 2.50 (q, 1H). Room temperature, 1-20 (1.1 g '2.3 mmol) of MeOH 8 〇 0:12 (1.17 g, 9.9 mmol) was added to a solution (20 mL). MS: m/z 389.1 (M++1), mp (1 - (1 - s), </ RTI> </ RTI> <RTIgt; , 3,3-tetramethylurea cation hexafluoro-salt sulphate (HATU, 1.12 g, 3.0 mmol), N-hydroxybenzotriazole (HOBT, 0.4 g, 3.0 mmol) and 2-un To a solution of butoxycarbonylamino-indol-8-enoic acid (1.19 g, 5.2 mmol) in CH2C12 (20 mL) Purification by gel column chromatography gave compound 1-22 (1.02 g, 80.7%). MS: m/z 642.3 (M++1);]H NMR (CDC13) δ 8.24 (d, 1H), 8.05 (d, 2H), 7.58 (m, 2H), 7.56-7.41 (m, 4H), 7.28(d, 1H), 5.83-5.76(q, 1H), 5.71(s, 1H), 5.24(d, 1H), 5.01-4.82(m, 2H), 4.76(dd, 1H), 4.75-4.34( m, 2H), 4.03(m, 1H), 3.77(s, 3H), 2.78(m, 1H), 2.36(q, 1H), 2.01(m, 2H), 1.75(m, 1H), 1.54(m , 1H), 1.42 (m, 6H), 79 5 201109028 1.31 (s, 9H). To a solution of 1-22 (1.0 g, 1.6 mmol) in THF (20 mL). The reaction mixture was stirred overnight before being acidified to pH. &lt;7&apos; and concentrated in vacuo to give a solid product which was filtered and washed with water to afford 1-23. MS: m/z 628. 1(M++1) * 'HNMRCCDCb) δ 8. 34(brs, 1H), 8. 04(d, 2H), 7. 62(m, 2H), 7. 60-7. 41(m, 4H), 7. 28(m, 2H), 5. 81-5. 72(q, 1H), 5. 70(s, 1H), 5. 29(d, 1H), 5. 00-4. 87(m, 3H), 4. 48 (m, 2H), 4. 01(m, 1H), 2. 77(m, 2H), 1. 98(m, 2H), 1. 72(m, 1H), 1. 61(m, 1H), 1. 44 (m, 6H), 1. 33(s, 9H). At room temperature, the NMM (0. 12 grams, 1. 2 mmol) was added to compound 1-23 (0-26 g, 〇·41 mmol), HATU (0. 31 grams ‘ 0_81 millimoles), HOBT (0. 084 grams, 0. 61 mmol) and cyclopropanesulfonic acid (1-amino-2-vinyl-cyclopropanecarbonyl)-decylamine (0. 094 grams, 0. 41 mmol) in a solution of CH2C12 (10 mL). After the reaction mixture was stirred overnight, concentrated in vacuo. The residue was purified by silica gel column chromatography to give compound 1-24 (0. 15g, 45%). MS: m/z 804. 3(M++1) ; 'H NMR(CDC13) δ 10. 22(s, 1H), 8. 35(d, 1H), 8. 01(d, 2H), 7. 59(d, 2H), 7. 48-7. 30 (m, 5H), 7. 04(s, 1H), 5. 78(m, 3H), 5. 35(d, 1H), 5. 23(d, 1H), 5. 15(d, 1H), 4. 93(m, 2H), 4. 53(dd, 1H), 4. 41-4. 30 (m, 2H), 4. 05(m, 1H), 2. 91 (m, 1H), 2. 61(m, 2H), 2. 14 (dd, 1H), 2. 04(m, 3H), 1. 91-L52 (m, 3H), 1. 45-1. 22 (18H), 1. 21 (m, 2H). At room temperature, under N2 to compound 1-24 (100 mg, 0. 12 mmol) Add Hovida-Grubb second generation catalyst in a solution of CH2C12 (35 mil 80 201109028 g, 0. 056 mmol), then the reaction mixture was heated to 40 ° C and allowed to mix for 24 hours. The reaction mixture was concentrated and purified by column to afford compound 142 (30 mg, 31%). MS: m/z 812. 3(M++1); 'HNMR^CDCh) δ 10. 29 (s, 1H), 8. 28(d,lH), 8. 04(d, 2H), 7. 61-7. 41 (m, 7H), 7. 00(s, 1H), 5. 69 (m, 2H), 5. 19(d, 1H), 4. 97 (dd, 1H), 4. 67(m, 2H), 4. 31 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 55 (m, 1H), 2. 29(q, 1H), 1. 89-l. Ll(m, 13H), 1. 19(s, 9H), 0. 97-0. 86 (m, 2H) 0 room temperature ' to compound 142 (0. 1 gram' 0. A solution of excess 4 N HCl in dioxane (2 ml) was added to a solution of CH2Cl2 (5 mL). After stirring for 4 hours, HCl, dioxane and CH2C12 were evaporated to give crude compound 1-25. MS: m/z 712·3 (Μ++1). 1-25 was dissolved in acetonitrile (2 mL) then saturated NaHC03 (1 mL). The reaction mixture was stirred for 10 minutes. Add cyclopentyl chloroformate to the reaction mixture at room temperature (0. 02 g, 0_15 mmol). After stirring for an additional 2 hours, the reaction mixture was quenched with saturated NaHC. The residue was purified by silica gel column chromatography to afford compound 143 (0. 1 gram, 87%). MS: m/z 824. 3(M++1) ; 'H NMR(CDC13) δ 10. 26(s, 1Η), 8. 29(d,lH), 8. 07(d, 2H), 7. 62-7. 32(m, 7H), 7. 00(s, 1H), 5. 75(s, 1H), 5. 70(q, 1H), 5. 22(d, 1H), 4. 99(dd, 1H), 4. 75(m, 2H), 4. 56(d, 1H), 4. 32(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 52(m, 1H), 2. 29(q, 1H), 1. 91-0. 85 (m, 23H). 81 201109028 Examples 144-253: Synthesis of Compound M4-253 Compounds 144-253 were each prepared in a similar manner as described in Examples 142 and 143. Compound 144: MS: m/z 7887. 3(M++1) ; ^HNNlI^CDCb) δ 10. 36(s, 1H), 8. 40(s, 1H), 8. 21(d,lH), 8. 08(dd, 1H), 7. 56-7. 11 (m, 7H), 6. 80(s, 1H), 5. 63(m, 2H), 4. 93(m, 1H), 4. 79(m, 1H), 4. 31(m, 2H), 4. 05(m, 1H), 3. 45(s, 3H), 2. 87 (m, 1H), 2. 70 (m, 2H), 2. 52(m, 1H), 2. 25(q,1H), 1. 91-0. 84 (m, 15H). Compound 145: MS: m/z 872. 3 (M++1). Compound 146: MS: m/z 770. 3(M++1) ; 4 NMR(CDC13) δ 10. 35(s, 1H), 8. 25(d,lH), 8. 00(d, 2H), 7. 56-7. 25 (m, 7H), 6. 66(s, 1H), 5. 69 (m, 2H), 5. 45(d, 1H), 4. 95 (dd, 1H), 4. 70 (m, 1H), 4. 40-4. 28(m, 2H), 4. 05(m, 1H), 3. 52(s, 3H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 51(m, 1H), 2. 30(q, 1H), 1. 87-1. 09(m, 13H), 0. 97-0. 84 (m, 2H). Compound 147: MS: m/z 697·2 (Μ++1); 4 NMR (CDC13) δ 10. 37(s, 1H), 8. 24(d, 1H), 8. 04(d, 2H), 7. 56-7. 31 (m, 8H), 5. 63(m, 2H), 4. 97 (dd, 1H), 4. 63(m, 1H), 4. 09(m, 1H), 3. 96(m, 1H), 2. 84 (m, lH), 2. 62 (m, 2H), 2. 6-2. 03(m, 4H), 1. 95-0. 84(m, 15H) » Compound 148: MS: m/z 872·3 (Μ++1); 'H NMR (CDC13) δ 10. 29(s, 1H), 8. 09(dd, 1H), 7. 69(d, 1H), 7. 48-7. 14(m, 7H), 5. 71(m, 2H), 5. 31(d,lH), 4. 98 (dd, 1H), 4. 74 (m, 1H), 4. 55(d, 1H), 4. 36(m, 1H), 4. 05(m, 2H), 3. 96(s, 3H), 2. 89(m, 1H), 82 201109028 2. 68 (m, 2H), 2. 52(m, 1H), 2. 28(q,1H), 2. 00-0. 88 (m, 23H). Compound 149: MS: m/z 381. Compound 150: MS: m/z 802·2 (Μ++1); 'H NMR (CDC13) δ 10. 23(s, 1H), 8. 08(dd, 1H), 7. 68(d, 1H), 7. 49(d, 1H), 7. 39-7. 13(m, 6H), 6. 10(d, 1H), 5. 72(m, 2H), 4. 95 (dd, 1H), 4. 63(m, 2H), 4. 17(d, 1H), 4. 06(m, 1H), 3. 92(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 46(m, 1H), 2. 26(q, 1H), 1. 94-0. 86(m, 15H), 1. 91(s, 3H). Compound 151: MS: m/z 854·3 (Μ++1); 'H NMR (CDC13) δ 10. 26(s, 1H), 8. 27(d, 1H), 8. 03(d, 2H), 7. 59(m, 3H), 7. 45 (dd, 1H), 7. 01(d, 2H), 6. 88(m, 1H), 5. 74(m, 2H), 5. 19(d, 1H), 4. 96(m, 2H), 4. 75(s, 1H), 4. 53(d, 1H), 4. 32(m, 1H), 4. 04(m, 1H), 3. 87(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 46(m, 1H), 2_27(q, 1H), 1. 90-1. 12(m, 21H), 0. 92-0. 87 (m, 2H). Compound 152: MS: m/z 842. 3 (M++1). Compound 153: MS: m/z 854. 3(M++1) ; h NMR(CDC13) δ 10. 31(s, 1H), 8. 58(s, 1H), 8. 43(m,lH), 7. 85(d, 1H), 7. 59(m, 2H), 7. 37(m, 3H), 7. 12(dd, 1H), 7. 01(d, 1H), 5. 65 (m, 2H), 5. 31(d, 1H), 4. 94 (dd, 1H), 4. 72(m, 2H), 4. 53(d, 1H), 4. 37(m, 1H), 4. 07(m, 1H), 3. 87(s, 3H), 2. 88(m,lH), 2. 66(m, 2H), 2_50(m, 1H), 2. 28(q, 1H), l_88-0_82 (m, 23H). Compound 154: MS: m/z 854. 3(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 8. 50(s, 1H), 8. 29(d, 1H), 7. 63(s, 1H), 7. 56(m, 3H), 7. 43(m, 2H), 7. 28(m, 1H), 7. 11(s, 1H), 6. 98(dd,lH), 83 201109028 5. 74(s, 1H), 5. 69(q, 1H), 5. 29(d, 1H), 4. 94 (dd, 1H), 4. 73 (m, 1H), 4. 57(d,1H), 4. 34(m, 1H), 4. 04(m, 1H), 3. 92(s,3H), 2. 88(m, 1H), 2. 68 (m, 2H), 2. 51(m, 1H), 2. 29(q, 1H), 1. 87-0. 84 (m, 23H). Compound 155: MS: m/z 842. 3 (M++1); 丨 only NMR (CDC13) δ 10. 28(s, 1H), 8. 28(d,lH), 7. 85(d, 1H), 7. 57(m, 2H), 7. 40(tn, 3H), 7. 14(dd, 1H), 7. 01(d, 2H), 5. 68(q, 1H), 5. 58(s, 1H), 5. 19(d, 1H), 4. 92(dd, 1H), 4. 67(m, 2H), 4. 33(m, 1H), 4. 03(m, 1H), 3. 87(s, 3H), 2. 89(m,lH), 2. 68(m, 2H), 2. 54 (m, 1H), 2. 28(q, 1H), 1. 90-l. Ll(m, 13H), 1. 21(s, 9H), 0. 97-0. 87 (m, 2H). Compound 156: MS: m/z 854·3 (Μ++1); 'H NMR (CDC13) δ 10. 24(s, 1H), 8. 59(s, 1H), 8. 04(m, 2H), 7. 84(d, 1H), 7. 49-7. 28(m, 4H), 7. 08(d, 1H), 6. 91(s, 1H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 21(d, 1H), 4. 97 (dd, 1H), 4. 71-4. 67(m, 2H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 05(s, 3H), 4. 04(m, 1H), 2. 90 (m, 1H), 2. 69 (m, 2H), 2. 54 (m, 1H), 2. 31(q, 1H), 1. 96-1. 06(m, 21H), 0. 95-0. 83 (m, 2H). Compound 157: MS: m/z 838·3 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 59(s, 1H), 8. 27(d, 1H), 7. 92(d, 2H), 7. 57(m, 2H), 7. 44(m, 1 H), 7. 26-7. 17(m, 3H), 5. 68(s, 1H), 5. 64(q, 1H), 5. 37(d, 1H), 4. 96(m, 1H), 4. 76(m, 1H), 4. 67(m, 1H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 53 (m, 1H), 2. 40(s, 3H), 2. 31(q, 1H), 1. 94-1. 07(m, 21H), 84 201109028 0_95-0. 83 (m, 2H). Compound 158: MS: m/z 842·3 (Μ++1); 4 NMR (CDC13) δ 10. 31(s, 1H), 8. 26(d, 1H), 8. 05(m, 2H), 7. 58(m, 2H), 7. 43(m, 1H), 7. 25-7. 19(m, 4H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 35(d, 1H), 4. 96 (dd, 1H), 4. 75-4. 69 (m, 2H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 2. 87 (m, 1H), 2. 67(m, 2H), 2. 50 (m, 1H), 2. 28(q, 1H), 1. 91-1. 07(m, 21H), 0. 97-0. 84 (m, 2H). Compound 159: MS: m/z 872. 3 (M++1). Compound 160: MS: m/z 872. 1 (M++1) ; NMR (CDC13) δ 10. 48(s, 1H), 8. 02(m, 2H), 7. 68(d, 1H), 7. 47(d, 1H), 7. 23-7. 17(m, 4H), 5. 74(m, 2H), 5. 68(q, 1H), 5. 23(d, 1H), 4. 97 (dd, 1H), 4. 76(s, 1H), 4. 67(m, 1H), 4. 54(d, 1H), 4. 33(m, 1H), 4. 04(m, 1H), 3. 93(s, 3H), 2. 89 (m, 1H), 2. 67(m, 2H), 2. 52(m, 1H), 2. 27(q, 1H), 1. 92-1. 06(m, 21H), 0. 97-0. 84 (m, 2H). Compound 161: MS: m/z 860·2 (Μ++1); NMR (CDC13) δ 10. 34(s, 1H), 8. 01(m, 2H), 7. 67(d, 1H), 7. 47(d, 1H), 7. 29-7. 16(m, 5H), 5. 68(m, 2H), 5. 23(d, 1H), 4. 95 (dd, 1H), 4. 69-4. 63(m, 2H), 4. 31 (m, 1H), 4. 04(m, 1H), 3. 92(s, 3H), 2. 88(m, 1H), 2. 67(m, 2H), 2. 54 (m, 1H), 2. 27(q, 1H), 1. 92-0. 83(m, 15H), 1. 20(s, 9H). Compound 162: MS: m/z 856·1 (Μ++1); 4 NMR (CDC13) δ 10. 23(s, 1H), 8. 03(m, 2H), 7. 66(d, 1H), 7. 48(d, 1H), 7. 32(s, 1H), 7. 29-7. 15(m, 5H), 5. 73(m, 2H), 4. 92(dd, 1H), 4. 69 (m, 2H), 4. 31(d, 1H), 4. 06(m, 1H), 3. 91(s, 3H), 2. 85(m, 1H), 85 201109028 2. 68(m, 2H), 2. 44 (m, 1H), 2. 20(q, 1H), 1. 93-0. 83(m, 15H) ·&gt; Compound 163: MS: m/z 854·2 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 60(s, 1H), 8. 01(m, 2H), 7. 68(d, 1H), 7. 46(m, 4H), 7. 15(m, 2H), 5. 71(s, 1H), 5. 68(q, 1H), 5. 37(d, 1H), 4. 96 (dd, 1H), 4. 67(s, 1H), 4. 64 (m, 1H), 4. 55(d, 1H), 4. 36(tn, 1H), 4. 03(m, 1H), 3. 93(s, 3H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 94-1. 07(m, 21H), 0. 97-0. 84 (m, 2H). Compound 164: MS: m/z 830. 4(M++1) ; 'H NMR(CDC13) δ 10. 33(s, 1H), 8. 25(d, 1H), 8. 04(m, 2H), 7. 57(m, 2H), 7. 42(m, 1H), 7. 25-7. 14(m, 4H), 5. 68(m, 2H), 5. 25(d, 1H), 4. 92(dd, 1H), 4. 66(m, 2H), 4. 32(m, 1H), 4. 05(m, 1H), 2. 87 (m, 1H), 2. 68(m, 2H), 2. 55 (m, 1H), 2. 28(q, 1H), 1. 91-1. 06(m, 13H), 1. 20(s,9H),0. 97-0. 84 (m, 2H). Compound 165: MS: m/z 868. 2(M++1) ; NMR(CDC13) δ 10. 29(s, 1H), 8. 53(s, 1H), 8. 13(d, LH), 7. 91(m, 2H), 7. 58(m, 1H), 7. 19(m, 1H), 7. 00 (m, 3H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 28(d, 1H), 4. 95 (dd, 1H), 4. 79(s, 1H), 4. 68(m, 1H), 4. 53(d, 1H), 4. 37(m, 1H), 4. 05(m, 1H), 3. 91(s, 3H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 50 (m, 1H), 2. 40(s, 3H), 2. 25(q, 1H), 1. 90-1. 06(m, 21H), 0. 97-0. 83 (m, 2H). Compound 166: MS: m/z 868·3 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 59(s, 1H), 7. 98(m, 2H), 7. 71(s, 1H), 7. 46(d, 1H), 7. 27(m, 2H), 7. 15(m, 2H), 5. 71(s, 1H), 5. 68(q, 1H), 86 201109028 5. 29(d, 1H), 4. 94 (dd, 1H), 4. 78(s, 1H), 4. 67(m, 1H), 4. 54(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 3. 93(s, 3H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 40(s, 3H), 2. 28(q, 1H), 1. 92-1. 08(m, 21H), 0. 97-0. 83 (m, 2H). Compound 167: MS: m/z 872·4 (Μ++1); NMR (CDC13) δ 10. 29(s, 1H), 8. 51(s, 1H), 8. 08(d, 1H), 8. 01(m, 2H), 7. 15(d, 2H), 7. 04(m, 3H), 5. 73(s, 1H), 5. 69(q, 1H), 5. 30(d, 1H), 4. 95 (dd, 1H), 4. 79(s, 1H), 4. 65 (m, 1H), 4. 53(d, 1H), 4. 37(m, 1H), 4. 04(m, 1H), 3. 91(s, 3H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 50 (m, 1H), 2. 28(q, 1H), 1. 90-1. 05(m, 21H), 0. 97-0. 83 (m, 2H). Compound 168: MS: m/z 826. 4(M++1) ; NMR(CDC13) δ 10. 23(s, 1H), 8. 28(d, 1H), 7. 94(d, 2H), 7. 56(m, 2H), 7. 42(m, 1H), 7. 28(m, 3H), 7. 03(s, 1H), 5. 68(m, 2H), 5. 21(d, 1H), 4. 94 (dd, 1H), 4. 67(m, 2H), 4. 32(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 55 (m, 1H), 2. 55(s, 3H), 2. 35(q, 1H), 1. 94-1. 07(m, 13H), 1. 20(s, 9H), 0. 97-0. 84 (m, 2H). Compound 169: MS: m/z 858. 3,859·3(Μ++1) ; NMR (CDC13) δ 10. 35(s, 1H), 8. 58(s, 1H), 8. 24(d, 1H), 8. 00(d, 2H), 7. 57(m, 2H), 7. 45 (m, 3H), 7. 25(s, 1H), 5. 71(s, 1H), 5. 66(q, 1H), 5. 41(d, 1H), 4. 96 (dd, 1H), 4. 75(m, 2H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 87 (m, 1H), 2. 69 (m, 2H), 2. 57 (m, 1H), 2. 28(q,1H), 1. 92-0. 83 (m, 23H). Compound 170: MS: m/z 772. 2(M++1); NMR(CDC13) δ 87 201109028 10. 31(s, lH), 8. 22(d, 1H), 8. 00(m, 2H), 7. 59(m, 2H), 7. 41 (m, 1H), 7. 20-7. 10(m, 4H), 6. 12(d, 1H), 5. 72(m, 2H), 4. 96 (dd, 1H), 4. 64 (m, 1H), 4. 55 (m, 1H), 4. 40(d, IH), 4. 01(m, 1H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 50 (m, 1H), 2. 26(q, 1H), 1. 92-1. 05 (m, 13H), 1. 91(s,3H),0. 97-0. 85 (m, 2H). Compound 171: MS: m/z 768·2 (Μ++1); 4 NMR (CDC13) δ 10. 29(s, 1H), 8. 26(d, 1H), 7. 93(d, 2H), 7. 57(m, 2H), 7. 42(m, 1H), 7. 27(m, 4H), 6. 16(d, 1H), 5. 69 (m, 2H), 4. 94 (dd, 1H), 4. 67(m, 1H), 4. 57(m, 1H), 4. 40(d, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 51(m, 1H), 2. 39(s, 3H), 2. 30(q, 1H), 1. 94-1. 05(m5 13H), 1. 92(s, 3:H), 0. 97-0. 84 (m, 2H). Compound 172: MS: m/z 788. 2(M++1) ; b NMR(CDC13) δ 10. 32(s, 1H), 8. 22(d, 1H), 8. 01(m, 2H), 7. 57(m, 2H), 7. 42(m, 1H), 7. 22-7. 11 (m, 4H), 5. 72(m, 2H), 5. 39(d, 1H), 4. 96 (dd, 1H), 4. 71 (m, 1H), 4. 39(m, 2H), 4. 04(m, 1H), 3. 54(s, 3H), 2. 89 (m, lH), 2. 71 (m, 2H), 2. 54 (m, lH), 2. 25(q,lH), 1. 91-1. 06(m, 13H), 0. 93-0. 83 (m, 2H). Compound 173: MS: m/z 822. 2(M++1) ; 4 NMR(CDC13) δ 10. 15(s, 1H), 8. 27(d, 1H), 7. 91(d, 2H), 7. 59(m, 2H), 7. 44(m, 1H), 7. 27(m, 3H), 7. 15(d, 1H), 7. 07(s, 1H), 5. 75(s, 1H), 5. 69(q, 1H), 4. 91 (dd, 1H), 4. 68(m, 2H), 4. 32(d, 1H), 4. 06(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 41 (m, 1H), 2. 39(s, 3H), 2. 21(q,1H), 1. 96-1. 08(m,13H), 0. 96-0. 83 (m, 2H). Compound 174: MS: m/z 826_2 (M++1); 4 NMR (CDC13) δ 88 201109028 10. 21(s, 1H), 8. 22(d, 1H), 8. 02(m, 2H), 7. 59(m, 2H), 7. 41 (m, 1H), 7. 24-7. 13(m, 5H), 5. 73(s, 1H), 5. 67(q, 1H), 4. 89 (dd, 1H), 4. 72(m, 2H), 4. 31(d, 1H), 4. 05(m, 1H), 2. 87 (m, 1H), 2. 69 (m, 2H), 2. 47(m, 1H), 2. 24(q, 1H), 1. 93-1. 04(m, 13H), 0. 93-0. 82 (m, 2H). Compound 175: MS: m/z 842. 3(M++1) ; 4 NMR(CDC13) δ 10. 30(s,lH), 8. 58(s,lH), 8. 26(d,lH), 8. 10 (dd, lH), 7. 61-7. 14(m, 7H), 6. 91(s, 1H), 5. 67(m, 2H), 5. 38(d, 1H), 4. 96 (dd, 1H), 4. 70 (m, 1H), 4. 56(d, 1H), 4. 36(m, 1H), 4. 06(m, 1H), 2. 88(m, 1H), 2. 69 (m, 2H), 2. 51(m, 1H), 2. 28(q, 1H), 1. 87- 0. 88 (m, 23H). Compound 176: MS: m/z 844. 3(M++1) ; 'H NMR(CDC13) δ 10. 28(s, 1H), 8. 00(m, 3H), 7. 42(d, 1H), 7. 37(d, 1H), 7. 19(m, 3H), 6. 98(s, 1H), 5. 68(m, 2H), 5. 19(d, 1H), 4. 96 (dd, 1H), 4. 66(m, 2H), 4. 30 (m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 67(m, 2H), 2. 52(s, 3H), 2. 51(m, 1H), 2. 26(q, 1H), 1. 94-1. 05(m, 13H), 1. 20(s, 9H), 0. 98-0. 83 (m, 2H). Compound 177: MS: m/z 840. 2(M++1) ; !H NMR(CDC13) δ 10. 25(s, 1H), 8. 00(m, 3H), 7. 42(d, 1H), 7. 35-7. 11 (m, 6H), 5. 73(s, 1H), 5. 69(q, 1H), 4. 93(dd, 1H), 4. 66(m, 2H), 4. 32(d, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 51(s, 3H), 2. 48 (m, 1H), 2. 23(q, 1H), 1. 95-1. 04(m, 13H), 0. 96-0. 82 (m, 2H). Compound 178: MS: m/z 784. 2(M++1) ; 4 NMR(CDC13) δ 89 201109028 10. 33(s, 1H)S 8. 27(d, 1H), 7. 92(d, 2H), 7. 55(m, 2H), 7. 41 (m, 1H), 7. 27(m, 4H), 5. 70 (m, 2H), 5. 45(d, 1H), 4. 95 (dd, 1H), 4. 67(m, 1H), 4. 36(m, 2H)S 4. 06(m, 1H), 3. 49(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 51(m, 1H), 2. 39(s, 3H), 2. 26(q, 1H), 1. 96-1. 06(m,]3H), 0. 97-0. 83 (m, 2H). Compound 179: MS: m/z 856_3 (M++1); iH NMR (CDC13) δ 10. 28(s, 1H), 7. 92(d, 2H), 7. 69(d, 1H), 7. 44(d, 1H), 7. 29(d, 2H), 7. 15(s, 1H), 7. 05(dd, 1H), 6. 97(s, 1H), 5. 68(m, 2H), 5. 22(d, 1H), 4. 95 (dd, 1H), 4. 62(m, 2H), 4. 30 (m, 1H), 4. 03(m, 1H), 3. 93(s, 3H), 2. 87 (m, 1H), 2. 66(m, 2H), 2. 54 (m, 1H), 2. 41(s, 3H), , 2. 29(q, 1H), 1. 94-0. 82(m, 15H), 1. 21(s, 9H) ^ Compound 180: MS: m/z 814·3 (Μ++1); 'H NMR (CDC13) δ 10. 35(s, 1H), 7. 92(d, 2H), 7. 63(d, 1H), 7. 42(d, 1H), 7. 33-7. 21(m, 4H)S 7. 10(dd, 1H), 5. 66(m, 2H), 5. 41(d, 1H), 4. 94 (dd, 1H), 4. 65 (m, 1H), 4. 37(m, 2H), 4. 03(m, 1H), 3. 91(s, 3H), 3. 50(s, 3H), 2. 87 (m, 1H), 2. 66(m, 2H), 2. 51(m, 1H), 2. 41(s, 3H), 2. 25(q, 1H), 1. 94-1. 07(m,13H),0. 93-0. 83 (m, 2H). Compound 181: MS: m/z 852. 2(M++1); 丨H NMR (CDCl〇 δ 10. 19(s,lH), 7. 91(d, 2H), 7. 71 (d, lH), 7. 48(d,lH), 7. 30-7. 15(m, 5H), 7. 13(dd, 1H), 5. 66(s, 1H), 5. 64(q, 1H), 4. 94 (dd, 1H), 4. 65 (m, 2H), 4. 30(d, 1H), 4. 03(m, 1H), 3. 93(s, 3H), 2. 84 (m, 1H), 2. 67(m, 2H), 2. 46(m, 1H), 2. 40(s, 3H), 2. twenty two. (q, 1H), 1. 95-0. 84 (m, 15H). Compound 182: MS: m/z 798. 3(M++1);]H NMR(CDC13) δ 90 201109028 10. 33(s, 1H), 7. 92(d, 2H), 7. 72(d, 1H), 7. 43(d, 1H), 7. 39(s, 1H), 7. 21(m, 3H), 7. 11 (dd, 1H), 6. 18(d, 1H), 5. 70(q, 1H), 5. 64(s, 1H), 4. 94 (dd, 1H), 4. 66(dd, 1H), 4. 56(m, 1H), 4. 39(d, 1H), 4. 02(m, 1H), 3. 93(s, 3H), 2. 84 (m, 1H), 2. 68(m, 2H), 2. 47(m, 1H), 2. 39(s, 3H), 2. 25(q, 1H), 1. 95-0. 83(m, 15H), 1. 91(s, 3H). Compound 183: MS: m/z 802. 2(M++1) ; iH NMR(CDC13) δ 10. 39(s, 1H), 7. 96(m, 3H), 7. 44(m, 2H), 7. 35 (m, 1H), 7. 14(m, 3H), 5. 66(m, 2H), 5. 41(d, 1H), 4. 92(dd, 1H), 4. 61 (m, 1H), 4. 30 (m, 2H), 4. 00 (m, 1H), 3. 50(s, 3H), 2. 89 (m, 1H), 2. 72(m, 2H), 2. 51(s, 3H), 2. 50 (m, 1H), 2. 26(q, 1H), 1. 93-1. 06(m, 13H), 0. 97-0_83 (m, 2H). Compound 184: MS: m/z 786. 2(M++1) ; 4 NMR(CDC13) δ 10. 36(s, 1H), 7. 96(m, 3H), 7. 42(m, 2H), 7. 32(m, 1H), 7. 15(m, 3H), 6. 12(d, 1H), 5. 69(q, 1H), 5. 65(s, 1H), 4. 94 (dd, 1H), 4. 64 (m, 1H), 4. 54(m, 1H), 4. 38(d, 1H), 3. 98(m, 1H), 2. 88(m, 1H), 2. 71(m, 2H), 2. 50 (m, 1H), 2. 49(s, 3H), 2. 27(q, 1H), 1. 92-0. 82 (m, 15H), 1. 91(s, 3H). Compound 185: MS: m/z 812·3 (Μ++1); b NMR (CDC13) δ 10. 37(s, 1H), 7. 96(m, 3H), 7. 41(d, 1H), 7. 36(d, 1H), 7. 25(m, 1H), 7. 10(m, 3H), 6. 19(d, 1H), 5. 71(q, 1H), 5. 64(s, 1H), 4. 95 (dd, 1H), 4. 66(m, 1H), 4. 48 (m, 2H), 3. 99(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 51(m, 1H), 2. 50(s, 3H), 2. 27(q, 1H), 1. 91-1. 10 (m, 14H), 0. 97-0. 80 (m, 2H), 0. 80-0. 68 (m, 4H). 91 201109028 Compound 186: MS: m/z 856. 3(M++1) ; 'H NMR(CDC13) δ 10. 28(s, 1H), 8. 00(m, 3H), 7. 42(d, 1H), 7. 37(d, 1H), 7. 25-7. 13(m, 3H), 7. 04(s, 1H), 5. 72(s, 1H), 5. 69(q, 1H), 5. 23(d, 1H), 4. 97 (dd, 1H), 4. 77(s, 1H), 4. 67(m, 1H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 52(s, 3H), 2. 51(m, 1H), 2. 25(q, 1H), 1. 93-1. 06(m, 21H), 0. 97-0. 83 (m, 2H). Compound 187: MS: m/z 830. 2(M++1) ; 4 NMR(CDC13) δ 10. 29(s,]H), 8. 01(d, 2H), 7. 93(d, 1H), 7. 50 (m, 4H), 7. 29(m, 2H), 7. 07(s, 1H), 5. 67(m, 2H), 5. 19(d, 1H), 4. 94 (dd, 1H), 4. 67(m, 2H)3 4. 30 (m, 1H), 4. 04(m, 1H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 52(m, 1H), 2. 28(q, IH), 1. 94-1. 05(m, 13H), 1. 19(s, 9H), 0. 97-0. 84 (m, 2H). Compound 188: MS: m/z 842. 2 (M++1); [H NMR (CDC13) δ 10. 27(s, 1H), 8. 02(d, 2H), 7. 93(d, 1H), 7. 52(m, 4H), 7. 32. (s, 1H), 7. 26(m, 1H), 7. 08(s, 1H), 5. 68(s, 1H), 5. 66(q, 1H), 5. 22(d, 1H), 4. 92(dd, 1H), 4. 71(m, 2H), 4. 57(d, 1H), 4. 33(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 28(q,1H), 1. 95-0. 83 (m, 23H). Compound 189: MS: m/z 882. 4 (M++1). Compound 190: MS: m/z 884. 2(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 7. 96(m, 3H), 7. 54(m, 1H), 7. 36-7. 26(m, 5H), 5. 70 (m, 2H), 5. 27(d, 1H), 4. 95 (dd, 1H), 4. 74 (m, 1H), 4. 53(d, 1H), 4. 32(m, 1H), 4. 05(m, 2H), 2. 95 (m, 2H), 2. 69(m, 2H), 92 201109028 2. 52 (m, 1H), 2. 28(q,1H), 1. 94-0. 83(m, 23H), 1. 29 (d, 6H). Compound 191: MS: m/z 8 98·2 ( Μ ++1). Compound 192: MS: m/z 880·2 (Μ++1); &apos;H NMR (CDC13) δ 10. 31(s, 1H), 8. 28(d, 1H), 7. 95(d, 2H), 7. 50 (m, 4H), 7. 42 (dd, 1H), 7. 27(s, 1H), 7. 21(s, 1H), 5. 68(s, 1H), 5. 65(q, 1H), 5. 35(d, 1H), 4. 94 (dd, 1H), 4. 72(m, 2H), 4. 57(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 28(q, 1H), 1. 93-1. 05(m, 21H), 1. 36(s, 9H), 0. 97-0. 82 (m, 2H). Compound 193: MS: m/z 894. 2(M++1) ; NMR(CDC13) δ 10. 21(s, 1H), 8. 28(d, 1H), 7. 95(d, 2H), 7. 52(m, 4H), 7. 41 (dd, 1H), 7. 34(s, 1H), 7. 26(s, 1H), 5. 70(s, 1H), 5. 65(q, 1H), 5. 41(d, 1H), 4. 95 (dd, 1H), 4. 75(m, 2H), 4. 57(d, 1H), 4. 36(m, 1H), 4. 05(m, 1H), 2. 70 (m, 2H), 2. 50 (m, 1H), 2. 29(q, 1H), 1. 93-0. 82(m, 23H), 1. 46(s, 3H), 1. 36(s, 9H). Compound 194: MS: m/z 857. 3 (M++1). Compound 195: MS: m/z 857·3 (Μ++1). Compound 196: MS: m/z 784·3 (Μ++1); 4 NMR (CDC13) δ 10. 20(s, 1H), 8. 27(d,lH), 7. 88(d, 1H), 7. 57(m, 2H), 7. 39(m, 3H), 7. 13(dd, 1H), 7. 01(d, 2H), 6. 14(d, 1H), 5. 68(q, 1H), 5. 62(s, 1H), 4. 97 (dd, 1H), 4. 64 (m, 2H), 4. 41(d, 1H), 4. 07(m, 1H), 3. 87(s, 3H), 2. 87 (m, lH), 2. 67(m, 2H), 2. 45 (m, 1H), 2. 25(q, 1H), 1. 93-0. 85 (m, 15H), 1. 92(s, 3H). Compound 197: MS: m/z 856. 3(M++1) ; 4 NMR(CDC13) δ s; 93 201109028 10. 34(s, 1H), 8. 03(s, 1H), 8. 00(d, 2H), 7. 45(d, 1H), 7. 35{d, 1H), 7. 16(m, 2H), 7. 00(d, 2H), 5. 71(s, 1H), 5. 69(q, 1H), 5. 23(d, 1H), 4. 95 (dd, 1H), 4. 62(m, 2H), 4. 30 (m, 1H), 4. 03(m, 1H), 3. 86(s, 3H), 2. 88(m, 1H), 2. 66(ra, 2H), 2. 5l(s, 3H), 2. 50 (m, 1H), 2. 31(q,1H), 1. 91-0. 82 (m, 15H), 1. 22(s, 9H). Compound 198: MS: m/z 784. 2 (M++1). Compound 199: MS: m/z 798. 3 (M++1); i. H NMR (CDC13) δ 10. 37(s, 1H), 7. 96(m, 3H), 7. 58(s, 1H), 7. 43(d, 1H), 7. 32(d, 1H), 7. 16(s, 1H), 6. 97(d, 2H), 6. 24(d, 1H), 5. 69(q, 1H), 5. 64(s, 1H), 4. 96(dd, 1H)S 4. 66(m, 1H), 4. 55 (m, 1H), 4. 40(d, 1H), 4. 02(m, 1H), 3. 84(s, 3H), 2. 87 (m, 1H), 2. 68(m, 2H), 2. 49(s, 3H), 2. 50 (m, 1H), 2. 28(q, 1H), 1. 91-0. 83(m, 15H), 1. 91 (s, 3H). Compound 200: MS: m/z 852. 2(M++1) ; iH NMR(CDC13) δ 10. 26(s, 1H), 8. 03(s, 1H), 7. 96(d, 2H), 7. 52(s, 1H), 7. 45(d, 1H), 7. 34(d, 1H), 7. 23(s, 1H), 6. 98(d, 2H), 5. 67(s, 1H), 5. 64(q, 1H), 5. 21 (m, 1H), 4. 93(dd, 1H), 4. 67(m, 2H), 4. 30(d, 1H), 4. 04(m, 1H), 3. 85(s, 3H), 2. 87 (m, 1H), 2. 66-2. 40 (m, 3H), 2. 51(s,3H), 2. 22(q,1H), 1. 95-0. 82 (m, 】 5H). Compound 201: MS: m/z 814·3 (Μ++1); NMR (CDC13) δ 10. 41(s, 1H), 7. 98(m, 3H), 7. 60(s, 1H), 7. 43(d, 1H), 7. 33(d, 1H), 7. 16(s, 1H), 6. 98(d, 2H), 5. 64 (m, 2H), 5. 29(m, 2H), 4. 93(dd, 1H), 4. 69 (m, 1H), 4. 36(m, 1H), 4. 01(m, lH), 3. 84(s, 3H), 3. 42(s, 3H), 2. 87(m, IH), 2. 66(m, 2H), 2. 50(m, 1H), 94 201109028 2. 49(s,3H), 2. 25(q,1H), 1. 94-0. 82 (m, 15H). Compound 202: MS: m/z 838. 2(M++1) ; 4 NMR(CDC13) δ 10. 23(s, 1H), 8. 26(d, 1H), 8. 00(d, 2H), 7. 60 (m, 2H), 7. 44(m, 2H), 7. 23(m, 2H), 7. 01(d, 2H), 5. 73(s, 1H), 5. 67(q, 1H), 4. 94 (dd, 1H), 4. 68(m, 2H), 4. 32(d, 1H), 4. 07(m, 1H), 3. 86(s, 3H), 2. 86(m, 1H), 2. 67(m, 2H), 2. 41 (m, 1H), 2. 23(q, 1H), 1. 94-1. 08(m, 13H), 0. 94-0. 87 (m, 2H). Compound 203: MS: m/z 842·3 (Μ++1); 'H NMR (CDC13) δ 10. 30(s, 1H), 8. 28(d, 1H), 7. 63(s, 1H), 7. 57(m, 3H), 7. 42(m, 2H), 7. 25(m, 1H), 7. 08(s, 1H), 6. 97(dd,lH), 5. 71(m, 2H), 5. 22(d, 1H), 4. 92(dd, 1H), 4. 64 (m, 2H), 4. 3l (m, 1H), 4. 00 (m, 1H), 3. 91(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 55 (m, 1H), 2. 29(q, 1H), 1. 85-0. 83 (m, 15H), l-19 (s, 9H). Compound 204: MS: m/z 784·2 (Μ++1); 4 NMR (CDC13) δ 10. 28(s, 1H), 8. 26(d, 1H), 7. 62(s, 1H), 7. 58(m, 3H), 7. 41(m, 2H), 7. 25(m, 2H), 6. 96 (dd, lH), 6. 13(d, 1H), 5. 71(q, 1H), 5. 68(s, 1H), 4. 95 (dd, 1H), 4. 63(t, 1H), 4. 59(m, 1H), 4. 41(d, 1H), 4. 04(m, 1H), 3. 90(s, 3H), 2. 88(m, 1H), 2. 71 (m, 2H), 2. 52(m, 1H), 2. 29(q, 1H), 1. 92-1. 1. 05(m, 13H), 1. 91(s, 3H), 0. 97-0. 84 (m, 2H). Compound 205: MS: m/z 801. 3 (M++1); NMR (CDC13) δ 10. 34(s, 1H), 8. 25(d, 1H), 7. 61(s, 1H), 7. 57(m, 3H), 7. 39-7. 25(m, 4H), 6. 93(dd,lH), 5. 70 (m, 2H), 5. 44(d, 1H), 4. 94 (dd, 1H), 4. 70 (m, 1H), 4. 39(d, 1H), 4. 32(m, 1H), 4. 03(m, 1H), 95 201109028 3. 90(s, 3H), 3. 48(s, 3H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 52(m, 1H), 2. 26(q,1H), 1. 89-0. 82 (m, 15H). Compound 206: MS: m/z 838_2 (M++1); 丨 "[ NMR(CDC13) δ 10. 19(s, 1H), 8. 27(d, 1H), 7. 62(s, 1H), 7. 58(m, 3H), 7. 41(m, 2H), 7. 25(m, 3H), 6. 97(dd,lH), 5. 71(s, 1H), 5. 63(q,lH), 4. 92(dd, 1H), 4. 64 (m, 2H), 4. 33(d, 1H), 4. 05(m, 1H), 3. 90(s, 3H), 2. 88(m, 1H), 2. 69 (m, 2H), 2. 46(m, 1H), 2. 23(q, 1H), 1. 94- 1. 1. 03(m,13H), 0. 95-0. 84 (m, 2H). Compound 207: MS: m/z 8 (1). 2(M++1) ; b NMR(CDC13) δ 10. 24(s, 1H), 8. 27(d,lH), 7. 86(d, 1H), 7. 55(m, 2H), 7. 42(m, 3H), 7. 12(m, 2H), 7. 00(d, 1H), 5. 68(q, 1H), 5. 62(s, 1H), 5. 47(d, 1H), 4. 92(dd, 1H)S 4. 68(m, 1H), 4. 40 (m, 2H), 4. 04(m, 1H), 3. 87(s, 3H), 3. 50(s, :3H), 2. 89(m,lH), 2. 68(m, 2H), 2. 50 (m, 1H), 2. 25(q, 1H), 1. 91-1. 03(m, 13H), 0. 98-0. 82 (m, 2H). Compound 208: MS: m/z 838. 2(M++1) : 'H NMR(CDC13) δ 10. 19(s, 1H), 8. 27(d,lH), 7. 82(d, 1H), 7. 57(m, 2H), 7. 39(m, 5H), 7. 12(dd, 1H), 7. 02(d, 1H), 5. 63(q, 1H), 5. 60(s, 1H), 4. 90 (dd, 1H), 4. 70 (m, 2H), 4. 32(d, 1H), 4. 03(m, 1H), 3. 85(s, 3H), 2. 86(m,lH), 2. 71-2. 52(m, 2H), 2. 39(m, 1H), 2. 20(q, 1H), 1. 94- 0. 84 (m, 15H). Compound 209: MS: m/z 896. 4(M++1) ; 4 NMR(CDC13) δ 10. 20(s,1H), 8. 31(d,1H), 7. 99(d, 2H), 7. 58(m, 2H), 7. 42(m, 1H), 7. 30-7. 22(m, 2H), 7. 01(d, 2H), 5. 68(s, 1H), 5. 66(q, 1H), 96 201109028 5. 37(d, 1H), 4. 96 (dd, 1H), 4. 78-4. 51(m, 4H), 4. 37(m, 1H), 4. 06(m, 1H), 2. 69 (m, 2H), 2. 51(m, 1H), 2. 28(q, 1H), 1. 94-0. 83(m, 23H), 1. 46(s, 3H), 1. 37 (d, 6H). Compound 210: MS: m/z 882. 4 (M++1); NMR (CDC13) δ 10. 24(s, 1H), 8. 27(d, 1H), 7. 98(d, 2H), 7. 58(m, 2H), 7. 42(m, 1H), 7. 24(m, 1H), 7. 01(d, 2H), 6. 89(s, 1H), 5. 68(s, 1H), 5. 66(q, 1H), 5. 22(d, 1H), 4. 97 (dd, 1H), 4. 78-4. 52(m, 4H), 4. 36(m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 68(m, 2H), 2. 54 (m, 1H), 2. 29(q, 1H), 1. 94-1. 05(m, 21H), 1. 37(d, 6H), 0. 97-0. 83 (m, 2H). Compound 211: MS: m/z 922·2 (Μ++1); 'H NMR (CDC13) δ 10. 13(s, 1H), 8. 26(d, 1H), 8. 10(d, 2H), 7. 59(m, 2H), 7. 42(m, 1H), 7. 35-7. 25(m, 3H), 7. 03(s, 1H), 5. 77(s, 1H), 5. 66(q, 1H), 5. 20(d, 1H), 4. 99(dd, 1H), 4. 71(m, 2H), 4. 56(d, 1H), 4. 35 (m, 1H), 4. 03(m, 1H), 2. 70 (m, 2H), 2. 50 (m, 1H), 2. 29(q, 1H), 1. 90-0. 84(m, 23H), 0. 85(s, 3H). Compound 212: MS: m/z 892·4 (Μ++1); 'H NMR (CDC13) δ 10. 36(s, 1H), 8. 59(s, 1H), 8. 25(d, 1H), 8. 18(d, 2H), 7. 73(d, 2H), 7. 58(m, 2H), 7. 45 (m, 1H), 7. 34(s, 1H), 5. 74(s, 1H), 5. 68(q, 1H), 5. 39(d, 1H), 4. 94 (dd, 1H), 4. 72(m, 2H), 4. 55(d, 1H), 4. 31 (m, 1H), 4. 04(m, 1H), 2. 86(m, 1H), 2. 67(m, 2H), 2. 49 (m, 1H), 2. 26(q,1H), 1. 91-1. 05 (m, 23H). Compound 213: MS: m/z 880. 4(M++1) ; 'H NMR(CDC13) δ 10. 36(s, 1H), 8. 26(d, 1H), 8. 16(d, 2H), 7. 74(d, 2H), 7. 59(m, s 97 201109028 2H), 7. 45 (m, 1H), 7. 30 (m, 2H), 5. 71(s, 1H), 5. 66(q, 1H), 5. 25(d, 1H), 4. 95 (dd, 1H), 4. 71 (m, 1H), 4. 65(d, 1H), 4. 28(m, 1H), 4. 03(m, 1H), 2. 87 (m, 1H), 2. 70 (m, 2H), 2. 5l (m, 1H), 2. 27(q, 1H), 1. 92-1. 06(m, 13H), 1. 19(s, 9H), 0. 97-0. 82 (m, 2H). Compound 214: MS: m/z 780. Compound 215:]^8:111/2 822. 2 (1^++1). Compound 216: MS: m/z 910_3 (M++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 15(d, 2H), 7. 75(d, 2H), 7. 61(s, 1H), 7. 47(d, 1H), 7. 25-7. 15(m, 3H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 18(d, 1H), 4. 98 (dd, 1H), 4. 67(m, 2H), 4. 28(m, 1H), 4. 04(m, 1H), 3. 93(s, 3H), 2. 89 (m, 1H), 2. 69 (m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 91-0. 85(m5 】5H), 1. 20 (s, 9H). Compound 217: MS: m/z 9:22. 3(M++1) ; h NMR(CDC13) δ 10. 28(s, 1H), 8. 17(m, 3H), 7. 74(d, 2H), 7. 26(m, 1H), 7. 17(s, 1H), 7. 02(m, 2H), 5. 77(s, 1H), 5. 69(q, 1H), 5. 20(d, 1H), 4. 96 (dd, 1H), 4. 77(s, 1H), 4. 69 (m, 1H), 4. 54(d, 1H), 4. 33(m, 1H), 4. 04(m, 1H), 3. 92(s, 3H), 2. 89 (m, 1H), 2. 71(m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 90-1. 05(m, 21H), 0. 97-0. 83 (m, 2H). Compound 218: MS: m/z 892·4 (Μ++1); NMR (CDC13) δ 10. 29(s, 1H), 8. 35(s,1H), 8. 28(d, 1H), 8. 24(d,1H), 7. 59(m, 4H), 7. 44(m, 1H), 7. 33(s, 1H), 7. 15(s, 1H), 5. 80(s, 1H), 5. 67 (q, 1H), 5. 27(d, 1H), 4. 95 (dd, 1H), 4. 70 (m, 2H), 4. 58(d, 1 H), 98 201109028 4. 30 (m, 1H), 4. 06(m, 1H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 54 (m, 1H), 2. 28(q, 1H), 1. 92-0. 83 (m, 23H). Compound 219: MS: m/z 880 (M++1); 4 NMR (CDC13) δ 10. 3l(s, 1H), 8. 34(s, 1H), 8. 28(d, 1H), 8. 20(d, 1H), 7. 60 (m, 4H), 7. 45 (m, 1H), 7. 29(s, 1H), 7. 13(s, 1H), 5. 77(s, 1H), 5. 67(q, 1H), 5. 19(m, 1H), 4. 94 (dd, 1H), 4. 67(m, 2H), 4. 26(m, 1H), 4. 05(m, 1H), 2. 88(m, 1H), 2. 71(m, 2H), 2. 53 (m, 1H), 2. 29(q, 1H), 1. 90-0. 83 (m, 15H), 1. 18(s, 9H). Compound 220: MS: m/z 892. 2(M++1) ; 'H NMR(CDC13) δ 10. 29(s, 1H), 8. 39(d, 1H), 8. 06(d, 2H), 7. 88(s, 1H), 7. 71(d, 1H), 7. 45 (m, 3H), 7. 36(s, 1H), 7. 18(s, 1H), 5. 68(s, 1H), 5. 65(q, 1H), 5. 33(d, 1H), 4. 93(dd, 1H), 4. 72(m, 2H), 4. 67(d, 1H), 4. 36(m, 1H), 4. 05(m, 1H), 2. 88(m, 1H), 2. 70 (m, 2H), 2. 53 (m, 1H), 2. 28(q,1H), 1. 92-0. 84 (m, 23H). Compound 221: MS: m/z 880·4 (Μ++1); NMR (CDC13) δ 10. 30(s, 1H), 8. 39(d, 1H), 8. 04(d, 2H), 7. 87(s, 1H), 7. 69(d, 1H), 7. 48(m, 3H), 7. 33(s, 1H), 7. 25(s, 1H), 5. 67(m, 2H), 5. 21(d, 1H), 4. 94 (dd, 1H), 4. 68(m, 2H), 4. 30 (m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 69 (m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 93-0. 84 (m, 15H), 1. 17(s, 9H). Compound 222: MS: m/z 814·3 (Μ++1); &apos;H NMR (CDC13) δ 10. 29(s, 1H), 8. 46(s, 1H), 8. 27(d,lH), 7. 47(m, 3H), 7. 41 (m, 1H), 7. 33(s, 1H), 7. 16(d, 1H), 7. 05(s, 1H), 6. 56(d, 1H), 5. 69 (m, 2H), 5. 24(d, 1H), 4. 95 (dd, 1H), 4. 66(m, 1H), 4. 58(d, 1H), 99 201109028 4. 38(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 34(m, 1H), 2. 29(q, 1H), 1. 90-1. 06(m, 21H), 0. 96-0. 83 (m, 2H). Compound 223: MS: m/z 802. 2(M++1) ; 'H NMR(CDC13) δ 10. 30(s, 1H), 8. 28(d,lH), 7. 54(m, 3H), 7. 42(m, 1H), 7. 29(s, 1H), 7. 20(d, IH), 7. 08(s, 1H), 6. 56(d, 1H), 5. 66(m, 2H), 5. 15(d, 1H), 4. 95 (dd, 1H), 4. 69 (m, 2H), 4. 30 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 35 (m, 1H), 2. 29(q, 1H), ]. 89-l_04 (m, 13H), 1. 19(s,9H),0. 97-0. 83 (m, 2H). Compound 224: MS: m/z 848·2 (Μ++1); 'H NMR (CDC13) δ 10. 30(s, 1H), 8. 08(d,lH), 7. 58(d, 1H), 7. 39(d, 1H), 7. 14(s, 1H), 7. 12-6. 95(m, 4H), 5. 70 (m, 2H), 5. 20(d, 1H), 4. 95 (dd, 1H), 4. 66(m, 1H), 4. 59(d, IH), 4. 33(m, 1H), 4. 03(m, 1H), 3. 91(s, 3H), 2. 90 (m, 1H), 2. 66(m, 2H), 2. 52(m, 1H), 2. 28(q, 1H), 1. 89-1. 06(m,13H),]. 24(s, 9H), 0. 94-0. 83 (m, 2H). Compound 225: MS: m/z 760. 2 (M++1); 4 NMR (CDC13&gt; δ 10. 35(s,1H), 8. 25(d,lH), 7. 55 (m, 3H), 7. 40 (m, 1H), 7_27 (m, 2H), 7. 16(d, 1H), 6. 54(d, 1H), 5. 66(m, 2H), 5. 42(d, 1H), 4. 94 (dd, 1H), 4. 67(m, 1H), 4. 46(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 3. 50(s, 3H), 2. 89 (m, 1H), 2. 66(m, 2H), 2. 33(m, 1H), 2. 26(q,1H), 1. 92-0. 83 (m, 15H). Compound 226: MS: m/z 798. 2(M++1) ; 'H NMR(CDC13) δ 10. 20(s, 1H), 8. 25(d, 1H), 7. 55(m, 3H), 7. 4l (m, 1H), 7. 27(m, 3H), 7. 16(d, IH), 6. 56(d, 1H), 5. 66(m, 2H), 4. 94 (dd, 1H), 4. 67(m, 2H), 4. 35(d, 1H), 4. 05(m, 1H), 2. 88(m, 1H), 2. 66(m, 100 201109028 2H), 2. 43 (m, 1H), 2. 26(q,1H), 1. 96-0. 83 (m, 15H). Compound 227: MS: m/z 744. 2(M++1) ; iH NMR(CDC13) δ 10. 31(s, 1H), 8. 21(d,lH), 7. 55(m, 3H), 7. 39(m, 1H), 7. 33-7. 25(m, 2H), 7. 12(d, 1H), 6. 56(d, 1H), 6. 16(d, 1H), 5. 66(q, 1H), 5. 62(s, 1H), 4. 94 (dd, 1H), 4. 62 (m, 1H), 4. 59(m, 1H), 4. 41(d, 1H), 4. 06(m, 1H), 2. 87 (m, 1H), 2. 68(m, 2H), 2. 50 (m, 1H), 2. 26(q,1H), 1. 95-0. 83 (m, 15H), 1. 90 (s, 3H). Compound 228: MS: m/z 857. Compound 229: MS: m/z 830. 3(M++1) ; h NMR(CDC13) δ 10. 25(s, 1H), 8. 26(d,lH), 7. 59(m, 2H), 7. 43(m, 2H), 7. 25(m, 2H), 7. 19(m, 1H), 7. 06(m, 1H), 5. 76(s, 1H), 5. 72(q, 1H), 5. 18(m, 1H), 4. 97 (dd, 1H), 4. 68(m, 2H), 4. 56(d, 1H), 4. 30 (m, 1H), 4. 04(m, 1H), 2. 90 (m, 1H), 2. 70 (m, 2H), 2. 39(m, 1H), 2. 27(q, 1H), 1. 90-0. 80 (m, 23H). Compound 230·· MS: m/z 860_3 (M++1); 4 NMR (CDC13) δ 10. 28(s, 1H), 8. 10(d,lH), 7. 58(d, 1H), 7. 39(d, 1H), 7. 18(s, 1H), 7. 09-6. 97(m, 4H), 5. 72(s, 1H), 5. 68(q, 1H), 5. 24(d, 1H), 4. 95 (dd, 1H), 4. 80(s, 1H), 4. 65 (m, 1H), 4. 54(d, 1H), 4. 32(m, 1H), 4. 03(m, 1H), 3. 91(s, 3H), 2. 94 (m, 1H), 2. 68(m, 2H), 2. 54 (m, 1H), 2. 28(q, 1H), 1. 90-1. 05(m, 21H), 0. 95-0. 84 (m, 2H). Compound 231: MS: m/z 848. 2(M++1) ; 'H NMR(CDC13) δ 10. 26(s, 1H), 7. 64(d,lH), 7. 60(d, 1H), 7. 48(d, 1H), 7. 40(d, 1H), 7. 20(s, 1H), 7. 15(m, 2H), 6. 88(s, 1H), 5. 65(m, 2H), 101 201109028 5. 10(d, 1H), 4. 96 (dd, 1H), 4. 63(m, 2H), 4. 31 (m, 1H), 4. 04(m, 1H), 3. 94(s, 3H), 2. 86(m, 1H), 2. 68(m, 2H), 2. 56(m, 1H), 2. 29(q,1H), 1. 94-0. 83 (m, 15H), 1. 22 (s, 9H). Compound 232: MS: m/z 836. 2(M++1) ; 4 NMR(CDC13) δ 10. 29(s, 1H), 7. 89 (dd, lH), 7. 60(d, 1H), 7. 50 (dd, 1H), 7. 40(d, 1H), 7. 22(m, 2H), 7. 10(m, 1H), 7. 00(s, 1H), 5. 68(m, 2H), 5. 18(d, 1H), 4. 95 (dd, 1H), 4. 66(m, 2H), 4. 29(m, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 67(m, 2H), 2. 53 (m, 1H), 2. 26(q, 1H), 1. 92-0. 83 (m, 15H), 1. 20(s, 9H). Compound 233: MS: m/z 806·2 (Μ++1); NMR (CDC13) δ 10. 36(s,]H), 8. 05(d,lH), 7. 59(d,lH), 7. 38 (m, 2H), 7. 14-6. 97 (m, 4H), 5. 70 (m, 2H), 5. 64(d, 1H), 4. 96 (dd, 1H), 4. 65 (m, 1H), 4. 58(m, 2H), 4. 04(m, 1H), 3. 90(s, 3H), 3. 58(s, 3H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 53(m, LH), 2. 25(q, 1H), 1. 88-0. 82 (m, 15H). Compound 234: MS: m/z 860. 2(M++1) ; A NMR(CDC13) δ 10. 31(s, 1H), 7. 63(d,lH), 7. 60(d, 1H), 7. 45(d, 1H), 7. 40(d, 1H), 7. 20(m, 2H), 7. 10(m, 2H), 5. 69(s, 1H), 5. 67(q, 1H), 5. 30(d, 1H), 4. 94 (dd, 1H), 4. 78(s, 1H), 4. 64 (m, 1H), 4. 55(d, 1H), 4. 36(m, 1H), 4. 04(m, 1H), 3. 94(s, 3H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 26(q, 1H), 1. 93-1. 04(m, 21H), 0. 97-0. 82 (m, 2H). Compound 235: MS: m/z 844·2 (Μ++1); 'H NMR (CDC13) δ 10. 24(s, 1H), 8. 04(d,lH), 7. 58(d, 1H), 7. 39(d, lH), 7. 31 (m, 102 201109028 2H), 7. 18(s, 1H), 7. 08(m, 3H), 5. 70(s, 1H), 5. 67(q, 1H), 4. 86 (dd, 1H), 4. 64 (m, 2H), 4. 26(d, 1H), 4. 02(m, 1H), 3. 90(s, 3H), 2. 84 (m, 1H), 2. 65 (m, 2H), 2. 44 (m, 1H), 2. 20(q, 1H), 1. 91-0_83 (m, 15H). Compound 236: MS: m/z 832·2 (Μ++1); 'H NMR (CDC13) δ 10. 27(s, 1H), 8. 22(d,lH), 7. 58(m, 2H), 7. 44(m, 1H), 7. 29(m, 1H), 7. 10(s, 1H), 6. 94(d, 1H), 6. 90(s, 1H), 5. 69 (m, 2H), 5. 18(d, 1H), 4. 93(dd, 1H), 4. 67(m, 2H), 4. 28(m, 1H), 4. 05(m, 1H), 2. 85 (m, 1H), 2. 68(m, 2H), 2. 55(s, 3H), 2. 54 (m, 1H), 2. 28(q,1H), 1. 91-0_83 (m, 15H), 1. 19 (s, 9H). Compound 237: MS: m/z 844_3 (M++1); NMR (CDC13) δ 10. 23(s, 1H), 8. 22(d,lH), 7. 58(m, 2H), 7. 40 (m, 1H), 7. 29(m, 2H), 6. 96(d, 1H), 6. 84(s, 1H), 5. 69(s, 1H), 5. 66(q, 1H), 5. 20(d, 1H), 4. 94 (dd, 1H), 4. 73(s, 1H), 4. 67(m, 1H), 4. 58(d, 1H), 4. 35 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 56(s,3H), 2. 54 (m, 1H), 2. 26(q,1H), 1. 91-0. 83 (m, 23H). Compound 238: MS: m/z 844. 3(M++1) ; NMR(CDC13) δ 10. 26(s,1H), 8. 22(d,lH), 7. 55 (m, 2H), 7. 43 (m, 2H), 7. 18(m, 1H), 6. 93(s, 1H), 6. 75(s, 1H), 5. 70 (m, 2H), 5. 21(d, 1H), 4. 94 (dd, 1H), 4. 78(s, 1H), 4. 63(m, 1H), 4. 53(d, 1H), 4. 35 (m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 67(m, 2H), 2. 53(s, 3H), 2. 52(m, 1H), 2. 26(q, 1H), 1. 92-1. 04(m, 21H), 0. 95-0. 83 (m, 2H). Compound 239: MS: m/z 790. 2(M++1) ; 4 NMR(CDC13) δ s 103 201109028 10. 34(s, 1H), 8. 20(d,lH), 7. 54(m, 2H), 7. 38(m, 2H), 7. 28(s, 1H), 7. 14(s, 1H), 6. 73(s, 1H), 5. 68(m, 2H), 5. 43(d, 1H), 4. 94 (dd, 1H), 4. 65 (m, 1H), 4. 39(m, 2H), 4. 04(m, 1H), 3. 58(s, 3H), 2. 89 (m, 1H), 2. 68(m, 2H), 2. 5 l(s, 3H), 2. 50 (m, 1H), 2. 28(q,1H), 1. 93-1. 06(m, 13H), 0. 94-0. 82 (m, 2H). Compound 240: MS: m/z 828. 2(M++1) ; 4 NMR(CDC13) δ 10. 18(s, 1H), 8. 22(d,lH), 7. 56(m, 2H), 7. 40 (m, 2H), 7. 20(s, 2H), 7. 08(s, 1H), 6. 76(d, IH), 5. 71(s, 1H), 5. 66(q, 1H), 4. 94 (dd, 1H), 4. 66(m, 2H), 4. 29(d, 1H), 4. 04(m, 1H), 2. 88(m, 1H), 2. 65 (m, 2H), 2. 53(s, 3H), 2. 45 (m, 1H), 2. 23(q, 1H), 1. 96-1. 05(m, 13H), 0. 95-0. 83 (m, 2H). Compound 241: MS: m/z </RTI> </RTI> <RTI ID=0.0></RTI> <RTI ID=0.0> 38(s, 1H), 7. 89 (dd, lH), 7. 58(d, 2H), 7. 44 (dd, 1H), 7. 35(d, 1H), 7. 24(m, 2H), 7. 05(m, 1H), 6. 18(d, 1H), 5. 7l (q, 1H), 5. 62(s, 1H), 4. 95 (dd, 1H), 4. 63(m, 1H), 4. 50 (m, 1H), 4. 40(d, 1H), 4. 00 (m, 1H), 2. 88(m, 1H), 2. 66(m, 2H), 2. 53 (m, 1H), 2. 22 (q, lil), 1. 96-0. 82(m, 15H), 1. 91(s, 3H). Compound 242: MS: m/z 846. 4 (M++1). Compound 243: MS: m/z 858. 3(M++1) ; i NMR(CDC13) δ 10. 28(s, 1H), 8. 24(d, 1H), 7. 57(m, 2H), 7. 42. (m, 2H), 7. 19(s, 1H), 7. 08(ss 1H), 6. 79(d, IH), 5. 66(m, 2H), 5. 24(d, 1H), 4. 96(m, 1H), 4. 78(s, 1H), 4. 67(m, 1H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 03(m, 1H), 2. 85 (ra, 3H), 2. 67(m, 2H), 2. 53 (m, 1H), 2. 28(q, 1H), :1. 94-0. 84 (m, 26H). 104 201109028 Compound 244: MS: m/z 872. 3(M++1) ; 'H NMR(CDC13) δ 10. 13(s, 1H), 8. 24(d, 1H), 7. 53(m, 2H), 7. 41(m, 2H), 7. 19(s, 1H), 6. 99(s, 1H), 6. 79(d, 1H), 5. 69 (m, 2H), 5. 23(d, 1H), 4. 98 (dd, 1H), 4. 77(s, 1H), 4. 65 (m, 1H), 4. 55(d, 1H), 4. 35 (m, 1H), 4. 04(m, 1H), 2. 87(q, 2H), 2. 68(m, 2H), 2. 53 (m, 1H), 2. 29(q, 1H), 1. 94-0. 84 (m, 26H), 0. 83(s, 3H). Compound 245: MS: m/z 831. 2(M++1) ; iH NMR(CDC13) δ 10. 21(s, 1H), 8. 26(d,lH), 7. 90(d, 2H), 7. 58(m, 2H), 7. 46(d, 2H), 7. 00(s, 1H), 5. 69 (m, 2H), 5. 09(d, 1H), 4. 99(dd, 1H), 4. 62(m, 3H), 4. 27(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2_56 (m, 1H), 2. 29(q,1H), 1. 94-0. 84 (m, 23H). Compound 246: MS: m/z 761. 4(M++1) ; 4 NMR(CDC13) δ 10. 21(s, 1H), 8. 17(d,lH), 7. 80(d, 3H), 7. 56(m, 2H), 7. 41(d, 2H), 6. 58(s, 1H), 5. 61(m, 2H), 5. 21(d, 1H), 4. 65 (m, 2H), 4. 24(m, 1H), 4. 05(m, 1H), 2. 89 (m, 1H), 2. 70 (m, 2H), 2. 56-2. 21(m, 2H), 1. 94-0. 84(m, 15H), 1. 87(s,3H) 化合物 Compound 247: MS: m/z 803. 4 (M++1). Compound 248: MS: m/z 845. 3 (M++1). Compound 249: MS: m/z 917. 2(M++1) ; 4 NMR(CDC13) δ 10. 22(s, 1H), 8. 08(d,lH), 7. 78(s,1H), 7. 40 (s, 1H), 7. 06(s, 1H), 6. 97(m, 2H), 5. 64 (m, 2H), 5. 32(d, 1H), 4. 94 (dd, 1H), 4. 70 (m, 2H), 4. 54(d, 1H), 4. 34 (dd, 1H), 4. 08(m, 1H), 3. 83(s, 3H), 3. 18(m, 1H), 2. 73-2. 43(m, 2H), 2. 33(q, 1H), 2. 15-1. 20 (m, 30H), 0. 83 (s, 3H). 105 201109028 Compound 250: MS: m/z 905·4 (Μ++1). Compound 251: MS: m/z 901. 3 (Μ++1). Compound 252: MS: m/z 917. 4 (Μ++1). Compound 253: MS: m/z 903. 3 (Μ++1). Example 254: Synthesis of [4-cyclopropanesulfonylaminocarbonyl-18-(2-fluoro-benzo[4,5]furo[3,2-b]quinolin-11-yloxy)-2 , 15-dioxo-3,16-diazatricyclo[14. 3. 0. 04,6]nonadecane-14-yl]-carbamic acid cyclopentyl ester (Compound 254) Compound 254 was prepared by the following synthetic route. 106 201109028

Cl 1-26 P〇Cl3 reflux, 3 hours

]-27

ΙΜΐυ,ΗΟΒ^Μ

1·29

Lb/Pd-C MeOIi

°°°

Ct 1-31. To a solution of Boc-trans-4-hydroxy-L-proline (0.53 g, 2.30 mmol) in DMSO (10 mL) was added i-BuONa (0.49 g, 5.08 mmol). ). Warm to room temperature and stir for an additional hour, then at 1 Torr. 〇 Slowly add intermediate I-26 (G.62 g ' 2.31 mmol _). The reaction mixture was mixed for 4 hours, devoid of 107 201109028 and then quenched with a 10% aqueous HCl solution to a pH of 6-7. The crude suspended solid was filtered, washed with water and dried to give 1-27 (0.92 g, 86%). MS: m/z 467.1 (M++1). 5 ° C, to 1-27 (0.90 g, 1.93 mmol), HATU (58.9 g, 1.55 mmol), HOBt (7.0 g, 0.52 mmol) and NMM (38.3 g, 3.86 mmol) in CH2C12 (10 Cyclohexane propanesulfonic acid (丨-amino-2-vinyl-cyclopropanecarbonyl)-decylamine (54.0 g, 2.03 mmol) and NMM (0.19 g, 1.93 mmol) were dissolved in CH2C12 dropwise. mixture. The mixture was warmed to rt. MS: m/z 679·1 (Μ++1). Compound 1-28 (1.20 g, 1.77 mmol) was dissolved in MeOH (18 mL). Thionium gas (0.39 ml, 5, 30 mmol) was added dropwise to the reaction mixture. After removing the ice bath, the reaction mixture was heated at 65 ° C for 1 hour. The resulting solution was cooled to 4 ° C, filtered, washed with cold MeOH and ether to afford pale yellow powder to afford white powders 1-29, which was used in the next reaction step without further purification. MS: m/z 579·1 (Μ++1). 5 ° C to 2-cyclopentyloxycarbonylamino-indole-8-enoic acid (0.87 g, 2,34 mmol), HATU (1.16 g, 3_05 mmol) and H〇Bt (0.14 g, 1.02 m a mixture of 1-29 (1.18 g, 2.03 mmol; ^,]^11^ (0.49 g, 4.87 mmol) dissolved in DMF (1 () mL) was added dropwise to a solution of CH2C12 (10 mL) After warming to room temperature and re-mixing for 16 hours, '1.0% HCl (1 mL) was added and the reaction mixture was concentrated. The residue was cooled to 5 ° C, using 108 201109028 5% HCl (aq) (10 ml χ) 2) Washed sequentially with NaHC03 (aq.) (10 mL EtOAc) (EtOAc) (EtOAc) The solution was degassed for 1 hour by a bubbling of a solution of compound 1-30 (0.50 g, 0·59 mmol) in CH2C12 (120 ml). A second generation Hovda-Grubb catalyst (48 mg, 0.076 mmol) was added and the reaction mixture was heated at 40 ° C for 16 hours. After the reaction was indicated by HPLC, the reaction mixture was cooled to 30 ° C. Concentrated and purified by silica gel column chromatography to obtain product I-31 (0.30 g, yield 62 ° / c)). MS: m/z 816·3 (M++1); 1HNMR (CDC13) δ 10.33 (s, 1H), 8.30 (d, 1H), 8.11 (dd, 1H), 7.88 (dd, 1H), 7.67-7.56 (m, 2H), 7.46(dd, 1H), 7.43-7.30(m, 2H), 6.12(s, 1H), 5.64(q, 1H), 5.22(d, 1H), 4.92(dd, 1H), 4.77(d, 1H), 4.66(dd, 1H), 4.32-4.22(m, 1H), 4.04(dd, 1H), 2.93-2.46(m,3H), 2_31(q, 1H), 1.92-0.80 ( m, 25H). To a solution of the compound i_3i (5 mg, 〇〇61 mmol) in MeOH (10 ml) was added 5 〇/〇Pd_c (5 mg). Then, the reaction mixture was stirred under a hydrogen atmosphere at a pressure of 60 psi and room temperature for 4 hours. The reaction mixture was filtered and purified by EtOAc EtOAc (EtOAc: EtOAc: EtOAc: ssssssssssssssssssssssssssss ), 8.l3 (dd, 1H), 7 8 〇 (dd, m), 7.65-7.57 (m5 2H), 7.45 (dd, 1H), 7.39-7.30 (m, 2H), 6.1 l(s, 1H ), 5.25(d, 1H), 4.96(brs, 1H), 4.68(dd, 1H), 4.60(d, 1H), 4.37(dd, 1H), 4.14(dd, 1H), 3.02.2.57(m, 3H), 1.92-0.80 (m, 109 201109028 29H). Examples 255-281: Synthesis of Compound 255-281 Compounds 255-281 were each prepared in a similar manner as described in Example 254. </ RTI> <RTI ), 7.37(m, 1H), 7.18(m, 1H), 6.20(d, 1H), 5.97(s, 1H), 5.64(q, 1H), 4.94(dd, 1H), 4.68(m, 1H) , 4.61(d, 1H), 4.44(m, 1H), 4.02(m, 1H), 2.85(m, 2H), 2.70(m, 1H), 2.58(m, 1H), 2..25(q, 1H), 1.92 (s, 3H), 1.90 - 1.03 (m, 15H). Compound 256: MS: m/z 815.6 (M++1); 'H NMR (CDC13) δ 10.31 (s, H), 8.32 (d, 1H), 8.25 (m, 1H), 7.81 (dd, 1H) ), 7.64(m, 2H), 7.46(dd, 1H), 7.23-7.12(m, 2H), 6.20(s, 1H), 5.66(q, 1H), 5.16(d, 1H), 4.98(dd, 1H), 4.75-4.64(m, 3H), 4.31(m, 1H), 4.08(m, 1H), 2.88(m, 1H), 2.78(m, 2H), 2.55(m, 1H), 2.29(q , 1H), 1.92-0.84 (m, 23H). Compound 257: MS: m/z (m/z) (m/m), NMR (CD, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, s, , 7.63-7.42(m, 3H), 7.21(m, 1H), 5.97(s, 1H), 5.60(q, 1H), 5.44(d, 1H), 4.85(dd, 1H), 4.66(m, 2H) ), 4.29 (m, 1H), 4.02 (m, 1H), 3.88-3.62 (m, 2H), 2.87-2.58 (m, 5H), 2.33 (q, 1H), 1.90-0.78 (m, 15H), 0.97 (s, 6H). Compound 258: MS: m/z </ </ </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; , 7.84(s, 1H), 7.62(m, 110 201109028 3H), 7.44(m, 2H), 7.18(m, 1H), 6.06(s, 1H), 5.67(q, 1H), 4.96(dd, 1H ), 4.80(d, 1H), 4.60(m, 1H), 4.41(m, 1H), 4.10(m, 2H), 3.66(m, 1H), 3.39(m, 2H), 3.22(s, 3H) , 2.91-2.58 (m, 4H), 2.20 (q, 1H), 1.90-0.86 (m, 15H). Compound 259: MS: m/z 788.1 (M++1); 'H NMR (CDC13) δ 10.51 (s, 1H), 8.28(d, 1H), 7.94(m, 1H), 7.86(s, 1H), 7.64(d, 1H), 7.60-7.43(m, 4H), 7.16(m, 1H), 6.00(s, 1H), 5.85(m, 1H), 5.62(m, 2H), 5.30-5.19(m, 2H), 4.93(dd, 1H), 4.66(m, 1H), 4.58-4.36(m, 3H), 4.02 (m, 1H), 2.87-2.56 (m, 4H), 2.26 (q, 1H), 1-86-0.86 (m, 15H). Compound 260: MS m/z 762.2(M++1); 4 NMR(CDC13) δ 10.63(s, 1H), 8.26(d, 1H), 8.10(s, 1H), 7.88(d, 1H), 7.67-7.44 ( m, 4H), 6.84(s, 1H), 5.89(s, 1H), 5.68(q, 1H), 5.38(d, 1H), 4.97(dd, 1H), 4.76(m, 1H), 4.58(d , 1H), 4.21 (m, 1H), 3.96 (m, 1H), 3.66 (s, 3H), 2.91-2.60 (m, 4H), 2.25 (q, 1H), 1.89-0.89 (m, 15H). Compound 261: MS: m/z: 704.2 (M++1); iH NMR (CD3OD) δ 9.26 (s, 1H), 8.47 (d, 1H), 8.26 (m, 1H), 8.15 (dd, 1H), 7.97-7.82(m, 3H), 7.66(m, 1H), 6.54(s, 1H), 5.74(q, 1H), 5.13(dd, 1H), 4.60(d, 1H), 4.35(m, 2H) , 3.72-3.58 (m, 2H), 2.97-2.81 (m, 3H), 2.51 (m, 1H), 2.33 (q, 1H), 1.99-1.06 (m, 15H). Compound 262: MS: m/z 818.3 (M++1); iH NMR (CDC13) δ 10.42 (s, 1H), 8.30 (d, 1H), 8.12 (m, 1H), 7.86 (m, 1H), 7.49- 7.33(m, 5H), 6.10(s, 1H), 5.66(m, 2H), 5.08-4.66(m, 4H), 111 201109028 4.28(m, 1H), 4.03(m, 1H), 3.86- 3.58 (m, 4H), 2.86-2.57 (m, 4H), 2.34 (q, 1H), 2.03-0.87 (m, 17H). Compound 263: MS: m/z 780·2 ( Μ +1); 4 NMR (CDC13) δ 10.60 (s, 1H), 8.04-7.92 (m, 3H), 7.78 (m, 1H), 7. , 1H), 7.38 (m, 1H), 6.94 (m, 1H), 5.89 (s, 1H), 5.67 (q, 1H), 5.40 (d, 1H), 4.95 (dd, 1H), 4.76 (ra, 1H), 4.57(d, 1H), 4.20(m, 1H), 3.97(m, 1H), 3.64(s, 3H), :2.94-2.63(m, 4H), 2.23(q, 1H), 1.88- 1.09 (m, 15H). Compound 264: MS: m/z 9: Π.3 (Μ+1); NMR (CDC13) δ 10.43 (s, 1H), 8.30 (d, 1H), 8.10 (m, 1H), 7.86 (d, 1H), 7.62- 7.34(m, 5H), 6.08(s, 1H), 5.60(q, 1H), 5.38(s, 1H), 4.90- 4.62(m, 4H), 4.26(m, 1H), 4.03 (m, 1H), 3.64(m, 2H), 3.15(m, 2H), 2.85-2.55(m, 4H), 2.:33(q, 1H), 1.83-0.86(m, 19H), 1.44( s, 9H). Compound 265: MS: m/z 780.2 (M++1); 4 NMR (CDC13) δ 10.45 (s, 1H), 8.29 (d, 1H), 8.05 (m, 1H), 7.78 (d, 1H), 7.63-7.25(m, 4H), 6.04(m, 2H), 5.63(q, 1H), 4.91(dd, 1H), 4.72-4.63(m, 3H), 4.43-4.32(m, 2H), 4.02( m, 1H), 3.78-3.58 (m, 1H), 2.85-2.35 (m, 6H), 2.03-0.86 (m, 15H). Compound 266: MS: m/z 776.3 (M++1); 'H NMR (CDC13) δ 10.56 (s, 1H), 8.24 (d, 1H), 8.00 (s, 1H), 7.87-7.79 (m, 2H), 7.61-7.42(m, 4H), 7.06(m, 1H), 5.93(s, 1H), 5.61(q, 1H), 5.44(m, 1H), 4.91(dd, 1H), 4.68(m , 1H), 4.25-3.96 (m, 4H), 2.86-2.57 (m, 4H), 2.29 (q, 1H), 1.8, 0.88 (m, 18H). 112 201109028 Compound 267: MS: m/z 812·2 (Μ++1); NMR (CDC13) δ 10.47 (s, 1 Η), 8.27 (d, 1H), 7.90 (m, 1H), 7.81 (m, 2H), 7.76-7.43(m, 4H), 7.17(m, 1H), 6.03-5.85(m, 2H), 5.61(q, 1H), 4.88(dd, 1H), 4.72-4.61(m, 2H) , 4.25-3.98 (m, 4H), 2.86-2.58 (m, 4H), 2.30 (q, 1H), 1.84-0_88 (m, 15H). Compound 268: MS: m/z 832·2 (Μ+1); 'H NMR (CDC13) δ 10.50 (s, 1H), 8.35-8.29 (m, 1H), 8.15-8.01 (m, 1H), 7.84-7.32 (m, 5H), 7.13-7.03(m, 1H), 6.10(s, 1H), 5.54(m, 1H), 5.36(d, 1H), 5.05-4.83(m, 2H), 4.74- 4.65 (m, 1H), 4.36 (m, 1H), 4.14-4.05 (m, 1H), 2.88-2.51 (m, 4H), 2.12-0.88 (m, 24H). Compound 269: MS: m/z 834.3 (M++1). Compound 270: MS: m/z 792.2 (M++1). Compound 271: MS: m/z 822.2 (M++1); NMR (CDC13) δ 10.38 (s, 1H), 8.09 (m, 1H), 7.99 (dd, 1H), 7.83 (dd, 1H), 7.58 (dd, 1H), 7.41-7.25(m, 3H), 6.15(s, 1H), 5.59(q, 1H), 5.16(d, 1H), 4.89(dd, 1H), 4.78-4.67(m, 2H ), 4.25(m, 1H), 4.07(m, 1H), 2.77-2.70(m, 3H), 2.57(m, 1H), 2.30(q, 1H), 1.90-0.82(m, 15H), 1.23( s, 9H). Compound 272: MS: m/z 822·2 ( Μ +1); 'H NMR (CDC13) δ 10.37 (s, 1H), 8.10 (m, 1H), 7.98 (dd, 1H), 7.83 (dd, 1H), 7.58(dd, 1H), 7.42-7.27(m, 2H), 7.19(s, 1H), 6.16(s, 1H), 5.62(q, 1H), 5.11(d, 1H), 4.92(dd , 1H), 4.78-4.67 (m, 2H), 4.24 (m, 1H), 4.07 (m, 1H), 2.86-2.77 (m, 3H), 2.56 (m, 1H), 2.32 (q, 1H), 1.90-0.82 (m, 15H), 1.23 (s, 9H). 113 201109028 Compound 273: MS: m/z 850.3, 852.3 (M++1). Compound 274: MS: m/z 8:34.2 (M++1); 4 NMR (CDC13) δ 10.43 (s, 1H), 8.08 (m, 1H), 7.95 (dd, 1H), 7.91 (dd, 1H) ), 7.56 (dd, 1H), 7.50 (s, 1H), 7.37-7.31 (m, 2H), 6.05 (s, 1H), 5.58 (q, 1H), 5.39 (d, 1H), 4.72-4.67 ( m, 4H), 4.27(m, 1H), 4.03(m, 1H), 2.89-2.67(m, 3H), 2.55(m, 1H), 2.29(q, 1H), 1.90-0.87(m,23H) . Compound 275: MS: m/z 780 </RTI> (M++1); 4 NMR (CDC13) δ 10.61 (s, 1H), 8.06-7.92 (m, 3H), 7.75 (m, 1H), 7.55 (dd, 1H) ), 7.39(m, 1H), 6.90(m, 1H), 5.89(s, 1H), 5.66(q, 1H), 5.44(d, 1H), 4.94(dd, 1H), 4.77(m, 1H) , 4.58(d, 1H), 4.20(m, 1H), 3.96(m, 1H), 3.65(s, 3H), 2.93-2.67(m, 4H), 2.24(q, 1H), 1.87-1.09(m5 15H). Compound 276: MS: m/z 818.1 (M++1); NMR (CDC13) δ 10.35 (s, 1H), 8.05 (m, 1H), 7.96 (dd, 1H), 7.75 (dd, 1H), 7.57 -7.52(m, 2H), 7.39-7.32(m, 3H), 6.06(s, 1H), 5.60(q, 1H), 4.85-4.73(m, 2H), 4.55-4.48(m, 2H), 4.06 (m, 1H), 2.83 (m, 2H), 2.69 (m, 1H), 2.50 (m, 1H), 2.23 (q, 1H), 1.85-1.05 (m, 15H). Compound 277: MS: m/z 856.3 (M++1). Compound 278: MS: m/z 764·2 ( Μ +1); 4 NMR (CDC13) δ 10.49 (s, 1H), 7.94-7.82 (m, 3H), 7.72 (s, 1H), 7.55 (dd , 1H), 7.38(m, 1H), 7.17(m, 1H), 6.21(d, 1H), 5.99(s, 1H), 5.62.(q, 1H), 4.94(dd, 1H), 4.68(m , 1H), 4.61(d, 1H), 4.45(m, 1H), 114 201109028 4.02(m, 1H), 2.85(m, 2H), 2.71(m, 1H), 2.56(m, 1H), 2.27( q, 1H), 1.92 (s, 3H), 1.90-1.03 (m, 15H). Compound 279: MS: m/z 834.3 (M++1); 'H NMR (CDC13) δ 10.43 (s, 1H), 8.05 (m, 1H), 7.96 (dd, 1H), 7.91 (dd, 1H) , 7.55(dd, 1H), 7.48(s, 1H), 7.37-7.32(m, 2H), 6.05(s, 1H), 5.57(q, 1H), 5.39(d, 1H), 4.79-4.67(m , 4H), 4.28 (m, 1H), 4.03 (m, 1H), 2.87-2.67 (m, 3H), 2.54 (m, 1H), 2.29 (q, 1H), 1.90-0.87 (m, 23H). Compound 280: MS: m/z 818.2 (M++1); 4 NMR (CDC13) δ 10.36 (s, 1H), 8.02 (m, 1H), 7.94 (dd, 1H), 7.71 (dd, 1H), 7.60(s, 1H), 7.54-7.51(dd, 1H), 7.42(d, 1H), 7.36-7.30(m, 2H), 6.03(s, 1H), 5.60(q, 1H), 4.86-4.72( m, 2H), 4.56-4.48 (m, 2H), 4.05 (m, 1H), 2.84 (m, 2H), 2.68 (m, 1H), 2.48 (m, 1H), 2.23 (q, 1H), 1.88 -1.05 (m, 15H). Compound 2 81 was prepared in a similar manner as described in Example 1: Compound 281: MS: m/z: s.ss.ssssssssssssssssssssssssssssssssssssss , 7.59(dd, 1H), 7.39(d, 1H), 7.32(dd, 1H), 7.15(s, 1H), 7.04(s, 1H), 6.14(s, 1H), 5.69(ddd, 1H), 5.04(m, 2H), 4.72(m, 1H), 4.56(m, 2H), 4.24-4.15(m, 2H), 3.97(s, 3H), 3.34(tt, 1H), 2.55(m, 1H) , 2.24-2.26 (m, 1H), 2.01-0.69 (m, 34H). Example 282: Inhibition of NS3/4A protease Protein expression and purification A plasmid containing the N-terminal His6-tagged NS4A(21_32)-GSGS-115 201109028 1^3 (3-181) gene was transformed into Novakine. The company (]^0¥3§611) was overexpressed in the E. coli (five co//) strain BL21(DE3) pLysS. Transformed BL21 (DE3) pLysS single colonies were grown overnight in 200 ml of Lauria-Bertani (LB) medium containing cadinacin and oxytetracycline at 37 °C. The bacterial culture was transferred to 6 liters of antibiotic-containing L B medium of Difico (D i fc 〇) and incubated at 22t with shaking. After the absorbance at 600 nm reached 0.6, the culture was induced with 1 mM isopropyl-1-thio-β-D-galactopyranoside (IPTG) at 22 °C for 5 hours. The culture was then collected by centrifugation (4 ° C, 6,000 X g, 15 minutes). The cell pellet was resuspended in 150 ml of buffer A (50 rnM HEPES, pH 7.4, 0.3 M NaCl, 0.1% (w/v) CHAPS, 10 mM imidazole, 10% (v/v) glycerol). The mixture was allowed to flow through a Microfluidizer operated at 30 psi four times to disperse, and then centrifuged (4. 〇, 58, 250 X g, 3 Torr) to remove cell debris. There are 10 mMu meters. In the presence of Pharmacia's GradiFrac system, a His6-tagged protein-containing lysate was loaded at 3 ml/min onto a 25 ml 恰ι-ΝΤΑ column of Chagan (() § 611). The column was washed with 1 column volume of lysis buffer. The bound NS4A (2丨·32Γ&lt;3808-Ν83(3-ι8ι) was eluted with 8 column volumes of buffer a supplemented with 300 mM sigma saliva. By using buffer β (5〇 ηιΜ)

HEPES 'pH 7.4, 0_1% (w/v) CHAPS, 10% (v/v) glycerol, 5 mM dithiothreitol (DTT) and 1 M NaCl) equilibrated Q·Sepharose column for further purification of the combined Component. The contained eluate was collected and pre-equilibrated with buffer C (50 mM HEPES, pH 7.4, 〇.1〇/0 (w/v) CHAPS, 5 mM DTT, 10% (v/v) glycerol) Sephacryl-75 column (16 x 100 cm, Pharmacia) was further purified by size exclusion chromatography at a flow rate of 116 201109028 5 ml/min. The purified protein was frozen and stored at -80 °C until use. HPLC micropore test preparation containing 50 mM Tris, pH 7.4, 100 mM NaCl, 20% glycerol, 0.012% CHAPS, 10 mM DTT, 5 μΜ Substrate Ac-Asp-Glu-Asp (EDANS)-Glu-Glu-Abu- A solution of y-[COOAla]-Ser-Lys(DABCYL)-NH2(RET S1,ANASPEC) and 10 μΜ test compound. 80 microliters of the solution was added to each well of a 96-well plate. Add 20 pL with 50 mMTris buffer, pH 7.4, 100 mM Naα, 20°/. The 10 nM NS3/4A protease formulated with glycerol and 0.012o/o CHAPS buffer began to react. The final concentration of the NS3/4A protease is 2 η Μ, which is lower than the Km of the substrate RET S1. The test solution was incubated at 30 ° C for 30 minutes. The reaction was then terminated by the addition of 1 〇〇 pL 1% TFA. Aliquots of 200 pL were transferred to each well of a 96-well plate from Agilent. The reaction product was analyzed by reverse phase HPLC as described below. The HPLC system consisted of: Agilent 1100' degassing column G1379A, binary pump G1312A, autosampler G1I367A, column thermostat G1316A, diode array detector G1315B, column: Agilent, ZORBAX Eclipse XDB-C18, 4.6 mm, 5 μιη, P/N 993967-902, column thermostat: room temperature, injection volume: 1 〇〇 pL; solvent A = HPLC grade water + 0.09% TFA, solvent B = HPLC grade acetonitrile + 0.09% TFA. The total run time of the HPLC was 7 6 minutes, including a 4 minute linear gradient from 25 to 50 ° / 〇 solvent B ' 50% solvent B for 30 seconds, and a gradient from 50 to 25% solvent B for another 30 seconds. The column was again equilibrated with 25% solvent B for 2-6 minutes and then the next sample was injected. The 1 Cso value of each test compound 117 201109028 was calculated according to the HPLC result (concentration at which 50% of NS3/4A activity was inhibited was observed). β The compound 丨 _28 was tested in the above inhibition test, and the ICw of 274 compounds was lower than that. 20 ηΜ, 7 compounds of 1 (:5() in the range of 2〇_1〇〇ηΜ. Furthermore, it has been found that certain compounds of the invention unexpectedly inhibit the tolerance to one or more other HCV drugs in an effective manner. HcV protease mutant. Example 283: HCV replicon cell assay protocol Culture of HCV-containing replicons in DMEM (medium A) containing 10% fetal calf serum (FBS), 1.0 mg/ml G4 8 and appropriate supplements On day 1-3, the replicon cell monolayer was treated with trypsin/EDTA mixture, the cell monolayer was removed, and diluted to a final concentration of 48,000 cells/ml with medium A. This solution (1 ml) was inoculated into 24- The wells of the well tissue culture plate were cultured overnight in a tissue incubator at 37 ° C ' 5 ° / C C 2 atmosphere. On day 2 'DMEM containing 1% FBS and appropriate supplements (medium) B) Serial dilution of test compound (with 100% DMSO) In all series of releases, the final concentration of DMSO was maintained at 〇20/〇. The medium on the replicon cell monolayer was removed, and then the medium B containing various concentrations of the compound was added. Additional wells were added as controls without compound. Cells were incubated with compound or 0.2% DMSO in medium B for 72 hours at 37 ° C, 5% CO 2 atmosphere. Then, the medium was removed and the replicon was washed with PBS. The cell monolayer is once. RNA extraction reagents (eg, reagents from the Rneasy kit or TRIZOL reagent) are immediately added to the cells to avoid RNA degradation at 118 201109028. Total RNA is extracted according to the manufacturer's instructions for improved extraction efficiency and consistency. Finally, the total RNA of the cells containing the hcv replicon RNA was eluted and stored at -80 ° C for further processing. TaqMan® real-time RT-PCR quantitative assay was performed with two sets of specific primers: one for HCV and one for HCV. Α (: ΤΒ (β-actin). Total RNA was added to the PCR reaction to quantify HCV and ACTB RNA in the same PCR hole. According to ACTB RNA in each well The experimental failure was marked and discarded. The HCV RNA level in each well was calculated from the standard curve obtained in the same PCR plate. The percent inhibition of HCV RNA level by compound treatment was calculated using DMSO or no compound control as 〇% inhibition. Calculate EC5() based on the titration curve of any given compound (concentration at which HCV RNA levels reach 50% inhibition). The compound 丨_281 was tested in the HCV replicon cell assay. The results showed that 274 compounds had ECso values below 20 nM and 7 compounds had EC50 values between 20 and 100 nM. Example 284: Pharmacokinetic Study One day prior to the experiment, male Sprague-Dawley rats (300-400 g) underwent a jugular vein grafted polyethylene cannula under pentobarbital anesthesia for blood sampling. The rats were fasted overnight with any drinking water, and then the test compound was administered by oral gavage (p〇) the next day. A series of rat blood samples were collected 48 hours after administration, and heparinized plasma was recovered after centrifugation. The test compound in plasma was extracted and assayed by liquid chromatography-mass spectrometry (LC_MS/MS) analysis. Standard pharmacokinetic parameters were evaluated by non-compartmental analysis using WinN〇nlin (version 4 〇, Pharsight, CA, USA). Plasma test 119 201109028 The largest point in the curve of the concentration of the compound versus time is denoted as c a. The apparent final phase elimination (?1/2) is calculated as 1η(2)/λζ, where λζ is the elimination rate constant. The area under the concentration-time curve from the time point of administration to the infinity (AUC^im) was calculated according to the linear trapezoidal rule.

Certain compounds of the invention exhibit extended half-lives and large AIJC values. Other Embodiments All of the features disclosed in the specification can be combined in any combination. The various features disclosed in the specification can be replaced by features that serve the same, equivalent or similar purpose. Accordingly, the various features disclosed are only one example of a series of equivalent or similar features, unless otherwise indicated. From the above description, those skilled in the art can easily determine the main features of the present invention, and various modifications and improvements can be made to the various applications and without departing from the spirit and scope of the invention. condition. Accordingly, other embodiments are also within the scope of the appended claims. I: Simple description of the diagram 3 (none) [Description of main component symbols] (none) 120

Claims (1)

201109028 VII. Patent application scope: 1. A compound of the following structural formula: Wherein, the heart is seven, -OH, Cm alkyl, Cw alkoxy, C3.1G cycloalkyl, CM〇 heterocycloalkyl, aryl, heteroaryl or -ZR, or -NH-ZR; wherein R Is a hydrazine, or a moiety selected from the group consisting of Cm alkyl, C3_1G cycloalkyl, CMG heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: Il, nitro, cyano, amino, C, _6 alkyl, (^_6 alkoxy, C2_6 alkenyl, C2_6 alkynyl, aryl or heteroaryl; Z is -c(o)-, -c (o)o-, -c(o)c(o)o-, -C(0)C(0)NH-, -C(0)NR,-, -OC(S)-, -C(S )NR'- or -C(NH)0-, R' is H, Cw alkyl, C3.1()cycloalkyl, CM. Heterocycloalkyl, aryl or heteroaryl; R2 is hydrazine, or Is a moiety selected from the group consisting of Ci-6 alkyl, C3.10 cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by halogen: , cyano, amino, CN6 alkyl, CN6 alkoxy, C2.6 alkenyl, C2_6 alkynyl, aryl or heteroaryl; A is CH or N; 121 201109028 U is -Ο-, -NH- , -NH(CO)-, -NHSO- or -NHS02-; W -(CH2)m-, -NH(CH2)n-, -(CH2)nNH-, -0(CH2)n-, -(CH2)nO-, -S(CH2)n-, -(CH2)nS -, -SO-, -SO(C:H2)n-, -(CH2)nSO-, -S02(CH2)n- or -(CH2)nS02-, m is 1, 2 or 3, n is 0, ] or 2 ; X is -Ο-, -S-, -NH- or -OCH2-; Y is ^ or T, wherein V and T are each independently -CH- or -N-; and octagonal and octa 2 are each independently selected from the group consisting of C4.1Q cycloalkyl, Cm nonheterocycloalkane a aryl group, an aryl group and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: halogen, schlossyl, cyano, thiol, C|.6 alkyl, Ci-6 oxi , C2-6 alkenyl, C2-6 alkynyl, aryl or heteroaryl, or optionally fused to c3_1()cycloalkyl, CM〇'cycloalkyl, aryl or heteroaryl; Ri is Anthracene, halogen, nitro, cyano or amino, or a moiety selected from the group consisting of Cw alkyl, C|-6 alkoxy, C2-6 dilute, ()2.6 fast radical, C3-H) a group, a C=. Trisubstituted: halogen, moth, cyano, amino, C|_6, Cu_6 calcined, C2-6, C2-6, C3-1G ring, Ci-io heterocyclic , aryl or heteroaryl, c3.1()cycloalkyl, CMG heterocycloalkyl, aryl and heteroaryl are each optionally substituted by Monosubstituted, disubstituted or trisubstituted: halogen, nitro, cyano, amino, CN6 alkyl, c, -6 alkoxy, c2.6 122 201109028 alkenyl, c2_6 alkynyl, c3_1G cycloalkyl, cMG heterocycle An alkyl group, an aryl group or a heteroaryl group, or optionally fused to a c3_1()cycloalkyl group, a CMG heterocycloalkyl group, an aryl group or a heteroaryl group; and a di- or a single bond or a double bond. 2. The compound according to claim 1, wherein X is 0. 3. The compound according to claim 1, wherein A is CH and W is -CH2CH2-, -OCH2-, -SCH2- or -SOCH2-. 4. The compound according to claim 1, wherein A is N and W is -CH2CH2-, -OCH2-, -SCH2- or -SOCH2-. 5. The compound of claim 1, wherein U is -nhso2-. 6. The compound according to claim 1, wherein = is a double bond. 7. The compound according to claim 1, wherein Y Riv , wherein T is CH or N, and Ri, Rib Rm, Riv and Rv are each independently oxime, halogen, nitro, cyano, amino, Q.6 alkyl, CV6 alkoxy, C2.6 olefin Or a C2.6 alkynyl group, or a moiety selected from the group consisting of C3.1()cycloalkyl, CM〇heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted by the following substituents, Disubstituted or trisubstituted: halogen, cyclyl, cyano, amino, Ck alkyl, CN6 alkoxy, C2_6 123 201109028 alkenyl, c2.6 alkynyl, aryl or heteroaryl, or with c3_l() ring Alkyl, CM0 heterocycloalkyl, aryl or heteroaryl is fused. 8. The compound according to claim 7, wherein Ri is a phenyl group or a singyl optionally substituted by halogen, amino, Cm alkyl or Cm alkoxy. Sitting on the base. 9. The compound of claim 1, wherein R2 is Δ or Δ. 10. The compound according to claim 9 which is characterized in that Y Is T, wherein T is CH or N: &amp; is phenyl or thiazolyl optionally substituted by halogen, amino, CU6 alkyl or Cu6 alkoxy; Rn, Rm, Riv*Rv are each independently: Η, Halogen, nitro, cyano, amino, Ci-6 alkyl, C,-6 alkoxy, C2.6 alkenyl or C2-6 alkynyl, or a moiety selected from the group consisting of C3.1()cycloalkyl, C1- 10 heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by halogen, wall group, cyano group, amino group, C1-6 alkyl group, C:.6 Alkoxy, c2_6 alkenyl, c2.6 alkynyl, aryl or heteroaryl, or fused to c3..10 cycloalkyl, CM〇 heterocycloalkyl, aryl or heteroaryl. The compound according to claim 1, wherein R is -NH-ZR, wherein hydrazine is -C(O)-, -C(0)0-, -C(0) C(0)0- or -C(0)C(0)NH-. 12. The compound according to claim 11, wherein: R, 124 201109028 is -NH-C(0)0-t-Bu or -NH-C(0)0-cyclopentyl. The compound according to claim 12, wherein R 2 .CH is Δ or 14. The compound according to claim 13 is characterized in that Y Is a wherein T is CH or N; Ri is phenyl or thiazolyl optionally substituted by halogen, amino, CN6 alkyl or Cw alkoxy; RhRiii, Riv*Rv are each independently: H, halogen, nitro , cyano, amino, CN6 alkyl, Cm alkoxy, C2_6 alkenyl or C2.6 alkynyl, or a moiety selected from the group consisting of C3.1G cycloalkyl, C1-10 heterocycloalkyl, aryl And a heteroaryl group, each of which is optionally mono-, di- or tri-substituted with a halogen, ruthenyl, cyano, amino, C1.6 alkyl, C 1 -6 alkoxy, c 2-6 alkenyl, C2.6 alkynyl, aryl or heteroaryl, or fused to c3.10 cycloalkyl, CM〇 heterocycloalkyl, aryl or heteroaryl. 15. The compound of claim 14, wherein X is Ο, A is CH, W is -CH2CH2-, -OCH2-, -SCH2- or -SOCH2-; U is -nhso2-; The second is a double bond. 16. The compound of claim 11, wherein Ri is -NH-C(O)-furanyl. 17. The compound of claim 16, wherein R2.CH, 125 201109028 is a compound according to claim 17, characterized in that γ Amino, C, 6 alkyl or CM, alkoxy substituted phenyl or thiazolyl; Rii, Rm, RiV and Rv are each independently: fluorene, halogen, schlossyl, cyano, amino, Ci·6 Hyun, C, -6 alkoxy, c2-6 or C2-6 alkynyl, or a moiety selected from the group consisting of C3-IG cycloalkyl, C1-10 heterocycloalkyl, aryl and heteroaryl And each of them is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: dentate, nitro 'cyano, amino, Ci 6 alkyl, C| 6 alkoxy, C 2 · alkenyl, C 2 · 6 alkynyl, aryl or heteroaryl, or slightly coincident with c3l%, a C|.1Q heterocycloalkyl, aryl or heteroaryl. 19. The compound according to claim 18, wherein X is 〇, A is CH, W is _CH2CH2-, _OCH2-, -SCH2- or -soch2-; U is -nhso2-; It is a double bond. The compound according to claim 1, wherein γ is the following compound: 126 201109028 Rii Rvi Rv wherein Ri' Rii, Riii, Riv, Hv and Rvi are each independently: H, _, cis, cyano, amino, Ci6, Ci 6 alkoxy, C26 alkenyl, C: 2 • 6 alkynyl, (: 3-10 cycloalkyl, Ci i 〇 heterocycloalkyl, aryl or heteroaryl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl each optionally substituted by the following substituents Substituted, disubstituted or trisubstituted: _, nitro, cyano, amino, Cw decyl, c, .6 oxime, c 2 6 dilute, c 2 6 alkynyl, aryl or heteroaryl, or A C3-10 cycloalkyl group, a CMG heterocycloalkyl group, an aryl group or a heteroaryl group. 21. The compound according to claim 20, wherein Ri is the following compound 127 201109028 Where η is 1 or 2. 22. The compound of claim 1, wherein the compound is a compound of the compound 1-281. 23. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. 24. A method of treating a hepatitis C virus infection, the method comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition according to the compound of claim 1 of the patent application. 25. The method of claim 24, wherein the composition is administered to the subject once a day. 26. The method of claim 25, wherein the composition is administered orally. 27. The method of claim 24, wherein the compound is a compound of compound 1-281. 128 201109028 IV. Designated representative map: (1) The representative representative of the case is: ( ). (None) (2) A brief description of the symbol of the representative circle: 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 201109028 Application No. 98131053 Application for Patent Scope Amendment Revision Date: 99 Hidden March VII. Patent Application Range: 1. A compound of the following structural formula: Wherein Ri is -H, -OH, Cy alkyl, (^_6 alkoxy, c3_1G cycloalkyl, CU1()heterocycloalkyl, aryl, heteroaryl or -NH-ZR; wherein R is H Or a moiety selected from the group consisting of Q.6 alkyl, (:3_1()cycloalkyl, Cmq heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted by the following substituents Or trisubstituted: halogen, nitro, cyano, amino, cU6 alkyl, a6 alkoxy, c2-6 alkenyl, C2.6 alkynyl, aryl or heteroaryl; Z is -C(o)- , -C(0)0-, -C(0)c(0)0-, -C(0)C(0)NH-, -C(0)NR,-, -〇C(S)-, -C(S)NR,- or -C(NH)〇- 'R' is H, Cw alkyl, C3_1()cycloalkyl, Cw.heterocycloalkyl, aryl or heteroaryl; & H, or a moiety selected from the group consisting of CU6 alkyl, C3_1 () cycloalkyl, Cho heterocycloalkyl, aryl and heteroaryl, each of which is optionally mono-, di- or tri-substituted by the following substituents : halogen, nitro, cyano, amino, Cl_6 alkyl, Cm alkoxy, C2_6 alkenyl, C2-6 alkynyl, aryl or heteroaryl; A is N or CH; U is -〇-, - NH-, -NH(CO)-, -NHSO- or _NHS02-; W is -(CH2)m- -NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n-, 121 201109028 -(CH2)n〇. , -S(CH2)n- ^ &gt;(CH2)nS- ^ - SO-^-SO(CH2)n- &gt; -(cH2)nS〇-. -S02(CH2)n^_(CH2)nS〇2., m^1? 2^3 , n^〇5 { or 2 ; X is -〇·, _s---NH- or _〇ch2-; and Wherein V and T are each independently _CH_ or _N_; Αι and A2 are each independently selected from the group consisting of C4-1G cycloalkyl, (:(tetra)heterocycloalkyl, aryl and heteroaryl) Each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro, aryl, amino, Q-6 alkyl, Cl-6 alkoxy, (: 2-6 alkenyl, c2 6 alkyne a aryl group, an aryl group or a heteroaryl group, or optionally fused to a C3_1G cycloalkyl group, a (hetero-7 heterocycloalkyl group, an aryl group or a heteroaryl group; Ri is a hydrazine, a hydrazine, a nitro group, a cyano group or an amino group, Or a moiety selected from the group consisting of Cw alkyl 'Cl_6 alkoxy, C26 alkenyl, C26 alkynyl, Cwo cycloalkyl, (:]-10 heterocycloalkyl, aryl and heteroaryl 'Ci6 alkyl Each of Ci 6 alkoxy, CM alkenyl and CM alkynyl is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: i, schwitz, cyano, amino, Ci 6, Q 6 , c2_6 dilute group, c2_6 block group, C31G ring-based group 'Ci iD heterocycloalkyl group, aryl or heteroaryl group, Q.丨Q cycloalkyl group, CMG heterocycloalkyl group, aryl group and heteroaryl group Monosubstituted, disubstituted or trisubstituted by the following substituents: , nitro, cyano, amino, C]-6 alkyl, CV6 alkoxy, c2.6 dilute, c2 6 block, C^o cycloalkyl, CMG heterocycloalkyl, aryl or hetero An aryl group, or optionally fused to a cycloalkyl group, a (^-(1)heterocycloalkyl group, an aryl group or a heteroaryl group. 2. A compound according to claim </RTI> wherein X is hydrazine. The compound according to claim 1 or 2, wherein Α is CH, W is -CH2CH2-, -OCHr, -SCH2- or -SOCH2-. 4. Patent application scope The compound of any one of the preceding claims, wherein U is -NHSOr. R匕 Ο , wherein T is CH or N, and Rb Rib Riii, and Rv are each independently η, halogen, exact, gas, amino, (^_6 alkyl, C!-6 alkoxy, C2-6晞Or a C2-6 alkynyl group, or a moiety selected from the group consisting of 匸3_1()cycloalkyl, heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or Trisubstituted: _, nitro, cyano, carbyl, Ci_6 alkyl, 〇μ6 alkoxy, C2-6 alkenyl, C2-6 fast radical, aryl or heteroaryl, or optionally with C3_1 ( A cycloalkyl, Ckk) heterocycloalkyl, aryl or heteroaryl group is fused. 6. - Compounds of the following structural formula: R1 is -H, -OH, Q_6 alkyl, Cn6 alkoxy, Cy. Cycloalkyl, Cw heterocycloalkyl, aryl, heteroaryl or -ZR; wherein R is deuterium or is selected from the group under 123 201109028: Q. Alkyl, aryl and heteroaryl' each of which is optionally taken to monosubstituted, disubstituted or trisubstituted Schottyl, aryl, amino, Ci•concentrator, &amp;oxyalkyl, CM alkenyl, 'block Base, aryl or heteroaryl; 2 is ((9)_, _c(〇)〇_, -C(0)C(0)0-, -C(0)C(0)NH-, -C(〇) NR, _, _0C(8)_, _ C(S)NR'- or -C_〇-, R, is Η, Ci 6 院, Q i〇, C, a heterocycloalkyl, aryl or heteroaryl base; R2 is Η ' or a portion selected from the following: &amp; * silk, C3i. Ring-burning, C丨-丨. An alkyl group, an aryl group, and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by a substituent: hexa, cyano, amino, C"6 alkyl, Ci.6. a group, (: 2.6 dilute, C26 alkynyl, aryl or heteroaryl; A is CH or N; U is -Ο-, -NH-, -NH(CO)-, -NHSO- or -NHS02-; W is -(CH2)m-, -NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n-, -(CH2)nO- &gt; -S(CH2)n- &gt; -(CH2)nS- ' -SO- ' -SO(CH2)n- &gt; -(CH2)nSO-, -S02(CH2)n -or _(CH2)nS〇2_,m is i,2 or 3,^〇, ! Or 2; X is -O-, -S-, -NH- or -〇CHr; Wherein V and T are each independently -CH- or -N-; Aj〇A2 are each independently selected from the group consisting of Qm cycloalkyl, CMQ heterocycloalkyl, aryl and heteroaryl, each of which Optionally, monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro, 124 201109028 cyano, gas, Cl.6, C!-6 alkoxy, C2·6 fluorenyl, C2- a 6-based, aryl or heteroaryl group, or optionally fused to a C3_1G cycloalkyl, Cmo heterocycloalkyl, aryl or hetero group, Ri is a hydrazine, a hydrazine, a nitro group, a cyano group or an amino group Or a moiety selected from the group consisting of: (""alkyl, C"-6 alkoxy, CM alkenyl, C2_6 fast radical, C3-l〇cycloalkyl, Cl-IQ heterocycloalkyl, aryl and hetero The aryl group, the CN6 alkyl group, the C16 alkoxy group, the C2·6 alkenyl group and the C2·6 alkynyl group are each optionally monosubstituted, disubstituted or trisubstituted by the following substituents: i, nitro, cyano, amino, Cl_6 alkyl, Cm oxime oxime, C2·6 alkenyl, Gw alkynyl, Cwq cycloalkyl, cM()heterocyclic, aryl or heteroaryl, Cwg cycloalkyl, CM 〇 heterocycloalkane The aryl group, the aryl group and the heteroaryl group are each optionally substituted by the following substituents, Substituted or trisubstituted: south, nitro, cyano, amino, Cw fluorenyl, C, -6 alkyloxy, c^6 alkenyl, c2 6 block, C3-i fluorene, CuH) heterocycle An alkyl, aryl or heteroaryl group, or optionally a slight combination with a q% phenyl group, a Cuo heterocyclic group, a aryl group or a heteroaryl group; and = is a single bond or a double bond. 9. The compound of claim 6, wherein X is hydrazine. The compound according to claim 6 or 7, wherein - is -CH2CHr, -〇CH2-, -SCH2- or -S〇CHr; and the second is a double bond. The compound according to any one of claims 6-8, wherein U is -NHSOr. For example, if you apply for a special compound in Weiwei, No. 6/9, the compound is characterized by 125 10. 201109028 Riv and Rv are each independently H, _, nitro, cyano, amino, C, 6, 1 6', gas, C: 2·6 or C 2-6, or selected from The following knife 310 is a decyl group, a CM0 heterocycloalkyl group, an aryl group and a heteroaryl group, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: dentate nitro, cyano, amino 'cN6 A silk, an oxy group, a C2 6 alkenyl group, a C26 block group, an aryl group or a heteroaryl group' is fused to a C31G-Weiyl group, a Q-reading group, a silk or a heteroaryl group. 11. A compound of the formula: Wherein, Ritc H -oh, c _6 alkyl, c丨·6 methoxy, C3_丨〇:) 3⁄4, Cmo, alkyl, aryl, heteroaryl, -ZR or -NH -ZR; wherein R is η or a moiety selected from the group consisting of Ci6 alkyl, c(tetra)cycloalkyl, Cii. Heterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, succinyl, cyano, amino, Q.6 alkyl, CV6 methoxy, C2-6 alkenyl, C2_6 alkynyl, aryl or heteroaryl; z is _c(0)_, _c(〇)〇_, -C(0)C(0)0-^-C(0) C(0)NH- '-C(0)NR,- '-OC(S)- '-C(S)NR'- or _c(NH)〇-,r, is h, Cm alkyl, 3_ι〇5 fruit alkyl, Ci-io heterocycloalkyl, aryl or heteroaryl; A is N or CH; 201109028 υ is -Ο-, -ΝΗ·, -NH(CO)-, -NHSO- or -NHS〇2-; W is -(CH2)m-, -NH(CH2)n-, -(CH2)nNH-, -〇(CH2)n-, _(CH2)nO-, -S(CH2) N-, -(CH2)nS-, -SO-,,SO(CH2)n-, -(CH2)nSO-, -S02(CH2)n- or -(CH2)nS02-,m is 1,2 or 3, n is 〇, 1 or 2; X is -Ο-, -S-, -NH- or -CHr; Ο , where V and T are each From independently -CH- or -N-; octagonal and octa 2 are each independently selected from the group consisting of C4-IO cycloalkyl, Cw heterocycloalkyl, aryl and heteroaryl, each of which Monosubstituted, disubstituted or trisubstituted by the following substituents: a cyclin, a nitro group, a cyano group, an amino group, a Q-6 alkyl group, a Q-6 alkoxy group, a C2-6 alkenyl group, a C2-6 alkynyl group, an aryl group or a hetero group. An aryl group, or optionally fused to a C3.1()cycloalkyl, heterocycloalkyl, aryl or heteroaryl group; Ri is an anthracene, a halogen, a nitro group, a cyano group or an amino group, or is selected from the group consisting of Part: CN6 alkyl, Cw alkoxy, C2-6 alkenyl, C2_6 alkynyl, 匸3-10 decyl, Ci-i 〇 heterocycloalkyl, aryl and heteroaryl, Ci-6 alkyl Each of Ci_6 alkoxy, C2_6 alkenyl and (:2_6 alkynyl) is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: dentate, nitro, cyano, amino, (:!_6 alkyl, Cl 6 morphineoxy, C2-6 alkenyl, C2·6 fast radical, C3-10 cycloalkyl, Ci_1G heterocycloalkyl, aryl or heteroaryl, C3.1Q ring, Qw heterocycloalkyl, Each of the aryl and heteroaryl groups is optionally monosubstituted, disubstituted or trisubstituted by the following substituents: _, nitro Cyano, I-based, Ci.6 alkyl, Ci.6 alkoxy, C2-6, C2-6 alkynyl, C3-U)cycloalkyl, QU)heterocycloalkyl, aryl or hetero An aryl group, or optionally fused to a C31() 127 201109028 cycloalkyl group, (: MG heterocycloalkyl, aryl or heteroaryl group; and bis is a single bond or a double bond. The compound according to the above item, wherein X is hydrazine. 13. The compound according to claim </RTI> or wherein the a is CH; W is -CH2CH2-, -〇CHr And -SCHr or -SOCH2-; the heart is a double bond. 14. The compound according to any one of claims 1 to 3, wherein U is -nhso2-. 15. Patent Application No. ιι_14 The compound according to any one of the preceding claims, wherein Wherein, Τ is CH or Ν, and Rb Rib R Riv and Rv are each independently oxime, halogen, nitro, cyano, amino, ci6 alkyl, alkoxy, C2·6 alkenyl or c:2. Alkynyl, or a moiety selected from the group consisting of C3.1()cycloalkyl, Cwoheterocycloalkyl, aryl and heteroaryl, each of which is optionally monosubstituted, disubstituted or trisubstituted by the following substituents : a lignin, a nitro group, a cyano group, an amino group, a Q_6 alkyl group, a Cw alkoxy group, a c2-6 alkenyl group, a c2_6 alkynyl group, an aryl group or a heteroaryl group, or optionally with a &lt;:3_1() naphthenic group The group, C1_1() heterocycloalkyl, aryl or heteroaryl is fused. 16. A compound, a compound of the compound 丨 281. A pharmaceutical composition comprising a compound according to any one of the claims and a pharmaceutically acceptable carrier. 18. The use of a compound according to any one of claims 1 to 16 for the treatment of a hepatitis C virus infection of hepatitis C 201109028. 19. The use according to claim 18, wherein the compound is administered orally to a subject in need of treatment. 20. The use of claim 9, wherein the compound is administered once a day. The use of a compound according to any one of claims 1 to 16 for the preparation of a medicament for the treatment of hepatitis C virus infection. 〇 129